Datasets:

bigbio

/

euadr

like 3

[ { "id": "5587", "type": "title", "text": [ "Iatrogenic botulism in a child with spastic quadriparesis." ], "offsets": [ [ 0, 58 ] ] }, { "id": "5588", "type": "abstract", "text": [ "Botulinum toxins are potent neurotoxins used in a variety of neurological disorders. Few pediatric reports have been published to date regarding the potential hazards of therapeutic use of botulinum toxins. We describe the case of a 10-year-old boy who developed systemic weakness following treatment of spasticity with botulinum toxin type B. The patient developed iatrogenic botulism with ptosis, facial diplegia, neck flexor and extensor weakness, and profound hypopharyngeal laxity with respiratory compromise from which he eventually recovered. Clinicians should be mindful of the risk for systemic botulism when using local injections of the neurotoxin." ], "offsets": [ [ 59, 718 ] ] } ]

[ { "id": "5589", "type": "Diseases & Disorders", "text": [ "Iatrogenic botulism" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "5590", "type": "Diseases & Disorders", "text": [ "spastic quadriparesis" ], "offsets": [ [ 36, 57 ] ], "normalized": [] }, { "id": "5591", "type": "Chemicals & Drugs", "text": [ "Botulinum toxins" ], "offsets": [ [ 59, 75 ] ], "normalized": [] }, { "id": "5592", "type": "Diseases & Disorders", "text": [ "neurological disorders" ], "offsets": [ [ 120, 142 ] ], "normalized": [] }, { "id": "5593", "type": "Chemicals & Drugs", "text": [ "botulinum toxins" ], "offsets": [ [ 248, 264 ] ], "normalized": [] }, { "id": "5594", "type": "Diseases & Disorders", "text": [ "systemic weakness" ], "offsets": [ [ 322, 339 ] ], "normalized": [] }, { "id": "5595", "type": "Diseases & Disorders", "text": [ "spasticity" ], "offsets": [ [ 363, 373 ] ], "normalized": [] }, { "id": "5596", "type": "Chemicals & Drugs", "text": [ "botulinum toxin type B" ], "offsets": [ [ 379, 401 ] ], "normalized": [] }, { "id": "5597", "type": "Diseases & Disorders", "text": [ "iatrogenic botulism" ], "offsets": [ [ 425, 444 ] ], "normalized": [] }, { "id": "5598", "type": "Diseases & Disorders", "text": [ "ptosis" ], "offsets": [ [ 450, 456 ] ], "normalized": [] }, { "id": "5599", "type": "Diseases & Disorders", "text": [ "facial diplegia" ], "offsets": [ [ 458, 473 ] ], "normalized": [] }, { "id": "5600", "type": "Diseases & Disorders", "text": [ "neck flexor" ], "offsets": [ [ 475, 486 ] ], "normalized": [] }, { "id": "5601", "type": "Diseases & Disorders", "text": [ "extensor weakness" ], "offsets": [ [ 491, 508 ] ], "normalized": [] }, { "id": "5602", "type": "Diseases & Disorders", "text": [ "profound hypopharyngeal laxity" ], "offsets": [ [ 514, 544 ] ], "normalized": [] }, { "id": "5603", "type": "Diseases & Disorders", "text": [ "systemic botulism" ], "offsets": [ [ 654, 671 ] ], "normalized": [] }, { "id": "5604", "type": "Chemicals & Drugs", "text": [ "neurotoxin" ], "offsets": [ [ 707, 717 ] ], "normalized": [] }, { "id": "5605", "type": "", "text": [ "Botulinum toxins" ], "offsets": [ [ 59, 75 ] ], "normalized": [] }, { "id": "5606", "type": "", "text": [ "neurological disorders" ], "offsets": [ [ 120, 142 ] ], "normalized": [] }, { "id": "5608", "type": "", "text": [ "botulinum toxin type B" ], "offsets": [ [ 379, 401 ] ], "normalized": [] }, { "id": "5609", "type": "", "text": [ "spasticity" ], "offsets": [ [ 363, 373 ] ], "normalized": [] }, { "id": "5611", "type": "", "text": [ "botulinum toxin type B" ], "offsets": [ [ 379, 401 ] ], "normalized": [] }, { "id": "5612", "type": "", "text": [ "systemic weakness" ], "offsets": [ [ 322, 339 ] ], "normalized": [] }, { "id": "5614", "type": "", "text": [ "neurotoxin" ], "offsets": [ [ 707, 717 ] ], "normalized": [] }, { "id": "5615", "type": "", "text": [ "systemic botulism" ], "offsets": [ [ 654, 671 ] ], "normalized": [] } ]

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[ { "id": "5607", "type": "PA", "arg1_id": "5605", "arg2_id": "5606", "normalized": [] }, { "id": "5610", "type": "PA", "arg1_id": "5608", "arg2_id": "5609", "normalized": [] }, { "id": "5613", "type": "PA", "arg1_id": "5611", "arg2_id": "5612", "normalized": [] }, { "id": "5616", "type": "PA", "arg1_id": "5614", "arg2_id": "5615", "normalized": [] } ]

[ { "id": "5619", "type": "title", "text": [ "Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors." ], "offsets": [ [ 0, 219 ] ] }, { "id": "5620", "type": "abstract", "text": [ "SU11248 sunitinib malate sutent is a selective inhibitor of certain protein tyrosine kinases including VEGF-R types 1-3 PDGF-R-a and -b, c-kit, and RET. Its antitumor activity may result from both inhibition of angiogenesis and direct antiproliferative effects on certain tumor types. In several phase I/II/III studies, sutent was found to be effective as second and first line treatment in metastatic renal cell carcinoma (RCC). In fact, with a 37% response rate and an additional 48% stable disease sutent became the drug of choice for first line treatment in RCC. Sutent was also effective as second line treatment in patients with gastrointestinal stromal tumors (GIST) with 8% response rate, 70% stable disease and a 20-month median survival. Prolonged stable disease was also documented in neuroendocrine tumors. In addition, a phase II study in multitreated women with breast cancer, sutent demonstrated a moderate activity with 16% clinical benefit. Finally, in non-small cell lung cancer (NSCLC) in patients' progressing on chemotherapy sutent was able to achieve a 10% response rate, a level of activity similar to those documented by other agents approved for lung cancer. The agent is being tested in other tumors with a modified schedule of dosage." ], "offsets": [ [ 220, 1481 ] ] } ]

[ { "id": "5621", "type": "Chemicals & Drugs", "text": [ "SU11248" ], "offsets": [ [ 12, 19 ] ], "normalized": [] }, { "id": "5622", "type": "Chemicals & Drugs", "text": [ "multitargeted inhibitor of vascular endothelial growth factor receptor" ], "offsets": [ [ 23, 93 ] ], "normalized": [] }, { "id": "5623", "type": "Chemicals & Drugs", "text": [ "platelet-derived growth factor receptor" ], "offsets": [ [ 98, 137 ] ], "normalized": [] }, { "id": "5624", "type": "Diseases & Disorders", "text": [ "metastatic renal cell carcinoma" ], "offsets": [ [ 156, 187 ] ], "normalized": [] }, { "id": "5625", "type": "Diseases & Disorders", "text": [ "solid tumors" ], "offsets": [ [ 206, 218 ] ], "normalized": [] }, { "id": "5626", "type": "Chemicals & Drugs", "text": [ "SU11248" ], "offsets": [ [ 220, 227 ] ], "normalized": [] }, { "id": "5627", "type": "Chemicals & Drugs", "text": [ "sunitinib malate" ], "offsets": [ [ 228, 244 ] ], "normalized": [] }, { "id": "5628", "type": "Chemicals & Drugs", "text": [ "sutent" ], "offsets": [ [ 245, 251 ] ], "normalized": [] }, { "id": "5629", "type": "Chemicals & Drugs", "text": [ "inhibitor of certain protein tyrosine kinases" ], "offsets": [ [ 267, 312 ] ], "normalized": [] }, { "id": "5630", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 492, 497 ] ], "normalized": [] }, { "id": "5631", "type": "Chemicals & Drugs", "text": [ "sutent" ], "offsets": [ [ 540, 546 ] ], "normalized": [] }, { "id": "5632", "type": "Diseases & Disorders", "text": [ "metastatic renal cell carcinoma" ], "offsets": [ [ 611, 642 ] ], "normalized": [] }, { "id": "5633", "type": "Diseases & Disorders", "text": [ "RCC" ], "offsets": [ [ 644, 647 ] ], "normalized": [] }, { "id": "5634", "type": "Chemicals & Drugs", "text": [ "sutent" ], "offsets": [ [ 721, 727 ] ], "normalized": [] }, { "id": "5635", "type": "Diseases & Disorders", "text": [ "RCC" ], "offsets": [ [ 782, 785 ] ], "normalized": [] }, { "id": "5636", "type": "Chemicals & Drugs", "text": [ "Sutent" ], "offsets": [ [ 787, 793 ] ], "normalized": [] }, { "id": "5637", "type": "Diseases & Disorders", "text": [ "gastrointestinal stromal tumors" ], "offsets": [ [ 855, 886 ] ], "normalized": [] }, { "id": "5638", "type": "Diseases & Disorders", "text": [ "GIST" ], "offsets": [ [ 888, 892 ] ], "normalized": [] }, { "id": "5639", "type": "Diseases & Disorders", "text": [ "neuroendocrine tumors" ], "offsets": [ [ 1016, 1037 ] ], "normalized": [] }, { "id": "5640", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 1096, 1109 ] ], "normalized": [] }, { "id": "5641", "type": "Chemicals & Drugs", "text": [ "sutent" ], "offsets": [ [ 1111, 1117 ] ], "normalized": [] }, { "id": "5642", "type": "Diseases & Disorders", "text": [ "non-small cell lung cancer" ], "offsets": [ [ 1190, 1216 ] ], "normalized": [] }, { "id": "5643", "type": "Diseases & Disorders", "text": [ "NSCLC" ], "offsets": [ [ 1218, 1223 ] ], "normalized": [] }, { "id": "5644", "type": "Chemicals & Drugs", "text": [ "sutent" ], "offsets": [ [ 1266, 1272 ] ], "normalized": [] }, { "id": "5645", "type": "Diseases & Disorders", "text": [ "lung cancer" ], "offsets": [ [ 1391, 1402 ] ], "normalized": [] }, { "id": "5646", "type": "Diseases & Disorders", "text": [ "tumors" ], "offsets": [ [ 1439, 1445 ] ], "normalized": [] }, { "id": "5647", "type": "", "text": [ "sutent" ], "offsets": [ [ 540, 546 ] ], "normalized": [] }, { "id": "5648", "type": "", "text": [ "metastatic renal cell carcinoma" ], "offsets": [ [ 611, 642 ] ], "normalized": [] }, { "id": "5650", "type": "", "text": [ "sutent" ], "offsets": [ [ 540, 546 ] ], "normalized": [] }, { "id": "5651", "type": "", "text": [ "RCC" ], "offsets": [ [ 644, 647 ] ], "normalized": [] }, { "id": "5653", "type": "", "text": [ "sutent" ], "offsets": [ [ 721, 727 ] ], "normalized": [] }, { "id": "5654", "type": "", "text": [ "RCC" ], "offsets": [ [ 782, 785 ] ], "normalized": [] }, { "id": "5656", "type": "", "text": [ "Sutent" ], "offsets": [ [ 787, 793 ] ], "normalized": [] }, { "id": "5657", "type": "", "text": [ "GIST" ], "offsets": [ [ 888, 892 ] ], "normalized": [] }, { "id": "5659", "type": "", "text": [ "sutent" ], "offsets": [ [ 1111, 1117 ] ], "normalized": [] }, { "id": "5660", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 1096, 1109 ] ], "normalized": [] }, { "id": "5662", "type": "", "text": [ "sutent" ], "offsets": [ [ 1266, 1272 ] ], "normalized": [] }, { "id": "5663", "type": "", "text": [ "NSCLC" ], "offsets": [ [ 1218, 1223 ] ], "normalized": [] }, { "id": "5665", "type": "", "text": [ "sutent" ], "offsets": [ [ 245, 251 ] ], "normalized": [] }, { "id": "5666", "type": "", "text": [ "VEGF" ], "offsets": [ [ 323, 327 ] ], "normalized": [] }, { "id": "5668", "type": "", "text": [ "sutent" ], "offsets": [ [ 245, 251 ] ], "normalized": [] }, { "id": "5669", "type": "", "text": [ "c-kit" ], "offsets": [ [ 357, 362 ] ], "normalized": [] }, { "id": "5671", "type": "", "text": [ "sutent" ], "offsets": [ [ 245, 251 ] ], "normalized": [] }, { "id": "5672", "type": "", "text": [ "RET" ], "offsets": [ [ 368, 371 ] ], "normalized": [] }, { "id": "5674", "type": "", "text": [ "sutent" ], "offsets": [ [ 1266, 1272 ] ], "normalized": [] }, { "id": "5675", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 1391, 1402 ] ], "normalized": [] }, { "id": "5677", "type": "", "text": [ "SU11248" ], "offsets": [ [ 12, 19 ] ], "normalized": [] }, { "id": "5678", "type": "", "text": [ "metastatic renal cell carcinoma" ], "offsets": [ [ 156, 187 ] ], "normalized": [] }, { "id": "5680", "type": "", "text": [ "SU11248" ], "offsets": [ [ 12, 19 ] ], "normalized": [] }, { "id": "5681", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 206, 218 ] ], "normalized": [] }, { "id": "5683", "type": "", "text": [ "multitargeted inhibitor of vascular endothelial growth factor receptor" ], "offsets": [ [ 23, 93 ] ], "normalized": [] }, { "id": "5684", "type": "", "text": [ "metastatic renal cell carcinoma" ], "offsets": [ [ 156, 187 ] ], "normalized": [] }, { "id": "5686", "type": "", "text": [ "multitargeted inhibitor of vascular endothelial growth factor receptor" ], "offsets": [ [ 23, 93 ] ], "normalized": [] }, { "id": "5687", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 206, 218 ] ], "normalized": [] }, { "id": "5689", "type": "", "text": [ "platelet-derived growth factor receptor" ], "offsets": [ [ 98, 137 ] ], "normalized": [] }, { "id": "5690", "type": "", "text": [ "metastatic renal cell carcinoma" ], "offsets": [ [ 156, 187 ] ], "normalized": [] }, { "id": "5692", "type": "", "text": [ "platelet-derived growth factor receptor" ], "offsets": [ [ 98, 137 ] ], "normalized": [] }, { "id": "5693", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 206, 218 ] ], "normalized": [] } ]

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[ { "id": "5649", "type": "PA", "arg1_id": "5647", "arg2_id": "5648", "normalized": [] }, { "id": "5652", "type": "PA", "arg1_id": "5650", "arg2_id": "5651", "normalized": [] }, { "id": "5655", "type": "PA", "arg1_id": "5653", "arg2_id": "5654", "normalized": [] }, { "id": "5658", "type": "PA", "arg1_id": "5656", "arg2_id": "5657", "normalized": [] }, { "id": "5661", "type": "PA", "arg1_id": "5659", "arg2_id": "5660", "normalized": [] }, { "id": "5664", "type": "PA", "arg1_id": "5662", "arg2_id": "5663", "normalized": [] }, { "id": "5667", "type": "PA", "arg1_id": "5665", "arg2_id": "5666", "normalized": [] }, { "id": "5670", "type": "PA", "arg1_id": "5668", "arg2_id": "5669", "normalized": [] }, { "id": "5673", "type": "PA", "arg1_id": "5671", "arg2_id": "5672", "normalized": [] }, { "id": "5676", "type": "PA", "arg1_id": "5674", "arg2_id": "5675", "normalized": [] }, { "id": "5679", "type": "PA", "arg1_id": "5677", "arg2_id": "5678", "normalized": [] }, { "id": "5682", "type": "PA", "arg1_id": "5680", "arg2_id": "5681", "normalized": [] }, { "id": "5685", "type": "PA", "arg1_id": "5683", "arg2_id": "5684", "normalized": [] }, { "id": "5688", "type": "PA", "arg1_id": "5686", "arg2_id": "5687", "normalized": [] }, { "id": "5691", "type": "PA", "arg1_id": "5689", "arg2_id": "5690", "normalized": [] }, { "id": "5694", "type": "PA", "arg1_id": "5692", "arg2_id": "5693", "normalized": [] } ]

[ { "id": "5697", "type": "title", "text": [ "Intravitreal bevacizumab (Avastin) treatment of diffuse diabetic macular edema in an Indian population." ], "offsets": [ [ 0, 103 ] ] }, { "id": "5698", "type": "abstract", "text": [ "BACKGROUND: To report the anatomic and visual acuity response after intravitreal bevacizumab (Avastin) in patients with diffuse diabetic macular edema. DESIGN: Prospective, interventional case series study. MATERIALS AND METHODS: This study included 20 eyes of metabolically stable diabetes mellitus with diffuse diabetic macular edema with a mean age of 59 years who were treated with two intravitreal injections of bevacizumab 1.25 mg in 0.05 ml six weeks apart. Main outcome measures were 1) early treatment diabetic retinopathy study visual acuity, 2) central macular thickness by optical coherence tomography imaging. Each was evaluated at baseline and follow-up visits. RESULTS: All the eyes had received some form of laser photocoagulation before (not less than six months ago), but all of these patients had persistent diffuse macular edema with no improvement in visual acuity. All the patients received two injections of bevacizumab at an interval of six weeks per eye. No adverse events were observed, including endophthalmitis, inflammation and increased intraocular pressure or thromboembolic events in any patient. The mean baseline acuity was 20/494 (log Mar=1.338+/-0.455) and the mean acuity at three months following the second intravitreal injection was 20/295 (log Mar=1.094+/-0.254), a difference that was highly significant ( P =0.008). The mean central macular thickness at baseline was 492 microm which decreased to 369 microm ( P =0.001) at the end of six months. CONCLUSIONS: Initial treatment results of patients with diffuse diabetic macular edema not responding to previous photocoagulation did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular thickness and improvement in visual acuity at three months but the effect was somewhat blunted, though still statistically significant at the end of six months." ], "offsets": [ [ 104, 2002 ] ] } ]

[ { "id": "5699", "type": "Chemicals & Drugs", "text": [ "Intravitreal bevacizumab" ], "offsets": [ [ 0, 24 ] ], "normalized": [] }, { "id": "5700", "type": "Chemicals & Drugs", "text": [ "Avastin" ], "offsets": [ [ 26, 33 ] ], "normalized": [] }, { "id": "5701", "type": "Chemicals & Drugs", "text": [ "intravitreal bevacizumab" ], "offsets": [ [ 172, 196 ] ], "normalized": [] }, { "id": "5702", "type": "Chemicals & Drugs", "text": [ "Avastin" ], "offsets": [ [ 198, 205 ] ], "normalized": [] }, { "id": "5703", "type": "Chemicals & Drugs", "text": [ "injections of bevacizumab" ], "offsets": [ [ 507, 532 ] ], "normalized": [] }, { "id": "5704", "type": "Chemicals & Drugs", "text": [ "injections of bevacizumab" ], "offsets": [ [ 1021, 1046 ] ], "normalized": [] }, { "id": "5705", "type": "Genes & Molecular Sequences", "text": [ "Mar" ], "offsets": [ [ 1274, 1277 ] ], "normalized": [] }, { "id": "5706", "type": "Genes & Molecular Sequences", "text": [ "Mar" ], "offsets": [ [ 1389, 1392 ] ], "normalized": [] }, { "id": "5707", "type": "Chemicals & Drugs", "text": [ "Intravitreal bevacizumab" ], "offsets": [ [ 1771, 1795 ] ], "normalized": [] } ]

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[ { "id": "5710", "type": "title", "text": [ "Calcified tissue of fetal origin in utero." ], "offsets": [ [ 0, 42 ] ] }, { "id": "5711", "type": "abstract", "text": [ "Hysteroscopic examination in a woman with secondary infertility revealed calcified tissue in the uterine cavity. Histopathological examination demonstrated mature bone. Genetic analysis supports its fetal origin." ], "offsets": [ [ 43, 255 ] ] } ]

[ { "id": "5712", "type": "Diseases & Disorders", "text": [ "Calcified" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "5713", "type": "Diseases & Disorders", "text": [ "secondary infertility" ], "offsets": [ [ 85, 106 ] ], "normalized": [] }, { "id": "5714", "type": "Diseases & Disorders", "text": [ "calcified" ], "offsets": [ [ 116, 125 ] ], "normalized": [] }, { "id": "5715", "type": "Diseases & Disorders", "text": [ "cavity" ], "offsets": [ [ 148, 154 ] ], "normalized": [] } ]

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[ { "id": "5718", "type": "title", "text": [ "In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the central nervous system." ], "offsets": [ [ 0, 126 ] ] }, { "id": "5719", "type": "abstract", "text": [ "Thirty-one structurally diverse marketed central nervous system (CNS)-active drugs, one active metabolite, and seven non-CNS-active compounds were tested in three P-glycoprotein (P-gp) in vitro assays: transwell assays using MDCK, human MDR1-MDCK, and mouse Mdr1a-MDCK cells, ATPase, and calcein AM inhibition. Additionally, the permeability for these compounds was measured in two in vitro models: parallel artificial membrane permeation assay and apical-to-basolateral apparent permeability in MDCK. The exposure of the same set of compounds in brain and plasma was measured in P-gp knockout (KO) and wild-type (WT) mice after subcutaneous administration. One drug and its metabolite, risperidone and 9-hydroxyrisperidone, of the 32 CNS compounds, and 6 of the 7 non-CNS drugs were determined to have positive efflux using ratio of ratios in MDR1-MDCK versus MDCK transwell assays. Data from transwell studies correlated well with the brain-to-plasma area under the curve ratios between P-gp KO and WT mice for the 32 CNS compounds. In addition, 3300 Pfizer compounds were tested in MDR1-MDCK and Mdr1a-MDCK transwell assays, with a good correlation (R(2) = 0.92) between the efflux ratios in human MDR1-MDCK and mouse Mdr1a-MDCK cells. Permeability data showed that the majority of the 32 CNS compounds have moderate to high passive permeability. This work has demonstrated that in vitro transporter assays help in understanding the role of P-gp-mediated efflux activity in determining the disposition of CNS drugs in vivo, and the transwell assay is a valuable in vitro assay to evaluate human P-gp interaction with compounds for assessing brain penetration of new chemical entities to treat CNS disorders." ], "offsets": [ [ 127, 1837 ] ] } ]

[ { "id": "5720", "type": "Genes & Molecular Sequences", "text": [ "P-glycoprotein" ], "offsets": [ [ 9, 23 ] ], "normalized": [] }, { "id": "5721", "type": "Genes & Molecular Sequences", "text": [ "P-glycoprotein" ], "offsets": [ [ 70, 84 ] ], "normalized": [] }, { "id": "5722", "type": "Chemicals & Drugs", "text": [ "central nervous system" ], "offsets": [ [ 103, 125 ] ], "normalized": [] }, { "id": "5723", "type": "Chemicals & Drugs", "text": [ "central nervous system" ], "offsets": [ [ 168, 190 ] ], "normalized": [] }, { "id": "5724", "type": "Chemicals & Drugs", "text": [ "CNS)-active drugs" ], "offsets": [ [ 192, 209 ] ], "normalized": [] }, { "id": "5725", "type": "Chemicals & Drugs", "text": [ "non-CNS-active compounds" ], "offsets": [ [ 244, 268 ] ], "normalized": [] }, { "id": "5726", "type": "Genes & Molecular Sequences", "text": [ "P-glycoprotein" ], "offsets": [ [ 290, 304 ] ], "normalized": [] }, { "id": "5727", "type": "Genes & Molecular Sequences", "text": [ "P-gp" ], "offsets": [ [ 306, 310 ] ], "normalized": [] }, { "id": "5728", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 364, 368 ] ], "normalized": [] }, { "id": "5729", "type": "Genes & Molecular Sequences", "text": [ "Mdr1a" ], "offsets": [ [ 385, 390 ] ], "normalized": [] }, { "id": "5730", "type": "Genes & Molecular Sequences", "text": [ "ATPase" ], "offsets": [ [ 403, 409 ] ], "normalized": [] }, { "id": "5731", "type": "Chemicals & Drugs", "text": [ "calcein AM" ], "offsets": [ [ 415, 425 ] ], "normalized": [] }, { "id": "5732", "type": "Genes & Molecular Sequences", "text": [ "P-gp" ], "offsets": [ [ 707, 711 ] ], "normalized": [] }, { "id": "5733", "type": "Chemicals & Drugs", "text": [ "risperidone" ], "offsets": [ [ 814, 825 ] ], "normalized": [] }, { "id": "5734", "type": "Chemicals & Drugs", "text": [ "9-hydroxyrisperidone" ], "offsets": [ [ 830, 850 ] ], "normalized": [] }, { "id": "5735", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 971, 975 ] ], "normalized": [] }, { "id": "5736", "type": "Genes & Molecular Sequences", "text": [ "P-gp" ], "offsets": [ [ 1116, 1120 ] ], "normalized": [] }, { "id": "5737", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 1212, 1216 ] ], "normalized": [] }, { "id": "5738", "type": "Genes & Molecular Sequences", "text": [ "Mdr1a" ], "offsets": [ [ 1226, 1231 ] ], "normalized": [] }, { "id": "5739", "type": "Genes & Molecular Sequences", "text": [ "MDR1" ], "offsets": [ [ 1328, 1332 ] ], "normalized": [] }, { "id": "5740", "type": "Genes & Molecular Sequences", "text": [ "Mdr1a" ], "offsets": [ [ 1348, 1353 ] ], "normalized": [] }, { "id": "5741", "type": "Genes & Molecular Sequences", "text": [ "P-gp" ], "offsets": [ [ 1571, 1575 ] ], "normalized": [] }, { "id": "5742", "type": "Genes & Molecular Sequences", "text": [ "P-gp" ], "offsets": [ [ 1725, 1729 ] ], "normalized": [] }, { "id": "5743", "type": "", "text": [ "risperidone" ], "offsets": [ [ 814, 825 ] ], "normalized": [] }, { "id": "5744", "type": "", "text": [ "MDR1" ], "offsets": [ [ 971, 975 ] ], "normalized": [] }, { "id": "5746", "type": "", "text": [ "9-hydroxyrisperidone" ], "offsets": [ [ 830, 850 ] ], "normalized": [] }, { "id": "5747", "type": "", "text": [ "MDR1" ], "offsets": [ [ 971, 975 ] ], "normalized": [] } ]

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[]

[ { "id": "5745", "type": "PA", "arg1_id": "5743", "arg2_id": "5744", "normalized": [] }, { "id": "5748", "type": "PA", "arg1_id": "5746", "arg2_id": "5747", "normalized": [] } ]

[ { "id": "5751", "type": "title", "text": [ "Scavenger receptor of class B expressed by osteoblastic cells are implicated in the uptake of cholesteryl ester and estradiol from LDL and HDL3." ], "offsets": [ [ 0, 144 ] ] }, { "id": "5752", "type": "abstract", "text": [ "Lipoproteins transport many vitamins and hormones that have been shown to be necessary for bone formation. However, the metabolism of LDL and HDL3 by bone-forming osteoblastic cells remains unknown. Here we report that osteoblastic cells express scavenger receptors of class B that are implicated in the uptake of cholesterol and estradiol from LDL and HDL3. INTRODUCTION: The bone tissue is continuously remodeled, and its integrity requires a balance between osteoclastic bone resorption and osteoblastic bone formation. Recent studies have reported the importance of triglyceride-rich lipoproteins for the delivery of lipophilic vitamins necessary for normal bone metabolism. However, the ability of osteoblastic cells to process low- and high-density lipoproteins (LDL and HDL3) and the receptors involved remain unknown. MATERIALS AND METHODS: Binding, competition, degradation, and selective uptake assays with LDL and HDL3 radiolabeled in their protein and lipid moieties or with [3H]estradiol were conducted on human osteoblasts (MG-63 cell line and primary cultures of human osteoblasts [hOB cells]) and on mouse osteoblasts (MC3T3-E1 cell line and primary cultures of murine osteoblasts [mOB cells]). The expression of scavenger receptors (SRs) by osteoblastic cells was determined by RT-PCR and Western immunoblotting, and cellular localization was assessed by sucrose gradient fractionation. RESULTS: Osteoblastic cells were able to bind, internalize, and degrade HDL3 and LDL and are capable of selectively taking up cholesteryl esters (CEs) from these lipoproteins. Also, we provide evidence that osteoblastic cells express SR-BI, SR-BII, and CD36 (SR-Bs receptors) and that these receptors are localized in membrane lipid rafts or caveolin-rich membranes. The selective uptake of CE from LDL and HDL3 by osteoblastic cells was strongly inhibited by the known SR-B ligand oxidized LDL, indicating that SR-B receptors are responsible for the selective uptake. Finally, estradiol carried by LDL and HDL3 was selectively transferred to the osteoblastic cells also through SR-B receptors. CONCLUSIONS: Overall, our results suggest a novel mechanism for the routing of cholesterol and estradiol to osteoblasts involving the metabolism of LDL and HDL3 by SR-B receptors." ], "offsets": [ [ 145, 2423 ] ] } ]

[ { "id": "5753", "type": "Genes & Molecular Sequences", "text": [ "Scavenger receptor of class B" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "5754", "type": "Chemicals & Drugs", "text": [ "cholesteryl ester" ], "offsets": [ [ 94, 111 ] ], "normalized": [] }, { "id": "5755", "type": "Genes & Molecular Sequences", "text": [ "cholesteryl ester" ], "offsets": [ [ 94, 111 ] ], "normalized": [] }, { "id": "5756", "type": "Chemicals & Drugs", "text": [ "estradiol" ], "offsets": [ [ 116, 125 ] ], "normalized": [] }, { "id": "5757", "type": "Genes & Molecular Sequences", "text": [ "estradiol" ], "offsets": [ [ 116, 125 ] ], "normalized": [] }, { "id": "5758", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 131, 134 ] ], "normalized": [] }, { "id": "5759", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 139, 143 ] ], "normalized": [] }, { "id": "5760", "type": "Genes & Molecular Sequences", "text": [ "Lipoproteins" ], "offsets": [ [ 145, 157 ] ], "normalized": [] }, { "id": "5761", "type": "Genes & Molecular Sequences", "text": [ "vitamins" ], "offsets": [ [ 173, 181 ] ], "normalized": [] }, { "id": "5762", "type": "Genes & Molecular Sequences", "text": [ "hormones" ], "offsets": [ [ 186, 194 ] ], "normalized": [] }, { "id": "5763", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 279, 282 ] ], "normalized": [] }, { "id": "5764", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 287, 291 ] ], "normalized": [] }, { "id": "5765", "type": "Genes & Molecular Sequences", "text": [ "scavenger receptors" ], "offsets": [ [ 391, 410 ] ], "normalized": [] }, { "id": "5766", "type": "Chemicals & Drugs", "text": [ "cholesterol" ], "offsets": [ [ 459, 470 ] ], "normalized": [] }, { "id": "5767", "type": "Genes & Molecular Sequences", "text": [ "cholesterol" ], "offsets": [ [ 459, 470 ] ], "normalized": [] }, { "id": "5768", "type": "Chemicals & Drugs", "text": [ "estradiol" ], "offsets": [ [ 475, 484 ] ], "normalized": [] }, { "id": "5769", "type": "Genes & Molecular Sequences", "text": [ "estradiol" ], "offsets": [ [ 475, 484 ] ], "normalized": [] }, { "id": "5770", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "5771", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 498, 502 ] ], "normalized": [] }, { "id": "5772", "type": "Genes & Molecular Sequences", "text": [ "triglyceride-rich lipoproteins" ], "offsets": [ [ 715, 745 ] ], "normalized": [] }, { "id": "5773", "type": "Chemicals & Drugs", "text": [ "triglyceride-rich lipoproteins" ], "offsets": [ [ 715, 745 ] ], "normalized": [] }, { "id": "5774", "type": "Genes & Molecular Sequences", "text": [ "lipophilic vitamins" ], "offsets": [ [ 766, 785 ] ], "normalized": [] }, { "id": "5775", "type": "Genes & Molecular Sequences", "text": [ "low" ], "offsets": [ [ 878, 881 ] ], "normalized": [] }, { "id": "5776", "type": "Genes & Molecular Sequences", "text": [ "high-density lipoproteins" ], "offsets": [ [ 887, 912 ] ], "normalized": [] }, { "id": "5777", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 914, 917 ] ], "normalized": [] }, { "id": "5778", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 922, 926 ] ], "normalized": [] }, { "id": "5779", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 1062, 1065 ] ], "normalized": [] }, { "id": "5780", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 1070, 1074 ] ], "normalized": [] }, { "id": "5781", "type": "Chemicals & Drugs", "text": [ "[3H]estradiol" ], "offsets": [ [ 1132, 1145 ] ], "normalized": [] }, { "id": "5782", "type": "Genes & Molecular Sequences", "text": [ "[3H]estradiol" ], "offsets": [ [ 1132, 1145 ] ], "normalized": [] }, { "id": "5783", "type": "Genes & Molecular Sequences", "text": [ "scavenger receptors" ], "offsets": [ [ 1374, 1393 ] ], "normalized": [] }, { "id": "5784", "type": "Genes & Molecular Sequences", "text": [ "SRs" ], "offsets": [ [ 1395, 1398 ] ], "normalized": [] }, { "id": "5785", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 1621, 1625 ] ], "normalized": [] }, { "id": "5786", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 1630, 1633 ] ], "normalized": [] }, { "id": "5787", "type": "Chemicals & Drugs", "text": [ "cholesteryl esters" ], "offsets": [ [ 1675, 1693 ] ], "normalized": [] }, { "id": "5788", "type": "Genes & Molecular Sequences", "text": [ "cholesteryl esters" ], "offsets": [ [ 1675, 1693 ] ], "normalized": [] }, { "id": "5789", "type": "Chemicals & Drugs", "text": [ "CEs" ], "offsets": [ [ 1695, 1698 ] ], "normalized": [] }, { "id": "5790", "type": "Genes & Molecular Sequences", "text": [ "CEs" ], "offsets": [ [ 1695, 1698 ] ], "normalized": [] }, { "id": "5791", "type": "Genes & Molecular Sequences", "text": [ "lipoproteins" ], "offsets": [ [ 1711, 1723 ] ], "normalized": [] }, { "id": "5792", "type": "Genes & Molecular Sequences", "text": [ "SR-BI" ], "offsets": [ [ 1783, 1788 ] ], "normalized": [] }, { "id": "5793", "type": "Genes & Molecular Sequences", "text": [ "SR-BII" ], "offsets": [ [ 1790, 1796 ] ], "normalized": [] }, { "id": "5794", "type": "Genes & Molecular Sequences", "text": [ "CD36" ], "offsets": [ [ 1802, 1806 ] ], "normalized": [] }, { "id": "5795", "type": "Genes & Molecular Sequences", "text": [ "SR-Bs receptors" ], "offsets": [ [ 1808, 1823 ] ], "normalized": [] }, { "id": "5796", "type": "Genes & Molecular Sequences", "text": [ "caveolin" ], "offsets": [ [ 1891, 1899 ] ], "normalized": [] }, { "id": "5797", "type": "Chemicals & Drugs", "text": [ "CE" ], "offsets": [ [ 1940, 1942 ] ], "normalized": [] }, { "id": "5798", "type": "Genes & Molecular Sequences", "text": [ "CE" ], "offsets": [ [ 1940, 1942 ] ], "normalized": [] }, { "id": "5799", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 1948, 1951 ] ], "normalized": [] }, { "id": "5800", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 1956, 1960 ] ], "normalized": [] }, { "id": "5801", "type": "Chemicals & Drugs", "text": [ "SR-B ligand oxidized LDL" ], "offsets": [ [ 2019, 2043 ] ], "normalized": [] }, { "id": "5802", "type": "Genes & Molecular Sequences", "text": [ "SR-B ligand oxidized LDL" ], "offsets": [ [ 2019, 2043 ] ], "normalized": [] }, { "id": "5803", "type": "Genes & Molecular Sequences", "text": [ "SR-B receptors" ], "offsets": [ [ 2061, 2075 ] ], "normalized": [] }, { "id": "5804", "type": "Chemicals & Drugs", "text": [ "estradiol" ], "offsets": [ [ 2127, 2136 ] ], "normalized": [] }, { "id": "5805", "type": "Genes & Molecular Sequences", "text": [ "estradiol" ], "offsets": [ [ 2127, 2136 ] ], "normalized": [] }, { "id": "5806", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 2148, 2151 ] ], "normalized": [] }, { "id": "5807", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 2156, 2160 ] ], "normalized": [] }, { "id": "5808", "type": "Genes & Molecular Sequences", "text": [ "SR-B receptors" ], "offsets": [ [ 2228, 2242 ] ], "normalized": [] }, { "id": "5809", "type": "Chemicals & Drugs", "text": [ "cholesterol" ], "offsets": [ [ 2323, 2334 ] ], "normalized": [] }, { "id": "5810", "type": "Genes & Molecular Sequences", "text": [ "cholesterol" ], "offsets": [ [ 2323, 2334 ] ], "normalized": [] }, { "id": "5811", "type": "Chemicals & Drugs", "text": [ "estradiol" ], "offsets": [ [ 2339, 2348 ] ], "normalized": [] }, { "id": "5812", "type": "Genes & Molecular Sequences", "text": [ "estradiol" ], "offsets": [ [ 2339, 2348 ] ], "normalized": [] }, { "id": "5813", "type": "Genes & Molecular Sequences", "text": [ "LDL" ], "offsets": [ [ 2392, 2395 ] ], "normalized": [] }, { "id": "5814", "type": "Genes & Molecular Sequences", "text": [ "HDL3" ], "offsets": [ [ 2400, 2404 ] ], "normalized": [] }, { "id": "5815", "type": "Genes & Molecular Sequences", "text": [ "SR-B receptors" ], "offsets": [ [ 2408, 2422 ] ], "normalized": [] }, { "id": "5816", "type": "", "text": [ "cholesteryl ester" ], "offsets": [ [ 94, 111 ] ], "normalized": [] }, { "id": "5817", "type": "", "text": [ "Scavenger receptor of class B" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "5819", "type": "", "text": [ "cholesteryl ester" ], "offsets": [ [ 94, 111 ] ], "normalized": [] }, { "id": "5820", "type": "", "text": [ "LDL" ], "offsets": [ [ 131, 134 ] ], "normalized": [] }, { "id": "5822", "type": "", "text": [ "cholesteryl ester" ], "offsets": [ [ 94, 111 ] ], "normalized": [] }, { "id": "5823", "type": "", "text": [ "HDL3" ], "offsets": [ [ 139, 143 ] ], "normalized": [] }, { "id": "5825", "type": "", "text": [ "estradiol" ], "offsets": [ [ 116, 125 ] ], "normalized": [] }, { "id": "5826", "type": "", "text": [ "Scavenger receptor of class B" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "5828", "type": "", "text": [ "estradiol" ], "offsets": [ [ 116, 125 ] ], "normalized": [] }, { "id": "5829", "type": "", "text": [ "LDL" ], "offsets": [ [ 131, 134 ] ], "normalized": [] }, { "id": "5831", "type": "", "text": [ "estradiol" ], "offsets": [ [ 116, 125 ] ], "normalized": [] }, { "id": "5832", "type": "", "text": [ "HDL3" ], "offsets": [ [ 139, 143 ] ], "normalized": [] }, { "id": "5834", "type": "", "text": [ "estradiol" ], "offsets": [ [ 475, 484 ] ], "normalized": [] }, { "id": "5835", "type": "", "text": [ "LDL" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "5837", "type": "", "text": [ "estradiol" ], "offsets": [ [ 475, 484 ] ], "normalized": [] }, { "id": "5838", "type": "", "text": [ "HDL3" ], "offsets": [ [ 498, 502 ] ], "normalized": [] }, { "id": "5840", "type": "", "text": [ "estradiol" ], "offsets": [ [ 475, 484 ] ], "normalized": [] }, { "id": "5841", "type": "", "text": [ "scavenger receptors" ], "offsets": [ [ 391, 410 ] ], "normalized": [] }, { "id": "5843", "type": "", "text": [ "cholesterol" ], "offsets": [ [ 459, 470 ] ], "normalized": [] }, { "id": "5844", "type": "", "text": [ "LDL" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "5846", "type": "", "text": [ "cholesterol" ], "offsets": [ [ 459, 470 ] ], "normalized": [] }, { "id": "5847", "type": "", "text": [ "HDL3" ], "offsets": [ [ 498, 502 ] ], "normalized": [] }, { "id": "5849", "type": "", "text": [ "cholesterol" ], "offsets": [ [ 459, 470 ] ], "normalized": [] }, { "id": "5850", "type": "", "text": [ "scavenger receptors" ], "offsets": [ [ 391, 410 ] ], "normalized": [] }, { "id": "5852", "type": "", "text": [ "cholesteryl esters" ], "offsets": [ [ 1675, 1693 ] ], "normalized": [] }, { "id": "5853", "type": "", "text": [ "LDL" ], "offsets": [ [ 1630, 1633 ] ], "normalized": [] }, { "id": "5855", "type": "", "text": [ "cholesteryl esters" ], "offsets": [ [ 1675, 1693 ] ], "normalized": [] }, { "id": "5856", "type": "", "text": [ "HDL3" ], "offsets": [ [ 1621, 1625 ] ], "normalized": [] }, { "id": "5858", "type": "", "text": [ "cholesteryl esters" ], "offsets": [ [ 1675, 1693 ] ], "normalized": [] }, { "id": "5859", "type": "", "text": [ "lipoproteins" ], "offsets": [ [ 1711, 1723 ] ], "normalized": [] }, { "id": "5861", "type": "", "text": [ "CEs" ], "offsets": [ [ 1695, 1698 ] ], "normalized": [] }, { "id": "5862", "type": "", "text": [ "LDL" ], "offsets": [ [ 1630, 1633 ] ], "normalized": [] }, { "id": "5864", "type": "", "text": [ "CEs" ], "offsets": [ [ 1695, 1698 ] ], "normalized": [] }, { "id": "5865", "type": "", "text": [ "HDL3" ], "offsets": [ [ 1621, 1625 ] ], "normalized": [] }, { "id": "5867", "type": "", "text": [ "CEs" ], "offsets": [ [ 1695, 1698 ] ], "normalized": [] }, { "id": "5868", "type": "", "text": [ "lipoproteins" ], "offsets": [ [ 1711, 1723 ] ], "normalized": [] }, { "id": "5870", "type": "", "text": [ "CE" ], "offsets": [ [ 1940, 1942 ] ], "normalized": [] }, { "id": "5871", "type": "", "text": [ "LDL" ], "offsets": [ [ 1948, 1951 ] ], "normalized": [] }, { "id": "5873", "type": "", "text": [ "CE" ], "offsets": [ [ 1940, 1942 ] ], "normalized": [] }, { "id": "5874", "type": "", "text": [ "HDL3" ], "offsets": [ [ 1956, 1960 ] ], "normalized": [] }, { "id": "5876", "type": "", "text": [ "CE" ], "offsets": [ [ 1940, 1942 ] ], "normalized": [] }, { "id": "5877", "type": "", "text": [ "SR-B receptors" ], "offsets": [ [ 2061, 2075 ] ], "normalized": [] }, { "id": "5879", "type": "", "text": [ "SR-B ligand oxidized LDL" ], "offsets": [ [ 2019, 2043 ] ], "normalized": [] }, { "id": "5880", "type": "", "text": [ "LDL" ], "offsets": [ [ 1948, 1951 ] ], "normalized": [] }, { "id": "5882", "type": "", "text": [ "SR-B ligand oxidized LDL" ], "offsets": [ [ 2019, 2043 ] ], "normalized": [] }, { "id": "5883", "type": "", "text": [ "HDL3" ], "offsets": [ [ 1956, 1960 ] ], "normalized": [] }, { "id": "5885", "type": "", "text": [ "estradiol" ], "offsets": [ [ 2127, 2136 ] ], "normalized": [] }, { "id": "5886", "type": "", "text": [ "LDL" ], "offsets": [ [ 2148, 2151 ] ], "normalized": [] }, { "id": "5888", "type": "", "text": [ "estradiol" ], "offsets": [ [ 2127, 2136 ] ], "normalized": [] }, { "id": "5889", "type": "", "text": [ "HDL3" ], "offsets": [ [ 2156, 2160 ] ], "normalized": [] }, { "id": "5891", "type": "", "text": [ "estradiol" ], "offsets": [ [ 2127, 2136 ] ], "normalized": [] }, { "id": "5892", "type": "", "text": [ "SR-B receptors" ], "offsets": [ [ 2228, 2242 ] ], "normalized": [] }, { "id": "5894", "type": "", "text": [ "estradiol" ], "offsets": [ [ 2339, 2348 ] ], "normalized": [] }, { "id": "5895", "type": "", "text": [ "LDL" ], "offsets": [ [ 2392, 2395 ] ], "normalized": [] }, { "id": "5897", "type": "", "text": [ "estradiol" ], "offsets": [ [ 2339, 2348 ] ], "normalized": [] }, { "id": "5898", "type": "", "text": [ "HDL3" ], "offsets": [ [ 2400, 2404 ] ], "normalized": [] }, { "id": "5900", "type": "", "text": [ "estradiol" ], "offsets": [ [ 2339, 2348 ] ], "normalized": [] }, { "id": "5901", "type": "", "text": [ "SR-B receptors" ], "offsets": [ [ 2408, 2422 ] ], "normalized": [] }, { "id": "5903", "type": "", "text": [ "cholesterol" ], "offsets": [ [ 2323, 2334 ] ], "normalized": [] }, { "id": "5904", "type": "", "text": [ "LDL" ], "offsets": [ [ 2392, 2395 ] ], "normalized": [] }, { "id": "5906", "type": "", "text": [ "cholesterol" ], "offsets": [ [ 2323, 2334 ] ], "normalized": [] }, { "id": "5907", "type": "", "text": [ "HDL3" ], "offsets": [ [ 2400, 2404 ] ], "normalized": [] }, { "id": "5909", "type": "", "text": [ "cholesterol" ], "offsets": [ [ 2323, 2334 ] ], "normalized": [] }, { "id": "5910", "type": "", "text": [ "SR-B receptors" ], "offsets": [ [ 2408, 2422 ] ], "normalized": [] }, { "id": "5912", "type": "", "text": [ "triglyceride-rich lipoproteins" ], "offsets": [ [ 715, 745 ] ], "normalized": [] }, { "id": "5913", "type": "", "text": [ "triglyceride-rich lipoproteins" ], "offsets": [ [ 715, 745 ] ], "normalized": [] }, { "id": "5915", "type": "", "text": [ "[3H]estradiol" ], "offsets": [ [ 1132, 1145 ] ], "normalized": [] }, { "id": "5916", "type": "", "text": [ "LDL" ], "offsets": [ [ 1062, 1065 ] ], "normalized": [] }, { "id": "5918", "type": "", "text": [ "[3H]estradiol" ], "offsets": [ [ 1132, 1145 ] ], "normalized": [] }, { "id": "5919", "type": "", "text": [ "HDL3" ], "offsets": [ [ 1070, 1074 ] ], "normalized": [] } ]

[]

[]

[ { "id": "5818", "type": "PA", "arg1_id": "5816", "arg2_id": "5817", "normalized": [] }, { "id": "5821", "type": "PA", "arg1_id": "5819", "arg2_id": "5820", "normalized": [] }, { "id": "5824", "type": "PA", "arg1_id": "5822", "arg2_id": "5823", "normalized": [] }, { "id": "5827", "type": "PA", "arg1_id": "5825", "arg2_id": "5826", "normalized": [] }, { "id": "5830", "type": "PA", "arg1_id": "5828", "arg2_id": "5829", "normalized": [] }, { "id": "5833", "type": "PA", "arg1_id": "5831", "arg2_id": "5832", "normalized": [] }, { "id": "5836", "type": "PA", "arg1_id": "5834", "arg2_id": "5835", "normalized": [] }, { "id": "5839", "type": "PA", "arg1_id": "5837", "arg2_id": "5838", "normalized": [] }, { "id": "5842", "type": "PA", "arg1_id": "5840", "arg2_id": "5841", "normalized": [] }, { "id": "5845", "type": "PA", "arg1_id": "5843", "arg2_id": "5844", "normalized": [] }, { "id": "5848", "type": "PA", "arg1_id": "5846", "arg2_id": "5847", "normalized": [] }, { "id": "5851", "type": "PA", "arg1_id": "5849", "arg2_id": "5850", "normalized": [] }, { "id": "5854", "type": "PA", "arg1_id": "5852", "arg2_id": "5853", "normalized": [] }, { "id": "5857", "type": "PA", "arg1_id": "5855", "arg2_id": "5856", "normalized": [] }, { "id": "5860", "type": "PA", "arg1_id": "5858", "arg2_id": "5859", "normalized": [] }, { "id": "5863", "type": "PA", "arg1_id": "5861", "arg2_id": "5862", "normalized": [] }, { "id": "5866", "type": "PA", "arg1_id": "5864", "arg2_id": "5865", "normalized": [] }, { "id": "5869", "type": "PA", "arg1_id": "5867", "arg2_id": "5868", "normalized": [] }, { "id": "5872", "type": "PA", "arg1_id": "5870", "arg2_id": "5871", "normalized": [] }, { "id": "5875", "type": "PA", "arg1_id": "5873", "arg2_id": "5874", "normalized": [] }, { "id": "5878", "type": "PA", "arg1_id": "5876", "arg2_id": "5877", "normalized": [] }, { "id": "5881", "type": "PA", "arg1_id": "5879", "arg2_id": "5880", "normalized": [] }, { "id": "5884", "type": "PA", "arg1_id": "5882", "arg2_id": "5883", "normalized": [] }, { "id": "5887", "type": "PA", "arg1_id": "5885", "arg2_id": "5886", "normalized": [] }, { "id": "5890", "type": "PA", "arg1_id": "5888", "arg2_id": "5889", "normalized": [] }, { "id": "5893", "type": "PA", "arg1_id": "5891", "arg2_id": "5892", "normalized": [] }, { "id": "5896", "type": "PA", "arg1_id": "5894", "arg2_id": "5895", "normalized": [] }, { "id": "5899", "type": "PA", "arg1_id": "5897", "arg2_id": "5898", "normalized": [] }, { "id": "5902", "type": "PA", "arg1_id": "5900", "arg2_id": "5901", "normalized": [] }, { "id": "5905", "type": "PA", "arg1_id": "5903", "arg2_id": "5904", "normalized": [] }, { "id": "5908", "type": "PA", "arg1_id": "5906", "arg2_id": "5907", "normalized": [] }, { "id": "5911", "type": "PA", "arg1_id": "5909", "arg2_id": "5910", "normalized": [] }, { "id": "5914", "type": "PA", "arg1_id": "5912", "arg2_id": "5913", "normalized": [] }, { "id": "5917", "type": "PA", "arg1_id": "5915", "arg2_id": "5916", "normalized": [] }, { "id": "5920", "type": "PA", "arg1_id": "5918", "arg2_id": "5919", "normalized": [] } ]

[ { "id": "5923", "type": "title", "text": [ "TNF- alpha inhibitors." ], "offsets": [ [ 0, 22 ] ] }, { "id": "5924", "type": "abstract", "text": [ "Tumor necrosis-alpha (TNF-alpha) has been implicated in many forms of inflammation and is an end-stage product of the inflammatory cytokine cascade. It is an inducer of inflammation and is involved in many cutaneous and systemic inflammatory diseases. The development of agents that block the effects of TNF-alpha has aided in the treatment of many of these diseases. This article will briefly discuss the production, structure, and administration of the TNF-alpha inhibitors. There will be a focus on the mechanism of action of each of the TNF-alpha inhibitors as well as their benefit in their FDA approved and non FDA approved dermatologic conditions. The side effect profile and monitoring recommendations for these agents will also be discussed." ], "offsets": [ [ 23, 773 ] ] } ]

[ { "id": "5925", "type": "Chemicals & Drugs", "text": [ "TNF- alpha inhibitors" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "5926", "type": "Genes & Molecular Sequences", "text": [ "TNF- alpha inhibitors" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "5927", "type": "Genes & Molecular Sequences", "text": [ "Tumor necrosis-alpha" ], "offsets": [ [ 23, 43 ] ], "normalized": [] }, { "id": "5928", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha" ], "offsets": [ [ 45, 54 ] ], "normalized": [] }, { "id": "5929", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha" ], "offsets": [ [ 327, 336 ] ], "normalized": [] }, { "id": "5930", "type": "Chemicals & Drugs", "text": [ "TNF-alpha inhibitors" ], "offsets": [ [ 478, 498 ] ], "normalized": [] }, { "id": "5931", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha inhibitors" ], "offsets": [ [ 478, 498 ] ], "normalized": [] }, { "id": "5932", "type": "Chemicals & Drugs", "text": [ "TNF-alpha inhibitors" ], "offsets": [ [ 564, 584 ] ], "normalized": [] }, { "id": "5933", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha inhibitors" ], "offsets": [ [ 564, 584 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "5936", "type": "title", "text": [ "Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia." ], "offsets": [ [ 0, 155 ] ] }, { "id": "5937", "type": "abstract", "text": [ "Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and remains incurable with conventional therapies. Patients with relapsed or resistant CLL have a significantly shortened lifespan. MDM2 inhibitors have been developed and may have significant potential in the treatment of CLL. Clinical development of these compounds would be aided through knowledge of molecular predictors of activity. To understand determinants of sensitivity or resistance to MDM2 inhibitor therapy in CLL, we comprehensively analyzed a large cohort of CLL patient-derived samples for response to MDM2 inhibition and correlated these responses with clinically important biomarkers. Furthermore, we employed high-density single nucleotide polymorphism (SNP) arrays to analyze genomewide changes of copy number and allele status, including that of p53. The results of these studies conclusively demonstrate that p53 status is the major determinant of response to MDM2 inhibitors in CLL. Additional defects in the p53 regulatory cascade do not appear operational in this leukemia. Further, we identify a novel subgroup of patients with CLL with early progressive disease that appears particularly sensitive to MDM2 inhibitor treatment. These data provide definitive evidence for target-specific and predictive activity and a rationale to proceed with this potentially important class of compounds in the treatment of CLL." ], "offsets": [ [ 156, 1579 ] ] } ]

[ { "id": "5938", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 56, 59 ] ], "normalized": [] }, { "id": "5939", "type": "Chemicals & Drugs", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 107, 122 ] ], "normalized": [] }, { "id": "5940", "type": "Genes & Molecular Sequences", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 107, 122 ] ], "normalized": [] }, { "id": "5941", "type": "Chemicals & Drugs", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 372, 387 ] ], "normalized": [] }, { "id": "5942", "type": "Genes & Molecular Sequences", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 372, 387 ] ], "normalized": [] }, { "id": "5943", "type": "Chemicals & Drugs", "text": [ "MDM2 inhibitor" ], "offsets": [ [ 637, 651 ] ], "normalized": [] }, { "id": "5944", "type": "Genes & Molecular Sequences", "text": [ "MDM2 inhibitor" ], "offsets": [ [ 637, 651 ] ], "normalized": [] }, { "id": "5945", "type": "Genes & Molecular Sequences", "text": [ "MDM2" ], "offsets": [ [ 758, 762 ] ], "normalized": [] }, { "id": "5946", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 1007, 1010 ] ], "normalized": [] }, { "id": "5947", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] }, { "id": "5948", "type": "Chemicals & Drugs", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 1122, 1137 ] ], "normalized": [] }, { "id": "5949", "type": "Genes & Molecular Sequences", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 1122, 1137 ] ], "normalized": [] }, { "id": "5950", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 1172, 1175 ] ], "normalized": [] }, { "id": "5951", "type": "Chemicals & Drugs", "text": [ "MDM2 inhibitor" ], "offsets": [ [ 1368, 1382 ] ], "normalized": [] }, { "id": "5952", "type": "Genes & Molecular Sequences", "text": [ "MDM2 inhibitor" ], "offsets": [ [ 1368, 1382 ] ], "normalized": [] }, { "id": "5953", "type": "", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 107, 122 ] ], "normalized": [] }, { "id": "5954", "type": "", "text": [ "p53" ], "offsets": [ [ 56, 59 ] ], "normalized": [] }, { "id": "5956", "type": "", "text": [ "MDM2 inhibitor" ], "offsets": [ [ 637, 651 ] ], "normalized": [] }, { "id": "5957", "type": "", "text": [ "MDM2" ], "offsets": [ [ 758, 762 ] ], "normalized": [] }, { "id": "5959", "type": "", "text": [ "MDM2 inhibitors" ], "offsets": [ [ 1122, 1137 ] ], "normalized": [] }, { "id": "5960", "type": "", "text": [ "p53" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] } ]

[]

[]

[ { "id": "5955", "type": "PA", "arg1_id": "5953", "arg2_id": "5954", "normalized": [] }, { "id": "5958", "type": "PA", "arg1_id": "5956", "arg2_id": "5957", "normalized": [] }, { "id": "5961", "type": "PA", "arg1_id": "5959", "arg2_id": "5960", "normalized": [] } ]

[ { "id": "5964", "type": "title", "text": [ "Keratoacanthoma occurring within the red dye of a tattoo." ], "offsets": [ [ 0, 57 ] ] }, { "id": "5965", "type": "abstract", "text": [ "Keratoacanthoma (KA) is a common keratinizing squamous cell neoplasm of unknown origin characterized by rapid growth and spontaneous involution. Trauma-induced forms have been observed with various types of skin injury. To our knowledge, reports of KA arising at tattoo sites are scarce in the literature. A 41-year-old woman with no medical history presented for a rapidly growing nodule confined to the red part of a tattoo located on the scapula. Histology showed a keratin-filled cuplike crater with an epithelial proliferation (hyperkeratosis, parakeratosis, no keratinocyte atypia). An inflammatory infiltrate in the dermis composed of lymphocytes and histiocytes intermixed with red ink-related exogenous pigments was noted. Lack of papillomatosis and viral inclusions ruled out the diagnosis of viral wart, absence of granulomatous reaction ruled out deep fungal or mycobacterial infection and lack of cytological atypia and frank architectural abnormalities did not favour a squamous cell carcinoma. KA should be included in the list of cutaneous complications related to tattooing. Diagnosis can be challenging as differential diagnoses include pseudoepitheliomatous hyperplasia and squamous cell carcinoma. Removal of the entire area, thorough histological examination and careful follow up are mandatory." ], "offsets": [ [ 58, 1374 ] ] } ]

[ { "id": "5966", "type": "Diseases & Disorders", "text": [ "Keratoacanthoma" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "5967", "type": "Chemicals & Drugs", "text": [ "red dye of a tattoo" ], "offsets": [ [ 37, 56 ] ], "normalized": [] }, { "id": "5968", "type": "Diseases & Disorders", "text": [ "red dye of a tattoo" ], "offsets": [ [ 37, 56 ] ], "normalized": [] }, { "id": "5969", "type": "Diseases & Disorders", "text": [ "Keratoacanthoma" ], "offsets": [ [ 58, 73 ] ], "normalized": [] }, { "id": "5970", "type": "Diseases & Disorders", "text": [ "KA" ], "offsets": [ [ 75, 77 ] ], "normalized": [] }, { "id": "5971", "type": "Diseases & Disorders", "text": [ "keratinizing squamous cell neoplasm" ], "offsets": [ [ 91, 126 ] ], "normalized": [] }, { "id": "5972", "type": "Diseases & Disorders", "text": [ "KA" ], "offsets": [ [ 307, 309 ] ], "normalized": [] }, { "id": "5973", "type": "Chemicals & Drugs", "text": [ "tattoo" ], "offsets": [ [ 321, 327 ] ], "normalized": [] }, { "id": "5974", "type": "Diseases & Disorders", "text": [ "tattoo" ], "offsets": [ [ 321, 327 ] ], "normalized": [] }, { "id": "5975", "type": "Diseases & Disorders", "text": [ "nodule" ], "offsets": [ [ 440, 446 ] ], "normalized": [] }, { "id": "5976", "type": "Chemicals & Drugs", "text": [ "red part of a tattoo" ], "offsets": [ [ 463, 483 ] ], "normalized": [] }, { "id": "5977", "type": "Diseases & Disorders", "text": [ "red part of a tattoo" ], "offsets": [ [ 463, 483 ] ], "normalized": [] }, { "id": "5978", "type": "Diseases & Disorders", "text": [ "epithelial proliferation" ], "offsets": [ [ 565, 589 ] ], "normalized": [] }, { "id": "5979", "type": "Diseases & Disorders", "text": [ "hyperkeratosis" ], "offsets": [ [ 591, 605 ] ], "normalized": [] }, { "id": "5980", "type": "Diseases & Disorders", "text": [ "parakeratosis" ], "offsets": [ [ 607, 620 ] ], "normalized": [] }, { "id": "5981", "type": "Diseases & Disorders", "text": [ "keratinocyte atypia" ], "offsets": [ [ 625, 644 ] ], "normalized": [] }, { "id": "5982", "type": "Chemicals & Drugs", "text": [ "red ink-related exogenous pigments" ], "offsets": [ [ 744, 778 ] ], "normalized": [] }, { "id": "5983", "type": "Diseases & Disorders", "text": [ "papillomatosis" ], "offsets": [ [ 798, 812 ] ], "normalized": [] }, { "id": "5984", "type": "Diseases & Disorders", "text": [ "viral wart" ], "offsets": [ [ 861, 871 ] ], "normalized": [] }, { "id": "5985", "type": "Diseases & Disorders", "text": [ "absence" ], "offsets": [ [ 873, 880 ] ], "normalized": [] }, { "id": "5986", "type": "Diseases & Disorders", "text": [ "fungal" ], "offsets": [ [ 922, 928 ] ], "normalized": [] }, { "id": "5987", "type": "Diseases & Disorders", "text": [ "mycobacterial infection" ], "offsets": [ [ 932, 955 ] ], "normalized": [] }, { "id": "5988", "type": "Diseases & Disorders", "text": [ "cytological atypia" ], "offsets": [ [ 968, 986 ] ], "normalized": [] }, { "id": "5989", "type": "Diseases & Disorders", "text": [ "frank architectural abnormalities" ], "offsets": [ [ 991, 1024 ] ], "normalized": [] }, { "id": "5990", "type": "Diseases & Disorders", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 1042, 1065 ] ], "normalized": [] }, { "id": "5991", "type": "Diseases & Disorders", "text": [ "KA" ], "offsets": [ [ 1067, 1069 ] ], "normalized": [] }, { "id": "5992", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 1114, 1127 ] ], "normalized": [] }, { "id": "5993", "type": "Chemicals & Drugs", "text": [ "tattooing" ], "offsets": [ [ 1139, 1148 ] ], "normalized": [] }, { "id": "5994", "type": "Diseases & Disorders", "text": [ "tattooing" ], "offsets": [ [ 1139, 1148 ] ], "normalized": [] }, { "id": "5995", "type": "Diseases & Disorders", "text": [ "pseudoepitheliomatous hyperplasia" ], "offsets": [ [ 1213, 1246 ] ], "normalized": [] }, { "id": "5996", "type": "Diseases & Disorders", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 1251, 1274 ] ], "normalized": [] }, { "id": "5997", "type": "", "text": [ "red dye of a tattoo" ], "offsets": [ [ 37, 56 ] ], "normalized": [] }, { "id": "5998", "type": "", "text": [ "Keratoacanthoma" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "6000", "type": "", "text": [ "tattooing" ], "offsets": [ [ 1139, 1148 ] ], "normalized": [] }, { "id": "6001", "type": "", "text": [ "KA" ], "offsets": [ [ 1067, 1069 ] ], "normalized": [] } ]

[]

[]

[ { "id": "5999", "type": "PA", "arg1_id": "5997", "arg2_id": "5998", "normalized": [] }, { "id": "6002", "type": "PA", "arg1_id": "6000", "arg2_id": "6001", "normalized": [] } ]

[ { "id": "6005", "type": "title", "text": [ "Acid ceramidase inhibition: a novel target for cancer therapy." ], "offsets": [ [ 0, 62 ] ] }, { "id": "6006", "type": "abstract", "text": [ "During the last decade, sphingolipid deregulation, namely the balance between the pro-apoptotic molecule ceramide and the anti-apoptotic sphingolipid sphingosine-1-phosphate, has emerged as an important factor in cancer pathology and resistance to therapy. Thus, our research has been focused on developing drugs that are able to restore normal sphingolipid balance, precisely through increasing the levels of ceramide and decreasing sphingosine-1-phosphate. Particularly, inhibition of the ceramide metabolizing enzyme acid ceramidase, whose over-expression in cancer cells has been implicated in resistance to treatment, is proving to be an efficient and promising strategy. In this review, we consider our recent work with acid ceramidase inhibitors, in combination with radiation or gene therapy as a sensitizer that enhance cancer therapy." ], "offsets": [ [ 63, 907 ] ] } ]

[ { "id": "6007", "type": "Genes & Molecular Sequences", "text": [ "Acid ceramidase" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "6008", "type": "Chemicals & Drugs", "text": [ "Acid ceramidase" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "6009", "type": "Genes & Molecular Sequences", "text": [ "sphingolipid" ], "offsets": [ [ 87, 99 ] ], "normalized": [] }, { "id": "6010", "type": "Chemicals & Drugs", "text": [ "sphingolipid" ], "offsets": [ [ 87, 99 ] ], "normalized": [] }, { "id": "6011", "type": "Genes & Molecular Sequences", "text": [ "ceramide" ], "offsets": [ [ 168, 176 ] ], "normalized": [] }, { "id": "6012", "type": "Chemicals & Drugs", "text": [ "ceramide" ], "offsets": [ [ 168, 176 ] ], "normalized": [] }, { "id": "6013", "type": "Genes & Molecular Sequences", "text": [ "sphingolipid" ], "offsets": [ [ 200, 212 ] ], "normalized": [] }, { "id": "6014", "type": "Chemicals & Drugs", "text": [ "sphingolipid" ], "offsets": [ [ 200, 212 ] ], "normalized": [] }, { "id": "6015", "type": "Genes & Molecular Sequences", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 213, 236 ] ], "normalized": [] }, { "id": "6016", "type": "Chemicals & Drugs", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 213, 236 ] ], "normalized": [] }, { "id": "6017", "type": "Genes & Molecular Sequences", "text": [ "sphingolipid" ], "offsets": [ [ 408, 420 ] ], "normalized": [] }, { "id": "6018", "type": "Chemicals & Drugs", "text": [ "sphingolipid" ], "offsets": [ [ 408, 420 ] ], "normalized": [] }, { "id": "6019", "type": "Genes & Molecular Sequences", "text": [ "ceramide" ], "offsets": [ [ 473, 481 ] ], "normalized": [] }, { "id": "6020", "type": "Chemicals & Drugs", "text": [ "ceramide" ], "offsets": [ [ 473, 481 ] ], "normalized": [] }, { "id": "6021", "type": "Genes & Molecular Sequences", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 497, 520 ] ], "normalized": [] }, { "id": "6022", "type": "Chemicals & Drugs", "text": [ "sphingosine-1-phosphate" ], "offsets": [ [ 497, 520 ] ], "normalized": [] }, { "id": "6023", "type": "Genes & Molecular Sequences", "text": [ "ceramide metabolizing enzyme" ], "offsets": [ [ 554, 582 ] ], "normalized": [] }, { "id": "6024", "type": "Chemicals & Drugs", "text": [ "ceramide metabolizing enzyme" ], "offsets": [ [ 554, 582 ] ], "normalized": [] }, { "id": "6025", "type": "Genes & Molecular Sequences", "text": [ "acid ceramidase" ], "offsets": [ [ 583, 598 ] ], "normalized": [] }, { "id": "6026", "type": "Chemicals & Drugs", "text": [ "acid ceramidase inhibitors" ], "offsets": [ [ 789, 815 ] ], "normalized": [] }, { "id": "6027", "type": "Genes & Molecular Sequences", "text": [ "acid ceramidase inhibitors" ], "offsets": [ [ 789, 815 ] ], "normalized": [] }, { "id": "6028", "type": "", "text": [ "ceramide metabolizing enzyme" ], "offsets": [ [ 554, 582 ] ], "normalized": [] }, { "id": "6029", "type": "", "text": [ "acid ceramidase" ], "offsets": [ [ 583, 598 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6030", "type": "PA", "arg1_id": "6028", "arg2_id": "6029", "normalized": [] } ]

[ { "id": "6033", "type": "title", "text": [ "MAPK p38 regulates transcriptional activity of NF-kappaB in primary human astrocytes via acetylation of p65." ], "offsets": [ [ 0, 108 ] ] }, { "id": "6034", "type": "abstract", "text": [ "MAPK-p38 plays an important role in inflammation. Several studies have shown that blocking p38 activity attenuates the transcriptional activity of the proinflammatory transcription factor NF-kappaB without altering its DNA-binding activity. We have also observed that blocking p38 in human primary astrocytes suppresses the transcriptional but not the DNA-binding activity of NF-kappaB and down-regulates the expression of an NF-kappaB-dependent gene, inducible NO synthase. However, the molecular mechanism of p38-mediated regulation of NF-kappaB remains largely unknown. In this study, we delineate that p38 controls the transcriptional activity of NF-kappaB by regulating acetylation of p65, but not its phosphorylation. The combination of IL-1beta and IFN-gamma, previously shown to strongly induce inducible NO synthase in human primary astrocytes, induced p38-dependent phosphorylation of acetyltransferase coactivator p300, but not p65, and subsequent association of p300 with p65. Furthermore, immunocomplex-histone acetyltransferase assays demonstrated that cytokine-induced association of p65 with biologically active immunocomplex-histone acetyltransferase assay was dependent on p38. It has been previously reported that acetylation of p65 at K310 residue is important for transcriptional activity of NF-kappaB. Accordingly, we found that cytokine-induced association of p65 with p300 led to acetylation of p65 at K310. Because p38 regulated the association between p65 and p300, blocking p38 activity also led to attenuation of p65-K310 acetylation in cytokine-stimulated astrocytes. Taken together, this study illuminates a novel regulatory role of p38 during neuroinflammation where this MAP kinase controls acetylation of NF-kappaB p65 by regulating acetyltransferase activity of coactivator p300." ], "offsets": [ [ 109, 1922 ] ] } ]

[ { "id": "6035", "type": "Genes & Molecular Sequences", "text": [ "MAPK p38" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "6036", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 47, 56 ] ], "normalized": [] }, { "id": "6037", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 104, 107 ] ], "normalized": [] }, { "id": "6038", "type": "Genes & Molecular Sequences", "text": [ "MAPK-p38" ], "offsets": [ [ 109, 117 ] ], "normalized": [] }, { "id": "6039", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 200, 203 ] ], "normalized": [] }, { "id": "6040", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 297, 306 ] ], "normalized": [] }, { "id": "6041", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 386, 389 ] ], "normalized": [] }, { "id": "6042", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 485, 494 ] ], "normalized": [] }, { "id": "6043", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB-dependent gene" ], "offsets": [ [ 535, 559 ] ], "normalized": [] }, { "id": "6044", "type": "Genes & Molecular Sequences", "text": [ "inducible NO synthase" ], "offsets": [ [ 561, 582 ] ], "normalized": [] }, { "id": "6045", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 620, 623 ] ], "normalized": [] }, { "id": "6046", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 647, 656 ] ], "normalized": [] }, { "id": "6047", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "6048", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 760, 769 ] ], "normalized": [] }, { "id": "6049", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 799, 802 ] ], "normalized": [] }, { "id": "6050", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "6051", "type": "Chemicals & Drugs", "text": [ "IL-1beta" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "6052", "type": "Genes & Molecular Sequences", "text": [ "IFN-gamma" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "6053", "type": "Chemicals & Drugs", "text": [ "IFN-gamma" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "6054", "type": "Genes & Molecular Sequences", "text": [ "inducible NO synthase" ], "offsets": [ [ 912, 933 ] ], "normalized": [] }, { "id": "6055", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 971, 974 ] ], "normalized": [] }, { "id": "6056", "type": "Genes & Molecular Sequences", "text": [ "acetyltransferase" ], "offsets": [ [ 1004, 1021 ] ], "normalized": [] }, { "id": "6057", "type": "Genes & Molecular Sequences", "text": [ "p300" ], "offsets": [ [ 1034, 1038 ] ], "normalized": [] }, { "id": "6058", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1048, 1051 ] ], "normalized": [] }, { "id": "6059", "type": "Genes & Molecular Sequences", "text": [ "p300" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [] }, { "id": "6060", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1093, 1096 ] ], "normalized": [] }, { "id": "6061", "type": "Genes & Molecular Sequences", "text": [ "acetyltransferase" ], "offsets": [ [ 1133, 1150 ] ], "normalized": [] }, { "id": "6062", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1208, 1211 ] ], "normalized": [] }, { "id": "6063", "type": "Genes & Molecular Sequences", "text": [ "acetyltransferase" ], "offsets": [ [ 1259, 1276 ] ], "normalized": [] }, { "id": "6064", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 1300, 1303 ] ], "normalized": [] }, { "id": "6065", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1357, 1360 ] ], "normalized": [] }, { "id": "6066", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 1422, 1431 ] ], "normalized": [] }, { "id": "6067", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1492, 1495 ] ], "normalized": [] }, { "id": "6068", "type": "Genes & Molecular Sequences", "text": [ "p300" ], "offsets": [ [ 1501, 1505 ] ], "normalized": [] }, { "id": "6069", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1528, 1531 ] ], "normalized": [] }, { "id": "6070", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 1549, 1552 ] ], "normalized": [] }, { "id": "6071", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1587, 1590 ] ], "normalized": [] }, { "id": "6072", "type": "Genes & Molecular Sequences", "text": [ "p300" ], "offsets": [ [ 1595, 1599 ] ], "normalized": [] }, { "id": "6073", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 1610, 1613 ] ], "normalized": [] }, { "id": "6074", "type": "Genes & Molecular Sequences", "text": [ "p65-K310" ], "offsets": [ [ 1650, 1658 ] ], "normalized": [] }, { "id": "6075", "type": "Genes & Molecular Sequences", "text": [ "p38" ], "offsets": [ [ 1772, 1775 ] ], "normalized": [] }, { "id": "6076", "type": "Genes & Molecular Sequences", "text": [ "MAP kinase" ], "offsets": [ [ 1812, 1822 ] ], "normalized": [] }, { "id": "6077", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 1847, 1856 ] ], "normalized": [] }, { "id": "6078", "type": "Genes & Molecular Sequences", "text": [ "p65" ], "offsets": [ [ 1857, 1860 ] ], "normalized": [] }, { "id": "6079", "type": "Genes & Molecular Sequences", "text": [ "acetyltransferase" ], "offsets": [ [ 1875, 1892 ] ], "normalized": [] }, { "id": "6080", "type": "Genes & Molecular Sequences", "text": [ "p300" ], "offsets": [ [ 1917, 1921 ] ], "normalized": [] }, { "id": "6081", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "6082", "type": "", "text": [ "p38" ], "offsets": [ [ 971, 974 ] ], "normalized": [] }, { "id": "6084", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "6085", "type": "", "text": [ "p65" ], "offsets": [ [ 1093, 1096 ] ], "normalized": [] }, { "id": "6087", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "6088", "type": "", "text": [ "inducible NO synthase" ], "offsets": [ [ 912, 933 ] ], "normalized": [] }, { "id": "6090", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "6091", "type": "", "text": [ "p300" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [] }, { "id": "6093", "type": "", "text": [ "IFN-gamma" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "6094", "type": "", "text": [ "p38" ], "offsets": [ [ 971, 974 ] ], "normalized": [] }, { "id": "6096", "type": "", "text": [ "IFN-gamma" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "6097", "type": "", "text": [ "p65" ], "offsets": [ [ 1093, 1096 ] ], "normalized": [] }, { "id": "6099", "type": "", "text": [ "IFN-gamma" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "6100", "type": "", "text": [ "inducible NO synthase" ], "offsets": [ [ 912, 933 ] ], "normalized": [] }, { "id": "6102", "type": "", "text": [ "IFN-gamma" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "6103", "type": "", "text": [ "p300" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [] } ]

[]

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[ { "id": "6083", "type": "PA", "arg1_id": "6081", "arg2_id": "6082", "normalized": [] }, { "id": "6086", "type": "PA", "arg1_id": "6084", "arg2_id": "6085", "normalized": [] }, { "id": "6089", "type": "PA", "arg1_id": "6087", "arg2_id": "6088", "normalized": [] }, { "id": "6092", "type": "PA", "arg1_id": "6090", "arg2_id": "6091", "normalized": [] }, { "id": "6095", "type": "PA", "arg1_id": "6093", "arg2_id": "6094", "normalized": [] }, { "id": "6098", "type": "PA", "arg1_id": "6096", "arg2_id": "6097", "normalized": [] }, { "id": "6101", "type": "PA", "arg1_id": "6099", "arg2_id": "6100", "normalized": [] }, { "id": "6104", "type": "PA", "arg1_id": "6102", "arg2_id": "6103", "normalized": [] } ]

[ { "id": "6107", "type": "title", "text": [ "BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma." ], "offsets": [ [ 0, 190 ] ] }, { "id": "6108", "type": "abstract", "text": [ "This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203." ], "offsets": [ [ 191, 1512 ] ] } ]

[ { "id": "6109", "type": "Chemicals & Drugs", "text": [ "BiRD" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "6110", "type": "Chemicals & Drugs", "text": [ "Biaxin" ], "offsets": [ [ 6, 12 ] ], "normalized": [] }, { "id": "6111", "type": "Chemicals & Drugs", "text": [ "clarithromycin" ], "offsets": [ [ 14, 28 ] ], "normalized": [] }, { "id": "6112", "type": "Chemicals & Drugs", "text": [ "Revlimid" ], "offsets": [ [ 30, 38 ] ], "normalized": [] }, { "id": "6113", "type": "Chemicals & Drugs", "text": [ "lenalidomide" ], "offsets": [ [ 40, 52 ] ], "normalized": [] }, { "id": "6114", "type": "Chemicals & Drugs", "text": [ "dexamethasone" ], "offsets": [ [ 54, 67 ] ], "normalized": [] }, { "id": "6115", "type": "Diseases & Disorders", "text": [ "multiple myeloma" ], "offsets": [ [ 173, 189 ] ], "normalized": [] }, { "id": "6116", "type": "Chemicals & Drugs", "text": [ "clarithromycin" ], "offsets": [ [ 264, 278 ] ], "normalized": [] }, { "id": "6117", "type": "Chemicals & Drugs", "text": [ "Biaxin" ], "offsets": [ [ 280, 286 ] ], "normalized": [] }, { "id": "6118", "type": "Chemicals & Drugs", "text": [ "lenalidomide" ], "offsets": [ [ 289, 301 ] ], "normalized": [] }, { "id": "6119", "type": "Chemicals & Drugs", "text": [ "Revlimid" ], "offsets": [ [ 303, 311 ] ], "normalized": [] }, { "id": "6120", "type": "Chemicals & Drugs", "text": [ "dexamethasone" ], "offsets": [ [ 318, 331 ] ], "normalized": [] }, { "id": "6121", "type": "Chemicals & Drugs", "text": [ "BiRD" ], "offsets": [ [ 333, 337 ] ], "normalized": [] }, { "id": "6122", "type": "Diseases & Disorders", "text": [ "multiple myeloma" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6123", "type": "Chemicals & Drugs", "text": [ "BiRD" ], "offsets": [ [ 401, 405 ] ], "normalized": [] }, { "id": "6124", "type": "Chemicals & Drugs", "text": [ "Dexamethasone" ], "offsets": [ [ 424, 437 ] ], "normalized": [] }, { "id": "6125", "type": "Chemicals & Drugs", "text": [ "clarithromycin" ], "offsets": [ [ 476, 490 ] ], "normalized": [] }, { "id": "6126", "type": "Chemicals & Drugs", "text": [ "lenalidomide" ], "offsets": [ [ 534, 546 ] ], "normalized": [] }, { "id": "6127", "type": "Chemicals & Drugs", "text": [ "monoclonal protein" ], "offsets": [ [ 670, 688 ] ], "normalized": [] }, { "id": "6128", "type": "Chemicals & Drugs", "text": [ "M-protein" ], "offsets": [ [ 690, 699 ] ], "normalized": [] }, { "id": "6129", "type": "Chemicals & Drugs", "text": [ "M-protein" ], "offsets": [ [ 742, 751 ] ], "normalized": [] }, { "id": "6130", "type": "Chemicals & Drugs", "text": [ "M-protein" ], "offsets": [ [ 983, 992 ] ], "normalized": [] }, { "id": "6131", "type": "Diseases & Disorders", "text": [ "thromboembolic events" ], "offsets": [ [ 1246, 1267 ] ], "normalized": [] }, { "id": "6132", "type": "Diseases & Disorders", "text": [ "corticosteroid-related morbidity" ], "offsets": [ [ 1269, 1301 ] ], "normalized": [] }, { "id": "6133", "type": "Chemicals & Drugs", "text": [ "corticosteroid-related morbidity" ], "offsets": [ [ 1269, 1301 ] ], "normalized": [] }, { "id": "6134", "type": "Diseases & Disorders", "text": [ "cytopenias" ], "offsets": [ [ 1307, 1317 ] ], "normalized": [] }, { "id": "6135", "type": "Chemicals & Drugs", "text": [ "BiRD" ], "offsets": [ [ 1319, 1323 ] ], "normalized": [] }, { "id": "6136", "type": "Diseases & Disorders", "text": [ "side effects in the treatment" ], "offsets": [ [ 1364, 1393 ] ], "normalized": [] }, { "id": "6137", "type": "Diseases & Disorders", "text": [ "multiple myeloma" ], "offsets": [ [ 1426, 1442 ] ], "normalized": [] }, { "id": "6138", "type": "", "text": [ "clarithromycin" ], "offsets": [ [ 14, 28 ] ], "normalized": [] }, { "id": "6139", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 173, 189 ] ], "normalized": [] }, { "id": "6141", "type": "", "text": [ "lenalidomide" ], "offsets": [ [ 40, 52 ] ], "normalized": [] }, { "id": "6142", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 173, 189 ] ], "normalized": [] }, { "id": "6144", "type": "", "text": [ "dexamethasone" ], "offsets": [ [ 54, 67 ] ], "normalized": [] }, { "id": "6145", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 173, 189 ] ], "normalized": [] }, { "id": "6147", "type": "", "text": [ "BiRD" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "6148", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 173, 189 ] ], "normalized": [] }, { "id": "6150", "type": "", "text": [ "Biaxin" ], "offsets": [ [ 280, 286 ] ], "normalized": [] }, { "id": "6151", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6153", "type": "", "text": [ "Revlimid" ], "offsets": [ [ 303, 311 ] ], "normalized": [] }, { "id": "6154", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6156", "type": "", "text": [ "dexamethasone" ], "offsets": [ [ 318, 331 ] ], "normalized": [] }, { "id": "6157", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6159", "type": "", "text": [ "BiRD" ], "offsets": [ [ 333, 337 ] ], "normalized": [] }, { "id": "6160", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6162", "type": "", "text": [ "BiRD" ], "offsets": [ [ 1319, 1323 ] ], "normalized": [] }, { "id": "6163", "type": "", "text": [ "multiple myeloma" ], "offsets": [ [ 1426, 1442 ] ], "normalized": [] } ]

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[ { "id": "6140", "type": "PA", "arg1_id": "6138", "arg2_id": "6139", "normalized": [] }, { "id": "6143", "type": "PA", "arg1_id": "6141", "arg2_id": "6142", "normalized": [] }, { "id": "6146", "type": "PA", "arg1_id": "6144", "arg2_id": "6145", "normalized": [] }, { "id": "6149", "type": "PA", "arg1_id": "6147", "arg2_id": "6148", "normalized": [] }, { "id": "6152", "type": "PA", "arg1_id": "6150", "arg2_id": "6151", "normalized": [] }, { "id": "6155", "type": "PA", "arg1_id": "6153", "arg2_id": "6154", "normalized": [] }, { "id": "6158", "type": "PA", "arg1_id": "6156", "arg2_id": "6157", "normalized": [] }, { "id": "6161", "type": "PA", "arg1_id": "6159", "arg2_id": "6160", "normalized": [] }, { "id": "6164", "type": "PA", "arg1_id": "6162", "arg2_id": "6163", "normalized": [] } ]

[ { "id": "6167", "type": "title", "text": [ "Plasmodium falciparum erythrocyte membrane protein-1 specifically suppresses early production of host interferon-gamma." ], "offsets": [ [ 0, 119 ] ] }, { "id": "6168", "type": "abstract", "text": [ "Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a variable antigen expressed by P. falciparum, the malarial parasite. PfEMP-1, present on the surface of infected host erythrocytes, mediates erythrocyte binding to vascular endothelium, enabling the parasite to avoid splenic clearance. In addition, PfEMP-1 is proposed to regulate host immune responses via interactions with the CD36 receptor on antigen-presenting cells. We investigated the immunoregulatory function of PfEMP-1 by comparing host cell responses to erythrocytes infected with either wild-type parasites or transgenic parasites lacking PfEMP-1. We showed that PfEMP-1 suppresses the production of the cytokine interferon-gamma by human peripheral blood mononuclear cells early after exposure to P. falciparum. Suppression of this rapid proinflammatory response was CD36 independent and specific to interferon-gamma production by gammadelta-T, NK, and alphabeta-T cells. These data demonstrate a parasite strategy for downregulating the proinflammatory interferon-gamma response and further establish transgenic parasites lacking PfEMP-1 as powerful tools for elucidating PfEMP-1 functions." ], "offsets": [ [ 120, 1291 ] ] } ]

[ { "id": "6169", "type": "Genes & Molecular Sequences", "text": [ "Plasmodium falciparum erythrocyte membrane protein-1" ], "offsets": [ [ 0, 52 ] ], "normalized": [] }, { "id": "6170", "type": "Genes & Molecular Sequences", "text": [ "interferon-gamma" ], "offsets": [ [ 102, 118 ] ], "normalized": [] }, { "id": "6171", "type": "Chemicals & Drugs", "text": [ "interferon-gamma" ], "offsets": [ [ 102, 118 ] ], "normalized": [] }, { "id": "6172", "type": "Genes & Molecular Sequences", "text": [ "Plasmodium falciparum erythrocyte membrane protein-1" ], "offsets": [ [ 120, 172 ] ], "normalized": [] }, { "id": "6173", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 174, 181 ] ], "normalized": [] }, { "id": "6174", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 256, 263 ] ], "normalized": [] }, { "id": "6175", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 436, 443 ] ], "normalized": [] }, { "id": "6176", "type": "Genes & Molecular Sequences", "text": [ "CD36 receptor" ], "offsets": [ [ 516, 529 ] ], "normalized": [] }, { "id": "6177", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 608, 615 ] ], "normalized": [] }, { "id": "6178", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 738, 745 ] ], "normalized": [] }, { "id": "6179", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 762, 769 ] ], "normalized": [] }, { "id": "6180", "type": "Genes & Molecular Sequences", "text": [ "interferon-gamma" ], "offsets": [ [ 812, 828 ] ], "normalized": [] }, { "id": "6181", "type": "Chemicals & Drugs", "text": [ "interferon-gamma" ], "offsets": [ [ 812, 828 ] ], "normalized": [] }, { "id": "6182", "type": "Genes & Molecular Sequences", "text": [ "CD36" ], "offsets": [ [ 967, 971 ] ], "normalized": [] }, { "id": "6183", "type": "Genes & Molecular Sequences", "text": [ "interferon-gamma" ], "offsets": [ [ 1000, 1016 ] ], "normalized": [] }, { "id": "6184", "type": "Chemicals & Drugs", "text": [ "interferon-gamma" ], "offsets": [ [ 1000, 1016 ] ], "normalized": [] }, { "id": "6185", "type": "Genes & Molecular Sequences", "text": [ "interferon-gamma" ], "offsets": [ [ 1154, 1170 ] ], "normalized": [] }, { "id": "6186", "type": "Chemicals & Drugs", "text": [ "interferon-gamma" ], "offsets": [ [ 1154, 1170 ] ], "normalized": [] }, { "id": "6187", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 1231, 1238 ] ], "normalized": [] }, { "id": "6188", "type": "Genes & Molecular Sequences", "text": [ "PfEMP-1" ], "offsets": [ [ 1273, 1280 ] ], "normalized": [] } ]

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[ { "id": "6191", "type": "title", "text": [ "Can pregnancy rate be improved in gonadotropin-releasing hormone (GnRH) antagonist cycles by administering GnRH agonist before oocyte retrieval? A prospective, randomized study." ], "offsets": [ [ 0, 177 ] ] }, { "id": "6192", "type": "abstract", "text": [ "OBJECTIVE: To examine whether the addition of one dose of preovulatory GnRH agonist could improve implantation and pregnancy rates in GnRH antagonist IVF cycles. DESIGN: Prospective, randomized clinical trial. SETTING: University-affiliated IVF and infertility unit. PATIENT(S): Two hundred twenty-one patients intended for GnRH antagonist protocol IVF. INTERVENTION(S): Patients were prospectively randomized to two groups. The control group received hCG (5,000 U) 34 hours before oocyte aspiration, and the study group received triptorelin (0.2 mg SC) in addition to hCG. All other treatment parameters were identical. MAIN OUTCOME MEASURE(S): Oocyte pick-up day serum levels of E(2), P, LH, and FSH and implantation and pregnancy rates per started cycle and per completed cycle. RESULT(S): A total of 200 ET cycles were carried out: 97 in the study group and 103 in the control group. None of the cycle parameters of the study or control groups differed, excepting mean oocyte pick-up day FSH (11.26 IU/L [95% confidence interval (CI) 9.88-12.52] vs. 6.27 IU/L [95% CI 5.76-8.77]) and LH levels (5.19 IU/L [95% CI 4.47-5.9] vs. 3.28 IU/L [95% CI 2.22-4.18]). The implantation rate was 19.9% (52 of 261) for the study group and 13.9% (35 of 251) for the control group. The pregnancy rate in completed cycles and the ongoing pregnancy rate per ET were significantly higher in the study group than in the control group: 29.1% (30 of 103) in the control group and 44.3% (43 of 97) in the study group, and 22.3% (23 of 103) and 36.1% (35 of 97), respectively. However, the improvement in pregnancy rate per started cycle did not reach statistical significance (40.9% vs. 28.3%). CONCLUSIONS: The administration of triptorelin (0.2 mg) at the time of hCG administration in GnRH antagonist IVF cycles significantly improved overall and ongoing pregnancy rates in completed cycles but not in all started cycles. It is possible that this was achieved owing to an endometrial GnRH receptor effect, which should also be examined by direct endometrial studies." ], "offsets": [ [ 178, 2229 ] ] } ]

[ { "id": "6193", "type": "Chemicals & Drugs", "text": [ "gonadotropin-releasing hormone" ], "offsets": [ [ 34, 64 ] ], "normalized": [] }, { "id": "6194", "type": "Chemicals & Drugs", "text": [ "GnRH) antagonist" ], "offsets": [ [ 66, 82 ] ], "normalized": [] }, { "id": "6195", "type": "Chemicals & Drugs", "text": [ "GnRH agonist" ], "offsets": [ [ 107, 119 ] ], "normalized": [] }, { "id": "6196", "type": "Chemicals & Drugs", "text": [ "preovulatory GnRH agonist" ], "offsets": [ [ 236, 261 ] ], "normalized": [] }, { "id": "6197", "type": "Chemicals & Drugs", "text": [ "GnRH antagonist" ], "offsets": [ [ 312, 327 ] ], "normalized": [] }, { "id": "6198", "type": "Chemicals & Drugs", "text": [ "GnRH antagonist" ], "offsets": [ [ 502, 517 ] ], "normalized": [] }, { "id": "6199", "type": "Chemicals & Drugs", "text": [ "hCG" ], "offsets": [ [ 630, 633 ] ], "normalized": [] }, { "id": "6200", "type": "Genes & Molecular Sequences", "text": [ "hCG" ], "offsets": [ [ 630, 633 ] ], "normalized": [] }, { "id": "6201", "type": "Chemicals & Drugs", "text": [ "triptorelin" ], "offsets": [ [ 708, 719 ] ], "normalized": [] }, { "id": "6202", "type": "Chemicals & Drugs", "text": [ "hCG" ], "offsets": [ [ 747, 750 ] ], "normalized": [] }, { "id": "6203", "type": "Genes & Molecular Sequences", "text": [ "E(2)" ], "offsets": [ [ 859, 863 ] ], "normalized": [] }, { "id": "6204", "type": "Chemicals & Drugs", "text": [ "E(2)" ], "offsets": [ [ 859, 863 ] ], "normalized": [] }, { "id": "6205", "type": "Chemicals & Drugs", "text": [ "P" ], "offsets": [ [ 865, 866 ] ], "normalized": [] }, { "id": "6206", "type": "Genes & Molecular Sequences", "text": [ "LH" ], "offsets": [ [ 868, 870 ] ], "normalized": [] }, { "id": "6207", "type": "Chemicals & Drugs", "text": [ "LH" ], "offsets": [ [ 868, 870 ] ], "normalized": [] }, { "id": "6208", "type": "Genes & Molecular Sequences", "text": [ "FSH" ], "offsets": [ [ 876, 879 ] ], "normalized": [] }, { "id": "6209", "type": "Chemicals & Drugs", "text": [ "FSH" ], "offsets": [ [ 876, 879 ] ], "normalized": [] }, { "id": "6210", "type": "Genes & Molecular Sequences", "text": [ "FSH" ], "offsets": [ [ 1170, 1173 ] ], "normalized": [] }, { "id": "6211", "type": "Chemicals & Drugs", "text": [ "FSH" ], "offsets": [ [ 1170, 1173 ] ], "normalized": [] }, { "id": "6212", "type": "Genes & Molecular Sequences", "text": [ "LH" ], "offsets": [ [ 1266, 1268 ] ], "normalized": [] }, { "id": "6213", "type": "Chemicals & Drugs", "text": [ "LH" ], "offsets": [ [ 1266, 1268 ] ], "normalized": [] }, { "id": "6214", "type": "Chemicals & Drugs", "text": [ "triptorelin" ], "offsets": [ [ 1890, 1901 ] ], "normalized": [] }, { "id": "6215", "type": "Chemicals & Drugs", "text": [ "hCG" ], "offsets": [ [ 1926, 1929 ] ], "normalized": [] }, { "id": "6216", "type": "Chemicals & Drugs", "text": [ "GnRH antagonist" ], "offsets": [ [ 1948, 1963 ] ], "normalized": [] }, { "id": "6217", "type": "Genes & Molecular Sequences", "text": [ "endometrial GnRH receptor" ], "offsets": [ [ 2135, 2160 ] ], "normalized": [] }, { "id": "6218", "type": "", "text": [ "triptorelin" ], "offsets": [ [ 708, 719 ] ], "normalized": [] }, { "id": "6219", "type": "", "text": [ "hCG" ], "offsets": [ [ 630, 633 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6220", "type": "PA", "arg1_id": "6218", "arg2_id": "6219", "normalized": [] } ]

[ { "id": "6223", "type": "title", "text": [ "Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning." ], "offsets": [ [ 0, 95 ] ] }, { "id": "6224", "type": "abstract", "text": [ "Ischaemia-reperfusion (I/R) is a pivotal mechanism of organ injury during stroke, myocardial infarction, organ transplantation and vascular surgeries. Ischaemic preconditioning (IPC) is a potent endogenous form of tissue protection against I/R injury. On the one hand, endocannabinoids have been implicated in the protective effects of IPC through cannabinoid CB1/CB2 receptor-dependent and -independent mechanisms. However, there is evidence suggesting that endocannabinoids are overproduced during various forms of I/R, such as myocardial infarction or whole body I/R associated with circulatory shock, and may contribute to the cardiovascular depressive state associated with these pathologies. Previous studies using synthetic CB1 receptor agonists or knockout mice demonstrated CB1 receptor-dependent protection against cerebral I/R injury in various animal models. In contrast, several follow-up reports have shown protection afforded by CB1 receptor antagonists, but not agonists. Excitedly, emerging studies using potent CB2 receptor agonists and/or knockout mice have provided compelling evidence that CB2 receptor activation is protective against myocardial, cerebral and hepatic I/R injuries by decreasing the endothelial cell activation/inflammatory response (for example, expression of adhesion molecules, secretion of chemokines, and so on), and by attenuating the leukocyte chemotaxis, rolling, adhesion to endothelium, activation and transendothelial migration, and interrelated oxidative/nitrosative damage. This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB2 receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R-induced tissue damage." ], "offsets": [ [ 96, 2011 ] ] } ]

[ { "id": "6225", "type": "Chemicals & Drugs", "text": [ "Endocannabinoids" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "6226", "type": "Genes & Molecular Sequences", "text": [ "cannabinoid receptors" ], "offsets": [ [ 21, 42 ] ], "normalized": [] }, { "id": "6227", "type": "Chemicals & Drugs", "text": [ "endocannabinoids" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6228", "type": "Genes & Molecular Sequences", "text": [ "CB1" ], "offsets": [ [ 456, 459 ] ], "normalized": [] }, { "id": "6229", "type": "Genes & Molecular Sequences", "text": [ "CB2" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "6230", "type": "Chemicals & Drugs", "text": [ "endocannabinoids" ], "offsets": [ [ 555, 571 ] ], "normalized": [] }, { "id": "6231", "type": "Chemicals & Drugs", "text": [ "synthetic CB1 receptor agonists" ], "offsets": [ [ 817, 848 ] ], "normalized": [] }, { "id": "6232", "type": "Genes & Molecular Sequences", "text": [ "CB1" ], "offsets": [ [ 827, 830 ] ], "normalized": [] }, { "id": "6233", "type": "Genes & Molecular Sequences", "text": [ "CB1" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "6234", "type": "Chemicals & Drugs", "text": [ "CB1 receptor antagonists" ], "offsets": [ [ 1040, 1064 ] ], "normalized": [] }, { "id": "6235", "type": "Genes & Molecular Sequences", "text": [ "CB1 receptor antagonists" ], "offsets": [ [ 1040, 1064 ] ], "normalized": [] }, { "id": "6236", "type": "Chemicals & Drugs", "text": [ "CB2 receptor agonists" ], "offsets": [ [ 1125, 1146 ] ], "normalized": [] }, { "id": "6237", "type": "Genes & Molecular Sequences", "text": [ "CB2 receptor agonists" ], "offsets": [ [ 1125, 1146 ] ], "normalized": [] }, { "id": "6238", "type": "Genes & Molecular Sequences", "text": [ "CB2" ], "offsets": [ [ 1207, 1210 ] ], "normalized": [] }, { "id": "6239", "type": "Genes & Molecular Sequences", "text": [ "chemokines" ], "offsets": [ [ 1428, 1438 ] ], "normalized": [] }, { "id": "6240", "type": "Chemicals & Drugs", "text": [ "endocannabinoids" ], "offsets": [ [ 1665, 1681 ] ], "normalized": [] }, { "id": "6241", "type": "Genes & Molecular Sequences", "text": [ "CB receptors" ], "offsets": [ [ 1686, 1698 ] ], "normalized": [] }, { "id": "6242", "type": "Chemicals & Drugs", "text": [ "CB2 receptor agonists" ], "offsets": [ [ 1883, 1904 ] ], "normalized": [] }, { "id": "6243", "type": "Genes & Molecular Sequences", "text": [ "CB2 receptor agonists" ], "offsets": [ [ 1883, 1904 ] ], "normalized": [] }, { "id": "6244", "type": "", "text": [ "endocannabinoids" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6245", "type": "", "text": [ "CB1" ], "offsets": [ [ 456, 459 ] ], "normalized": [] }, { "id": "6247", "type": "", "text": [ "endocannabinoids" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "6248", "type": "", "text": [ "CB2" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "6250", "type": "", "text": [ "synthetic CB1 receptor agonists" ], "offsets": [ [ 817, 848 ] ], "normalized": [] }, { "id": "6251", "type": "", "text": [ "CB1" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "6253", "type": "", "text": [ "CB2 receptor agonists" ], "offsets": [ [ 1125, 1146 ] ], "normalized": [] }, { "id": "6254", "type": "", "text": [ "CB2" ], "offsets": [ [ 1207, 1210 ] ], "normalized": [] }, { "id": "6256", "type": "", "text": [ "CB2 receptor agonists" ], "offsets": [ [ 1125, 1146 ] ], "normalized": [] }, { "id": "6257", "type": "", "text": [ "chemokines" ], "offsets": [ [ 1428, 1438 ] ], "normalized": [] }, { "id": "6259", "type": "", "text": [ "endocannabinoids" ], "offsets": [ [ 1665, 1681 ] ], "normalized": [] }, { "id": "6260", "type": "", "text": [ "CB receptors" ], "offsets": [ [ 1686, 1698 ] ], "normalized": [] }, { "id": "6262", "type": "", "text": [ "CB2 receptor agonists" ], "offsets": [ [ 1883, 1904 ] ], "normalized": [] }, { "id": "6263", "type": "", "text": [ "CB receptors" ], "offsets": [ [ 1686, 1698 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6246", "type": "PA", "arg1_id": "6244", "arg2_id": "6245", "normalized": [] }, { "id": "6249", "type": "PA", "arg1_id": "6247", "arg2_id": "6248", "normalized": [] }, { "id": "6252", "type": "PA", "arg1_id": "6250", "arg2_id": "6251", "normalized": [] }, { "id": "6255", "type": "PA", "arg1_id": "6253", "arg2_id": "6254", "normalized": [] }, { "id": "6258", "type": "PA", "arg1_id": "6256", "arg2_id": "6257", "normalized": [] }, { "id": "6261", "type": "PA", "arg1_id": "6259", "arg2_id": "6260", "normalized": [] }, { "id": "6264", "type": "PA", "arg1_id": "6262", "arg2_id": "6263", "normalized": [] } ]

[ { "id": "6267", "type": "title", "text": [ "In vivo gene delivery for development of mammalian models for Parkinson's disease." ], "offsets": [ [ 0, 82 ] ] }, { "id": "6268", "type": "abstract", "text": [ "During the last decade, identification of the genes involved in familial forms of Parkinson's disease (PD) has advanced our understanding of the mechanisms underlying the development of different aspects of PD. However the available animal models still remain as the main limiting factor for the development of neuroprotective therapies that can halt the progression of the disease, through which we wish to provide a better quality of life for the PD patients. Here, we review the recently developed animal models based on overexpression of PD-associated genes using recombinant viral vectors. Recombinant adeno-associated viral vectors, in particular, have been very useful in targeting the nigral dopamine neurons both in the rodent and the primate brain. In order to provide insights into the establishment of these models in the laboratory, we will not only give an overview of the results from these studies but also cover practical issues related to the production and handling of the viral vectors, which are critical for the successful application of this approach." ], "offsets": [ [ 83, 1157 ] ] } ]

[ { "id": "6269", "type": "Diseases & Disorders", "text": [ "Parkinson's disease" ], "offsets": [ [ 62, 81 ] ], "normalized": [] }, { "id": "6270", "type": "Diseases & Disorders", "text": [ "Parkinson's disease" ], "offsets": [ [ 165, 184 ] ], "normalized": [] }, { "id": "6271", "type": "Diseases & Disorders", "text": [ "PD" ], "offsets": [ [ 186, 188 ] ], "normalized": [] }, { "id": "6272", "type": "Diseases & Disorders", "text": [ "PD" ], "offsets": [ [ 290, 292 ] ], "normalized": [] }, { "id": "6273", "type": "Diseases & Disorders", "text": [ "still" ], "offsets": [ [ 330, 335 ] ], "normalized": [] }, { "id": "6274", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 457, 464 ] ], "normalized": [] }, { "id": "6275", "type": "Diseases & Disorders", "text": [ "PD" ], "offsets": [ [ 532, 534 ] ], "normalized": [] }, { "id": "6276", "type": "Genes & Molecular Sequences", "text": [ "PD-associated genes" ], "offsets": [ [ 625, 644 ] ], "normalized": [] }, { "id": "6277", "type": "Diseases & Disorders", "text": [ "PD-associated genes" ], "offsets": [ [ 625, 644 ] ], "normalized": [] }, { "id": "6278", "type": "Genes & Molecular Sequences", "text": [ "Recombinant adeno-associated viral vectors" ], "offsets": [ [ 678, 720 ] ], "normalized": [] }, { "id": "6279", "type": "Genes & Molecular Sequences", "text": [ "dopamine" ], "offsets": [ [ 783, 791 ] ], "normalized": [] } ]

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[]

[]

[ { "id": "6282", "type": "title", "text": [ "Design and synthesis of indane-ureido-thioisobutyric acids: A novel class of PPARalpha agonists." ], "offsets": [ [ 0, 96 ] ] }, { "id": "6283", "type": "abstract", "text": [ "A series of aminoindane derivatives were synthesized and shown to be potent PPARalpha agonists. The compounds were obtained as racemates in 12 steps, and tested for PPARalpha activation and PPARalpha mediated induction of the HD gene. SAR was developed by variation to the core structure as shown within. Oral bioavailability was demonstrated in a Sprague-Dawley rat, while efficacy to reduce plasma triglycerides and plasma glucose was demonstrated in db/db mice." ], "offsets": [ [ 97, 561 ] ] } ]

[ { "id": "6284", "type": "Chemicals & Drugs", "text": [ "indane-ureido-thioisobutyric acids" ], "offsets": [ [ 24, 58 ] ], "normalized": [] }, { "id": "6285", "type": "Chemicals & Drugs", "text": [ "PPARalpha agonists" ], "offsets": [ [ 77, 95 ] ], "normalized": [] }, { "id": "6286", "type": "Genes & Molecular Sequences", "text": [ "PPARalpha agonists" ], "offsets": [ [ 77, 95 ] ], "normalized": [] }, { "id": "6287", "type": "Chemicals & Drugs", "text": [ "aminoindane derivatives" ], "offsets": [ [ 109, 132 ] ], "normalized": [] }, { "id": "6288", "type": "Chemicals & Drugs", "text": [ "PPARalpha agonists" ], "offsets": [ [ 173, 191 ] ], "normalized": [] }, { "id": "6289", "type": "Genes & Molecular Sequences", "text": [ "PPARalpha agonists" ], "offsets": [ [ 173, 191 ] ], "normalized": [] }, { "id": "6290", "type": "Genes & Molecular Sequences", "text": [ "PPARalpha" ], "offsets": [ [ 262, 271 ] ], "normalized": [] }, { "id": "6291", "type": "Genes & Molecular Sequences", "text": [ "PPARalpha" ], "offsets": [ [ 287, 296 ] ], "normalized": [] }, { "id": "6292", "type": "Genes & Molecular Sequences", "text": [ "HD" ], "offsets": [ [ 323, 325 ] ], "normalized": [] }, { "id": "6293", "type": "Genes & Molecular Sequences", "text": [ "SAR" ], "offsets": [ [ 332, 335 ] ], "normalized": [] }, { "id": "6294", "type": "Chemicals & Drugs", "text": [ "triglycerides" ], "offsets": [ [ 497, 510 ] ], "normalized": [] }, { "id": "6295", "type": "Genes & Molecular Sequences", "text": [ "triglycerides" ], "offsets": [ [ 497, 510 ] ], "normalized": [] }, { "id": "6296", "type": "Chemicals & Drugs", "text": [ "glucose" ], "offsets": [ [ 522, 529 ] ], "normalized": [] }, { "id": "6297", "type": "Genes & Molecular Sequences", "text": [ "glucose" ], "offsets": [ [ 522, 529 ] ], "normalized": [] }, { "id": "6298", "type": "", "text": [ "indane-ureido-thioisobutyric acids" ], "offsets": [ [ 24, 58 ] ], "normalized": [] }, { "id": "6299", "type": "", "text": [ "PPARalpha agonists" ], "offsets": [ [ 77, 95 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6300", "type": "PA", "arg1_id": "6298", "arg2_id": "6299", "normalized": [] } ]

[ { "id": "6303", "type": "title", "text": [ "Retained silicone sleeve as a cause of dacryocystorhinostomy failure." ], "offsets": [ [ 0, 69 ] ] }, { "id": "6304", "type": "abstract", "text": [ "Silicone sleeves are 1 method of stabilizing bicanalicular silicone intubation near the ostia during dacryocystorhinostomy surgery to prevent tube prolapse. Retained silicone sleeve following dacryocystorhinostomy is a rare and previously unreported complication that can occur despite endoscopic visualization during tube removal, particularly in narrow nasal passages. It is an easily reversible cause of dacryocystorhinostomy failure if identified." ], "offsets": [ [ 70, 521 ] ] } ]

[ { "id": "6305", "type": "Chemicals & Drugs", "text": [ "silicone sleeve" ], "offsets": [ [ 9, 24 ] ], "normalized": [] }, { "id": "6306", "type": "Diseases & Disorders", "text": [ "dacryocystorhinostomy failure" ], "offsets": [ [ 39, 68 ] ], "normalized": [] }, { "id": "6307", "type": "Chemicals & Drugs", "text": [ "Silicone" ], "offsets": [ [ 70, 78 ] ], "normalized": [] }, { "id": "6308", "type": "Chemicals & Drugs", "text": [ "silicone" ], "offsets": [ [ 129, 137 ] ], "normalized": [] }, { "id": "6309", "type": "Diseases & Disorders", "text": [ "tube prolapse" ], "offsets": [ [ 212, 225 ] ], "normalized": [] }, { "id": "6310", "type": "Chemicals & Drugs", "text": [ "silicone sleeve" ], "offsets": [ [ 236, 251 ] ], "normalized": [] }, { "id": "6311", "type": "Diseases & Disorders", "text": [ "complication" ], "offsets": [ [ 320, 332 ] ], "normalized": [] }, { "id": "6312", "type": "Diseases & Disorders", "text": [ "dacryocystorhinostomy failure" ], "offsets": [ [ 477, 506 ] ], "normalized": [] }, { "id": "6313", "type": "", "text": [ "silicone" ], "offsets": [ [ 129, 137 ] ], "normalized": [] }, { "id": "6314", "type": "", "text": [ "tube prolapse" ], "offsets": [ [ 212, 225 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6315", "type": "PA", "arg1_id": "6313", "arg2_id": "6314", "normalized": [] } ]

[ { "id": "6318", "type": "title", "text": [ "Toll-like receptors' two-edged sword: when immunity meets apoptosis." ], "offsets": [ [ 0, 68 ] ] }, { "id": "6319", "type": "abstract", "text": [ "Toll-like receptors (TLR) have emerged as key players in the detection of pathogens and the induction of anti-microbial immune response. TLR recognize pathogen-associated molecular patterns, and trigger anti-microbial innate immune responses ranging from the secretion of pro-inflammatory mediators to the increase of natural killer cell cytotoxicity. Besides activating the innate immune response, TLR engagement also shapes the adaptive immune response. Indeed, the broad diversity of signaling pathways initiated by TLR is progressively unraveled. Recent reports suggested that among the anti-microbial defenses they initiate, members of the TLR family can induce apoptosis. This review focuses on this newly described function of TLR, and emphasizes the similarities and differences between the different apoptosis-signaling pathways described downstream of TLR. The functional relevance of TLR-triggered apoptosis is also discussed, as therapeutic applications are likely to ensue in the near future." ], "offsets": [ [ 69, 1074 ] ] } ]

[ { "id": "6320", "type": "Genes & Molecular Sequences", "text": [ "Toll-like receptors" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "6321", "type": "Genes & Molecular Sequences", "text": [ "Toll-like receptors" ], "offsets": [ [ 69, 88 ] ], "normalized": [] }, { "id": "6322", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 90, 93 ] ], "normalized": [] }, { "id": "6323", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 206, 209 ] ], "normalized": [] }, { "id": "6324", "type": "Chemicals & Drugs", "text": [ "trigger" ], "offsets": [ [ 264, 271 ] ], "normalized": [] }, { "id": "6325", "type": "Genes & Molecular Sequences", "text": [ "pro-inflammatory mediators" ], "offsets": [ [ 341, 367 ] ], "normalized": [] }, { "id": "6326", "type": "Genes & Molecular Sequences", "text": [ "killer" ], "offsets": [ [ 395, 401 ] ], "normalized": [] }, { "id": "6327", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 468, 471 ] ], "normalized": [] }, { "id": "6328", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "6329", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 714, 717 ] ], "normalized": [] }, { "id": "6330", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 803, 806 ] ], "normalized": [] }, { "id": "6331", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 931, 934 ] ], "normalized": [] }, { "id": "6332", "type": "Genes & Molecular Sequences", "text": [ "TLR" ], "offsets": [ [ 964, 967 ] ], "normalized": [] }, { "id": "6333", "type": "", "text": [ "trigger" ], "offsets": [ [ 264, 271 ] ], "normalized": [] }, { "id": "6334", "type": "", "text": [ "killer" ], "offsets": [ [ 395, 401 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6335", "type": "PA", "arg1_id": "6333", "arg2_id": "6334", "normalized": [] } ]

[ { "id": "6338", "type": "title", "text": [ "Postoperative beneficial effects of esmolol in treated hypertensive patients undergoing laparoscopic cholecystectomy." ], "offsets": [ [ 0, 117 ] ] }, { "id": "6339", "type": "abstract", "text": [ "BACKGROUND: In an attempt to decrease haemodynamic instability and early postoperative complications such as nausea, vomiting, and pain, esmolol was added to the routine alfentanil infusion of patients with treated hypertension undergoing laparoscopic cholecystectomy. METHODS: Forty consecutive ASA class II patients with controlled hypertension about to undergo laparoscopic cholecystectomy were randomized into two groups: an esmolol group (Group E, n=20) was given a 1 mg kg(-1) bolus of esmolol and a placebo group (Group P, n=20) was given an identical volume of Ringer's lactate. The rate of esmolol infusion was adjusted to keep the heart rate between 65 and 75 beats min(-1) and was 5-10 microg kg(-1) min(-1) throughout the procedure. After operation, patients reported their nausea using a four-point scale. RESULTS: Esmolol had an opioid-sparing effect intraoperatively (P=0.001). Postoperative requirements for antiemetics were significantly less in the esmolol group, with no antiemetics given to eight patients. In the placebo group, however, all patients required at least one dose of antiemetic (P=0.007). The frequency of PONV did not correlate to the amounts of alfentanil, propofol, postoperative antiemetics consumed, or to female gender, non-smoking status, and history of PONV or motion sickness. Postoperative analgesic consumption in Group E was significantly lower than in Group P (P=0.012). CONCLUSIONS: Esmolol had an opioid-sparing effect in the intraoperative and immediate postoperative period in hypertensive patients undergoing laparoscopy. When combined with alfentanil, it was more effective than placebo in decreasing early PONV." ], "offsets": [ [ 118, 1783 ] ] } ]

[ { "id": "6340", "type": "Chemicals & Drugs", "text": [ "esmolol" ], "offsets": [ [ 36, 43 ] ], "normalized": [] }, { "id": "6341", "type": "Diseases & Disorders", "text": [ "hypertensive" ], "offsets": [ [ 55, 67 ] ], "normalized": [] }, { "id": "6342", "type": "Diseases & Disorders", "text": [ "haemodynamic instability" ], "offsets": [ [ 156, 180 ] ], "normalized": [] }, { "id": "6343", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 205, 218 ] ], "normalized": [] }, { "id": "6344", "type": "Diseases & Disorders", "text": [ "nausea" ], "offsets": [ [ 227, 233 ] ], "normalized": [] }, { "id": "6345", "type": "Diseases & Disorders", "text": [ "vomiting" ], "offsets": [ [ 235, 243 ] ], "normalized": [] }, { "id": "6346", "type": "Diseases & Disorders", "text": [ "pain" ], "offsets": [ [ 249, 253 ] ], "normalized": [] }, { "id": "6347", "type": "Chemicals & Drugs", "text": [ "esmolol" ], "offsets": [ [ 255, 262 ] ], "normalized": [] }, { "id": "6348", "type": "Chemicals & Drugs", "text": [ "alfentanil" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "6349", "type": "Diseases & Disorders", "text": [ "hypertension" ], "offsets": [ [ 333, 345 ] ], "normalized": [] }, { "id": "6350", "type": "Chemicals & Drugs", "text": [ "ASA" ], "offsets": [ [ 414, 417 ] ], "normalized": [] }, { "id": "6351", "type": "Diseases & Disorders", "text": [ "hypertension" ], "offsets": [ [ 452, 464 ] ], "normalized": [] }, { "id": "6352", "type": "Chemicals & Drugs", "text": [ "esmolol" ], "offsets": [ [ 547, 554 ] ], "normalized": [] }, { "id": "6353", "type": "Chemicals & Drugs", "text": [ "esmolol" ], "offsets": [ [ 610, 617 ] ], "normalized": [] }, { "id": "6354", "type": "Chemicals & Drugs", "text": [ "Ringer's lactate" ], "offsets": [ [ 687, 703 ] ], "normalized": [] }, { "id": "6355", "type": "Chemicals & Drugs", "text": [ "esmolol" ], "offsets": [ [ 717, 724 ] ], "normalized": [] }, { "id": "6356", "type": "Diseases & Disorders", "text": [ "nausea" ], "offsets": [ [ 904, 910 ] ], "normalized": [] }, { "id": "6357", "type": "Chemicals & Drugs", "text": [ "Esmolol" ], "offsets": [ [ 946, 953 ] ], "normalized": [] }, { "id": "6358", "type": "Chemicals & Drugs", "text": [ "antiemetics" ], "offsets": [ [ 1042, 1053 ] ], "normalized": [] }, { "id": "6359", "type": "Chemicals & Drugs", "text": [ "esmolol" ], "offsets": [ [ 1085, 1092 ] ], "normalized": [] }, { "id": "6360", "type": "Chemicals & Drugs", "text": [ "antiemetics" ], "offsets": [ [ 1108, 1119 ] ], "normalized": [] }, { "id": "6361", "type": "Chemicals & Drugs", "text": [ "antiemetic" ], "offsets": [ [ 1219, 1229 ] ], "normalized": [] }, { "id": "6362", "type": "Diseases & Disorders", "text": [ "PONV" ], "offsets": [ [ 1258, 1262 ] ], "normalized": [] }, { "id": "6363", "type": "Chemicals & Drugs", "text": [ "alfentanil" ], "offsets": [ [ 1299, 1309 ] ], "normalized": [] }, { "id": "6364", "type": "Chemicals & Drugs", "text": [ "propofol" ], "offsets": [ [ 1311, 1319 ] ], "normalized": [] }, { "id": "6365", "type": "Chemicals & Drugs", "text": [ "antiemetics" ], "offsets": [ [ 1335, 1346 ] ], "normalized": [] }, { "id": "6366", "type": "Diseases & Disorders", "text": [ "PONV" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] }, { "id": "6367", "type": "Diseases & Disorders", "text": [ "motion sickness" ], "offsets": [ [ 1421, 1436 ] ], "normalized": [] }, { "id": "6368", "type": "Diseases & Disorders", "text": [ "consumption" ], "offsets": [ [ 1462, 1473 ] ], "normalized": [] }, { "id": "6369", "type": "Chemicals & Drugs", "text": [ "Esmolol" ], "offsets": [ [ 1549, 1556 ] ], "normalized": [] }, { "id": "6370", "type": "Diseases & Disorders", "text": [ "hypertensive" ], "offsets": [ [ 1646, 1658 ] ], "normalized": [] }, { "id": "6371", "type": "Chemicals & Drugs", "text": [ "alfentanil" ], "offsets": [ [ 1711, 1721 ] ], "normalized": [] }, { "id": "6372", "type": "Diseases & Disorders", "text": [ "PONV" ], "offsets": [ [ 1778, 1782 ] ], "normalized": [] }, { "id": "6373", "type": "", "text": [ "Esmolol" ], "offsets": [ [ 1549, 1556 ] ], "normalized": [] }, { "id": "6374", "type": "", "text": [ "hypertensive" ], "offsets": [ [ 1646, 1658 ] ], "normalized": [] }, { "id": "6376", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 1711, 1721 ] ], "normalized": [] }, { "id": "6377", "type": "", "text": [ "PONV" ], "offsets": [ [ 1778, 1782 ] ], "normalized": [] }, { "id": "6379", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 1299, 1309 ] ], "normalized": [] }, { "id": "6380", "type": "", "text": [ "motion sickness" ], "offsets": [ [ 1421, 1436 ] ], "normalized": [] }, { "id": "6382", "type": "", "text": [ "propofol" ], "offsets": [ [ 1311, 1319 ] ], "normalized": [] }, { "id": "6383", "type": "", "text": [ "motion sickness" ], "offsets": [ [ 1421, 1436 ] ], "normalized": [] }, { "id": "6385", "type": "", "text": [ "esmolol" ], "offsets": [ [ 255, 262 ] ], "normalized": [] }, { "id": "6386", "type": "", "text": [ "haemodynamic instability" ], "offsets": [ [ 156, 180 ] ], "normalized": [] }, { "id": "6388", "type": "", "text": [ "esmolol" ], "offsets": [ [ 255, 262 ] ], "normalized": [] }, { "id": "6389", "type": "", "text": [ "complications" ], "offsets": [ [ 205, 218 ] ], "normalized": [] }, { "id": "6391", "type": "", "text": [ "esmolol" ], "offsets": [ [ 255, 262 ] ], "normalized": [] }, { "id": "6392", "type": "", "text": [ "nausea" ], "offsets": [ [ 227, 233 ] ], "normalized": [] }, { "id": "6394", "type": "", "text": [ "esmolol" ], "offsets": [ [ 255, 262 ] ], "normalized": [] }, { "id": "6395", "type": "", "text": [ "vomiting" ], "offsets": [ [ 235, 243 ] ], "normalized": [] }, { "id": "6397", "type": "", "text": [ "esmolol" ], "offsets": [ [ 255, 262 ] ], "normalized": [] }, { "id": "6398", "type": "", "text": [ "pain" ], "offsets": [ [ 249, 253 ] ], "normalized": [] }, { "id": "6400", "type": "", "text": [ "esmolol" ], "offsets": [ [ 255, 262 ] ], "normalized": [] }, { "id": "6401", "type": "", "text": [ "hypertension" ], "offsets": [ [ 333, 345 ] ], "normalized": [] }, { "id": "6403", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "6404", "type": "", "text": [ "haemodynamic instability" ], "offsets": [ [ 156, 180 ] ], "normalized": [] }, { "id": "6406", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "6407", "type": "", "text": [ "complications" ], "offsets": [ [ 205, 218 ] ], "normalized": [] }, { "id": "6409", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "6410", "type": "", "text": [ "nausea" ], "offsets": [ [ 227, 233 ] ], "normalized": [] }, { "id": "6412", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "6413", "type": "", "text": [ "vomiting" ], "offsets": [ [ 235, 243 ] ], "normalized": [] }, { "id": "6415", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "6416", "type": "", "text": [ "pain" ], "offsets": [ [ 249, 253 ] ], "normalized": [] }, { "id": "6418", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "6419", "type": "", "text": [ "hypertension" ], "offsets": [ [ 333, 345 ] ], "normalized": [] }, { "id": "6421", "type": "", "text": [ "esmolol" ], "offsets": [ [ 610, 617 ] ], "normalized": [] }, { "id": "6422", "type": "", "text": [ "hypertension" ], "offsets": [ [ 452, 464 ] ], "normalized": [] }, { "id": "6424", "type": "", "text": [ "ASA" ], "offsets": [ [ 414, 417 ] ], "normalized": [] }, { "id": "6425", "type": "", "text": [ "hypertension" ], "offsets": [ [ 452, 464 ] ], "normalized": [] }, { "id": "6427", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 1299, 1309 ] ], "normalized": [] }, { "id": "6428", "type": "", "text": [ "PONV" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] }, { "id": "6430", "type": "", "text": [ "alfentanil" ], "offsets": [ [ 1299, 1309 ] ], "normalized": [] }, { "id": "6431", "type": "", "text": [ "motion sickness" ], "offsets": [ [ 1421, 1436 ] ], "normalized": [] }, { "id": "6433", "type": "", "text": [ "propofol" ], "offsets": [ [ 1311, 1319 ] ], "normalized": [] }, { "id": "6434", "type": "", "text": [ "PONV" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] }, { "id": "6436", "type": "", "text": [ "propofol" ], "offsets": [ [ 1311, 1319 ] ], "normalized": [] }, { "id": "6437", "type": "", "text": [ "motion sickness" ], "offsets": [ [ 1421, 1436 ] ], "normalized": [] }, { "id": "6439", "type": "", "text": [ "esmolol" ], "offsets": [ [ 36, 43 ] ], "normalized": [] }, { "id": "6440", "type": "", "text": [ "hypertensive" ], "offsets": [ [ 55, 67 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6375", "type": "PA", "arg1_id": "6373", "arg2_id": "6374", "normalized": [] }, { "id": "6378", "type": "PA", "arg1_id": "6376", "arg2_id": "6377", "normalized": [] }, { "id": "6381", "type": "NA", "arg1_id": "6379", "arg2_id": "6380", "normalized": [] }, { "id": "6384", "type": "NA", "arg1_id": "6382", "arg2_id": "6383", "normalized": [] }, { "id": "6387", "type": "PA", "arg1_id": "6385", "arg2_id": "6386", "normalized": [] }, { "id": "6390", "type": "PA", "arg1_id": "6388", "arg2_id": "6389", "normalized": [] }, { "id": "6393", "type": "PA", "arg1_id": "6391", "arg2_id": "6392", "normalized": [] }, { "id": "6396", "type": "PA", "arg1_id": "6394", "arg2_id": "6395", "normalized": [] }, { "id": "6399", "type": "PA", "arg1_id": "6397", "arg2_id": "6398", "normalized": [] }, { "id": "6402", "type": "PA", "arg1_id": "6400", "arg2_id": "6401", "normalized": [] }, { "id": "6405", "type": "PA", "arg1_id": "6403", "arg2_id": "6404", "normalized": [] }, { "id": "6408", "type": "PA", "arg1_id": "6406", "arg2_id": "6407", "normalized": [] }, { "id": "6411", "type": "PA", "arg1_id": "6409", "arg2_id": "6410", "normalized": [] }, { "id": "6414", "type": "PA", "arg1_id": "6412", "arg2_id": "6413", "normalized": [] }, { "id": "6417", "type": "PA", "arg1_id": "6415", "arg2_id": "6416", "normalized": [] }, { "id": "6420", "type": "PA", "arg1_id": "6418", "arg2_id": "6419", "normalized": [] }, { "id": "6423", "type": "PA", "arg1_id": "6421", "arg2_id": "6422", "normalized": [] }, { "id": "6426", "type": "PA", "arg1_id": "6424", "arg2_id": "6425", "normalized": [] }, { "id": "6429", "type": "PA", "arg1_id": "6427", "arg2_id": "6428", "normalized": [] }, { "id": "6432", "type": "PA", "arg1_id": "6430", "arg2_id": "6431", "normalized": [] }, { "id": "6435", "type": "PA", "arg1_id": "6433", "arg2_id": "6434", "normalized": [] }, { "id": "6438", "type": "PA", "arg1_id": "6436", "arg2_id": "6437", "normalized": [] }, { "id": "6441", "type": "PA", "arg1_id": "6439", "arg2_id": "6440", "normalized": [] } ]

[ { "id": "6444", "type": "title", "text": [ "Photodynamic therapy update 2007." ], "offsets": [ [ 0, 33 ] ] }, { "id": "6445", "type": "abstract", "text": [ "The use of photodynamic therapy (PDT) in the US has shown record growth in 2007 with more clinicians utilizing PDT for more clinical entities than ever before. Research endeavors utilizing PDT in published clinical manuscripts have been slow in 2007 and yet the use continues to rise significantly. This manuscript will highlight the state of PDT in the US as 2007 comes to a close and focus on the future of PDT as we move toward 2008." ], "offsets": [ [ 34, 470 ] ] } ]

[ { "id": "6446", "type": "Chemicals & Drugs", "text": [ "Photodynamic therapy" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "6447", "type": "Chemicals & Drugs", "text": [ "photodynamic therapy" ], "offsets": [ [ 45, 65 ] ], "normalized": [] }, { "id": "6448", "type": "Chemicals & Drugs", "text": [ "PDT" ], "offsets": [ [ 67, 70 ] ], "normalized": [] }, { "id": "6449", "type": "Chemicals & Drugs", "text": [ "PDT" ], "offsets": [ [ 145, 148 ] ], "normalized": [] }, { "id": "6450", "type": "Chemicals & Drugs", "text": [ "PDT" ], "offsets": [ [ 223, 226 ] ], "normalized": [] }, { "id": "6451", "type": "Chemicals & Drugs", "text": [ "PDT" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "6452", "type": "Chemicals & Drugs", "text": [ "PDT" ], "offsets": [ [ 443, 446 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "6455", "type": "title", "text": [ "Malignant fibrous histiocytoma associated with coxofemoral arthrodesis." ], "offsets": [ [ 0, 71 ] ] }, { "id": "6456", "type": "abstract", "text": [ "The discovery of biomaterials led to their use in the manufacture of implants for biomedical applications. In vivo, no metal or alloy is completely inert. The potential toxicity of some of the metals most frequently employed in the manufacture of orthopedic implants has been reported. Their carcinogenic potential has been evaluated in experimental animal models. However, few reports have discussed the potential development of malignant tumors associated with prosthetic structures in humans. The present study documents a case of intraosseous sarcoma that developed in the vicinity of a metallic prosthesis 43 months after a coxofemoral arthrodesis with metallic pins and screws. With this report the authors seek to contribute to the understanding of the potential toxicity and risks of using metallic implants. Since metallic implants employed in the rehabilitation of osteo-muscular-articular disorders usually remain in the organism for long periods of time, the need to monitor the metallic structures and the adjacent tissues is extremely relevant." ], "offsets": [ [ 72, 1130 ] ] } ]

[ { "id": "6457", "type": "Diseases & Disorders", "text": [ "Malignant fibrous histiocytoma" ], "offsets": [ [ 0, 30 ] ], "normalized": [] }, { "id": "6458", "type": "Diseases & Disorders", "text": [ "arthrodesis" ], "offsets": [ [ 59, 70 ] ], "normalized": [] }, { "id": "6459", "type": "Diseases & Disorders", "text": [ "malignant tumors" ], "offsets": [ [ 502, 518 ] ], "normalized": [] }, { "id": "6460", "type": "Chemicals & Drugs", "text": [ "prosthetic structures" ], "offsets": [ [ 535, 556 ] ], "normalized": [] }, { "id": "6461", "type": "Diseases & Disorders", "text": [ "intraosseous sarcoma" ], "offsets": [ [ 606, 626 ] ], "normalized": [] }, { "id": "6462", "type": "Chemicals & Drugs", "text": [ "metallic prosthesis" ], "offsets": [ [ 663, 682 ] ], "normalized": [] }, { "id": "6463", "type": "Diseases & Disorders", "text": [ "arthrodesis" ], "offsets": [ [ 713, 724 ] ], "normalized": [] }, { "id": "6464", "type": "Chemicals & Drugs", "text": [ "metallic implants" ], "offsets": [ [ 870, 887 ] ], "normalized": [] }, { "id": "6465", "type": "Chemicals & Drugs", "text": [ "metallic implants" ], "offsets": [ [ 895, 912 ] ], "normalized": [] }, { "id": "6466", "type": "Diseases & Disorders", "text": [ "osteo-muscular-articular disorders" ], "offsets": [ [ 947, 981 ] ], "normalized": [] }, { "id": "6467", "type": "", "text": [ "prosthetic structures" ], "offsets": [ [ 535, 556 ] ], "normalized": [] }, { "id": "6468", "type": "", "text": [ "malignant tumors" ], "offsets": [ [ 502, 518 ] ], "normalized": [] }, { "id": "6470", "type": "", "text": [ "metallic prosthesis" ], "offsets": [ [ 663, 682 ] ], "normalized": [] }, { "id": "6471", "type": "", "text": [ "intraosseous sarcoma" ], "offsets": [ [ 606, 626 ] ], "normalized": [] }, { "id": "6473", "type": "", "text": [ "metallic implants" ], "offsets": [ [ 895, 912 ] ], "normalized": [] }, { "id": "6474", "type": "", "text": [ "osteo-muscular-articular disorders" ], "offsets": [ [ 947, 981 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6469", "type": "PA", "arg1_id": "6467", "arg2_id": "6468", "normalized": [] }, { "id": "6472", "type": "PA", "arg1_id": "6470", "arg2_id": "6471", "normalized": [] }, { "id": "6475", "type": "PA", "arg1_id": "6473", "arg2_id": "6474", "normalized": [] } ]

[ { "id": "6478", "type": "title", "text": [ "Cardiovascular thromboembolic adverse effects associated with cyclooxygenase-2 selective inhibitors and nonselective antiinflammatory drugs." ], "offsets": [ [ 0, 140 ] ] }, { "id": "6479", "type": "abstract", "text": [ "BACKGROUND: Concerns of increased cardiovascular (CV) thromboembolic adverse effects from nonsteroidal antiinflammatory drugs (NSAIDs, both nonselective [NS]-NSAIDs and cyclooxygenase [COX]-2 selective inhibitors) have prevented their use despite numerous benefits. METHODS: In this descriptive review, we critically examine the randomized, active- and placebo-controlled studies, observational trials, and meta-analyses evaluating the CV adverse effects associated with long-term and short-term use of COX-2 selective inhibitors and NS-NSAIDs. The potential mechanisms for these CV effects are also presented. RESULTS: Although the studies evaluating the CV risks have limitations, there appears to be an increased CV risk with both COX-2 selective inhibitors and NS-NSAIDs, particularly in high-risk patients. Therefore, the United States Food and Drug Administration has given a similar \"boxed\" warning highlighting the potential for increased risk of CV events associated with their use. Nevertheless, there are differences in the CV risks between COX-2 selective inhibitors (e.g., higher CV risk with rofecoxib than celecoxib) as well as differences in the CV risks between individual NS-NSAIDs (e.g., higher CV risks with diclofenac than naproxen). CONCLUSIONS: Until long-term, prospective, randomized, adequately powered, clinical studies in relevant patient populations have been completed, the CV risks associated with the use of NSAIDs, especially in high-risk patients, will likely continue to be controversial. Nevertheless, the benefits of their short-term (e.g., perioperative) use in patients without CV risks probably outweigh their potential CV adverse effects. Finally, careful risk/benefit assessment should be undertaken and both COX-2 selective inhibitors and NS-NSAIDs should be used with caution in patients with CV risk factors." ], "offsets": [ [ 141, 1994 ] ] } ]

[ { "id": "6480", "type": "Diseases & Disorders", "text": [ "Cardiovascular thromboembolic adverse effects" ], "offsets": [ [ 0, 45 ] ], "normalized": [] }, { "id": "6481", "type": "Chemicals & Drugs", "text": [ "cyclooxygenase" ], "offsets": [ [ 62, 76 ] ], "normalized": [] }, { "id": "6482", "type": "Chemicals & Drugs", "text": [ "nonselective antiinflammatory drugs" ], "offsets": [ [ 104, 139 ] ], "normalized": [] }, { "id": "6483", "type": "Diseases & Disorders", "text": [ "cardiovascular" ], "offsets": [ [ 175, 189 ] ], "normalized": [] }, { "id": "6484", "type": "Diseases & Disorders", "text": [ "CV) thromboembolic adverse effects" ], "offsets": [ [ 191, 225 ] ], "normalized": [] }, { "id": "6485", "type": "Chemicals & Drugs", "text": [ "nonsteroidal antiinflammatory drugs" ], "offsets": [ [ 231, 266 ] ], "normalized": [] }, { "id": "6486", "type": "Chemicals & Drugs", "text": [ "NSAIDs" ], "offsets": [ [ 268, 274 ] ], "normalized": [] }, { "id": "6487", "type": "Chemicals & Drugs", "text": [ "[NS]-NSAIDs" ], "offsets": [ [ 294, 305 ] ], "normalized": [] }, { "id": "6488", "type": "Chemicals & Drugs", "text": [ "cyclooxygenase" ], "offsets": [ [ 310, 324 ] ], "normalized": [] }, { "id": "6489", "type": "Chemicals & Drugs", "text": [ "[COX]-2 selective inhibitors" ], "offsets": [ [ 325, 353 ] ], "normalized": [] }, { "id": "6490", "type": "Diseases & Disorders", "text": [ "CV adverse effects" ], "offsets": [ [ 577, 595 ] ], "normalized": [] }, { "id": "6491", "type": "Chemicals & Drugs", "text": [ "COX-2 selective inhibitors" ], "offsets": [ [ 644, 670 ] ], "normalized": [] }, { "id": "6492", "type": "Chemicals & Drugs", "text": [ "NS-NSAIDs" ], "offsets": [ [ 675, 684 ] ], "normalized": [] }, { "id": "6493", "type": "Diseases & Disorders", "text": [ "CV effects" ], "offsets": [ [ 721, 731 ] ], "normalized": [] }, { "id": "6494", "type": "Chemicals & Drugs", "text": [ "COX-2 selective inhibitors" ], "offsets": [ [ 875, 901 ] ], "normalized": [] }, { "id": "6495", "type": "Chemicals & Drugs", "text": [ "NS-NSAIDs" ], "offsets": [ [ 906, 915 ] ], "normalized": [] }, { "id": "6496", "type": "Diseases & Disorders", "text": [ "CV events" ], "offsets": [ [ 1096, 1105 ] ], "normalized": [] }, { "id": "6497", "type": "Chemicals & Drugs", "text": [ "COX-2 selective inhibitors" ], "offsets": [ [ 1193, 1219 ] ], "normalized": [] }, { "id": "6498", "type": "Chemicals & Drugs", "text": [ "rofecoxib" ], "offsets": [ [ 1247, 1256 ] ], "normalized": [] }, { "id": "6499", "type": "Chemicals & Drugs", "text": [ "celecoxib" ], "offsets": [ [ 1262, 1271 ] ], "normalized": [] }, { "id": "6500", "type": "Chemicals & Drugs", "text": [ "NS-NSAIDs" ], "offsets": [ [ 1331, 1340 ] ], "normalized": [] }, { "id": "6501", "type": "Chemicals & Drugs", "text": [ "diclofenac" ], "offsets": [ [ 1369, 1379 ] ], "normalized": [] }, { "id": "6502", "type": "Chemicals & Drugs", "text": [ "naproxen" ], "offsets": [ [ 1385, 1393 ] ], "normalized": [] }, { "id": "6503", "type": "Chemicals & Drugs", "text": [ "NSAIDs" ], "offsets": [ [ 1581, 1587 ] ], "normalized": [] }, { "id": "6504", "type": "Diseases & Disorders", "text": [ "CV adverse effects" ], "offsets": [ [ 1801, 1819 ] ], "normalized": [] }, { "id": "6505", "type": "Chemicals & Drugs", "text": [ "COX-2 selective inhibitors" ], "offsets": [ [ 1892, 1918 ] ], "normalized": [] }, { "id": "6506", "type": "Chemicals & Drugs", "text": [ "NS-NSAIDs" ], "offsets": [ [ 1923, 1932 ] ], "normalized": [] }, { "id": "6507", "type": "", "text": [ "nonselective antiinflammatory drugs" ], "offsets": [ [ 104, 139 ] ], "normalized": [] }, { "id": "6508", "type": "", "text": [ "Cardiovascular thromboembolic adverse effects" ], "offsets": [ [ 0, 45 ] ], "normalized": [] }, { "id": "6510", "type": "", "text": [ "cyclooxygenase" ], "offsets": [ [ 62, 76 ] ], "normalized": [] }, { "id": "6511", "type": "", "text": [ "Cardiovascular thromboembolic adverse effects" ], "offsets": [ [ 0, 45 ] ], "normalized": [] }, { "id": "6513", "type": "", "text": [ "nonsteroidal antiinflammatory drugs" ], "offsets": [ [ 231, 266 ] ], "normalized": [] }, { "id": "6514", "type": "", "text": [ "cardiovascular" ], "offsets": [ [ 175, 189 ] ], "normalized": [] }, { "id": "6516", "type": "", "text": [ "NSAIDs" ], "offsets": [ [ 268, 274 ] ], "normalized": [] }, { "id": "6517", "type": "", "text": [ "cardiovascular" ], "offsets": [ [ 175, 189 ] ], "normalized": [] }, { "id": "6519", "type": "", "text": [ "[NS]-NSAIDs" ], "offsets": [ [ 294, 305 ] ], "normalized": [] }, { "id": "6520", "type": "", "text": [ "cardiovascular" ], "offsets": [ [ 175, 189 ] ], "normalized": [] }, { "id": "6522", "type": "", "text": [ "cyclooxygenase" ], "offsets": [ [ 310, 324 ] ], "normalized": [] }, { "id": "6523", "type": "", "text": [ "cardiovascular" ], "offsets": [ [ 175, 189 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6509", "type": "PA", "arg1_id": "6507", "arg2_id": "6508", "normalized": [] }, { "id": "6512", "type": "PA", "arg1_id": "6510", "arg2_id": "6511", "normalized": [] }, { "id": "6515", "type": "PA", "arg1_id": "6513", "arg2_id": "6514", "normalized": [] }, { "id": "6518", "type": "PA", "arg1_id": "6516", "arg2_id": "6517", "normalized": [] }, { "id": "6521", "type": "PA", "arg1_id": "6519", "arg2_id": "6520", "normalized": [] }, { "id": "6524", "type": "PA", "arg1_id": "6522", "arg2_id": "6523", "normalized": [] } ]

[ { "id": "6527", "type": "title", "text": [ "Spontaneous abortions in female populations occupationally exposed to ionizing radiation." ], "offsets": [ [ 0, 89 ] ] }, { "id": "6528", "type": "abstract", "text": [ "OBJECTIVE: Exposure to radioisotopes of metals and halogen elements occurring in medical practice may cause spontaneous abortions. The potential role of occupational exposure to X-rays and internal radioisotopes on pregnancy outcome in childbearing age women employed in hospital departments were analyzed in order to estimate miscarriage risk. METHODS: Over a period of 16 years, the occurrence of miscarriages in 61 women exposed to radioisotopes was compared to that reported in 170 X-ray exposed women. Chromosomal aberrations (CA) were measured in both radiation-exposed groups and in 53 non-exposed women. RESULTS: Women exposed to radioisotopes experienced at least a threefold higher rate of spontaneous abortions than those exposed to X-ray (OR = 3.68, 95% CI = 1.39-9.74, P < 0.01). Although X-ray and radioisotopes exposed women had significantly higher levels of chromosome type frequency (0.51 +/- 0.82, and 0.63 +/- 0.99, respectively) than referents (0.17 +/- 0.34), there was no clear difference between radiation-exposed women. CONCLUSIONS: For exposure levels within standard recommended guidelines, radioisotopes are far more likely to play a role in the occurrence of spontaneous abortions than X-rays. Such biological effect is not detectable by deviations in CA frequency." ], "offsets": [ [ 90, 1384 ] ] } ]

[ { "id": "6529", "type": "Diseases & Disorders", "text": [ "Spontaneous abortions" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "6530", "type": "Chemicals & Drugs", "text": [ "ionizing radiation" ], "offsets": [ [ 70, 88 ] ], "normalized": [] }, { "id": "6531", "type": "Chemicals & Drugs", "text": [ "radioisotopes of metals and halogen elements" ], "offsets": [ [ 113, 157 ] ], "normalized": [] }, { "id": "6532", "type": "Diseases & Disorders", "text": [ "spontaneous abortions" ], "offsets": [ [ 198, 219 ] ], "normalized": [] }, { "id": "6533", "type": "Chemicals & Drugs", "text": [ "X-rays" ], "offsets": [ [ 268, 274 ] ], "normalized": [] }, { "id": "6534", "type": "Chemicals & Drugs", "text": [ "radioisotopes" ], "offsets": [ [ 288, 301 ] ], "normalized": [] }, { "id": "6535", "type": "Diseases & Disorders", "text": [ "miscarriage" ], "offsets": [ [ 417, 428 ] ], "normalized": [] }, { "id": "6536", "type": "Diseases & Disorders", "text": [ "miscarriages" ], "offsets": [ [ 489, 501 ] ], "normalized": [] }, { "id": "6537", "type": "Chemicals & Drugs", "text": [ "radioisotopes" ], "offsets": [ [ 525, 538 ] ], "normalized": [] }, { "id": "6538", "type": "Chemicals & Drugs", "text": [ "X-ray" ], "offsets": [ [ 576, 581 ] ], "normalized": [] }, { "id": "6539", "type": "Diseases & Disorders", "text": [ "Chromosomal aberrations" ], "offsets": [ [ 597, 620 ] ], "normalized": [] }, { "id": "6540", "type": "Diseases & Disorders", "text": [ "CA" ], "offsets": [ [ 622, 624 ] ], "normalized": [] }, { "id": "6541", "type": "Chemicals & Drugs", "text": [ "radioisotopes" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "6542", "type": "Diseases & Disorders", "text": [ "spontaneous abortions" ], "offsets": [ [ 790, 811 ] ], "normalized": [] }, { "id": "6543", "type": "Chemicals & Drugs", "text": [ "X-ray" ], "offsets": [ [ 834, 839 ] ], "normalized": [] }, { "id": "6544", "type": "Chemicals & Drugs", "text": [ "X-ray" ], "offsets": [ [ 892, 897 ] ], "normalized": [] }, { "id": "6545", "type": "Chemicals & Drugs", "text": [ "radioisotopes" ], "offsets": [ [ 902, 915 ] ], "normalized": [] }, { "id": "6546", "type": "Chemicals & Drugs", "text": [ "radioisotopes" ], "offsets": [ [ 1208, 1221 ] ], "normalized": [] }, { "id": "6547", "type": "Diseases & Disorders", "text": [ "spontaneous abortions" ], "offsets": [ [ 1278, 1299 ] ], "normalized": [] }, { "id": "6548", "type": "Chemicals & Drugs", "text": [ "X-rays" ], "offsets": [ [ 1305, 1311 ] ], "normalized": [] }, { "id": "6549", "type": "Diseases & Disorders", "text": [ "CA" ], "offsets": [ [ 1371, 1373 ] ], "normalized": [] }, { "id": "6550", "type": "", "text": [ "radioisotopes of metals and halogen elements" ], "offsets": [ [ 113, 157 ] ], "normalized": [] }, { "id": "6551", "type": "", "text": [ "spontaneous abortions" ], "offsets": [ [ 198, 219 ] ], "normalized": [] }, { "id": "6553", "type": "", "text": [ "radioisotopes" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "6554", "type": "", "text": [ "spontaneous abortions" ], "offsets": [ [ 790, 811 ] ], "normalized": [] }, { "id": "6556", "type": "", "text": [ "radioisotopes" ], "offsets": [ [ 1208, 1221 ] ], "normalized": [] }, { "id": "6557", "type": "", "text": [ "spontaneous abortions" ], "offsets": [ [ 1278, 1299 ] ], "normalized": [] }, { "id": "6559", "type": "", "text": [ "X-rays" ], "offsets": [ [ 268, 274 ] ], "normalized": [] }, { "id": "6560", "type": "", "text": [ "miscarriage" ], "offsets": [ [ 417, 428 ] ], "normalized": [] }, { "id": "6562", "type": "", "text": [ "radioisotopes" ], "offsets": [ [ 288, 301 ] ], "normalized": [] }, { "id": "6563", "type": "", "text": [ "miscarriage" ], "offsets": [ [ 417, 428 ] ], "normalized": [] }, { "id": "6565", "type": "", "text": [ "radioisotopes" ], "offsets": [ [ 525, 538 ] ], "normalized": [] }, { "id": "6566", "type": "", "text": [ "miscarriages" ], "offsets": [ [ 489, 501 ] ], "normalized": [] }, { "id": "6568", "type": "", "text": [ "X-ray" ], "offsets": [ [ 576, 581 ] ], "normalized": [] }, { "id": "6569", "type": "", "text": [ "miscarriages" ], "offsets": [ [ 489, 501 ] ], "normalized": [] }, { "id": "6571", "type": "", "text": [ "X-ray" ], "offsets": [ [ 834, 839 ] ], "normalized": [] }, { "id": "6572", "type": "", "text": [ "spontaneous abortions" ], "offsets": [ [ 790, 811 ] ], "normalized": [] }, { "id": "6574", "type": "", "text": [ "X-rays" ], "offsets": [ [ 1305, 1311 ] ], "normalized": [] }, { "id": "6575", "type": "", "text": [ "spontaneous abortions" ], "offsets": [ [ 1278, 1299 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6552", "type": "SA", "arg1_id": "6550", "arg2_id": "6551", "normalized": [] }, { "id": "6555", "type": "PA", "arg1_id": "6553", "arg2_id": "6554", "normalized": [] }, { "id": "6558", "type": "PA", "arg1_id": "6556", "arg2_id": "6557", "normalized": [] }, { "id": "6561", "type": "PA", "arg1_id": "6559", "arg2_id": "6560", "normalized": [] }, { "id": "6564", "type": "PA", "arg1_id": "6562", "arg2_id": "6563", "normalized": [] }, { "id": "6567", "type": "PA", "arg1_id": "6565", "arg2_id": "6566", "normalized": [] }, { "id": "6570", "type": "PA", "arg1_id": "6568", "arg2_id": "6569", "normalized": [] }, { "id": "6573", "type": "PA", "arg1_id": "6571", "arg2_id": "6572", "normalized": [] }, { "id": "6576", "type": "PA", "arg1_id": "6574", "arg2_id": "6575", "normalized": [] } ]

[ { "id": "6579", "type": "title", "text": [ "Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury." ], "offsets": [ [ 0, 99 ] ] }, { "id": "6580", "type": "abstract", "text": [ "The mechanisms of pulmonary repair in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are poorly known. Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are key factors involved in alveolar epithelial repair, present in the bronchoalveolar lavage fluid (BALF) from patients with ALI/ARDS. The role of BALF mediators in their production remains to be determined. We evaluated the overall effect of BALF from 52 patients (27 ventilated patients with ALI/ARDS, 10 ventilated patients without ALI, and 15 nonventilated control patients) on HGF and KGF synthesis by lung fibroblasts. Fibroblasts were cultured in the presence of BALF. HGF and KGF protein secretion was measured using ELISA, and mRNA expression was evaluated using quantitative real-time RT-PCR. Only BALF from ALI/ARDS patients upregulated both HGF and KGF mRNA expression and protein synthesis (+271 and +146% for HGF and KGF, respectively). BALF-induced HGF synthesis from ALI/ARDS patients was higher than that from ventilated patients without ALI (P < 0.05). HGF secretion was correlated with BALF IL-1beta levels (rho = 0.62, P < 0.001) and BALF IL-1beta/IL-1 receptor antagonist ratio (rho = 0.54, P < 0.007) in the ALI/ARDS group. An anti-IL-1beta antibody partially (>50%) inhibited the BALF-induced HGF and PGE(2) secretion, whereas NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, completely inhibited it. Anti-IL-1beta antibodies as well as NS-398 reversed the COX-2 upregulation induced by BALF. Therefore, IL-1beta is a main BALF mediator involved in HGF secretion, which is mediated through a PGE(2)/COX-2-dependent mechanism. BALF mediators may participate in vivo in the production of HGF and KGF by lung fibroblasts during ALI/ARDS." ], "offsets": [ [ 100, 1859 ] ] } ]

[ { "id": "6581", "type": "Genes & Molecular Sequences", "text": [ "hepatocyte growth factor" ], "offsets": [ [ 14, 38 ] ], "normalized": [] }, { "id": "6582", "type": "Genes & Molecular Sequences", "text": [ "Hepatocyte growth factor" ], "offsets": [ [ 227, 251 ] ], "normalized": [] }, { "id": "6583", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 253, 256 ] ], "normalized": [] }, { "id": "6584", "type": "Genes & Molecular Sequences", "text": [ "keratinocyte growth factor" ], "offsets": [ [ 262, 288 ] ], "normalized": [] }, { "id": "6585", "type": "Genes & Molecular Sequences", "text": [ "KGF" ], "offsets": [ [ 290, 293 ] ], "normalized": [] }, { "id": "6586", "type": "Chemicals & Drugs", "text": [ "BALF mediators" ], "offsets": [ [ 443, 457 ] ], "normalized": [] }, { "id": "6587", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 678, 681 ] ], "normalized": [] }, { "id": "6588", "type": "Genes & Molecular Sequences", "text": [ "KGF" ], "offsets": [ [ 686, 689 ] ], "normalized": [] }, { "id": "6589", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 772, 775 ] ], "normalized": [] }, { "id": "6590", "type": "Genes & Molecular Sequences", "text": [ "KGF" ], "offsets": [ [ 780, 783 ] ], "normalized": [] }, { "id": "6591", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 949, 952 ] ], "normalized": [] }, { "id": "6592", "type": "Genes & Molecular Sequences", "text": [ "KGF" ], "offsets": [ [ 957, 960 ] ], "normalized": [] }, { "id": "6593", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 1019, 1022 ] ], "normalized": [] }, { "id": "6594", "type": "Genes & Molecular Sequences", "text": [ "KGF" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "6595", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 1060, 1063 ] ], "normalized": [] }, { "id": "6596", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 1167, 1170 ] ], "normalized": [] }, { "id": "6597", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 1206, 1214 ] ], "normalized": [] }, { "id": "6598", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 1255, 1263 ] ], "normalized": [] }, { "id": "6599", "type": "Chemicals & Drugs", "text": [ "IL-1 receptor antagonist" ], "offsets": [ [ 1264, 1288 ] ], "normalized": [] }, { "id": "6600", "type": "Genes & Molecular Sequences", "text": [ "IL-1 receptor antagonist" ], "offsets": [ [ 1264, 1288 ] ], "normalized": [] }, { "id": "6601", "type": "Genes & Molecular Sequences", "text": [ "anti-IL-1beta antibody" ], "offsets": [ [ 1345, 1367 ] ], "normalized": [] }, { "id": "6602", "type": "Chemicals & Drugs", "text": [ "anti-IL-1beta antibody" ], "offsets": [ [ 1345, 1367 ] ], "normalized": [] }, { "id": "6603", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 1412, 1415 ] ], "normalized": [] }, { "id": "6604", "type": "Genes & Molecular Sequences", "text": [ "PGE(2)" ], "offsets": [ [ 1420, 1426 ] ], "normalized": [] }, { "id": "6605", "type": "Chemicals & Drugs", "text": [ "PGE(2)" ], "offsets": [ [ 1420, 1426 ] ], "normalized": [] }, { "id": "6606", "type": "Chemicals & Drugs", "text": [ "NS-398" ], "offsets": [ [ 1446, 1452 ] ], "normalized": [] }, { "id": "6607", "type": "Genes & Molecular Sequences", "text": [ "NS-398" ], "offsets": [ [ 1446, 1452 ] ], "normalized": [] }, { "id": "6608", "type": "Genes & Molecular Sequences", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 1465, 1481 ] ], "normalized": [] }, { "id": "6609", "type": "Chemicals & Drugs", "text": [ "COX-2) inhibitor" ], "offsets": [ [ 1483, 1499 ] ], "normalized": [] }, { "id": "6610", "type": "Genes & Molecular Sequences", "text": [ "COX-2) inhibitor" ], "offsets": [ [ 1483, 1499 ] ], "normalized": [] }, { "id": "6611", "type": "Genes & Molecular Sequences", "text": [ "Anti-IL-1beta antibodies" ], "offsets": [ [ 1526, 1550 ] ], "normalized": [] }, { "id": "6612", "type": "Chemicals & Drugs", "text": [ "Anti-IL-1beta antibodies" ], "offsets": [ [ 1526, 1550 ] ], "normalized": [] }, { "id": "6613", "type": "Chemicals & Drugs", "text": [ "NS-398" ], "offsets": [ [ 1562, 1568 ] ], "normalized": [] }, { "id": "6614", "type": "Genes & Molecular Sequences", "text": [ "NS-398" ], "offsets": [ [ 1562, 1568 ] ], "normalized": [] }, { "id": "6615", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 1582, 1587 ] ], "normalized": [] }, { "id": "6616", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 1629, 1637 ] ], "normalized": [] }, { "id": "6617", "type": "Chemicals & Drugs", "text": [ "BALF mediator" ], "offsets": [ [ 1648, 1661 ] ], "normalized": [] }, { "id": "6618", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 1674, 1677 ] ], "normalized": [] }, { "id": "6619", "type": "Genes & Molecular Sequences", "text": [ "PGE(2)" ], "offsets": [ [ 1717, 1723 ] ], "normalized": [] }, { "id": "6620", "type": "Chemicals & Drugs", "text": [ "PGE(2)" ], "offsets": [ [ 1717, 1723 ] ], "normalized": [] }, { "id": "6621", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 1724, 1729 ] ], "normalized": [] }, { "id": "6622", "type": "Chemicals & Drugs", "text": [ "BALF mediators" ], "offsets": [ [ 1751, 1765 ] ], "normalized": [] }, { "id": "6623", "type": "Genes & Molecular Sequences", "text": [ "HGF" ], "offsets": [ [ 1811, 1814 ] ], "normalized": [] }, { "id": "6624", "type": "Genes & Molecular Sequences", "text": [ "KGF" ], "offsets": [ [ 1819, 1822 ] ], "normalized": [] }, { "id": "6625", "type": "", "text": [ "NS-398" ], "offsets": [ [ 1446, 1452 ] ], "normalized": [] }, { "id": "6626", "type": "", "text": [ "HGF" ], "offsets": [ [ 1412, 1415 ] ], "normalized": [] }, { "id": "6628", "type": "", "text": [ "NS-398" ], "offsets": [ [ 1446, 1452 ] ], "normalized": [] }, { "id": "6629", "type": "", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 1465, 1481 ] ], "normalized": [] }, { "id": "6631", "type": "", "text": [ "NS-398" ], "offsets": [ [ 1446, 1452 ] ], "normalized": [] }, { "id": "6632", "type": "", "text": [ "PGE(2)" ], "offsets": [ [ 1420, 1426 ] ], "normalized": [] }, { "id": "6634", "type": "", "text": [ "COX-2) inhibitor" ], "offsets": [ [ 1483, 1499 ] ], "normalized": [] }, { "id": "6635", "type": "", "text": [ "HGF" ], "offsets": [ [ 1412, 1415 ] ], "normalized": [] }, { "id": "6637", "type": "", "text": [ "COX-2) inhibitor" ], "offsets": [ [ 1483, 1499 ] ], "normalized": [] }, { "id": "6638", "type": "", "text": [ "PGE(2)" ], "offsets": [ [ 1420, 1426 ] ], "normalized": [] }, { "id": "6640", "type": "", "text": [ "NS-398" ], "offsets": [ [ 1562, 1568 ] ], "normalized": [] }, { "id": "6641", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1582, 1587 ] ], "normalized": [] }, { "id": "6643", "type": "", "text": [ "anti-IL-1beta antibody" ], "offsets": [ [ 1345, 1367 ] ], "normalized": [] }, { "id": "6644", "type": "", "text": [ "HGF" ], "offsets": [ [ 1412, 1415 ] ], "normalized": [] }, { "id": "6646", "type": "", "text": [ "Anti-IL-1beta antibodies" ], "offsets": [ [ 1526, 1550 ] ], "normalized": [] }, { "id": "6647", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1582, 1587 ] ], "normalized": [] }, { "id": "6649", "type": "", "text": [ "PGE(2)" ], "offsets": [ [ 1717, 1723 ] ], "normalized": [] }, { "id": "6650", "type": "", "text": [ "HGF" ], "offsets": [ [ 1674, 1677 ] ], "normalized": [] }, { "id": "6652", "type": "", "text": [ "PGE(2)" ], "offsets": [ [ 1717, 1723 ] ], "normalized": [] }, { "id": "6653", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 1629, 1637 ] ], "normalized": [] }, { "id": "6655", "type": "", "text": [ "PGE(2)" ], "offsets": [ [ 1717, 1723 ] ], "normalized": [] }, { "id": "6656", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1724, 1729 ] ], "normalized": [] }, { "id": "6658", "type": "", "text": [ "BALF mediator" ], "offsets": [ [ 1648, 1661 ] ], "normalized": [] }, { "id": "6659", "type": "", "text": [ "HGF" ], "offsets": [ [ 1674, 1677 ] ], "normalized": [] }, { "id": "6661", "type": "", "text": [ "BALF mediator" ], "offsets": [ [ 1648, 1661 ] ], "normalized": [] }, { "id": "6662", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 1629, 1637 ] ], "normalized": [] }, { "id": "6664", "type": "", "text": [ "BALF mediator" ], "offsets": [ [ 1648, 1661 ] ], "normalized": [] }, { "id": "6665", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1724, 1729 ] ], "normalized": [] }, { "id": "6667", "type": "", "text": [ "BALF mediator" ], "offsets": [ [ 1648, 1661 ] ], "normalized": [] }, { "id": "6668", "type": "", "text": [ "PGE(2)" ], "offsets": [ [ 1717, 1723 ] ], "normalized": [] }, { "id": "6670", "type": "", "text": [ "BALF mediators" ], "offsets": [ [ 1751, 1765 ] ], "normalized": [] }, { "id": "6671", "type": "", "text": [ "HGF" ], "offsets": [ [ 1811, 1814 ] ], "normalized": [] }, { "id": "6673", "type": "", "text": [ "BALF mediators" ], "offsets": [ [ 1751, 1765 ] ], "normalized": [] }, { "id": "6674", "type": "", "text": [ "KGF" ], "offsets": [ [ 1819, 1822 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6627", "type": "PA", "arg1_id": "6625", "arg2_id": "6626", "normalized": [] }, { "id": "6630", "type": "PA", "arg1_id": "6628", "arg2_id": "6629", "normalized": [] }, { "id": "6633", "type": "PA", "arg1_id": "6631", "arg2_id": "6632", "normalized": [] }, { "id": "6636", "type": "PA", "arg1_id": "6634", "arg2_id": "6635", "normalized": [] }, { "id": "6639", "type": "PA", "arg1_id": "6637", "arg2_id": "6638", "normalized": [] }, { "id": "6642", "type": "PA", "arg1_id": "6640", "arg2_id": "6641", "normalized": [] }, { "id": "6645", "type": "PA", "arg1_id": "6643", "arg2_id": "6644", "normalized": [] }, { "id": "6648", "type": "PA", "arg1_id": "6646", "arg2_id": "6647", "normalized": [] }, { "id": "6651", "type": "PA", "arg1_id": "6649", "arg2_id": "6650", "normalized": [] }, { "id": "6654", "type": "PA", "arg1_id": "6652", "arg2_id": "6653", "normalized": [] }, { "id": "6657", "type": "PA", "arg1_id": "6655", "arg2_id": "6656", "normalized": [] }, { "id": "6660", "type": "PA", "arg1_id": "6658", "arg2_id": "6659", "normalized": [] }, { "id": "6663", "type": "PA", "arg1_id": "6661", "arg2_id": "6662", "normalized": [] }, { "id": "6666", "type": "PA", "arg1_id": "6664", "arg2_id": "6665", "normalized": [] }, { "id": "6669", "type": "PA", "arg1_id": "6667", "arg2_id": "6668", "normalized": [] }, { "id": "6672", "type": "PA", "arg1_id": "6670", "arg2_id": "6671", "normalized": [] }, { "id": "6675", "type": "PA", "arg1_id": "6673", "arg2_id": "6674", "normalized": [] } ]

[ { "id": "6678", "type": "title", "text": [ "Infection by Panton-Valentine leukocidin-producing Staphylococcus aureus clinically mimicking Lemierre's syndrome." ], "offsets": [ [ 0, 114 ] ] }, { "id": "6679", "type": "abstract", "text": [ "Lemierre's syndrome is an oropharyngeal infection which leads to severe septic thrombophlebitis of the internal jugular vein and metastatic abscesses of the lungs and other organs. It is usually caused by Fusobacterium necrophorum, a Gram-negative obligate anaerobe. An unusual case of Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus infection masquerading as Lemierre's syndrome is reported here. A 32-year-old fit and otherwise healthy male presented on Christmas morning with a boil on his left cheek for 2 days and generalized rash for 3 h. His general condition began to worsen, he developed facial swelling and loss of vision in the left eye and was transferred to the intensive care unit. His treatment was taken over by team of specialists and further investigations revealed thrombophlebitis of the left internal jugular vein and cavernous sinus thrombosis with multiple brain infarcts and lung abscesses. His condition remained critical with multiple cranial nerve involvement despite being on broad-spectrum antibiotics. Blood cultures grew S. aureus which was producing PVL toxin. He improved gradually over several weeks. He underwent intensive physiotherapy and made a good recovery. Although a rare entity, it is important to consider Lemierre's syndrome in septic patients who present with rapidly worsening symptoms." ], "offsets": [ [ 115, 1466 ] ] } ]

[ { "id": "6680", "type": "Diseases & Disorders", "text": [ "Infection by Panton-Valentine leukocidin-producing Staphylococcus aureus" ], "offsets": [ [ 0, 72 ] ], "normalized": [] }, { "id": "6681", "type": "Diseases & Disorders", "text": [ "Lemierre's syndrome" ], "offsets": [ [ 94, 113 ] ], "normalized": [] }, { "id": "6682", "type": "Diseases & Disorders", "text": [ "Lemierre's syndrome" ], "offsets": [ [ 115, 134 ] ], "normalized": [] }, { "id": "6683", "type": "Diseases & Disorders", "text": [ "oropharyngeal infection" ], "offsets": [ [ 141, 164 ] ], "normalized": [] }, { "id": "6684", "type": "Diseases & Disorders", "text": [ "septic thrombophlebitis" ], "offsets": [ [ 187, 210 ] ], "normalized": [] }, { "id": "6685", "type": "Diseases & Disorders", "text": [ "metastatic abscesses of the lungs" ], "offsets": [ [ 244, 277 ] ], "normalized": [] }, { "id": "6686", "type": "Diseases & Disorders", "text": [ "PVL)-producing Staphylococcus aureus infection" ], "offsets": [ [ 430, 476 ] ], "normalized": [] }, { "id": "6687", "type": "Diseases & Disorders", "text": [ "Lemierre's syndrome" ], "offsets": [ [ 493, 512 ] ], "normalized": [] }, { "id": "6688", "type": "Diseases & Disorders", "text": [ "fit" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "6689", "type": "Diseases & Disorders", "text": [ "boil" ], "offsets": [ [ 614, 618 ] ], "normalized": [] }, { "id": "6690", "type": "Diseases & Disorders", "text": [ "facial swelling" ], "offsets": [ [ 730, 745 ] ], "normalized": [] }, { "id": "6691", "type": "Diseases & Disorders", "text": [ "loss of vision in the left eye" ], "offsets": [ [ 750, 780 ] ], "normalized": [] }, { "id": "6692", "type": "Diseases & Disorders", "text": [ "thrombophlebitis" ], "offsets": [ [ 917, 933 ] ], "normalized": [] }, { "id": "6693", "type": "Diseases & Disorders", "text": [ "cavernous sinus thrombosis" ], "offsets": [ [ 972, 998 ] ], "normalized": [] }, { "id": "6694", "type": "Diseases & Disorders", "text": [ "brain infarcts" ], "offsets": [ [ 1013, 1027 ] ], "normalized": [] }, { "id": "6695", "type": "Diseases & Disorders", "text": [ "lung abscesses" ], "offsets": [ [ 1032, 1046 ] ], "normalized": [] }, { "id": "6696", "type": "Chemicals & Drugs", "text": [ "antibiotics" ], "offsets": [ [ 1152, 1163 ] ], "normalized": [] }, { "id": "6697", "type": "Diseases & Disorders", "text": [ "Lemierre's syndrome" ], "offsets": [ [ 1383, 1402 ] ], "normalized": [] }, { "id": "6698", "type": "Diseases & Disorders", "text": [ "septic" ], "offsets": [ [ 1406, 1412 ] ], "normalized": [] }, { "id": "6699", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 1457, 1465 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "6702", "type": "title", "text": [ "Relationship between pathogenicity for humans and stx genotype in Shiga toxin-producing Escherichia coli serotype O157." ], "offsets": [ [ 0, 119 ] ] }, { "id": "6703", "type": "abstract", "text": [ "To examine the reason why people infected with Shiga toxin (Stx) producing Escherichia coli (STEC) O157 strains develop varying clinical manifestations, 65 STEC O157 isolates originating from 64 different occurrences of infection in Miyazaki Prefecture in 2001-2003 and their 79 infected individuals were analyzed by stx genotyping, quantitative analysis of reversed passive latex agglutination (RPLA), genomic DNA analysis using pulsed-field gel electrophoresis (PFGE), and clinical manifestations. The isolates were found to carry the following stx genes: stx2vha alone (60.0%), stx1/stx2 (27.7%), stx1/stx2vha (6.1%), stx2 alone (3.1%), and stx2/stx2vha (3.1%). No strain carried the stx1 gene alone. STEC strains carrying stx2 were more frequently associated with clinical manifestations of hemolytic-uremic syndrome (HUS) or bloody diarrhea than those carrying stx2vha. Clusters of PFGE banding patterns were correlated well with the stx genotypes. We conclude that stx genotype is one of the important factors of clinical outcome of STEC O157 infection and that pathogenicity for humans was higher in the stx2 genotype strains than in the stx2vha genotype strains, as reported previously by other researchers. Further, we newly found that four clusters identified by PFGE using restriction enzyme XbaI, stx genotypes and clinical manifestations were well correlated with each other." ], "offsets": [ [ 120, 1508 ] ] } ]

[ { "id": "6704", "type": "Genes & Molecular Sequences", "text": [ "stx" ], "offsets": [ [ 50, 53 ] ], "normalized": [] }, { "id": "6705", "type": "Diseases & Disorders", "text": [ "Shiga" ], "offsets": [ [ 66, 71 ] ], "normalized": [] }, { "id": "6706", "type": "Diseases & Disorders", "text": [ "Escherichia" ], "offsets": [ [ 88, 99 ] ], "normalized": [] }, { "id": "6707", "type": "Genes & Molecular Sequences", "text": [ "Escherichia" ], "offsets": [ [ 88, 99 ] ], "normalized": [] }, { "id": "6708", "type": "Diseases & Disorders", "text": [ "infected with Shiga toxin (Stx) producing Escherichia coli (STEC) O157" ], "offsets": [ [ 153, 223 ] ], "normalized": [] }, { "id": "6709", "type": "Diseases & Disorders", "text": [ "Shiga" ], "offsets": [ [ 167, 172 ] ], "normalized": [] }, { "id": "6710", "type": "Diseases & Disorders", "text": [ "Escherichia" ], "offsets": [ [ 195, 206 ] ], "normalized": [] }, { "id": "6711", "type": "Diseases & Disorders", "text": [ "strains" ], "offsets": [ [ 224, 231 ] ], "normalized": [] }, { "id": "6712", "type": "Diseases & Disorders", "text": [ "infection" ], "offsets": [ [ 340, 349 ] ], "normalized": [] }, { "id": "6713", "type": "Genes & Molecular Sequences", "text": [ "stx" ], "offsets": [ [ 437, 440 ] ], "normalized": [] }, { "id": "6714", "type": "Genes & Molecular Sequences", "text": [ "stx" ], "offsets": [ [ 667, 670 ] ], "normalized": [] }, { "id": "6715", "type": "Genes & Molecular Sequences", "text": [ "stx2vha" ], "offsets": [ [ 678, 685 ] ], "normalized": [] }, { "id": "6716", "type": "Genes & Molecular Sequences", "text": [ "stx1/stx2" ], "offsets": [ [ 701, 710 ] ], "normalized": [] }, { "id": "6717", "type": "Genes & Molecular Sequences", "text": [ "stx1/stx2vha" ], "offsets": [ [ 720, 732 ] ], "normalized": [] }, { "id": "6718", "type": "Genes & Molecular Sequences", "text": [ "stx2" ], "offsets": [ [ 741, 745 ] ], "normalized": [] }, { "id": "6719", "type": "Genes & Molecular Sequences", "text": [ "stx2/stx2vha" ], "offsets": [ [ 764, 776 ] ], "normalized": [] }, { "id": "6720", "type": "Diseases & Disorders", "text": [ "strain" ], "offsets": [ [ 788, 794 ] ], "normalized": [] }, { "id": "6721", "type": "Genes & Molecular Sequences", "text": [ "stx1" ], "offsets": [ [ 807, 811 ] ], "normalized": [] }, { "id": "6722", "type": "Diseases & Disorders", "text": [ "strains" ], "offsets": [ [ 829, 836 ] ], "normalized": [] }, { "id": "6723", "type": "Genes & Molecular Sequences", "text": [ "stx2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "6724", "type": "Diseases & Disorders", "text": [ "hemolytic-uremic syndrome" ], "offsets": [ [ 915, 940 ] ], "normalized": [] }, { "id": "6725", "type": "Diseases & Disorders", "text": [ "HUS" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "6726", "type": "Genes & Molecular Sequences", "text": [ "HUS" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "6727", "type": "Diseases & Disorders", "text": [ "bloody diarrhea" ], "offsets": [ [ 950, 965 ] ], "normalized": [] }, { "id": "6728", "type": "Genes & Molecular Sequences", "text": [ "stx2vha" ], "offsets": [ [ 986, 993 ] ], "normalized": [] }, { "id": "6729", "type": "Genes & Molecular Sequences", "text": [ "stx" ], "offsets": [ [ 1059, 1062 ] ], "normalized": [] }, { "id": "6730", "type": "Genes & Molecular Sequences", "text": [ "stx" ], "offsets": [ [ 1091, 1094 ] ], "normalized": [] }, { "id": "6731", "type": "Diseases & Disorders", "text": [ "STEC O157 infection" ], "offsets": [ [ 1159, 1178 ] ], "normalized": [] }, { "id": "6732", "type": "Genes & Molecular Sequences", "text": [ "stx2" ], "offsets": [ [ 1231, 1235 ] ], "normalized": [] }, { "id": "6733", "type": "Diseases & Disorders", "text": [ "strains" ], "offsets": [ [ 1245, 1252 ] ], "normalized": [] }, { "id": "6734", "type": "Genes & Molecular Sequences", "text": [ "stx2vha" ], "offsets": [ [ 1265, 1272 ] ], "normalized": [] }, { "id": "6735", "type": "Diseases & Disorders", "text": [ "strains" ], "offsets": [ [ 1282, 1289 ] ], "normalized": [] }, { "id": "6736", "type": "Genes & Molecular Sequences", "text": [ "XbaI" ], "offsets": [ [ 1423, 1427 ] ], "normalized": [] }, { "id": "6737", "type": "Genes & Molecular Sequences", "text": [ "stx" ], "offsets": [ [ 1429, 1432 ] ], "normalized": [] }, { "id": "6738", "type": "", "text": [ "stx2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "6739", "type": "", "text": [ "HUS" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "6741", "type": "", "text": [ "stx2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "6742", "type": "", "text": [ "hemolytic-uremic syndrome" ], "offsets": [ [ 915, 940 ] ], "normalized": [] }, { "id": "6744", "type": "", "text": [ "stx2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "6745", "type": "", "text": [ "bloody diarrhea" ], "offsets": [ [ 950, 965 ] ], "normalized": [] }, { "id": "6747", "type": "", "text": [ "stx2" ], "offsets": [ [ 1231, 1235 ] ], "normalized": [] }, { "id": "6748", "type": "", "text": [ "STEC O157 infection" ], "offsets": [ [ 1159, 1178 ] ], "normalized": [] }, { "id": "6750", "type": "", "text": [ "stx1" ], "offsets": [ [ 807, 811 ] ], "normalized": [] }, { "id": "6751", "type": "", "text": [ "strain" ], "offsets": [ [ 788, 794 ] ], "normalized": [] }, { "id": "6753", "type": "", "text": [ "stx2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "6754", "type": "", "text": [ "strains" ], "offsets": [ [ 829, 836 ] ], "normalized": [] }, { "id": "6756", "type": "", "text": [ "HUS" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "6757", "type": "", "text": [ "strains" ], "offsets": [ [ 829, 836 ] ], "normalized": [] }, { "id": "6759", "type": "", "text": [ "HUS" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "6760", "type": "", "text": [ "hemolytic-uremic syndrome" ], "offsets": [ [ 915, 940 ] ], "normalized": [] }, { "id": "6762", "type": "", "text": [ "HUS" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "6763", "type": "", "text": [ "bloody diarrhea" ], "offsets": [ [ 950, 965 ] ], "normalized": [] }, { "id": "6765", "type": "", "text": [ "stx2" ], "offsets": [ [ 1231, 1235 ] ], "normalized": [] }, { "id": "6766", "type": "", "text": [ "strains" ], "offsets": [ [ 1282, 1289 ] ], "normalized": [] }, { "id": "6768", "type": "", "text": [ "stx2vha" ], "offsets": [ [ 986, 993 ] ], "normalized": [] }, { "id": "6769", "type": "", "text": [ "HUS" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "6771", "type": "", "text": [ "stx2vha" ], "offsets": [ [ 986, 993 ] ], "normalized": [] }, { "id": "6772", "type": "", "text": [ "hemolytic-uremic syndrome" ], "offsets": [ [ 915, 940 ] ], "normalized": [] }, { "id": "6774", "type": "", "text": [ "stx2vha" ], "offsets": [ [ 986, 993 ] ], "normalized": [] }, { "id": "6775", "type": "", "text": [ "bloody diarrhea" ], "offsets": [ [ 950, 965 ] ], "normalized": [] }, { "id": "6777", "type": "", "text": [ "stx2vha" ], "offsets": [ [ 1265, 1272 ] ], "normalized": [] }, { "id": "6778", "type": "", "text": [ "STEC O157 infection" ], "offsets": [ [ 1159, 1178 ] ], "normalized": [] }, { "id": "6780", "type": "", "text": [ "stx" ], "offsets": [ [ 437, 440 ] ], "normalized": [] }, { "id": "6781", "type": "", "text": [ "infected with Shiga toxin (Stx) producing Escherichia coli (STEC) O157" ], "offsets": [ [ 153, 223 ] ], "normalized": [] }, { "id": "6783", "type": "", "text": [ "stx" ], "offsets": [ [ 1091, 1094 ] ], "normalized": [] }, { "id": "6784", "type": "", "text": [ "STEC O157 infection" ], "offsets": [ [ 1159, 1178 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6740", "type": "PA", "arg1_id": "6738", "arg2_id": "6739", "normalized": [] }, { "id": "6743", "type": "PA", "arg1_id": "6741", "arg2_id": "6742", "normalized": [] }, { "id": "6746", "type": "PA", "arg1_id": "6744", "arg2_id": "6745", "normalized": [] }, { "id": "6749", "type": "PA", "arg1_id": "6747", "arg2_id": "6748", "normalized": [] }, { "id": "6752", "type": "PA", "arg1_id": "6750", "arg2_id": "6751", "normalized": [] }, { "id": "6755", "type": "PA", "arg1_id": "6753", "arg2_id": "6754", "normalized": [] }, { "id": "6758", "type": "PA", "arg1_id": "6756", "arg2_id": "6757", "normalized": [] }, { "id": "6761", "type": "PA", "arg1_id": "6759", "arg2_id": "6760", "normalized": [] }, { "id": "6764", "type": "PA", "arg1_id": "6762", "arg2_id": "6763", "normalized": [] }, { "id": "6767", "type": "PA", "arg1_id": "6765", "arg2_id": "6766", "normalized": [] }, { "id": "6770", "type": "PA", "arg1_id": "6768", "arg2_id": "6769", "normalized": [] }, { "id": "6773", "type": "PA", "arg1_id": "6771", "arg2_id": "6772", "normalized": [] }, { "id": "6776", "type": "PA", "arg1_id": "6774", "arg2_id": "6775", "normalized": [] }, { "id": "6779", "type": "PA", "arg1_id": "6777", "arg2_id": "6778", "normalized": [] }, { "id": "6782", "type": "PA", "arg1_id": "6780", "arg2_id": "6781", "normalized": [] }, { "id": "6785", "type": "PA", "arg1_id": "6783", "arg2_id": "6784", "normalized": [] } ]

[ { "id": "6788", "type": "title", "text": [ "Long-term exposure to medium-dose glucocorticoid therapy associates with hypertension in patients with rheumatoid arthritis." ], "offsets": [ [ 0, 124 ] ] }, { "id": "6789", "type": "abstract", "text": [ "OBJECTIVE: Rheumatoid arthritis (RA) associates with increased cardiovascular morbidity and mortality that is due to both traditional and novel cardiovascular risk factors. Hypertension (HT), one of the most common risk factors for cardiovascular disease, is highly prevalent in RA. The effects of long-term glucocorticoid (GC) therapy on blood pressure have not been established yet. This study examined whether GC exposure associates with HT in patients with RA. METHODS: Four hundred consecutive RA patients with detailed clinical and laboratory assessments were categorized into three groups according to GC exposure: no or limited exposure (N/L-E); a low-dose (< 7.5 mg) long-term exposure (LD/LT-E); and medium-dose (> or = 7.5 mg) long-term exposure (MD/LT-E). The association of GC exposure with HT was evaluated using logistic regression analysis. RESULTS: HT was more prevalent in the MD/LT-E group (84.7%) than the LD/LT-E or N/L-E groups (70.7 and 67.3%, respectively, P = 0.028). Logistic regression revealed increased odds for HT when comparing MD/LT-E with N/L-E, after adjustment for HT risk factors [odds ratio (OR) = 2.57, 95% CI 1.01-6.56, P = 0.049] and RA disease characteristics (OR = 3.64, 95% CI: 1.36-9.77, P = 0.01). CONCLUSIONS: MD/LT GC exposure associates with a very high prevalence of HT. This appears to be independent of other risk factors for HT or of channelling bias due to disease severity, even though the latter cannot be excluded given the cross-sectional nature of our study. RA patients in this GC exposure group should be particularly targeted for early identification and aggressive management of HT." ], "offsets": [ [ 125, 1769 ] ] } ]

[ { "id": "6790", "type": "Chemicals & Drugs", "text": [ "medium-dose glucocorticoid" ], "offsets": [ [ 22, 48 ] ], "normalized": [] }, { "id": "6791", "type": "Diseases & Disorders", "text": [ "hypertension" ], "offsets": [ [ 73, 85 ] ], "normalized": [] }, { "id": "6792", "type": "Diseases & Disorders", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 103, 123 ] ], "normalized": [] }, { "id": "6793", "type": "Diseases & Disorders", "text": [ "Rheumatoid arthritis" ], "offsets": [ [ 136, 156 ] ], "normalized": [] }, { "id": "6794", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 158, 160 ] ], "normalized": [] }, { "id": "6795", "type": "Diseases & Disorders", "text": [ "cardiovascular morbidity" ], "offsets": [ [ 188, 212 ] ], "normalized": [] }, { "id": "6796", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 217, 226 ] ], "normalized": [] }, { "id": "6797", "type": "Diseases & Disorders", "text": [ "cardiovascular risk factors" ], "offsets": [ [ 269, 296 ] ], "normalized": [] }, { "id": "6798", "type": "Diseases & Disorders", "text": [ "Hypertension" ], "offsets": [ [ 298, 310 ] ], "normalized": [] }, { "id": "6799", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 312, 314 ] ], "normalized": [] }, { "id": "6800", "type": "Diseases & Disorders", "text": [ "cardiovascular disease" ], "offsets": [ [ 357, 379 ] ], "normalized": [] }, { "id": "6801", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 404, 406 ] ], "normalized": [] }, { "id": "6802", "type": "Chemicals & Drugs", "text": [ "glucocorticoid" ], "offsets": [ [ 433, 447 ] ], "normalized": [] }, { "id": "6803", "type": "Chemicals & Drugs", "text": [ "GC" ], "offsets": [ [ 449, 451 ] ], "normalized": [] }, { "id": "6804", "type": "Chemicals & Drugs", "text": [ "GC" ], "offsets": [ [ 538, 540 ] ], "normalized": [] }, { "id": "6805", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 566, 568 ] ], "normalized": [] }, { "id": "6806", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 586, 588 ] ], "normalized": [] }, { "id": "6807", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 624, 626 ] ], "normalized": [] }, { "id": "6808", "type": "Chemicals & Drugs", "text": [ "GC" ], "offsets": [ [ 734, 736 ] ], "normalized": [] }, { "id": "6809", "type": "Chemicals & Drugs", "text": [ "MD" ], "offsets": [ [ 883, 885 ] ], "normalized": [] }, { "id": "6810", "type": "Chemicals & Drugs", "text": [ "GC" ], "offsets": [ [ 912, 914 ] ], "normalized": [] }, { "id": "6811", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 929, 931 ] ], "normalized": [] }, { "id": "6812", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 961, 971 ] ], "normalized": [] }, { "id": "6813", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 991, 993 ] ], "normalized": [] }, { "id": "6814", "type": "Chemicals & Drugs", "text": [ "MD" ], "offsets": [ [ 1020, 1022 ] ], "normalized": [] }, { "id": "6815", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 1127, 1137 ] ], "normalized": [] }, { "id": "6816", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 1166, 1168 ] ], "normalized": [] }, { "id": "6817", "type": "Chemicals & Drugs", "text": [ "MD" ], "offsets": [ [ 1184, 1186 ] ], "normalized": [] }, { "id": "6818", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 1225, 1227 ] ], "normalized": [] }, { "id": "6819", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 1299, 1301 ] ], "normalized": [] }, { "id": "6820", "type": "Diseases & Disorders", "text": [ "disease characteristics" ], "offsets": [ [ 1302, 1325 ] ], "normalized": [] }, { "id": "6821", "type": "Chemicals & Drugs", "text": [ "MD/LT GC" ], "offsets": [ [ 1381, 1389 ] ], "normalized": [] }, { "id": "6822", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 1441, 1443 ] ], "normalized": [] }, { "id": "6823", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 1502, 1504 ] ], "normalized": [] }, { "id": "6824", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 1535, 1542 ] ], "normalized": [] }, { "id": "6825", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 1642, 1644 ] ], "normalized": [] }, { "id": "6826", "type": "Chemicals & Drugs", "text": [ "GC" ], "offsets": [ [ 1662, 1664 ] ], "normalized": [] }, { "id": "6827", "type": "Diseases & Disorders", "text": [ "aggressive" ], "offsets": [ [ 1741, 1751 ] ], "normalized": [] }, { "id": "6828", "type": "Diseases & Disorders", "text": [ "HT" ], "offsets": [ [ 1766, 1768 ] ], "normalized": [] }, { "id": "6829", "type": "", "text": [ "medium-dose glucocorticoid" ], "offsets": [ [ 22, 48 ] ], "normalized": [] }, { "id": "6830", "type": "", "text": [ "hypertension" ], "offsets": [ [ 73, 85 ] ], "normalized": [] }, { "id": "6832", "type": "", "text": [ "GC" ], "offsets": [ [ 538, 540 ] ], "normalized": [] }, { "id": "6833", "type": "", "text": [ "HT" ], "offsets": [ [ 566, 568 ] ], "normalized": [] }, { "id": "6835", "type": "", "text": [ "GC" ], "offsets": [ [ 912, 914 ] ], "normalized": [] }, { "id": "6836", "type": "", "text": [ "HT" ], "offsets": [ [ 929, 931 ] ], "normalized": [] }, { "id": "6838", "type": "", "text": [ "MD/LT GC" ], "offsets": [ [ 1381, 1389 ] ], "normalized": [] }, { "id": "6839", "type": "", "text": [ "HT" ], "offsets": [ [ 1441, 1443 ] ], "normalized": [] }, { "id": "6841", "type": "", "text": [ "GC" ], "offsets": [ [ 1662, 1664 ] ], "normalized": [] }, { "id": "6842", "type": "", "text": [ "HT" ], "offsets": [ [ 1766, 1768 ] ], "normalized": [] }, { "id": "6844", "type": "", "text": [ "medium-dose glucocorticoid" ], "offsets": [ [ 22, 48 ] ], "normalized": [] }, { "id": "6845", "type": "", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 103, 123 ] ], "normalized": [] }, { "id": "6847", "type": "", "text": [ "MD" ], "offsets": [ [ 1184, 1186 ] ], "normalized": [] }, { "id": "6848", "type": "", "text": [ "regression" ], "offsets": [ [ 1127, 1137 ] ], "normalized": [] }, { "id": "6850", "type": "", "text": [ "MD" ], "offsets": [ [ 1184, 1186 ] ], "normalized": [] }, { "id": "6851", "type": "", "text": [ "disease characteristics" ], "offsets": [ [ 1302, 1325 ] ], "normalized": [] }, { "id": "6853", "type": "", "text": [ "GC" ], "offsets": [ [ 538, 540 ] ], "normalized": [] }, { "id": "6854", "type": "", "text": [ "RA" ], "offsets": [ [ 586, 588 ] ], "normalized": [] }, { "id": "6856", "type": "", "text": [ "GC" ], "offsets": [ [ 1662, 1664 ] ], "normalized": [] }, { "id": "6857", "type": "", "text": [ "RA" ], "offsets": [ [ 1642, 1644 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6831", "type": "PA", "arg1_id": "6829", "arg2_id": "6830", "normalized": [] }, { "id": "6834", "type": "SA", "arg1_id": "6832", "arg2_id": "6833", "normalized": [] }, { "id": "6837", "type": "SA", "arg1_id": "6835", "arg2_id": "6836", "normalized": [] }, { "id": "6840", "type": "PA", "arg1_id": "6838", "arg2_id": "6839", "normalized": [] }, { "id": "6843", "type": "SA", "arg1_id": "6841", "arg2_id": "6842", "normalized": [] }, { "id": "6846", "type": "PA", "arg1_id": "6844", "arg2_id": "6845", "normalized": [] }, { "id": "6849", "type": "PA", "arg1_id": "6847", "arg2_id": "6848", "normalized": [] }, { "id": "6852", "type": "PA", "arg1_id": "6850", "arg2_id": "6851", "normalized": [] }, { "id": "6855", "type": "PA", "arg1_id": "6853", "arg2_id": "6854", "normalized": [] }, { "id": "6858", "type": "PA", "arg1_id": "6856", "arg2_id": "6857", "normalized": [] } ]

[ { "id": "6861", "type": "title", "text": [ "PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing." ], "offsets": [ [ 0, 129 ] ] }, { "id": "6862", "type": "abstract", "text": [ "Tandem PHD and bromodomains are often found in chromatin-associated proteins and have been shown to cooperate in gene silencing. Each domain can bind specifically modified histones: the mechanisms of cooperation between these domains are unknown. We show that the PHD domain of the KAP1 corepressor functions as an intramolecular E3 ligase for sumoylation of the adjacent bromodomain. The RING finger-like structure of the PHD domain is required for both Ubc9 binding and sumoylation and directs modification to specific lysine residues in the bromodomain. Sumoylation is required for KAP1-mediated gene silencing and functions by directly recruiting the SETDB1 histone methyltransferase and the CHD3/Mi2 component of the NuRD complex via SUMO-interacting motifs. Sumoylated KAP1 stimulates the histone methyltransferase activity of SETDB1. These data provide a mechanistic explanation for the cooperation of PHD and bromodomains in gene regulation and describe a function of the PHD domain as an intramolecular E3 SUMO ligase." ], "offsets": [ [ 130, 1157 ] ] } ]

[ { "id": "6863", "type": "Genes & Molecular Sequences", "text": [ "PHD domain" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "6864", "type": "Genes & Molecular Sequences", "text": [ "E3 ligase" ], "offsets": [ [ 20, 29 ] ], "normalized": [] }, { "id": "6865", "type": "Genes & Molecular Sequences", "text": [ "bromodomain" ], "offsets": [ [ 89, 100 ] ], "normalized": [] }, { "id": "6866", "type": "Genes & Molecular Sequences", "text": [ "PHD" ], "offsets": [ [ 137, 140 ] ], "normalized": [] }, { "id": "6867", "type": "Genes & Molecular Sequences", "text": [ "bromodomains" ], "offsets": [ [ 145, 157 ] ], "normalized": [] }, { "id": "6868", "type": "Genes & Molecular Sequences", "text": [ "chromatin-associated proteins" ], "offsets": [ [ 177, 206 ] ], "normalized": [] }, { "id": "6869", "type": "Genes & Molecular Sequences", "text": [ "histones" ], "offsets": [ [ 302, 310 ] ], "normalized": [] }, { "id": "6870", "type": "Genes & Molecular Sequences", "text": [ "PHD domain" ], "offsets": [ [ 394, 404 ] ], "normalized": [] }, { "id": "6871", "type": "Genes & Molecular Sequences", "text": [ "KAP1" ], "offsets": [ [ 412, 416 ] ], "normalized": [] }, { "id": "6872", "type": "Genes & Molecular Sequences", "text": [ "E3 ligase" ], "offsets": [ [ 460, 469 ] ], "normalized": [] }, { "id": "6873", "type": "Genes & Molecular Sequences", "text": [ "bromodomain" ], "offsets": [ [ 502, 513 ] ], "normalized": [] }, { "id": "6874", "type": "Genes & Molecular Sequences", "text": [ "PHD domain" ], "offsets": [ [ 553, 563 ] ], "normalized": [] }, { "id": "6875", "type": "Genes & Molecular Sequences", "text": [ "Ubc9" ], "offsets": [ [ 585, 589 ] ], "normalized": [] }, { "id": "6876", "type": "Genes & Molecular Sequences", "text": [ "lysine residues in the bromodomain" ], "offsets": [ [ 651, 685 ] ], "normalized": [] }, { "id": "6877", "type": "Chemicals & Drugs", "text": [ "lysine residues in the bromodomain" ], "offsets": [ [ 651, 685 ] ], "normalized": [] }, { "id": "6878", "type": "Genes & Molecular Sequences", "text": [ "KAP1" ], "offsets": [ [ 715, 719 ] ], "normalized": [] }, { "id": "6879", "type": "Genes & Molecular Sequences", "text": [ "SETDB1 histone methyltransferase" ], "offsets": [ [ 785, 817 ] ], "normalized": [] }, { "id": "6880", "type": "Genes & Molecular Sequences", "text": [ "CHD3/Mi2" ], "offsets": [ [ 826, 834 ] ], "normalized": [] }, { "id": "6881", "type": "Genes & Molecular Sequences", "text": [ "NuRD" ], "offsets": [ [ 852, 856 ] ], "normalized": [] }, { "id": "6882", "type": "Genes & Molecular Sequences", "text": [ "SUMO" ], "offsets": [ [ 869, 873 ] ], "normalized": [] }, { "id": "6883", "type": "Genes & Molecular Sequences", "text": [ "KAP1" ], "offsets": [ [ 905, 909 ] ], "normalized": [] }, { "id": "6884", "type": "Genes & Molecular Sequences", "text": [ "histone methyltransferase" ], "offsets": [ [ 925, 950 ] ], "normalized": [] }, { "id": "6885", "type": "Genes & Molecular Sequences", "text": [ "SETDB1" ], "offsets": [ [ 963, 969 ] ], "normalized": [] }, { "id": "6886", "type": "Genes & Molecular Sequences", "text": [ "PHD" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "6887", "type": "Genes & Molecular Sequences", "text": [ "bromodomains" ], "offsets": [ [ 1047, 1059 ] ], "normalized": [] }, { "id": "6888", "type": "Genes & Molecular Sequences", "text": [ "PHD domain" ], "offsets": [ [ 1110, 1120 ] ], "normalized": [] }, { "id": "6889", "type": "Genes & Molecular Sequences", "text": [ "SUMO" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "6890", "type": "", "text": [ "lysine residues in the bromodomain" ], "offsets": [ [ 651, 685 ] ], "normalized": [] }, { "id": "6891", "type": "", "text": [ "PHD domain" ], "offsets": [ [ 553, 563 ] ], "normalized": [] }, { "id": "6893", "type": "", "text": [ "lysine residues in the bromodomain" ], "offsets": [ [ 651, 685 ] ], "normalized": [] }, { "id": "6894", "type": "", "text": [ "Ubc9" ], "offsets": [ [ 585, 589 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6892", "type": "PA", "arg1_id": "6890", "arg2_id": "6891", "normalized": [] }, { "id": "6895", "type": "PA", "arg1_id": "6893", "arg2_id": "6894", "normalized": [] } ]

[ { "id": "6898", "type": "title", "text": [ "A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects." ], "offsets": [ [ 0, 124 ] ] }, { "id": "6899", "type": "abstract", "text": [ "OBJECTIVE: Open label studies have suggested that tumour necrosis factor (TNF) antagonists led to sustained improvement and corticosteroid sparing effect in patients with giant cell arteritis (GCA). To confirm these observations, we conducted a randomised, double-blind, placebo controlled trial with etanercept in patients with biopsy-proven GCA with side effects secondary to corticosteroids. METHODS: We randomly assigned patients with GCA to receive etanercept (n = 8) or placebo (n = 9) over 1 year together with corticosteroids that were reduced according to a predefined schedule. The primary outcome was the ability to withdraw the corticosteroid therapy and control the disease activity at 12 months. RESULTS: Baseline characteristics were similar in the two groups, although patients in the etanercept group showed higher levels of basal glycaemia (p = 0.02) and a higher erythrocyte sedimentation rate (ESR) (p = 0.01). After 12 months, 50% of the patients in the etanercept group and 22.2% in the placebo group were able to control the disease without corticosteroid therapy (p value not significant). Patients in the etanercept group had a significant lower dose of accumulated prednisone during the first year of treatment (p = 0.03). There were no differences in the number and type of adverse events. CONCLUSION: The limited number of patients included in this study does not allow us to draw definitive conclusions. Etanercept therapy was well tolerated in this aged population. The therapeutic role of etanercept in patients with GCA should be evaluated in studies with a larger number of patients." ], "offsets": [ [ 125, 1741 ] ] } ]

[ { "id": "6900", "type": "Chemicals & Drugs", "text": [ "etanercept" ], "offsets": [ [ 43, 53 ] ], "normalized": [] }, { "id": "6901", "type": "Genes & Molecular Sequences", "text": [ "etanercept" ], "offsets": [ [ 43, 53 ] ], "normalized": [] }, { "id": "6902", "type": "Chemicals & Drugs", "text": [ "corticosteroid" ], "offsets": [ [ 96, 110 ] ], "normalized": [] }, { "id": "6903", "type": "Chemicals & Drugs", "text": [ "label" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "6904", "type": "Chemicals & Drugs", "text": [ "tumour necrosis factor" ], "offsets": [ [ 175, 197 ] ], "normalized": [] }, { "id": "6905", "type": "Genes & Molecular Sequences", "text": [ "tumour necrosis factor" ], "offsets": [ [ 175, 197 ] ], "normalized": [] }, { "id": "6906", "type": "Chemicals & Drugs", "text": [ "TNF) antagonists" ], "offsets": [ [ 199, 215 ] ], "normalized": [] }, { "id": "6907", "type": "Genes & Molecular Sequences", "text": [ "TNF) antagonists" ], "offsets": [ [ 199, 215 ] ], "normalized": [] }, { "id": "6908", "type": "Chemicals & Drugs", "text": [ "corticosteroid" ], "offsets": [ [ 249, 263 ] ], "normalized": [] }, { "id": "6909", "type": "Genes & Molecular Sequences", "text": [ "GCA" ], "offsets": [ [ 318, 321 ] ], "normalized": [] }, { "id": "6910", "type": "Chemicals & Drugs", "text": [ "etanercept" ], "offsets": [ [ 426, 436 ] ], "normalized": [] }, { "id": "6911", "type": "Genes & Molecular Sequences", "text": [ "etanercept" ], "offsets": [ [ 426, 436 ] ], "normalized": [] }, { "id": "6912", "type": "Genes & Molecular Sequences", "text": [ "GCA" ], "offsets": [ [ 468, 471 ] ], "normalized": [] }, { "id": "6913", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 503, 518 ] ], "normalized": [] }, { "id": "6914", "type": "Genes & Molecular Sequences", "text": [ "GCA" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "6915", "type": "Chemicals & Drugs", "text": [ "etanercept" ], "offsets": [ [ 579, 589 ] ], "normalized": [] }, { "id": "6916", "type": "Genes & Molecular Sequences", "text": [ "etanercept" ], "offsets": [ [ 579, 589 ] ], "normalized": [] }, { "id": "6917", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 643, 658 ] ], "normalized": [] }, { "id": "6918", "type": "Chemicals & Drugs", "text": [ "corticosteroid" ], "offsets": [ [ 765, 779 ] ], "normalized": [] }, { "id": "6919", "type": "Chemicals & Drugs", "text": [ "etanercept" ], "offsets": [ [ 926, 936 ] ], "normalized": [] }, { "id": "6920", "type": "Genes & Molecular Sequences", "text": [ "etanercept" ], "offsets": [ [ 926, 936 ] ], "normalized": [] }, { "id": "6921", "type": "Genes & Molecular Sequences", "text": [ "ESR" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "6922", "type": "Chemicals & Drugs", "text": [ "etanercept" ], "offsets": [ [ 1100, 1110 ] ], "normalized": [] }, { "id": "6923", "type": "Genes & Molecular Sequences", "text": [ "etanercept" ], "offsets": [ [ 1100, 1110 ] ], "normalized": [] }, { "id": "6924", "type": "Chemicals & Drugs", "text": [ "corticosteroid" ], "offsets": [ [ 1189, 1203 ] ], "normalized": [] }, { "id": "6925", "type": "Chemicals & Drugs", "text": [ "etanercept" ], "offsets": [ [ 1255, 1265 ] ], "normalized": [] }, { "id": "6926", "type": "Genes & Molecular Sequences", "text": [ "etanercept" ], "offsets": [ [ 1255, 1265 ] ], "normalized": [] }, { "id": "6927", "type": "Chemicals & Drugs", "text": [ "prednisone" ], "offsets": [ [ 1316, 1326 ] ], "normalized": [] }, { "id": "6928", "type": "Chemicals & Drugs", "text": [ "Etanercept" ], "offsets": [ [ 1558, 1568 ] ], "normalized": [] }, { "id": "6929", "type": "Genes & Molecular Sequences", "text": [ "Etanercept" ], "offsets": [ [ 1558, 1568 ] ], "normalized": [] }, { "id": "6930", "type": "Chemicals & Drugs", "text": [ "etanercept" ], "offsets": [ [ 1645, 1655 ] ], "normalized": [] }, { "id": "6931", "type": "Genes & Molecular Sequences", "text": [ "etanercept" ], "offsets": [ [ 1645, 1655 ] ], "normalized": [] }, { "id": "6932", "type": "Genes & Molecular Sequences", "text": [ "GCA" ], "offsets": [ [ 1673, 1676 ] ], "normalized": [] }, { "id": "6933", "type": "", "text": [ "label" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "6934", "type": "", "text": [ "TNF) antagonists" ], "offsets": [ [ 199, 215 ] ], "normalized": [] }, { "id": "6936", "type": "", "text": [ "label" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "6937", "type": "", "text": [ "GCA" ], "offsets": [ [ 318, 321 ] ], "normalized": [] }, { "id": "6939", "type": "", "text": [ "prednisone" ], "offsets": [ [ 1316, 1326 ] ], "normalized": [] }, { "id": "6940", "type": "", "text": [ "etanercept" ], "offsets": [ [ 1255, 1265 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6935", "type": "PA", "arg1_id": "6933", "arg2_id": "6934", "normalized": [] }, { "id": "6938", "type": "PA", "arg1_id": "6936", "arg2_id": "6937", "normalized": [] }, { "id": "6941", "type": "PA", "arg1_id": "6939", "arg2_id": "6940", "normalized": [] } ]

[ { "id": "6944", "type": "title", "text": [ "Clinical presentation and pathophysiology of EGFRI dermatologic toxicities." ], "offsets": [ [ 0, 75 ] ] }, { "id": "6945", "type": "abstract", "text": [ "This review summarizes the pathophysiology and clinical presentation of the cutaneous toxicities associated with EGFR inhibition. Such effects include papulopustular reactions, xerosis, pruritus, fissures, nail changes, hair changes, telangiectasias, hyperpigmentation, and mucositis. Most management strategies for these toxicities have been based on anecdotal experience; clinical trials are needed to provide uniform characterization to allow for evidence-based treatment strategies." ], "offsets": [ [ 76, 562 ] ] } ]

[ { "id": "6946", "type": "Genes & Molecular Sequences", "text": [ "EGFRI" ], "offsets": [ [ 45, 50 ] ], "normalized": [] }, { "id": "6947", "type": "Chemicals & Drugs", "text": [ "EGFRI" ], "offsets": [ [ 45, 50 ] ], "normalized": [] }, { "id": "6948", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 189, 193 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "6951", "type": "title", "text": [ "Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors." ], "offsets": [ [ 0, 104 ] ] }, { "id": "6952", "type": "abstract", "text": [ "OBJECTIVE: To test the hypothesis that 5,10-methylenetetrahydroreductase (MTHFR) polymorphisms can partially explain the individual variation in developing attention-deficit/hyperactivity disorder (ADHD) after acute lymphoblastic leukemia (ALL) therapy. STUDY DESIGN: Parents of 48 survivors of childhood ALL completed a clinical diagnostic process to identify subtypes of ADHD. Genotyping was performed with peripheral blood DNA for MTHFR (C677T and A1298C) polymorphisms. RESULTS: Eleven of the 48 patients (22.9%) had scores consistent with the inattentive symptoms of ADHD. Patients with genotypes related to lower folate levels (11 out of 39; 39.2%) were more likely to have ADHD. The A1298C genotype appeared to be the predominant linkage to the inattentive symptoms, leading to a 7.4-fold increase in diagnosis, compared with a 1.3-fold increase for the C677T genotype. Age at diagnosis and sex were not associated with inattentiveness. CONCLUSIONS: Preliminary data imply a strong relationship between MTHFR polymorphisms and the inattentive symptoms of ADHD in survivors of childhood ALL." ], "offsets": [ [ 105, 1202 ] ] } ]

[ { "id": "6953", "type": "Chemicals & Drugs", "text": [ "Folate" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "6954", "type": "Diseases & Disorders", "text": [ "attention disorders" ], "offsets": [ [ 52, 71 ] ], "normalized": [] }, { "id": "6955", "type": "Diseases & Disorders", "text": [ "childhood leukemia" ], "offsets": [ [ 75, 93 ] ], "normalized": [] }, { "id": "6956", "type": "Diseases & Disorders", "text": [ "attention-deficit/hyperactivity disorder" ], "offsets": [ [ 261, 301 ] ], "normalized": [] }, { "id": "6957", "type": "Diseases & Disorders", "text": [ "ADHD" ], "offsets": [ [ 303, 307 ] ], "normalized": [] }, { "id": "6958", "type": "Diseases & Disorders", "text": [ "acute lymphoblastic leukemia" ], "offsets": [ [ 315, 343 ] ], "normalized": [] }, { "id": "6959", "type": "Diseases & Disorders", "text": [ "ALL" ], "offsets": [ [ 345, 348 ] ], "normalized": [] }, { "id": "6960", "type": "Diseases & Disorders", "text": [ "childhood" ], "offsets": [ [ 400, 409 ] ], "normalized": [] }, { "id": "6961", "type": "Diseases & Disorders", "text": [ "ALL" ], "offsets": [ [ 410, 413 ] ], "normalized": [] }, { "id": "6962", "type": "Diseases & Disorders", "text": [ "ADHD" ], "offsets": [ [ 478, 482 ] ], "normalized": [] }, { "id": "6963", "type": "Chemicals & Drugs", "text": [ "Eleven" ], "offsets": [ [ 588, 594 ] ], "normalized": [] }, { "id": "6964", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 665, 673 ] ], "normalized": [] }, { "id": "6965", "type": "Diseases & Disorders", "text": [ "ADHD" ], "offsets": [ [ 677, 681 ] ], "normalized": [] }, { "id": "6966", "type": "Chemicals & Drugs", "text": [ "folate" ], "offsets": [ [ 724, 730 ] ], "normalized": [] }, { "id": "6967", "type": "Diseases & Disorders", "text": [ "ADHD" ], "offsets": [ [ 785, 789 ] ], "normalized": [] }, { "id": "6968", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 869, 877 ] ], "normalized": [] }, { "id": "6969", "type": "Diseases & Disorders", "text": [ "inattentiveness" ], "offsets": [ [ 1032, 1047 ] ], "normalized": [] }, { "id": "6970", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 1155, 1163 ] ], "normalized": [] }, { "id": "6971", "type": "Diseases & Disorders", "text": [ "ADHD" ], "offsets": [ [ 1167, 1171 ] ], "normalized": [] }, { "id": "6972", "type": "Diseases & Disorders", "text": [ "childhood" ], "offsets": [ [ 1188, 1197 ] ], "normalized": [] }, { "id": "6973", "type": "Diseases & Disorders", "text": [ "ALL" ], "offsets": [ [ 1198, 1201 ] ], "normalized": [] }, { "id": "6974", "type": "", "text": [ "Folate" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "6975", "type": "", "text": [ "attention disorders" ], "offsets": [ [ 52, 71 ] ], "normalized": [] }, { "id": "6977", "type": "", "text": [ "Folate" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "6978", "type": "", "text": [ "childhood leukemia" ], "offsets": [ [ 75, 93 ] ], "normalized": [] }, { "id": "6980", "type": "", "text": [ "Eleven" ], "offsets": [ [ 588, 594 ] ], "normalized": [] }, { "id": "6981", "type": "", "text": [ "ADHD" ], "offsets": [ [ 677, 681 ] ], "normalized": [] }, { "id": "6983", "type": "", "text": [ "Eleven" ], "offsets": [ [ 588, 594 ] ], "normalized": [] }, { "id": "6984", "type": "", "text": [ "symptoms" ], "offsets": [ [ 665, 673 ] ], "normalized": [] }, { "id": "6986", "type": "", "text": [ "folate" ], "offsets": [ [ 724, 730 ] ], "normalized": [] }, { "id": "6987", "type": "", "text": [ "ADHD" ], "offsets": [ [ 785, 789 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6976", "type": "PA", "arg1_id": "6974", "arg2_id": "6975", "normalized": [] }, { "id": "6979", "type": "PA", "arg1_id": "6977", "arg2_id": "6978", "normalized": [] }, { "id": "6982", "type": "PA", "arg1_id": "6980", "arg2_id": "6981", "normalized": [] }, { "id": "6985", "type": "PA", "arg1_id": "6983", "arg2_id": "6984", "normalized": [] }, { "id": "6988", "type": "PA", "arg1_id": "6986", "arg2_id": "6987", "normalized": [] } ]

[ { "id": "6991", "type": "title", "text": [ "PPARgamma-dependent and -independent effects of rosiglitazone on lipotoxic human pancreatic islets." ], "offsets": [ [ 0, 99 ] ] }, { "id": "6992", "type": "abstract", "text": [ "We explored the in vitro effects of Rosiglitazone (RZG), a PPARgamma agonist, on human pancreatic islet dysfunctions induced by chronic free fatty acid exposure. We demonstrated that RZG beneficial effects on insulin secretion and apoptosis did not imply PDX-1 or insulin gene modulation. It rather involved, through a PPARgamma-dependent mechanism, a reduction of iNOS overexpressed in lipotoxic islets. This reduction likely led to the restoration of ATP level and insulin secretion as well as the decrease in apoptosis. More interestingly, we also demonstrated that RZG beneficial effects involved PPARgamma-independent mechanisms. RZG treatment led to a limitation of oxidative stress exemplified by an increase of GPx and SOD expression. It also increased UCP2 expression that seemed to display antioxidant action in this model. Thus, RZG did not appear to exert a direct action on insulin expression but rather an indirect action on insulin secretion and apoptosis, through PPARgamma-dependent and -independent mechanisms, via regulation of nitrogen and oxygen reactive species injury." ], "offsets": [ [ 100, 1191 ] ] } ]

[ { "id": "6993", "type": "Genes & Molecular Sequences", "text": [ "PPARgamma" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "6994", "type": "Chemicals & Drugs", "text": [ "rosiglitazone" ], "offsets": [ [ 48, 61 ] ], "normalized": [] }, { "id": "6995", "type": "Chemicals & Drugs", "text": [ "Rosiglitazone" ], "offsets": [ [ 136, 149 ] ], "normalized": [] }, { "id": "6996", "type": "Chemicals & Drugs", "text": [ "RZG" ], "offsets": [ [ 151, 154 ] ], "normalized": [] }, { "id": "6997", "type": "Chemicals & Drugs", "text": [ "PPARgamma agonist" ], "offsets": [ [ 159, 176 ] ], "normalized": [] }, { "id": "6998", "type": "Genes & Molecular Sequences", "text": [ "PPARgamma agonist" ], "offsets": [ [ 159, 176 ] ], "normalized": [] }, { "id": "6999", "type": "Chemicals & Drugs", "text": [ "RZG" ], "offsets": [ [ 283, 286 ] ], "normalized": [] }, { "id": "7000", "type": "Genes & Molecular Sequences", "text": [ "insulin" ], "offsets": [ [ 309, 316 ] ], "normalized": [] }, { "id": "7001", "type": "Genes & Molecular Sequences", "text": [ "PDX-1" ], "offsets": [ [ 355, 360 ] ], "normalized": [] }, { "id": "7002", "type": "Genes & Molecular Sequences", "text": [ "insulin" ], "offsets": [ [ 364, 371 ] ], "normalized": [] }, { "id": "7003", "type": "Genes & Molecular Sequences", "text": [ "PPARgamma" ], "offsets": [ [ 419, 428 ] ], "normalized": [] }, { "id": "7004", "type": "Genes & Molecular Sequences", "text": [ "iNOS" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "7005", "type": "Genes & Molecular Sequences", "text": [ "ATP" ], "offsets": [ [ 553, 556 ] ], "normalized": [] }, { "id": "7006", "type": "Chemicals & Drugs", "text": [ "ATP" ], "offsets": [ [ 553, 556 ] ], "normalized": [] }, { "id": "7007", "type": "Genes & Molecular Sequences", "text": [ "insulin" ], "offsets": [ [ 567, 574 ] ], "normalized": [] }, { "id": "7008", "type": "Chemicals & Drugs", "text": [ "RZG" ], "offsets": [ [ 669, 672 ] ], "normalized": [] }, { "id": "7009", "type": "Genes & Molecular Sequences", "text": [ "PPARgamma" ], "offsets": [ [ 701, 710 ] ], "normalized": [] }, { "id": "7010", "type": "Chemicals & Drugs", "text": [ "RZG" ], "offsets": [ [ 735, 738 ] ], "normalized": [] }, { "id": "7011", "type": "Genes & Molecular Sequences", "text": [ "GPx" ], "offsets": [ [ 819, 822 ] ], "normalized": [] }, { "id": "7012", "type": "Genes & Molecular Sequences", "text": [ "SOD" ], "offsets": [ [ 827, 830 ] ], "normalized": [] }, { "id": "7013", "type": "Genes & Molecular Sequences", "text": [ "UCP2" ], "offsets": [ [ 861, 865 ] ], "normalized": [] }, { "id": "7014", "type": "Chemicals & Drugs", "text": [ "RZG" ], "offsets": [ [ 940, 943 ] ], "normalized": [] }, { "id": "7015", "type": "Genes & Molecular Sequences", "text": [ "insulin" ], "offsets": [ [ 987, 994 ] ], "normalized": [] }, { "id": "7016", "type": "Genes & Molecular Sequences", "text": [ "insulin" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] }, { "id": "7017", "type": "Genes & Molecular Sequences", "text": [ "PPARgamma" ], "offsets": [ [ 1080, 1089 ] ], "normalized": [] }, { "id": "7018", "type": "", "text": [ "RZG" ], "offsets": [ [ 283, 286 ] ], "normalized": [] }, { "id": "7019", "type": "", "text": [ "PDX-1" ], "offsets": [ [ 355, 360 ] ], "normalized": [] }, { "id": "7021", "type": "", "text": [ "RZG" ], "offsets": [ [ 283, 286 ] ], "normalized": [] }, { "id": "7022", "type": "", "text": [ "insulin" ], "offsets": [ [ 364, 371 ] ], "normalized": [] }, { "id": "7024", "type": "", "text": [ "RZG" ], "offsets": [ [ 735, 738 ] ], "normalized": [] }, { "id": "7025", "type": "", "text": [ "GPx" ], "offsets": [ [ 819, 822 ] ], "normalized": [] }, { "id": "7027", "type": "", "text": [ "RZG" ], "offsets": [ [ 735, 738 ] ], "normalized": [] }, { "id": "7028", "type": "", "text": [ "SOD" ], "offsets": [ [ 827, 830 ] ], "normalized": [] }, { "id": "7030", "type": "", "text": [ "RZG" ], "offsets": [ [ 940, 943 ] ], "normalized": [] }, { "id": "7031", "type": "", "text": [ "insulin" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] }, { "id": "7033", "type": "", "text": [ "rosiglitazone" ], "offsets": [ [ 48, 61 ] ], "normalized": [] }, { "id": "7034", "type": "", "text": [ "PPARgamma" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "7036", "type": "", "text": [ "Rosiglitazone" ], "offsets": [ [ 136, 149 ] ], "normalized": [] }, { "id": "7037", "type": "", "text": [ "PPARgamma agonist" ], "offsets": [ [ 159, 176 ] ], "normalized": [] }, { "id": "7039", "type": "", "text": [ "RZG" ], "offsets": [ [ 151, 154 ] ], "normalized": [] }, { "id": "7040", "type": "", "text": [ "PPARgamma agonist" ], "offsets": [ [ 159, 176 ] ], "normalized": [] }, { "id": "7042", "type": "", "text": [ "RZG" ], "offsets": [ [ 283, 286 ] ], "normalized": [] }, { "id": "7043", "type": "", "text": [ "insulin" ], "offsets": [ [ 309, 316 ] ], "normalized": [] }, { "id": "7045", "type": "", "text": [ "RZG" ], "offsets": [ [ 669, 672 ] ], "normalized": [] }, { "id": "7046", "type": "", "text": [ "PPARgamma" ], "offsets": [ [ 701, 710 ] ], "normalized": [] }, { "id": "7048", "type": "", "text": [ "RZG" ], "offsets": [ [ 940, 943 ] ], "normalized": [] }, { "id": "7049", "type": "", "text": [ "PPARgamma" ], "offsets": [ [ 1080, 1089 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7020", "type": "NA", "arg1_id": "7018", "arg2_id": "7019", "normalized": [] }, { "id": "7023", "type": "NA", "arg1_id": "7021", "arg2_id": "7022", "normalized": [] }, { "id": "7026", "type": "PA", "arg1_id": "7024", "arg2_id": "7025", "normalized": [] }, { "id": "7029", "type": "PA", "arg1_id": "7027", "arg2_id": "7028", "normalized": [] }, { "id": "7032", "type": "PA", "arg1_id": "7030", "arg2_id": "7031", "normalized": [] }, { "id": "7035", "type": "PA", "arg1_id": "7033", "arg2_id": "7034", "normalized": [] }, { "id": "7038", "type": "PA", "arg1_id": "7036", "arg2_id": "7037", "normalized": [] }, { "id": "7041", "type": "PA", "arg1_id": "7039", "arg2_id": "7040", "normalized": [] }, { "id": "7044", "type": "PA", "arg1_id": "7042", "arg2_id": "7043", "normalized": [] }, { "id": "7047", "type": "PA", "arg1_id": "7045", "arg2_id": "7046", "normalized": [] }, { "id": "7050", "type": "PA", "arg1_id": "7048", "arg2_id": "7049", "normalized": [] } ]

[ { "id": "7053", "type": "title", "text": [ "Do statins decrease cardiovascular disease at the expense of increasing cancer?" ], "offsets": [ [ 0, 79 ] ] }, { "id": "7054", "type": "abstract", "text": [ "A recent report of an inverse relationship between achieved low-density lipoprotein (LDL) cholesterol levels and cancer incidence has refueled the debate on cholesterol lowering and cancer. This is timely, since aggressive cholesterol lowering with statins is the trend. There are data suggesting that cholesterol lowering increases cancer at the expense of decreasing cardiovascular disease in certain populations, such as the elderly and those treated with immunotherapy for cancer. Furthermore, there may be a relationship between statin dose and cancer. Future statin trials should accurately tract the incidence of new cancers over extended time periods. These issues deserve our attention." ], "offsets": [ [ 80, 775 ] ] } ]

[ { "id": "7055", "type": "Chemicals & Drugs", "text": [ "statins" ], "offsets": [ [ 3, 10 ] ], "normalized": [] }, { "id": "7056", "type": "Diseases & Disorders", "text": [ "cardiovascular disease" ], "offsets": [ [ 20, 42 ] ], "normalized": [] }, { "id": "7057", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 72, 78 ] ], "normalized": [] }, { "id": "7058", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 193, 199 ] ], "normalized": [] }, { "id": "7059", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 262, 268 ] ], "normalized": [] }, { "id": "7060", "type": "Diseases & Disorders", "text": [ "aggressive" ], "offsets": [ [ 292, 302 ] ], "normalized": [] }, { "id": "7061", "type": "Chemicals & Drugs", "text": [ "statins" ], "offsets": [ [ 329, 336 ] ], "normalized": [] }, { "id": "7062", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 413, 419 ] ], "normalized": [] }, { "id": "7063", "type": "Diseases & Disorders", "text": [ "cardiovascular disease" ], "offsets": [ [ 449, 471 ] ], "normalized": [] }, { "id": "7064", "type": "Chemicals & Drugs", "text": [ "immunotherapy" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "7065", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 557, 563 ] ], "normalized": [] }, { "id": "7066", "type": "Chemicals & Drugs", "text": [ "statin" ], "offsets": [ [ 614, 620 ] ], "normalized": [] }, { "id": "7067", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 630, 636 ] ], "normalized": [] }, { "id": "7068", "type": "Chemicals & Drugs", "text": [ "statin" ], "offsets": [ [ 645, 651 ] ], "normalized": [] }, { "id": "7069", "type": "Diseases & Disorders", "text": [ "cancers" ], "offsets": [ [ 704, 711 ] ], "normalized": [] }, { "id": "7070", "type": "", "text": [ "statins" ], "offsets": [ [ 3, 10 ] ], "normalized": [] }, { "id": "7071", "type": "", "text": [ "cardiovascular disease" ], "offsets": [ [ 20, 42 ] ], "normalized": [] }, { "id": "7073", "type": "", "text": [ "statins" ], "offsets": [ [ 3, 10 ] ], "normalized": [] }, { "id": "7074", "type": "", "text": [ "cancer" ], "offsets": [ [ 72, 78 ] ], "normalized": [] }, { "id": "7076", "type": "", "text": [ "statin" ], "offsets": [ [ 614, 620 ] ], "normalized": [] }, { "id": "7077", "type": "", "text": [ "cancer" ], "offsets": [ [ 630, 636 ] ], "normalized": [] }, { "id": "7079", "type": "", "text": [ "statin" ], "offsets": [ [ 645, 651 ] ], "normalized": [] }, { "id": "7080", "type": "", "text": [ "cancers" ], "offsets": [ [ 704, 711 ] ], "normalized": [] }, { "id": "7082", "type": "", "text": [ "immunotherapy" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "7083", "type": "", "text": [ "cardiovascular disease" ], "offsets": [ [ 449, 471 ] ], "normalized": [] }, { "id": "7085", "type": "", "text": [ "immunotherapy" ], "offsets": [ [ 539, 552 ] ], "normalized": [] }, { "id": "7086", "type": "", "text": [ "cancer" ], "offsets": [ [ 557, 563 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7072", "type": "PA", "arg1_id": "7070", "arg2_id": "7071", "normalized": [] }, { "id": "7075", "type": "SA", "arg1_id": "7073", "arg2_id": "7074", "normalized": [] }, { "id": "7078", "type": "SA", "arg1_id": "7076", "arg2_id": "7077", "normalized": [] }, { "id": "7081", "type": "SA", "arg1_id": "7079", "arg2_id": "7080", "normalized": [] }, { "id": "7084", "type": "PA", "arg1_id": "7082", "arg2_id": "7083", "normalized": [] }, { "id": "7087", "type": "PA", "arg1_id": "7085", "arg2_id": "7086", "normalized": [] } ]

[ { "id": "7090", "type": "title", "text": [ "The effect of a long term epidural infusion of ropivacaine on CYP2D6 activity." ], "offsets": [ [ 0, 78 ] ] }, { "id": "7091", "type": "abstract", "text": [ "BACKGROUND: Ropivacaine and one of its metabolites, pipecoloxylidide, inhibit CYP2D6 in. human liver microsomes in vitro with K(i) values of 5 microM (1.4 mg/L) and 13 microM (3.6 mg/L), respectively. We investigated the effect of a 50 h continuous epidural infusion of ropivacaine 2 mg/mL at a rate of 14 mL/h on CYP2D6 activity. METHODS: Nineteen patients (41-85 yr) undergoing hip or knee replacement, all extensive metabolizers with respect to CYP2D6 activity, were included. Medications known to inhibit or be metabolized by CYP2D6, or known to be strong inhibitors/inducers of CYP1A2 or CYP3A4 were not allowed. Patients received 10 mg debrisoquine (a marker for CYP2D6 activity) before surgery and after 40 h epidural infusion. The metabolic ratio (MR) for debrisoquine hydroxylation was calculated as the amount of debrisoquine/amount of 4-OH-debrisoquine excreted in 0-10 h urine. RESULTS: The median (range) of MR before and after ropivacaine were 0.54 (0.1-3.4) and 1.79 (0.3-6.7), respectively. The Hodges Lehman estimate of the ratio MR after/MR before ropivacaine was 2.2 with a 95% confidence interval 1.9-2.7 (P < 0.001). CONCLUSION: A continuous epidural infusion of ropivacaine inhibits CYP2D6 activity in patients who are extensive metabolizers resulting in a twofold increase in the MR for debrisoquine hydroxylation. However, since none of the patients was converted into a functional poor metabolizer (MR >12.6), the effect on the metabolism of other drugs metabolized by CYP2D6 is unlikely to be of major clinical importance." ], "offsets": [ [ 79, 1627 ] ] } ]

[ { "id": "7092", "type": "Chemicals & Drugs", "text": [ "epidural infusion of ropivacaine" ], "offsets": [ [ 26, 58 ] ], "normalized": [] }, { "id": "7093", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 62, 68 ] ], "normalized": [] }, { "id": "7094", "type": "Chemicals & Drugs", "text": [ "Ropivacaine" ], "offsets": [ [ 91, 102 ] ], "normalized": [] }, { "id": "7095", "type": "Chemicals & Drugs", "text": [ "pipecoloxylidide" ], "offsets": [ [ 131, 147 ] ], "normalized": [] }, { "id": "7096", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 157, 163 ] ], "normalized": [] }, { "id": "7097", "type": "Chemicals & Drugs", "text": [ "epidural infusion of ropivacaine" ], "offsets": [ [ 328, 360 ] ], "normalized": [] }, { "id": "7098", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 393, 399 ] ], "normalized": [] }, { "id": "7099", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 527, 533 ] ], "normalized": [] }, { "id": "7100", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 609, 615 ] ], "normalized": [] }, { "id": "7101", "type": "Chemicals & Drugs", "text": [ "CYP2D6" ], "offsets": [ [ 609, 615 ] ], "normalized": [] }, { "id": "7102", "type": "Genes & Molecular Sequences", "text": [ "CYP1A2" ], "offsets": [ [ 662, 668 ] ], "normalized": [] }, { "id": "7103", "type": "Chemicals & Drugs", "text": [ "CYP1A2" ], "offsets": [ [ 662, 668 ] ], "normalized": [] }, { "id": "7104", "type": "Genes & Molecular Sequences", "text": [ "CYP3A4" ], "offsets": [ [ 672, 678 ] ], "normalized": [] }, { "id": "7105", "type": "Chemicals & Drugs", "text": [ "debrisoquine" ], "offsets": [ [ 721, 733 ] ], "normalized": [] }, { "id": "7106", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 748, 754 ] ], "normalized": [] }, { "id": "7107", "type": "Chemicals & Drugs", "text": [ "debrisoquine" ], "offsets": [ [ 843, 855 ] ], "normalized": [] }, { "id": "7108", "type": "Chemicals & Drugs", "text": [ "debrisoquine" ], "offsets": [ [ 902, 914 ] ], "normalized": [] }, { "id": "7109", "type": "Chemicals & Drugs", "text": [ "4-OH-debrisoquine" ], "offsets": [ [ 925, 942 ] ], "normalized": [] }, { "id": "7110", "type": "Chemicals & Drugs", "text": [ "ropivacaine" ], "offsets": [ [ 1020, 1031 ] ], "normalized": [] }, { "id": "7111", "type": "Chemicals & Drugs", "text": [ "ropivacaine" ], "offsets": [ [ 1145, 1156 ] ], "normalized": [] }, { "id": "7112", "type": "Chemicals & Drugs", "text": [ "epidural infusion of ropivacaine" ], "offsets": [ [ 1242, 1274 ] ], "normalized": [] }, { "id": "7113", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 1284, 1290 ] ], "normalized": [] }, { "id": "7114", "type": "Chemicals & Drugs", "text": [ "debrisoquine" ], "offsets": [ [ 1389, 1401 ] ], "normalized": [] }, { "id": "7115", "type": "Genes & Molecular Sequences", "text": [ "CYP2D6" ], "offsets": [ [ 1573, 1579 ] ], "normalized": [] }, { "id": "7116", "type": "", "text": [ "Ropivacaine" ], "offsets": [ [ 91, 102 ] ], "normalized": [] }, { "id": "7117", "type": "", "text": [ "CYP2D6" ], "offsets": [ [ 157, 163 ] ], "normalized": [] }, { "id": "7119", "type": "", "text": [ "pipecoloxylidide" ], "offsets": [ [ 131, 147 ] ], "normalized": [] }, { "id": "7120", "type": "", "text": [ "CYP2D6" ], "offsets": [ [ 157, 163 ] ], "normalized": [] }, { "id": "7122", "type": "", "text": [ "epidural infusion of ropivacaine" ], "offsets": [ [ 1242, 1274 ] ], "normalized": [] }, { "id": "7123", "type": "", "text": [ "CYP2D6" ], "offsets": [ [ 1284, 1290 ] ], "normalized": [] }, { "id": "7125", "type": "", "text": [ "epidural infusion of ropivacaine" ], "offsets": [ [ 26, 58 ] ], "normalized": [] }, { "id": "7126", "type": "", "text": [ "CYP2D6" ], "offsets": [ [ 62, 68 ] ], "normalized": [] }, { "id": "7128", "type": "", "text": [ "epidural infusion of ropivacaine" ], "offsets": [ [ 328, 360 ] ], "normalized": [] }, { "id": "7129", "type": "", "text": [ "CYP2D6" ], "offsets": [ [ 393, 399 ] ], "normalized": [] }, { "id": "7131", "type": "", "text": [ "debrisoquine" ], "offsets": [ [ 721, 733 ] ], "normalized": [] }, { "id": "7132", "type": "", "text": [ "CYP2D6" ], "offsets": [ [ 748, 754 ] ], "normalized": [] }, { "id": "7134", "type": "", "text": [ "debrisoquine" ], "offsets": [ [ 1389, 1401 ] ], "normalized": [] }, { "id": "7135", "type": "", "text": [ "CYP2D6" ], "offsets": [ [ 1284, 1290 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7118", "type": "PA", "arg1_id": "7116", "arg2_id": "7117", "normalized": [] }, { "id": "7121", "type": "PA", "arg1_id": "7119", "arg2_id": "7120", "normalized": [] }, { "id": "7124", "type": "PA", "arg1_id": "7122", "arg2_id": "7123", "normalized": [] }, { "id": "7127", "type": "PA", "arg1_id": "7125", "arg2_id": "7126", "normalized": [] }, { "id": "7130", "type": "PA", "arg1_id": "7128", "arg2_id": "7129", "normalized": [] }, { "id": "7133", "type": "PA", "arg1_id": "7131", "arg2_id": "7132", "normalized": [] }, { "id": "7136", "type": "PA", "arg1_id": "7134", "arg2_id": "7135", "normalized": [] } ]

[ { "id": "7139", "type": "title", "text": [ "Is there a role for routine abdominal imaging in predicting postoperative intraabdominal abscess formation after appendectomy for pediatric ruptured appendix?" ], "offsets": [ [ 0, 158 ] ] }, { "id": "7140", "type": "abstract", "text": [ "To determine if there is a role for routine abdominal imaging in predicting postoperative intraabdominal abscess after appendectomy for the pediatric ruptured appendix. From January 2000 to December 2003 inclusive, 44 consecutive pediatric patients with a ruptured appendix had an open appendectomy and were treated for a minimum of 5 days with triple antibiotics. On postoperative day 5, each patient was evaluated for symptoms (fever, abdominal pain, gastrointestinal dysfunction) and radiological evidence of an intraabdominal fluid collection. Further treatment was determined by the clinical evidence of continuing infection. On postoperative day 5, 36 (82%) of the 44 patients were asymptomatic, had an intraabdominal fluid collection less than 5 cm, diagnosed by ultrasound or computed tomography and received no further treatment. Two of these 36 patients (6%) returned within a week, symptomatic and with a larger collection suspicious for an intraabdominal abscess and requiring further treatment. The other 8 (18%) were symptomatic, and had an intraabdominal abscess more than 5 cm on imaging. All required further treatment, and recovered well. The use of routine abdominal imaging on postoperative day 5, (compared with clinical evaluation), did not improve the ability to predict the development of an intraabdominal abscess." ], "offsets": [ [ 159, 1498 ] ] } ]

[ { "id": "7141", "type": "Diseases & Disorders", "text": [ "postoperative intraabdominal abscess" ], "offsets": [ [ 60, 96 ] ], "normalized": [] }, { "id": "7142", "type": "Diseases & Disorders", "text": [ "postoperative intraabdominal abscess" ], "offsets": [ [ 235, 271 ] ], "normalized": [] }, { "id": "7143", "type": "Chemicals & Drugs", "text": [ "triple antibiotics" ], "offsets": [ [ 504, 522 ] ], "normalized": [] }, { "id": "7144", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 579, 587 ] ], "normalized": [] }, { "id": "7145", "type": "Diseases & Disorders", "text": [ "fever" ], "offsets": [ [ 589, 594 ] ], "normalized": [] }, { "id": "7146", "type": "Diseases & Disorders", "text": [ "abdominal pain" ], "offsets": [ [ 596, 610 ] ], "normalized": [] }, { "id": "7147", "type": "Diseases & Disorders", "text": [ "gastrointestinal dysfunction" ], "offsets": [ [ 612, 640 ] ], "normalized": [] }, { "id": "7148", "type": "Diseases & Disorders", "text": [ "continuing infection" ], "offsets": [ [ 768, 788 ] ], "normalized": [] }, { "id": "7149", "type": "Diseases & Disorders", "text": [ "intraabdominal abscess" ], "offsets": [ [ 1111, 1133 ] ], "normalized": [] }, { "id": "7150", "type": "Diseases & Disorders", "text": [ "intraabdominal abscess" ], "offsets": [ [ 1214, 1236 ] ], "normalized": [] }, { "id": "7151", "type": "Diseases & Disorders", "text": [ "intraabdominal abscess" ], "offsets": [ [ 1475, 1497 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "7154", "type": "title", "text": [ "Lysine-specific demethylase 1 (LSD1) Is required for the transcriptional repression of the telomerase reverse transcriptase (hTERT) gene." ], "offsets": [ [ 0, 137 ] ] }, { "id": "7155", "type": "abstract", "text": [ "BACKGROUND: Lysine-specific demethylase 1 (LSD1), catalysing demethylation of mono- and di-methylated histone H3-K4 or K9, exhibits diverse transcriptional activities by mediating chromatin reconfiguration. The telomerase reverse transcriptase (hTERT) gene, encoding an essential component for telomerase activity that is involved in cellular immortalization and transformation, is silent in most normal human cells while activated in up to 90% of human cancers. It remains to be defined how exactly the transcriptional activation of the hTERT gene occurs during the oncogenic process. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we determined the effect of LSD1 on hTERT transcription. In normal human fibroblasts with a tight hTERT repression, a pharmacological inhibition of LSD1 led to a weak hTERT expression, and a robust induction of hTERT mRNA was observed when LSD1 and histone deacetylases (HDACs) were both inhibited. Small interference RNA-mediated depletion of both LSD1 and CoREST, a co-repressor in HDAC-containing complexes, synergistically activated hTERT transcription. In cancer cells, inhibition of LSD1 activity or knocking-down of its expression led to significant increases in levels of hTERT mRNA and telomerase activity. Chromatin immunoprecipitation assay showed that LSD1 occupied the hTERT proximal promoter, and its depletion resulted in elevated di-methylation of histone H3-K4 accompanied by increased H3 acetylation locally in cancer cells. Moreover, during the differentiation of leukemic HL60 cells, the decreased hTERT expression was accompanied by the LSD1 recruitment to the hTERT promoter. CONCLUSIONS/SIGNIFICANCE: LSD1 represses hTERT transcription via demethylating H3-K4 in normal and cancerous cells, and together with HDACs, participates in the establishment of a stable repression state of the hTERT gene in normal or differentiated malignant cells. The findings contribute to better understandings of hTERT/telomerase regulation, which may be implicated in the development of therapeutic strategies for telomerase dysregulation-associated human diseases including cancers." ], "offsets": [ [ 138, 2266 ] ] } ]

[ { "id": "7156", "type": "Genes & Molecular Sequences", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "7157", "type": "Chemicals & Drugs", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "7158", "type": "Genes & Molecular Sequences", "text": [ "demethylase" ], "offsets": [ [ 16, 27 ] ], "normalized": [] }, { "id": "7159", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 31, 35 ] ], "normalized": [] }, { "id": "7160", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 91, 101 ] ], "normalized": [] }, { "id": "7161", "type": "Genes & Molecular Sequences", "text": [ "reverse transcriptase" ], "offsets": [ [ 102, 123 ] ], "normalized": [] }, { "id": "7162", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 125, 130 ] ], "normalized": [] }, { "id": "7163", "type": "Genes & Molecular Sequences", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 150, 179 ] ], "normalized": [] }, { "id": "7164", "type": "Chemicals & Drugs", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 150, 179 ] ], "normalized": [] }, { "id": "7165", "type": "Genes & Molecular Sequences", "text": [ "demethylase" ], "offsets": [ [ 166, 177 ] ], "normalized": [] }, { "id": "7166", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 181, 185 ] ], "normalized": [] }, { "id": "7167", "type": "Genes & Molecular Sequences", "text": [ "H3-K4" ], "offsets": [ [ 248, 253 ] ], "normalized": [] }, { "id": "7168", "type": "Genes & Molecular Sequences", "text": [ "K9" ], "offsets": [ [ 257, 259 ] ], "normalized": [] }, { "id": "7169", "type": "Genes & Molecular Sequences", "text": [ "chromatin" ], "offsets": [ [ 318, 327 ] ], "normalized": [] }, { "id": "7170", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 349, 359 ] ], "normalized": [] }, { "id": "7171", "type": "Genes & Molecular Sequences", "text": [ "reverse transcriptase" ], "offsets": [ [ 360, 381 ] ], "normalized": [] }, { "id": "7172", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 383, 388 ] ], "normalized": [] }, { "id": "7173", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 432, 442 ] ], "normalized": [] }, { "id": "7174", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 676, 681 ] ], "normalized": [] }, { "id": "7175", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 806, 810 ] ], "normalized": [] }, { "id": "7176", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 814, 819 ] ], "normalized": [] }, { "id": "7177", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 876, 881 ] ], "normalized": [] }, { "id": "7178", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 926, 930 ] ], "normalized": [] }, { "id": "7179", "type": "Chemicals & Drugs", "text": [ "LSD1" ], "offsets": [ [ 926, 930 ] ], "normalized": [] }, { "id": "7180", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 945, 950 ] ], "normalized": [] }, { "id": "7181", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 989, 994 ] ], "normalized": [] }, { "id": "7182", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 1018, 1022 ] ], "normalized": [] }, { "id": "7183", "type": "Genes & Molecular Sequences", "text": [ "histone deacetylases" ], "offsets": [ [ 1027, 1047 ] ], "normalized": [] }, { "id": "7184", "type": "Genes & Molecular Sequences", "text": [ "HDACs" ], "offsets": [ [ 1049, 1054 ] ], "normalized": [] }, { "id": "7185", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 1127, 1131 ] ], "normalized": [] }, { "id": "7186", "type": "Genes & Molecular Sequences", "text": [ "CoREST" ], "offsets": [ [ 1136, 1142 ] ], "normalized": [] }, { "id": "7187", "type": "Genes & Molecular Sequences", "text": [ "HDAC" ], "offsets": [ [ 1162, 1166 ] ], "normalized": [] }, { "id": "7188", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 1215, 1220 ] ], "normalized": [] }, { "id": "7189", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 1267, 1271 ] ], "normalized": [] }, { "id": "7190", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 1358, 1363 ] ], "normalized": [] }, { "id": "7191", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 1373, 1383 ] ], "normalized": [] }, { "id": "7192", "type": "Genes & Molecular Sequences", "text": [ "Chromatin" ], "offsets": [ [ 1394, 1403 ] ], "normalized": [] }, { "id": "7193", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 1442, 1446 ] ], "normalized": [] }, { "id": "7194", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 1460, 1465 ] ], "normalized": [] }, { "id": "7195", "type": "Genes & Molecular Sequences", "text": [ "H3-K4" ], "offsets": [ [ 1550, 1555 ] ], "normalized": [] }, { "id": "7196", "type": "Genes & Molecular Sequences", "text": [ "H3" ], "offsets": [ [ 1581, 1583 ] ], "normalized": [] }, { "id": "7197", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 1696, 1701 ] ], "normalized": [] }, { "id": "7198", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 1736, 1740 ] ], "normalized": [] }, { "id": "7199", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 1760, 1765 ] ], "normalized": [] }, { "id": "7200", "type": "Genes & Molecular Sequences", "text": [ "LSD1" ], "offsets": [ [ 1802, 1806 ] ], "normalized": [] }, { "id": "7201", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 1817, 1822 ] ], "normalized": [] }, { "id": "7202", "type": "Genes & Molecular Sequences", "text": [ "H3-K4" ], "offsets": [ [ 1855, 1860 ] ], "normalized": [] }, { "id": "7203", "type": "Genes & Molecular Sequences", "text": [ "HDACs" ], "offsets": [ [ 1910, 1915 ] ], "normalized": [] }, { "id": "7204", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 1987, 1992 ] ], "normalized": [] }, { "id": "7205", "type": "Genes & Molecular Sequences", "text": [ "hTERT" ], "offsets": [ [ 2095, 2100 ] ], "normalized": [] }, { "id": "7206", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 2101, 2111 ] ], "normalized": [] }, { "id": "7207", "type": "Genes & Molecular Sequences", "text": [ "telomerase" ], "offsets": [ [ 2197, 2207 ] ], "normalized": [] }, { "id": "7208", "type": "", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "7209", "type": "", "text": [ "hTERT" ], "offsets": [ [ 125, 130 ] ], "normalized": [] }, { "id": "7211", "type": "", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "7212", "type": "", "text": [ "demethylase" ], "offsets": [ [ 16, 27 ] ], "normalized": [] }, { "id": "7214", "type": "", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "7215", "type": "", "text": [ "LSD1" ], "offsets": [ [ 31, 35 ] ], "normalized": [] }, { "id": "7217", "type": "", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 150, 179 ] ], "normalized": [] }, { "id": "7218", "type": "", "text": [ "demethylase" ], "offsets": [ [ 166, 177 ] ], "normalized": [] }, { "id": "7220", "type": "", "text": [ "Lysine-specific demethylase 1" ], "offsets": [ [ 150, 179 ] ], "normalized": [] }, { "id": "7221", "type": "", "text": [ "LSD1" ], "offsets": [ [ 181, 185 ] ], "normalized": [] }, { "id": "7223", "type": "", "text": [ "LSD1" ], "offsets": [ [ 926, 930 ] ], "normalized": [] }, { "id": "7224", "type": "", "text": [ "hTERT" ], "offsets": [ [ 945, 950 ] ], "normalized": [] }, { "id": "7226", "type": "", "text": [ "LSD1" ], "offsets": [ [ 926, 930 ] ], "normalized": [] }, { "id": "7227", "type": "", "text": [ "hTERT" ], "offsets": [ [ 989, 994 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7210", "type": "PA", "arg1_id": "7208", "arg2_id": "7209", "normalized": [] }, { "id": "7213", "type": "PA", "arg1_id": "7211", "arg2_id": "7212", "normalized": [] }, { "id": "7216", "type": "PA", "arg1_id": "7214", "arg2_id": "7215", "normalized": [] }, { "id": "7219", "type": "PA", "arg1_id": "7217", "arg2_id": "7218", "normalized": [] }, { "id": "7222", "type": "PA", "arg1_id": "7220", "arg2_id": "7221", "normalized": [] }, { "id": "7225", "type": "PA", "arg1_id": "7223", "arg2_id": "7224", "normalized": [] }, { "id": "7228", "type": "PA", "arg1_id": "7226", "arg2_id": "7227", "normalized": [] } ]

[ { "id": "7231", "type": "title", "text": [ "A novel role for villin in intestinal epithelial cell survival and homeostasis." ], "offsets": [ [ 0, 79 ] ] }, { "id": "7232", "type": "abstract", "text": [ "Apoptosis is a key regulator for the normal turnover of the intestinal mucosa, and abnormalities associated with this function have been linked to inflammatory bowel disease and colorectal cancer. Despite this, little is known about the mechanism(s) mediating intestinal epithelial cell apoptosis. Villin is an actin regulatory protein that is expressed in every cell of the intestinal epithelium as well as in exocrine glands associated with the gastrointestinal tract. In this study we demonstrate for the first time that villin is an epithelial cell-specific anti-apoptotic protein. Absence of villin predisposes mice to dextran sodium sulfate-induced colitis by promoting apoptosis. To better understand the cellular and molecular mechanisms of the anti-apoptotic function of villin, we overexpressed villin in the Madin-Darby canine kidney Tet-Off epithelial cell line to demonstrate that expression of villin protects cells from apoptosis by maintaining mitochondrial integrity thus inhibiting the activation of caspase-9 and caspase-3. Furthermore, we report that the anti-apoptotic response of villin depends on activation of the pro-survival proteins, phosphatidylinositol 3-kinase and phosphorylated Akt. The results of our studies shed new light on the previously unrecognized function of villin in the regulation of apoptosis in the gastrointestinal epithelium." ], "offsets": [ [ 80, 1453 ] ] } ]

[ { "id": "7233", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 17, 23 ] ], "normalized": [] }, { "id": "7234", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 163, 176 ] ], "normalized": [] }, { "id": "7235", "type": "Diseases & Disorders", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 227, 253 ] ], "normalized": [] }, { "id": "7236", "type": "Diseases & Disorders", "text": [ "colorectal cancer" ], "offsets": [ [ 258, 275 ] ], "normalized": [] }, { "id": "7237", "type": "Diseases & Disorders", "text": [ "little" ], "offsets": [ [ 291, 297 ] ], "normalized": [] }, { "id": "7238", "type": "Chemicals & Drugs", "text": [ "Villin" ], "offsets": [ [ 378, 384 ] ], "normalized": [] }, { "id": "7239", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 604, 610 ] ], "normalized": [] }, { "id": "7240", "type": "Diseases & Disorders", "text": [ "Absence" ], "offsets": [ [ 666, 673 ] ], "normalized": [] }, { "id": "7241", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 677, 683 ] ], "normalized": [] }, { "id": "7242", "type": "Chemicals & Drugs", "text": [ "dextran sodium sulfate" ], "offsets": [ [ 704, 726 ] ], "normalized": [] }, { "id": "7243", "type": "Diseases & Disorders", "text": [ "colitis" ], "offsets": [ [ 735, 742 ] ], "normalized": [] }, { "id": "7244", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 860, 866 ] ], "normalized": [] }, { "id": "7245", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 885, 891 ] ], "normalized": [] }, { "id": "7246", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 988, 994 ] ], "normalized": [] }, { "id": "7247", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 1182, 1188 ] ], "normalized": [] }, { "id": "7248", "type": "Chemicals & Drugs", "text": [ "villin" ], "offsets": [ [ 1380, 1386 ] ], "normalized": [] }, { "id": "7249", "type": "", "text": [ "dextran sodium sulfate" ], "offsets": [ [ 704, 726 ] ], "normalized": [] }, { "id": "7250", "type": "", "text": [ "colitis" ], "offsets": [ [ 735, 742 ] ], "normalized": [] }, { "id": "7252", "type": "", "text": [ "villin" ], "offsets": [ [ 677, 683 ] ], "normalized": [] }, { "id": "7253", "type": "", "text": [ "colitis" ], "offsets": [ [ 735, 742 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7251", "type": "PA", "arg1_id": "7249", "arg2_id": "7250", "normalized": [] }, { "id": "7254", "type": "PA", "arg1_id": "7252", "arg2_id": "7253", "normalized": [] } ]

[ { "id": "7257", "type": "title", "text": [ "Multiple regulatory inputs converge on cortactin to control invadopodia biogenesis and extracellular matrix degradation." ], "offsets": [ [ 0, 120 ] ] }, { "id": "7258", "type": "abstract", "text": [ "Invadopodia are proteolytically active protrusions formed by invasive tumoral cells when grown on an extracellular matrix (ECM) substratum. Although many molecular components have been defined, less is known of the formation and regulation of invadopodia. The multidomain protein cortactin, which is involved in the regulation of actin polymerisation, is one such component, but how cortactin is modulated to control the formation of invadopodia has not been elucidated. Here, a new invadopodia synchronization protocol is used to show that the cortactin N-terminal acidic and SH3 domains, involved in Arp2/3 complex and N-WASP binding and activation, respectively, are both required for invadopodia biogenesis. In addition, through a combination of RNA interference and a wide array of cortactin phosphorylation mutants, we were able to show that three convergent regulatory inputs based on the regulation of cortactin phosphorylation by Src-family kinases, Erk1/Erk2 and PAK are necessary for invadopodia formation and extracellular matrix degradation. These findings suggest that cortactin is a scaffold protein bringing together the different components necessary for the formation of the invadopodia, and that a fine balance between different phosphorylation events induces subtle changes in structure to calibrate cortactin function." ], "offsets": [ [ 121, 1460 ] ] } ]

[ { "id": "7259", "type": "Genes & Molecular Sequences", "text": [ "cortactin" ], "offsets": [ [ 39, 48 ] ], "normalized": [] }, { "id": "7260", "type": "Chemicals & Drugs", "text": [ "ECM" ], "offsets": [ [ 244, 247 ] ], "normalized": [] }, { "id": "7261", "type": "Genes & Molecular Sequences", "text": [ "ECM" ], "offsets": [ [ 244, 247 ] ], "normalized": [] }, { "id": "7262", "type": "Genes & Molecular Sequences", "text": [ "cortactin" ], "offsets": [ [ 401, 410 ] ], "normalized": [] }, { "id": "7263", "type": "Genes & Molecular Sequences", "text": [ "actin" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "7264", "type": "Genes & Molecular Sequences", "text": [ "cortactin" ], "offsets": [ [ 504, 513 ] ], "normalized": [] }, { "id": "7265", "type": "Genes & Molecular Sequences", "text": [ "cortactin N-terminal acidic" ], "offsets": [ [ 666, 693 ] ], "normalized": [] }, { "id": "7266", "type": "Genes & Molecular Sequences", "text": [ "SH3 domains" ], "offsets": [ [ 698, 709 ] ], "normalized": [] }, { "id": "7267", "type": "Genes & Molecular Sequences", "text": [ "Arp2/3" ], "offsets": [ [ 723, 729 ] ], "normalized": [] }, { "id": "7268", "type": "Genes & Molecular Sequences", "text": [ "N-WASP" ], "offsets": [ [ 742, 748 ] ], "normalized": [] }, { "id": "7269", "type": "SNP & Sequence variations", "text": [ "cortactin phosphorylation mutants" ], "offsets": [ [ 908, 941 ] ], "normalized": [] }, { "id": "7270", "type": "Genes & Molecular Sequences", "text": [ "cortactin phosphorylation mutants" ], "offsets": [ [ 908, 941 ] ], "normalized": [] }, { "id": "7271", "type": "Genes & Molecular Sequences", "text": [ "cortactin" ], "offsets": [ [ 1031, 1040 ] ], "normalized": [] }, { "id": "7272", "type": "Genes & Molecular Sequences", "text": [ "Src-family kinases" ], "offsets": [ [ 1060, 1078 ] ], "normalized": [] }, { "id": "7273", "type": "Genes & Molecular Sequences", "text": [ "Erk1" ], "offsets": [ [ 1080, 1084 ] ], "normalized": [] }, { "id": "7274", "type": "Genes & Molecular Sequences", "text": [ "Erk2" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "7275", "type": "Genes & Molecular Sequences", "text": [ "PAK" ], "offsets": [ [ 1094, 1097 ] ], "normalized": [] }, { "id": "7276", "type": "Genes & Molecular Sequences", "text": [ "cortactin" ], "offsets": [ [ 1204, 1213 ] ], "normalized": [] }, { "id": "7277", "type": "Genes & Molecular Sequences", "text": [ "cortactin" ], "offsets": [ [ 1441, 1450 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "7280", "type": "title", "text": [ "CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells." ], "offsets": [ [ 0, 157 ] ] }, { "id": "7281", "type": "abstract", "text": [ "Chronic myelogenous leukemia (CML) is driven by constitutively activated Bcr-Abl tyrosine kinase, which causes the defective adhesion of CML cells to bone marrow stroma. The overexpression of p210Bcr-Abl was reported to down-regulate CXCR4 expression, and this is associated with the cell migration defects in CML. We proposed that tyrosine kinase inhibitors, imatinib or INNO-406, may restore CXCR4 expression and cause the migration of CML cells to bone marrow microenvironment niches, which in turn results in acquisition of stroma-mediated chemoresistance of CML progenitor cells. In KBM5 and K562 cells, imatinib, INNO-406, or IFN-alpha increased CXCR4 expression and migration. This increase in CXCR4 levels on CML progenitor cells was likewise found in samples from CML patients treated with imatinib or IFN-alpha. Imatinib induced G0-G1 cell cycle block in CML cells, which was further enhanced in a mesenchymal stem cell (MSC) coculture system. MSC coculture protected KBM-5 cells from imatinib-induced cell death. These antiapoptotic effects were abrogated by the CXCR4 antagonist AMD3465 or by inhibitor of integrin-linked kinase QLT0267. Altogether, these findings suggest that the up-regulation of CXCR4 by imatinib promotes migration of CML cells to bone marrow stroma, causing the G0-G1 cell cycle arrest and hence ensuring the survival of quiescent CML progenitor cells." ], "offsets": [ [ 158, 1544 ] ] } ]

[ { "id": "7282", "type": "Genes & Molecular Sequences", "text": [ "CXCR4" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "7283", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 23, 31 ] ], "normalized": [] }, { "id": "7284", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 70, 73 ] ], "normalized": [] }, { "id": "7285", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 147, 150 ] ], "normalized": [] }, { "id": "7286", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 188, 191 ] ], "normalized": [] }, { "id": "7287", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl tyrosine kinase" ], "offsets": [ [ 231, 254 ] ], "normalized": [] }, { "id": "7288", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 295, 298 ] ], "normalized": [] }, { "id": "7289", "type": "Genes & Molecular Sequences", "text": [ "p210Bcr-Abl" ], "offsets": [ [ 350, 361 ] ], "normalized": [] }, { "id": "7290", "type": "Genes & Molecular Sequences", "text": [ "CXCR4" ], "offsets": [ [ 392, 397 ] ], "normalized": [] }, { "id": "7291", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 468, 471 ] ], "normalized": [] }, { "id": "7292", "type": "Chemicals & Drugs", "text": [ "tyrosine kinase inhibitors" ], "offsets": [ [ 490, 516 ] ], "normalized": [] }, { "id": "7293", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 518, 526 ] ], "normalized": [] }, { "id": "7294", "type": "Chemicals & Drugs", "text": [ "INNO-406" ], "offsets": [ [ 530, 538 ] ], "normalized": [] }, { "id": "7295", "type": "Genes & Molecular Sequences", "text": [ "CXCR4" ], "offsets": [ [ 552, 557 ] ], "normalized": [] }, { "id": "7296", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "7297", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 721, 724 ] ], "normalized": [] }, { "id": "7298", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 767, 775 ] ], "normalized": [] }, { "id": "7299", "type": "Chemicals & Drugs", "text": [ "INNO-406" ], "offsets": [ [ 777, 785 ] ], "normalized": [] }, { "id": "7300", "type": "Chemicals & Drugs", "text": [ "IFN-alpha" ], "offsets": [ [ 790, 799 ] ], "normalized": [] }, { "id": "7301", "type": "Genes & Molecular Sequences", "text": [ "CXCR4" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "7302", "type": "Genes & Molecular Sequences", "text": [ "CXCR4" ], "offsets": [ [ 859, 864 ] ], "normalized": [] }, { "id": "7303", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 875, 878 ] ], "normalized": [] }, { "id": "7304", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 931, 934 ] ], "normalized": [] }, { "id": "7305", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 957, 965 ] ], "normalized": [] }, { "id": "7306", "type": "Chemicals & Drugs", "text": [ "IFN-alpha" ], "offsets": [ [ 969, 978 ] ], "normalized": [] }, { "id": "7307", "type": "Chemicals & Drugs", "text": [ "Imatinib" ], "offsets": [ [ 980, 988 ] ], "normalized": [] }, { "id": "7308", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 1023, 1026 ] ], "normalized": [] }, { "id": "7309", "type": "Genes & Molecular Sequences", "text": [ "MSC" ], "offsets": [ [ 1089, 1092 ] ], "normalized": [] }, { "id": "7310", "type": "Genes & Molecular Sequences", "text": [ "MSC" ], "offsets": [ [ 1112, 1115 ] ], "normalized": [] }, { "id": "7311", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 1153, 1161 ] ], "normalized": [] }, { "id": "7312", "type": "Chemicals & Drugs", "text": [ "CXCR4 antagonist" ], "offsets": [ [ 1232, 1248 ] ], "normalized": [] }, { "id": "7313", "type": "Genes & Molecular Sequences", "text": [ "CXCR4 antagonist" ], "offsets": [ [ 1232, 1248 ] ], "normalized": [] }, { "id": "7314", "type": "Chemicals & Drugs", "text": [ "AMD3465" ], "offsets": [ [ 1249, 1256 ] ], "normalized": [] }, { "id": "7315", "type": "Chemicals & Drugs", "text": [ "inhibitor of integrin-linked kinase" ], "offsets": [ [ 1263, 1298 ] ], "normalized": [] }, { "id": "7316", "type": "Genes & Molecular Sequences", "text": [ "inhibitor of integrin-linked kinase" ], "offsets": [ [ 1263, 1298 ] ], "normalized": [] }, { "id": "7317", "type": "Chemicals & Drugs", "text": [ "QLT0267" ], "offsets": [ [ 1299, 1306 ] ], "normalized": [] }, { "id": "7318", "type": "Genes & Molecular Sequences", "text": [ "CXCR4" ], "offsets": [ [ 1369, 1374 ] ], "normalized": [] }, { "id": "7319", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "7320", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 1409, 1412 ] ], "normalized": [] }, { "id": "7321", "type": "Genes & Molecular Sequences", "text": [ "CML" ], "offsets": [ [ 1523, 1526 ] ], "normalized": [] }, { "id": "7322", "type": "", "text": [ "imatinib" ], "offsets": [ [ 23, 31 ] ], "normalized": [] }, { "id": "7323", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "7325", "type": "", "text": [ "imatinib" ], "offsets": [ [ 518, 526 ] ], "normalized": [] }, { "id": "7326", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 552, 557 ] ], "normalized": [] }, { "id": "7328", "type": "", "text": [ "tyrosine kinase inhibitors" ], "offsets": [ [ 490, 516 ] ], "normalized": [] }, { "id": "7329", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 552, 557 ] ], "normalized": [] }, { "id": "7331", "type": "", "text": [ "INNO-406" ], "offsets": [ [ 530, 538 ] ], "normalized": [] }, { "id": "7332", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 552, 557 ] ], "normalized": [] }, { "id": "7334", "type": "", "text": [ "imatinib" ], "offsets": [ [ 767, 775 ] ], "normalized": [] }, { "id": "7335", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "7337", "type": "", "text": [ "INNO-406" ], "offsets": [ [ 777, 785 ] ], "normalized": [] }, { "id": "7338", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "7340", "type": "", "text": [ "IFN-alpha" ], "offsets": [ [ 790, 799 ] ], "normalized": [] }, { "id": "7341", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "7343", "type": "", "text": [ "imatinib" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "7344", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 1369, 1374 ] ], "normalized": [] }, { "id": "7346", "type": "", "text": [ "imatinib" ], "offsets": [ [ 23, 31 ] ], "normalized": [] }, { "id": "7347", "type": "", "text": [ "CML" ], "offsets": [ [ 147, 150 ] ], "normalized": [] }, { "id": "7349", "type": "", "text": [ "imatinib" ], "offsets": [ [ 518, 526 ] ], "normalized": [] }, { "id": "7350", "type": "", "text": [ "CML" ], "offsets": [ [ 721, 724 ] ], "normalized": [] }, { "id": "7352", "type": "", "text": [ "imatinib" ], "offsets": [ [ 957, 965 ] ], "normalized": [] }, { "id": "7353", "type": "", "text": [ "CML" ], "offsets": [ [ 931, 934 ] ], "normalized": [] }, { "id": "7355", "type": "", "text": [ "imatinib" ], "offsets": [ [ 957, 965 ] ], "normalized": [] }, { "id": "7356", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 859, 864 ] ], "normalized": [] }, { "id": "7358", "type": "", "text": [ "Imatinib" ], "offsets": [ [ 980, 988 ] ], "normalized": [] }, { "id": "7359", "type": "", "text": [ "CML" ], "offsets": [ [ 1023, 1026 ] ], "normalized": [] }, { "id": "7361", "type": "", "text": [ "Imatinib" ], "offsets": [ [ 980, 988 ] ], "normalized": [] }, { "id": "7362", "type": "", "text": [ "MSC" ], "offsets": [ [ 1089, 1092 ] ], "normalized": [] }, { "id": "7364", "type": "", "text": [ "imatinib" ], "offsets": [ [ 1153, 1161 ] ], "normalized": [] }, { "id": "7365", "type": "", "text": [ "MSC" ], "offsets": [ [ 1112, 1115 ] ], "normalized": [] }, { "id": "7367", "type": "", "text": [ "imatinib" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "7368", "type": "", "text": [ "CML" ], "offsets": [ [ 1523, 1526 ] ], "normalized": [] }, { "id": "7370", "type": "", "text": [ "IFN-alpha" ], "offsets": [ [ 969, 978 ] ], "normalized": [] }, { "id": "7371", "type": "", "text": [ "CXCR4" ], "offsets": [ [ 859, 864 ] ], "normalized": [] }, { "id": "7373", "type": "", "text": [ "AMD3465" ], "offsets": [ [ 1249, 1256 ] ], "normalized": [] }, { "id": "7374", "type": "", "text": [ "CXCR4 antagonist" ], "offsets": [ [ 1232, 1248 ] ], "normalized": [] }, { "id": "7376", "type": "", "text": [ "AMD3465" ], "offsets": [ [ 1249, 1256 ] ], "normalized": [] }, { "id": "7377", "type": "", "text": [ "inhibitor of integrin-linked kinase" ], "offsets": [ [ 1263, 1298 ] ], "normalized": [] }, { "id": "7379", "type": "", "text": [ "QLT0267" ], "offsets": [ [ 1299, 1306 ] ], "normalized": [] }, { "id": "7380", "type": "", "text": [ "CXCR4 antagonist" ], "offsets": [ [ 1232, 1248 ] ], "normalized": [] }, { "id": "7382", "type": "", "text": [ "QLT0267" ], "offsets": [ [ 1299, 1306 ] ], "normalized": [] }, { "id": "7383", "type": "", "text": [ "inhibitor of integrin-linked kinase" ], "offsets": [ [ 1263, 1298 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7324", "type": "PA", "arg1_id": "7322", "arg2_id": "7323", "normalized": [] }, { "id": "7327", "type": "SA", "arg1_id": "7325", "arg2_id": "7326", "normalized": [] }, { "id": "7330", "type": "SA", "arg1_id": "7328", "arg2_id": "7329", "normalized": [] }, { "id": "7333", "type": "SA", "arg1_id": "7331", "arg2_id": "7332", "normalized": [] }, { "id": "7336", "type": "PA", "arg1_id": "7334", "arg2_id": "7335", "normalized": [] }, { "id": "7339", "type": "PA", "arg1_id": "7337", "arg2_id": "7338", "normalized": [] }, { "id": "7342", "type": "PA", "arg1_id": "7340", "arg2_id": "7341", "normalized": [] }, { "id": "7345", "type": "PA", "arg1_id": "7343", "arg2_id": "7344", "normalized": [] }, { "id": "7348", "type": "PA", "arg1_id": "7346", "arg2_id": "7347", "normalized": [] }, { "id": "7351", "type": "PA", "arg1_id": "7349", "arg2_id": "7350", "normalized": [] }, { "id": "7354", "type": "PA", "arg1_id": "7352", "arg2_id": "7353", "normalized": [] }, { "id": "7357", "type": "PA", "arg1_id": "7355", "arg2_id": "7356", "normalized": [] }, { "id": "7360", "type": "PA", "arg1_id": "7358", "arg2_id": "7359", "normalized": [] }, { "id": "7363", "type": "PA", "arg1_id": "7361", "arg2_id": "7362", "normalized": [] }, { "id": "7366", "type": "PA", "arg1_id": "7364", "arg2_id": "7365", "normalized": [] }, { "id": "7369", "type": "PA", "arg1_id": "7367", "arg2_id": "7368", "normalized": [] }, { "id": "7372", "type": "PA", "arg1_id": "7370", "arg2_id": "7371", "normalized": [] }, { "id": "7375", "type": "PA", "arg1_id": "7373", "arg2_id": "7374", "normalized": [] }, { "id": "7378", "type": "NA", "arg1_id": "7376", "arg2_id": "7377", "normalized": [] }, { "id": "7381", "type": "NA", "arg1_id": "7379", "arg2_id": "7380", "normalized": [] }, { "id": "7384", "type": "PA", "arg1_id": "7382", "arg2_id": "7383", "normalized": [] } ]

[ { "id": "7387", "type": "title", "text": [ "Differential effects of selective cyclooxygenase-2 inhibitors in inhibiting proliferation and induction of apoptosis in oral squamous cell carcinoma." ], "offsets": [ [ 0, 149 ] ] }, { "id": "7388", "type": "abstract", "text": [ "Cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, is made inducible by various stimuli such as inflammation. Although COX-2 is commonly overexpressed in a variety of premalignant and malignant conditions including oral leukoplakia and squamous cell carcinoma, relatively little research has compared the effects of various COX-2 inhibitors (celecoxib, NS-398, nimesulide and meloxicam). Therefore, we investigated the effects of four different selective COX-2 inhibitors on the growth of KB cells, derived from oral squamous cell carcinoma (OSCC) and its mechanisms. Celecoxib and NS-398 strongly suppressed the proliferation of KB cells at 10-100 microM, whereas nimesulide and meloxicam are less potent proliferation inhibitors. Only celecoxib induced apoptosis of the KB cells, as detected on the basis of DNA fragmentation, caspase-3/7 activation and cleaved poly(ADP-ribose) polymerase (PARP) fragmentation. All four COX-2 inhibitors increased COX-2 protein expression but suppressed prostaglandin (PG) E2 production in the KB cells, suggesting that the pro-apoptotic effect of celecoxib was unrelated to the inhibition of COX-2. Mechanistically, a high level of p53 protein and a low level of multidrug-resistant protein 1 (MRP1) and breast cancer resistant protein (BCRP) mRNA in KB cells with celecoxib may explain the differential effect of these selective COX-2 inhibitors in KB cells. Taken together, celecoxib is a good therapeutic candidate for treating OSCC through the suppression of cell proliferation and the induction of apoptosis in a COX-2 independent manner." ], "offsets": [ [ 150, 1763 ] ] } ]

[ { "id": "7389", "type": "Genes & Molecular Sequences", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 34, 50 ] ], "normalized": [] }, { "id": "7390", "type": "Diseases & Disorders", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 120, 148 ] ], "normalized": [] }, { "id": "7391", "type": "Genes & Molecular Sequences", "text": [ "Cyclooxygenase-2" ], "offsets": [ [ 150, 166 ] ], "normalized": [] }, { "id": "7392", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 168, 173 ] ], "normalized": [] }, { "id": "7393", "type": "Genes & Molecular Sequences", "text": [ "prostaglandins" ], "offsets": [ [ 218, 232 ] ], "normalized": [] }, { "id": "7394", "type": "Diseases & Disorders", "text": [ "inflammation" ], "offsets": [ [ 279, 291 ] ], "normalized": [] }, { "id": "7395", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 302, 307 ] ], "normalized": [] }, { "id": "7396", "type": "Diseases & Disorders", "text": [ "oral leukoplakia" ], "offsets": [ [ 398, 414 ] ], "normalized": [] }, { "id": "7397", "type": "Diseases & Disorders", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 419, 442 ] ], "normalized": [] }, { "id": "7398", "type": "Diseases & Disorders", "text": [ "little" ], "offsets": [ [ 455, 461 ] ], "normalized": [] }, { "id": "7399", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 507, 512 ] ], "normalized": [] }, { "id": "7400", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 638, 643 ] ], "normalized": [] }, { "id": "7401", "type": "Diseases & Disorders", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 695, 723 ] ], "normalized": [] }, { "id": "7402", "type": "Diseases & Disorders", "text": [ "OSCC" ], "offsets": [ [ 725, 729 ] ], "normalized": [] }, { "id": "7403", "type": "Diseases & Disorders", "text": [ "fragmentation" ], "offsets": [ [ 997, 1010 ] ], "normalized": [] }, { "id": "7404", "type": "Genes & Molecular Sequences", "text": [ "caspase-3/7" ], "offsets": [ [ 1012, 1023 ] ], "normalized": [] }, { "id": "7405", "type": "Genes & Molecular Sequences", "text": [ "poly(ADP-ribose) polymerase" ], "offsets": [ [ 1047, 1074 ] ], "normalized": [] }, { "id": "7406", "type": "Genes & Molecular Sequences", "text": [ "PARP" ], "offsets": [ [ 1076, 1080 ] ], "normalized": [] }, { "id": "7407", "type": "Diseases & Disorders", "text": [ "fragmentation" ], "offsets": [ [ 1082, 1095 ] ], "normalized": [] }, { "id": "7408", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 1106, 1111 ] ], "normalized": [] }, { "id": "7409", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 1133, 1138 ] ], "normalized": [] }, { "id": "7410", "type": "Genes & Molecular Sequences", "text": [ "prostaglandin" ], "offsets": [ [ 1173, 1186 ] ], "normalized": [] }, { "id": "7411", "type": "Genes & Molecular Sequences", "text": [ "PG) E2" ], "offsets": [ [ 1188, 1194 ] ], "normalized": [] }, { "id": "7412", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 1312, 1317 ] ], "normalized": [] }, { "id": "7413", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 1352, 1355 ] ], "normalized": [] }, { "id": "7414", "type": "Genes & Molecular Sequences", "text": [ "multidrug-resistant protein 1" ], "offsets": [ [ 1383, 1412 ] ], "normalized": [] }, { "id": "7415", "type": "Genes & Molecular Sequences", "text": [ "MRP1" ], "offsets": [ [ 1414, 1418 ] ], "normalized": [] }, { "id": "7416", "type": "Genes & Molecular Sequences", "text": [ "breast cancer resistant protein " ], "offsets": [ [ 1424, 1456 ] ], "normalized": [] }, { "id": "7417", "type": "Diseases & Disorders", "text": [ "breast cancer resistant protein " ], "offsets": [ [ 1424, 1456 ] ], "normalized": [] }, { "id": "7418", "type": "Genes & Molecular Sequences", "text": [ "BCRP" ], "offsets": [ [ 1457, 1461 ] ], "normalized": [] }, { "id": "7419", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 1550, 1555 ] ], "normalized": [] }, { "id": "7420", "type": "Diseases & Disorders", "text": [ "OSCC" ], "offsets": [ [ 1651, 1655 ] ], "normalized": [] }, { "id": "7421", "type": "Diseases & Disorders", "text": [ "suppression" ], "offsets": [ [ 1668, 1679 ] ], "normalized": [] }, { "id": "7422", "type": "Genes & Molecular Sequences", "text": [ "COX-2" ], "offsets": [ [ 1738, 1743 ] ], "normalized": [] }, { "id": "7423", "type": "", "text": [ "COX-2" ], "offsets": [ [ 168, 173 ] ], "normalized": [] }, { "id": "7424", "type": "", "text": [ "inflammation" ], "offsets": [ [ 279, 291 ] ], "normalized": [] }, { "id": "7426", "type": "", "text": [ "COX-2" ], "offsets": [ [ 507, 512 ] ], "normalized": [] }, { "id": "7427", "type": "", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 419, 442 ] ], "normalized": [] }, { "id": "7429", "type": "", "text": [ "COX-2" ], "offsets": [ [ 507, 512 ] ], "normalized": [] }, { "id": "7430", "type": "", "text": [ "oral leukoplakia" ], "offsets": [ [ 398, 414 ] ], "normalized": [] }, { "id": "7432", "type": "", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 34, 50 ] ], "normalized": [] }, { "id": "7433", "type": "", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 120, 148 ] ], "normalized": [] }, { "id": "7435", "type": "", "text": [ "COX-2" ], "offsets": [ [ 507, 512 ] ], "normalized": [] }, { "id": "7436", "type": "", "text": [ "little" ], "offsets": [ [ 455, 461 ] ], "normalized": [] }, { "id": "7438", "type": "", "text": [ "COX-2" ], "offsets": [ [ 638, 643 ] ], "normalized": [] }, { "id": "7439", "type": "", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 695, 723 ] ], "normalized": [] }, { "id": "7441", "type": "", "text": [ "PARP" ], "offsets": [ [ 1076, 1080 ] ], "normalized": [] }, { "id": "7442", "type": "", "text": [ "fragmentation" ], "offsets": [ [ 1082, 1095 ] ], "normalized": [] }, { "id": "7444", "type": "", "text": [ "caspase-3/7" ], "offsets": [ [ 1012, 1023 ] ], "normalized": [] }, { "id": "7445", "type": "", "text": [ "fragmentation" ], "offsets": [ [ 1082, 1095 ] ], "normalized": [] }, { "id": "7447", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1550, 1555 ] ], "normalized": [] }, { "id": "7448", "type": "", "text": [ "breast cancer resistant protein " ], "offsets": [ [ 1424, 1456 ] ], "normalized": [] }, { "id": "7450", "type": "", "text": [ "BCRP" ], "offsets": [ [ 1457, 1461 ] ], "normalized": [] }, { "id": "7451", "type": "", "text": [ "breast cancer resistant protein " ], "offsets": [ [ 1424, 1456 ] ], "normalized": [] }, { "id": "7453", "type": "", "text": [ "p53" ], "offsets": [ [ 1352, 1355 ] ], "normalized": [] }, { "id": "7454", "type": "", "text": [ "breast cancer resistant protein " ], "offsets": [ [ 1424, 1456 ] ], "normalized": [] }, { "id": "7456", "type": "", "text": [ "MRP1" ], "offsets": [ [ 1414, 1418 ] ], "normalized": [] }, { "id": "7457", "type": "", "text": [ "breast cancer resistant protein " ], "offsets": [ [ 1424, 1456 ] ], "normalized": [] }, { "id": "7459", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1738, 1743 ] ], "normalized": [] }, { "id": "7460", "type": "", "text": [ "suppression" ], "offsets": [ [ 1668, 1679 ] ], "normalized": [] }, { "id": "7462", "type": "", "text": [ "COX-2" ], "offsets": [ [ 638, 643 ] ], "normalized": [] }, { "id": "7463", "type": "", "text": [ "OSCC" ], "offsets": [ [ 725, 729 ] ], "normalized": [] }, { "id": "7465", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1738, 1743 ] ], "normalized": [] }, { "id": "7466", "type": "", "text": [ "OSCC" ], "offsets": [ [ 1651, 1655 ] ], "normalized": [] }, { "id": "7468", "type": "", "text": [ "COX-2" ], "offsets": [ [ 1738, 1743 ] ], "normalized": [] }, { "id": "7469", "type": "", "text": [ "OSCC" ], "offsets": [ [ 1651, 1655 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7425", "type": "PA", "arg1_id": "7423", "arg2_id": "7424", "normalized": [] }, { "id": "7428", "type": "PA", "arg1_id": "7426", "arg2_id": "7427", "normalized": [] }, { "id": "7431", "type": "PA", "arg1_id": "7429", "arg2_id": "7430", "normalized": [] }, { "id": "7434", "type": "PA", "arg1_id": "7432", "arg2_id": "7433", "normalized": [] }, { "id": "7437", "type": "PA", "arg1_id": "7435", "arg2_id": "7436", "normalized": [] }, { "id": "7440", "type": "PA", "arg1_id": "7438", "arg2_id": "7439", "normalized": [] }, { "id": "7443", "type": "PA", "arg1_id": "7441", "arg2_id": "7442", "normalized": [] }, { "id": "7446", "type": "PA", "arg1_id": "7444", "arg2_id": "7445", "normalized": [] }, { "id": "7449", "type": "PA", "arg1_id": "7447", "arg2_id": "7448", "normalized": [] }, { "id": "7452", "type": "PA", "arg1_id": "7450", "arg2_id": "7451", "normalized": [] }, { "id": "7455", "type": "PA", "arg1_id": "7453", "arg2_id": "7454", "normalized": [] }, { "id": "7458", "type": "PA", "arg1_id": "7456", "arg2_id": "7457", "normalized": [] }, { "id": "7461", "type": "PA", "arg1_id": "7459", "arg2_id": "7460", "normalized": [] }, { "id": "7464", "type": "PA", "arg1_id": "7462", "arg2_id": "7463", "normalized": [] }, { "id": "7467", "type": "PA", "arg1_id": "7465", "arg2_id": "7466", "normalized": [] }, { "id": "7470", "type": "NA", "arg1_id": "7468", "arg2_id": "7469", "normalized": [] } ]

[ { "id": "7473", "type": "title", "text": [ "Rotational thrombelastometry for the bedside monitoring of recombinant hirudin." ], "offsets": [ [ 0, 79 ] ] }, { "id": "7474", "type": "abstract", "text": [ "BACKGROUND: Recombinant hirudin is used as an alternative anticoagulant, particularly in patients with heparin-induced thrombocytopenia type II. However, bedside monitoring for hirudin is not available. The present study aims to evaluate rotational thrombelastometry regarding its suitability to detect the effects of recombinant hirudin on whole blood coagulation. Hirudin was added to whole blood samples from healthy donors (n=5) and thrombelastometry variables resulting from activation of samples with tissue factor, ellagic acid, and ecarin were determined. METHODS: Hirudin (0.1-10 microg/ml) was added to citrated blood. Thereafter, rotational thrombelastometry was performed by initiating coagulation via recalcification and addition of tissue factor, ellagic acid, and ecarin, respectively, using the commercially available assays. RESULTS: In the absence of hirudin, clotting times (CT) induced by ellagic acid, tissue factor, and ecarin, respectively, were 141.7+/-18.0, 54.0+/-7.6, and 64.5+/-4.1 s. Increasing concentrations of hirudin led to dose-dependent prolongation of the clotting time with the three activators. All assays were capable to detect hirudin concentrations in the range of 0.5-5 microg/ml. At a final hirudin concentration of 1 microg/ml, clotting time increased to 268.0+/-25.1, 84.0+/-9.3, and 107.5+/-9.9 s, respectively, with the above-mentioned activators. The other thrombelastographic variables, including clot formation time, angle alpha, and maximum clot firmness, were not altered by hirudin at concentrations up to 5 microg/ml. CONCLUSIONS: Our study demonstrates the suitability of rotational thrombelastometry to detect anticoagulant effects of recombinant hirudin." ], "offsets": [ [ 80, 1791 ] ] } ]

[ { "id": "7475", "type": "Chemicals & Drugs", "text": [ "recombinant hirudin" ], "offsets": [ [ 59, 78 ] ], "normalized": [] }, { "id": "7476", "type": "Chemicals & Drugs", "text": [ "Recombinant hirudin" ], "offsets": [ [ 92, 111 ] ], "normalized": [] }, { "id": "7477", "type": "Chemicals & Drugs", "text": [ "anticoagulant" ], "offsets": [ [ 138, 151 ] ], "normalized": [] }, { "id": "7478", "type": "Diseases & Disorders", "text": [ "heparin-induced thrombocytopenia type II" ], "offsets": [ [ 183, 223 ] ], "normalized": [] }, { "id": "7479", "type": "Chemicals & Drugs", "text": [ "hirudin" ], "offsets": [ [ 257, 264 ] ], "normalized": [] }, { "id": "7480", "type": "Chemicals & Drugs", "text": [ "recombinant hirudin" ], "offsets": [ [ 398, 417 ] ], "normalized": [] }, { "id": "7481", "type": "Chemicals & Drugs", "text": [ "Hirudin" ], "offsets": [ [ 446, 453 ] ], "normalized": [] }, { "id": "7482", "type": "Chemicals & Drugs", "text": [ "tissue factor" ], "offsets": [ [ 587, 600 ] ], "normalized": [] }, { "id": "7483", "type": "Chemicals & Drugs", "text": [ "ellagic acid" ], "offsets": [ [ 602, 614 ] ], "normalized": [] }, { "id": "7484", "type": "Chemicals & Drugs", "text": [ "ecarin" ], "offsets": [ [ 620, 626 ] ], "normalized": [] }, { "id": "7485", "type": "Chemicals & Drugs", "text": [ "Hirudin" ], "offsets": [ [ 653, 660 ] ], "normalized": [] }, { "id": "7486", "type": "Chemicals & Drugs", "text": [ "tissue factor" ], "offsets": [ [ 826, 839 ] ], "normalized": [] }, { "id": "7487", "type": "Chemicals & Drugs", "text": [ "ellagic acid" ], "offsets": [ [ 841, 853 ] ], "normalized": [] }, { "id": "7488", "type": "Chemicals & Drugs", "text": [ "ecarin" ], "offsets": [ [ 859, 865 ] ], "normalized": [] }, { "id": "7489", "type": "Diseases & Disorders", "text": [ "absence" ], "offsets": [ [ 938, 945 ] ], "normalized": [] }, { "id": "7490", "type": "Chemicals & Drugs", "text": [ "hirudin" ], "offsets": [ [ 949, 956 ] ], "normalized": [] }, { "id": "7491", "type": "Diseases & Disorders", "text": [ "clotting" ], "offsets": [ [ 958, 966 ] ], "normalized": [] }, { "id": "7492", "type": "Chemicals & Drugs", "text": [ "CT" ], "offsets": [ [ 974, 976 ] ], "normalized": [] }, { "id": "7493", "type": "Chemicals & Drugs", "text": [ "ellagic acid" ], "offsets": [ [ 989, 1001 ] ], "normalized": [] }, { "id": "7494", "type": "Chemicals & Drugs", "text": [ "tissue factor" ], "offsets": [ [ 1003, 1016 ] ], "normalized": [] }, { "id": "7495", "type": "Chemicals & Drugs", "text": [ "ecarin" ], "offsets": [ [ 1022, 1028 ] ], "normalized": [] }, { "id": "7496", "type": "Chemicals & Drugs", "text": [ "hirudin" ], "offsets": [ [ 1122, 1129 ] ], "normalized": [] }, { "id": "7497", "type": "Diseases & Disorders", "text": [ "clotting" ], "offsets": [ [ 1172, 1180 ] ], "normalized": [] }, { "id": "7498", "type": "Chemicals & Drugs", "text": [ "hirudin" ], "offsets": [ [ 1247, 1254 ] ], "normalized": [] }, { "id": "7499", "type": "Chemicals & Drugs", "text": [ "hirudin" ], "offsets": [ [ 1314, 1321 ] ], "normalized": [] }, { "id": "7500", "type": "Diseases & Disorders", "text": [ "clot" ], "offsets": [ [ 1526, 1530 ] ], "normalized": [] }, { "id": "7501", "type": "Diseases & Disorders", "text": [ "clot" ], "offsets": [ [ 1572, 1576 ] ], "normalized": [] }, { "id": "7502", "type": "Chemicals & Drugs", "text": [ "hirudin" ], "offsets": [ [ 1607, 1614 ] ], "normalized": [] }, { "id": "7503", "type": "Chemicals & Drugs", "text": [ "anticoagulant" ], "offsets": [ [ 1746, 1759 ] ], "normalized": [] }, { "id": "7504", "type": "Chemicals & Drugs", "text": [ "recombinant hirudin" ], "offsets": [ [ 1771, 1790 ] ], "normalized": [] }, { "id": "7505", "type": "", "text": [ "anticoagulant" ], "offsets": [ [ 138, 151 ] ], "normalized": [] }, { "id": "7506", "type": "", "text": [ "heparin-induced thrombocytopenia type II" ], "offsets": [ [ 183, 223 ] ], "normalized": [] }, { "id": "7508", "type": "", "text": [ "Recombinant hirudin" ], "offsets": [ [ 92, 111 ] ], "normalized": [] }, { "id": "7509", "type": "", "text": [ "heparin-induced thrombocytopenia type II" ], "offsets": [ [ 183, 223 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7507", "type": "PA", "arg1_id": "7505", "arg2_id": "7506", "normalized": [] }, { "id": "7510", "type": "PA", "arg1_id": "7508", "arg2_id": "7509", "normalized": [] } ]

[ { "id": "7513", "type": "title", "text": [ "Cognitive performance in recreational ecstasy polydrug users: a two-year follow-up study." ], "offsets": [ [ 0, 89 ] ] }, { "id": "7514", "type": "abstract", "text": [ "There is important preclinical evidence of long lasting neurotoxic and selective effects of ecstasy MDMA on serotonin systems in non-human primates. In humans long-term recreational use of ecstasy has been mainly associated with learning and memory impairments. The aim of the present study was to investigate the neuropsychological profile associated with ecstasy use within recreational polydrug users, and describe the cognitive changes related to maintained or variable ecstasy use along a two years period. We administered cognitive measures of attention, executive functions, memory and learning to three groups of participants: 37 current polydrug users with regular consumption of ecstasy and cannabis, 23 current cannabis users and 34 non-users free of illicit drugs. Four cognitive assessments were conducted during two years. At baseline, ecstasy polydrug users showed significantly poorer performance than cannabis users and non-drug using controls in a measure of semantic word fluency. When ecstasy users were classified according to lifetime use of ecstasy, the more severe users (more than 100 tablets) showed additional deficits on episodic memory. After two years ecstasy users showed persistent deficits on verbal fluency, working memory and processing speed. These findings should be interpreted with caution, since the possibility of premorbid group differences cannot be entirely excluded. Our findings support that ecstasy use, or ecstasy/cannabis synergic effects, are responsible for the sub-clinical deficits observed in ecstasy polydrug users, and provides additional evidence for long-term cognitive impairment owing to ecstasy consumption in the context of polydrug use." ], "offsets": [ [ 90, 1789 ] ] } ]

[ { "id": "7515", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 38, 45 ] ], "normalized": [] }, { "id": "7516", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 182, 189 ] ], "normalized": [] }, { "id": "7517", "type": "Chemicals & Drugs", "text": [ "MDMA" ], "offsets": [ [ 190, 194 ] ], "normalized": [] }, { "id": "7518", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 279, 286 ] ], "normalized": [] }, { "id": "7519", "type": "Diseases & Disorders", "text": [ "learning" ], "offsets": [ [ 319, 327 ] ], "normalized": [] }, { "id": "7520", "type": "Diseases & Disorders", "text": [ "memory impairments" ], "offsets": [ [ 332, 350 ] ], "normalized": [] }, { "id": "7521", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 447, 454 ] ], "normalized": [] }, { "id": "7522", "type": "Diseases & Disorders", "text": [ "cognitive changes" ], "offsets": [ [ 512, 529 ] ], "normalized": [] }, { "id": "7523", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 564, 571 ] ], "normalized": [] }, { "id": "7524", "type": "Diseases & Disorders", "text": [ "learning" ], "offsets": [ [ 683, 691 ] ], "normalized": [] }, { "id": "7525", "type": "Diseases & Disorders", "text": [ "consumption" ], "offsets": [ [ 764, 775 ] ], "normalized": [] }, { "id": "7526", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 779, 786 ] ], "normalized": [] }, { "id": "7527", "type": "Chemicals & Drugs", "text": [ "cannabis" ], "offsets": [ [ 791, 799 ] ], "normalized": [] }, { "id": "7528", "type": "Diseases & Disorders", "text": [ "cannabis" ], "offsets": [ [ 791, 799 ] ], "normalized": [] }, { "id": "7529", "type": "Chemicals & Drugs", "text": [ "cannabis" ], "offsets": [ [ 812, 820 ] ], "normalized": [] }, { "id": "7530", "type": "Diseases & Disorders", "text": [ "cannabis" ], "offsets": [ [ 812, 820 ] ], "normalized": [] }, { "id": "7531", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 940, 947 ] ], "normalized": [] }, { "id": "7532", "type": "Chemicals & Drugs", "text": [ "cannabis" ], "offsets": [ [ 1008, 1016 ] ], "normalized": [] }, { "id": "7533", "type": "Diseases & Disorders", "text": [ "cannabis" ], "offsets": [ [ 1008, 1016 ] ], "normalized": [] }, { "id": "7534", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 1095, 1102 ] ], "normalized": [] }, { "id": "7535", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 1154, 1161 ] ], "normalized": [] }, { "id": "7536", "type": "Diseases & Disorders", "text": [ "deficits on episodic memory" ], "offsets": [ [ 1227, 1254 ] ], "normalized": [] }, { "id": "7537", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 1272, 1279 ] ], "normalized": [] }, { "id": "7538", "type": "Diseases & Disorders", "text": [ "deficits on verbal fluency" ], "offsets": [ [ 1304, 1330 ] ], "normalized": [] }, { "id": "7539", "type": "Diseases & Disorders", "text": [ "working memory" ], "offsets": [ [ 1332, 1346 ] ], "normalized": [] }, { "id": "7540", "type": "Diseases & Disorders", "text": [ "processing speed" ], "offsets": [ [ 1351, 1367 ] ], "normalized": [] }, { "id": "7541", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 1528, 1535 ] ], "normalized": [] }, { "id": "7542", "type": "Chemicals & Drugs", "text": [ "ecstasy/cannabis" ], "offsets": [ [ 1544, 1560 ] ], "normalized": [] }, { "id": "7543", "type": "Diseases & Disorders", "text": [ "ecstasy/cannabis" ], "offsets": [ [ 1544, 1560 ] ], "normalized": [] }, { "id": "7544", "type": "Diseases & Disorders", "text": [ "deficits" ], "offsets": [ [ 1616, 1624 ] ], "normalized": [] }, { "id": "7545", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 1637, 1644 ] ], "normalized": [] }, { "id": "7546", "type": "Diseases & Disorders", "text": [ "long-term cognitive impairment" ], "offsets": [ [ 1698, 1728 ] ], "normalized": [] }, { "id": "7547", "type": "Chemicals & Drugs", "text": [ "ecstasy" ], "offsets": [ [ 1738, 1745 ] ], "normalized": [] }, { "id": "7548", "type": "Diseases & Disorders", "text": [ "consumption" ], "offsets": [ [ 1746, 1757 ] ], "normalized": [] }, { "id": "7549", "type": "Diseases & Disorders", "text": [ "polydrug use" ], "offsets": [ [ 1776, 1788 ] ], "normalized": [] }, { "id": "7550", "type": "", "text": [ "ecstasy" ], "offsets": [ [ 279, 286 ] ], "normalized": [] }, { "id": "7551", "type": "", "text": [ "memory impairments" ], "offsets": [ [ 332, 350 ] ], "normalized": [] }, { "id": "7553", "type": "", "text": [ "ecstasy" ], "offsets": [ [ 279, 286 ] ], "normalized": [] }, { "id": "7554", "type": "", "text": [ "learning" ], "offsets": [ [ 319, 327 ] ], "normalized": [] }, { "id": "7556", "type": "", "text": [ "ecstasy" ], "offsets": [ [ 1154, 1161 ] ], "normalized": [] }, { "id": "7557", "type": "", "text": [ "deficits on episodic memory" ], "offsets": [ [ 1227, 1254 ] ], "normalized": [] }, { "id": "7559", "type": "", "text": [ "ecstasy" ], "offsets": [ [ 1272, 1279 ] ], "normalized": [] }, { "id": "7560", "type": "", "text": [ "deficits on verbal fluency" ], "offsets": [ [ 1304, 1330 ] ], "normalized": [] }, { "id": "7562", "type": "", "text": [ "ecstasy" ], "offsets": [ [ 1272, 1279 ] ], "normalized": [] }, { "id": "7563", "type": "", "text": [ "working memory" ], "offsets": [ [ 1332, 1346 ] ], "normalized": [] }, { "id": "7565", "type": "", "text": [ "ecstasy" ], "offsets": [ [ 1272, 1279 ] ], "normalized": [] }, { "id": "7566", "type": "", "text": [ "processing speed" ], "offsets": [ [ 1351, 1367 ] ], "normalized": [] }, { "id": "7568", "type": "", "text": [ "ecstasy" ], "offsets": [ [ 1738, 1745 ] ], "normalized": [] }, { "id": "7569", "type": "", "text": [ "long-term cognitive impairment" ], "offsets": [ [ 1698, 1728 ] ], "normalized": [] }, { "id": "7571", "type": "", "text": [ "ecstasy/cannabis" ], "offsets": [ [ 1544, 1560 ] ], "normalized": [] }, { "id": "7572", "type": "", "text": [ "long-term cognitive impairment" ], "offsets": [ [ 1698, 1728 ] ], "normalized": [] }, { "id": "7574", "type": "", "text": [ "ecstasy/cannabis" ], "offsets": [ [ 1544, 1560 ] ], "normalized": [] }, { "id": "7575", "type": "", "text": [ "deficits" ], "offsets": [ [ 1616, 1624 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7552", "type": "PA", "arg1_id": "7550", "arg2_id": "7551", "normalized": [] }, { "id": "7555", "type": "PA", "arg1_id": "7553", "arg2_id": "7554", "normalized": [] }, { "id": "7558", "type": "PA", "arg1_id": "7556", "arg2_id": "7557", "normalized": [] }, { "id": "7561", "type": "PA", "arg1_id": "7559", "arg2_id": "7560", "normalized": [] }, { "id": "7564", "type": "PA", "arg1_id": "7562", "arg2_id": "7563", "normalized": [] }, { "id": "7567", "type": "PA", "arg1_id": "7565", "arg2_id": "7566", "normalized": [] }, { "id": "7570", "type": "PA", "arg1_id": "7568", "arg2_id": "7569", "normalized": [] }, { "id": "7573", "type": "PA", "arg1_id": "7571", "arg2_id": "7572", "normalized": [] }, { "id": "7576", "type": "PA", "arg1_id": "7574", "arg2_id": "7575", "normalized": [] } ]

[ { "id": "7579", "type": "title", "text": [ "Dose-response relationships between occupational exposure to potash, diesel exhaust and nitrogen oxides and lung function: cross-sectional and longitudinal study in two salt mines." ], "offsets": [ [ 0, 180 ] ] }, { "id": "7580", "type": "abstract", "text": [ "OBJECTIVE: Several studies have shown that underground salt miners may have an increased incidence of chest symptoms and sometimes decreased lung function. Miners of two salt mines were investigated to evaluate relationships between the lung function and the workplace exposure. The effect of nitrogen monoxide (NO) and nitrogen dioxide (NO(2)) was investigated in view of the recent debate on European occupational exposure limits. METHODS: A total of 410/463 miners (mine A/mine B) were examined cross-sectional and 75/64% of the first cohort were examined after a 5-year period. Exposure was measured by personal sampling. Personal lifetime exposure doses of salt dust, diesel exhaust, NO(2) and NO were calculated for all miners. Dose-response relationships were calculated by multiple regression analysis. Each exposure component acted as an indicator for the complex exposure. RESULTS: Exposure response relationships were shown in the cross-sectional and longitudinal investigations in both mines. In the 5-year period, the adjusted (age, smoking, etc.) effect of the exposure indicators resulted in a mean decrease of FEV(1) between -18 ml/year (mine A) and -10 ml/year (mine B). The personal concentrations related to this effect were 12.6/7.1 mg/m(3) inhalable dust, 2.4/0.8 mg/m(3) respirable dust, 0.09/0.09 mg/m(3) diesel exhaust, 0.4/0.5 ppm NO(2) and 1.7/1.4 ppm NO (mine A/B). Exposure was related to symptoms of chronic bronchitis only in mine B. CONCLUSION: The effects found in both mines indicate that the mixed exposure can cause lung function disorders in salt miners exposed over a long time. Because of the high correlation of the concentrations it was not possible to determine the effects of a single exposure component separately or to recommend a specific occupational exposure limit. However, possible maximum effects associated with the mixed exposure can be evaluated in the ranges of concentrations of the individual substances in the mines." ], "offsets": [ [ 181, 2154 ] ] } ]

[ { "id": "7581", "type": "Chemicals & Drugs", "text": [ "potash" ], "offsets": [ [ 61, 67 ] ], "normalized": [] }, { "id": "7582", "type": "Chemicals & Drugs", "text": [ "diesel exhaust" ], "offsets": [ [ 69, 83 ] ], "normalized": [] }, { "id": "7583", "type": "Diseases & Disorders", "text": [ "diesel exhaust" ], "offsets": [ [ 69, 83 ] ], "normalized": [] }, { "id": "7584", "type": "Chemicals & Drugs", "text": [ "nitrogen oxides" ], "offsets": [ [ 88, 103 ] ], "normalized": [] }, { "id": "7585", "type": "Chemicals & Drugs", "text": [ "salt" ], "offsets": [ [ 169, 173 ] ], "normalized": [] }, { "id": "7586", "type": "Chemicals & Drugs", "text": [ "salt" ], "offsets": [ [ 236, 240 ] ], "normalized": [] }, { "id": "7587", "type": "Diseases & Disorders", "text": [ "chest symptoms" ], "offsets": [ [ 283, 297 ] ], "normalized": [] }, { "id": "7588", "type": "Diseases & Disorders", "text": [ "decreased lung function" ], "offsets": [ [ 312, 335 ] ], "normalized": [] }, { "id": "7589", "type": "Chemicals & Drugs", "text": [ "salt" ], "offsets": [ [ 351, 355 ] ], "normalized": [] }, { "id": "7590", "type": "Chemicals & Drugs", "text": [ "nitrogen monoxide" ], "offsets": [ [ 474, 491 ] ], "normalized": [] }, { "id": "7591", "type": "Chemicals & Drugs", "text": [ "NO" ], "offsets": [ [ 493, 495 ] ], "normalized": [] }, { "id": "7592", "type": "Chemicals & Drugs", "text": [ "nitrogen dioxide" ], "offsets": [ [ 501, 517 ] ], "normalized": [] }, { "id": "7593", "type": "Chemicals & Drugs", "text": [ "NO(2)" ], "offsets": [ [ 519, 524 ] ], "normalized": [] }, { "id": "7594", "type": "Chemicals & Drugs", "text": [ "salt dust" ], "offsets": [ [ 843, 852 ] ], "normalized": [] }, { "id": "7595", "type": "Chemicals & Drugs", "text": [ "diesel exhaust" ], "offsets": [ [ 854, 868 ] ], "normalized": [] }, { "id": "7596", "type": "Diseases & Disorders", "text": [ "diesel exhaust" ], "offsets": [ [ 854, 868 ] ], "normalized": [] }, { "id": "7597", "type": "Chemicals & Drugs", "text": [ "NO(2)" ], "offsets": [ [ 870, 875 ] ], "normalized": [] }, { "id": "7598", "type": "Chemicals & Drugs", "text": [ "NO" ], "offsets": [ [ 880, 882 ] ], "normalized": [] }, { "id": "7599", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 971, 981 ] ], "normalized": [] }, { "id": "7600", "type": "Chemicals & Drugs", "text": [ "inhalable dust" ], "offsets": [ [ 1442, 1456 ] ], "normalized": [] }, { "id": "7601", "type": "Diseases & Disorders", "text": [ "inhalable dust" ], "offsets": [ [ 1442, 1456 ] ], "normalized": [] }, { "id": "7602", "type": "Chemicals & Drugs", "text": [ "respirable dust" ], "offsets": [ [ 1474, 1489 ] ], "normalized": [] }, { "id": "7603", "type": "Chemicals & Drugs", "text": [ "diesel exhaust" ], "offsets": [ [ 1509, 1523 ] ], "normalized": [] }, { "id": "7604", "type": "Diseases & Disorders", "text": [ "diesel exhaust" ], "offsets": [ [ 1509, 1523 ] ], "normalized": [] }, { "id": "7605", "type": "Chemicals & Drugs", "text": [ "NO(2)" ], "offsets": [ [ 1537, 1542 ] ], "normalized": [] }, { "id": "7606", "type": "Chemicals & Drugs", "text": [ "NO" ], "offsets": [ [ 1559, 1561 ] ], "normalized": [] }, { "id": "7607", "type": "Diseases & Disorders", "text": [ "symptoms" ], "offsets": [ [ 1598, 1606 ] ], "normalized": [] }, { "id": "7608", "type": "Diseases & Disorders", "text": [ "chronic bronchitis" ], "offsets": [ [ 1610, 1628 ] ], "normalized": [] }, { "id": "7609", "type": "Diseases & Disorders", "text": [ "lung function disorders" ], "offsets": [ [ 1732, 1755 ] ], "normalized": [] }, { "id": "7610", "type": "Chemicals & Drugs", "text": [ "salt" ], "offsets": [ [ 1759, 1763 ] ], "normalized": [] }, { "id": "7611", "type": "", "text": [ "inhalable dust" ], "offsets": [ [ 1442, 1456 ] ], "normalized": [] }, { "id": "7612", "type": "", "text": [ "diesel exhaust" ], "offsets": [ [ 1509, 1523 ] ], "normalized": [] }, { "id": "7614", "type": "", "text": [ "NO" ], "offsets": [ [ 1559, 1561 ] ], "normalized": [] }, { "id": "7615", "type": "", "text": [ "inhalable dust" ], "offsets": [ [ 1442, 1456 ] ], "normalized": [] }, { "id": "7617", "type": "", "text": [ "diesel exhaust" ], "offsets": [ [ 1509, 1523 ] ], "normalized": [] }, { "id": "7618", "type": "", "text": [ "inhalable dust" ], "offsets": [ [ 1442, 1456 ] ], "normalized": [] }, { "id": "7620", "type": "", "text": [ "respirable dust" ], "offsets": [ [ 1474, 1489 ] ], "normalized": [] }, { "id": "7621", "type": "", "text": [ "inhalable dust" ], "offsets": [ [ 1442, 1456 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7613", "type": "PA", "arg1_id": "7611", "arg2_id": "7612", "normalized": [] }, { "id": "7616", "type": "PA", "arg1_id": "7614", "arg2_id": "7615", "normalized": [] }, { "id": "7619", "type": "PA", "arg1_id": "7617", "arg2_id": "7618", "normalized": [] }, { "id": "7622", "type": "PA", "arg1_id": "7620", "arg2_id": "7621", "normalized": [] } ]

[ { "id": "7625", "type": "title", "text": [ "Analysis of preincisional and postincisional treatment with alpha2-adrenoreceptor agonist clonidine regarding analgesic consumption and hemodynamic stability in surgical patients." ], "offsets": [ [ 0, 179 ] ] }, { "id": "7626", "type": "abstract", "text": [ "Preemptive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. The aim of the study was to assess the effect of preincisional clonidine treatment on analgesic consumption and hemodynamic stability compared to clonidine administered at the end of the operation and control group. Ninety-one patients undergoing elective colorectal surgery were randomly assigned to four groups: peroral clonidine before operation, epidural clonidine before operation, epidural clonidine at the end of operation, and epidural saline before operation as a control group. After the operation, patient-controlled analgesia with epidural morphine was instituted. Analgesic consumption, blood pressure and heart rate were obtained at 1, 2, 6 and 24 h postoperatively, and the cumulative consumption of analgesics was assessed at the end of the study period. Significant differences (p < 0.05) in postoperative systolic blood pressure, with highest hemodynamic stability was observed at 1 h and 6 h in the group of patients administered epidural clonidine before operation. In this group of patients we found significant reduction in analgesic consumption during the study period (p < 0.05), compared to other groups. The cumulative consumption of analgesics assessed at the end of the study period was significantly reduced (p < 0.05) in the group of patients administered epidural clonidine before operation (8.40 +/- 3.74, respectively) as compared with the peroral clonidine before operation (16.79 +/- 5.75, respectively), epidural clonidine at the end of the operation (11.11 +/- 4.24, respectively) and control group of patients (18.00 +/- 6.45, respectively). Preincisional administration of epidural clonidine was associated with a significantly lower analgesic use, lower cumulative analgesic consumption and greater hemodynamic stability, in comparison with other groups." ], "offsets": [ [ 180, 2120 ] ] } ]

[ { "id": "7627", "type": "Chemicals & Drugs", "text": [ "alpha2-adrenoreceptor agonist" ], "offsets": [ [ 60, 89 ] ], "normalized": [] }, { "id": "7628", "type": "Genes & Molecular Sequences", "text": [ "alpha2-adrenoreceptor agonist" ], "offsets": [ [ 60, 89 ] ], "normalized": [] }, { "id": "7629", "type": "Chemicals & Drugs", "text": [ "clonidine" ], "offsets": [ [ 90, 99 ] ], "normalized": [] }, { "id": "7630", "type": "Chemicals & Drugs", "text": [ "clonidine" ], "offsets": [ [ 389, 398 ] ], "normalized": [] }, { "id": "7631", "type": "Chemicals & Drugs", "text": [ "clonidine" ], "offsets": [ [ 472, 481 ] ], "normalized": [] }, { "id": "7632", "type": "Chemicals & Drugs", "text": [ "peroral clonidine" ], "offsets": [ [ 640, 657 ] ], "normalized": [] }, { "id": "7633", "type": "Chemicals & Drugs", "text": [ "epidural clonidine" ], "offsets": [ [ 676, 694 ] ], "normalized": [] }, { "id": "7634", "type": "Chemicals & Drugs", "text": [ "epidural clonidine" ], "offsets": [ [ 713, 731 ] ], "normalized": [] }, { "id": "7635", "type": "Chemicals & Drugs", "text": [ "epidural saline" ], "offsets": [ [ 761, 776 ] ], "normalized": [] }, { "id": "7636", "type": "Chemicals & Drugs", "text": [ "epidural morphine" ], "offsets": [ [ 869, 886 ] ], "normalized": [] }, { "id": "7637", "type": "Chemicals & Drugs", "text": [ "epidural clonidine" ], "offsets": [ [ 1275, 1293 ] ], "normalized": [] }, { "id": "7638", "type": "Chemicals & Drugs", "text": [ "epidural clonidine" ], "offsets": [ [ 1612, 1630 ] ], "normalized": [] }, { "id": "7639", "type": "Chemicals & Drugs", "text": [ "peroral clonidine" ], "offsets": [ [ 1699, 1716 ] ], "normalized": [] }, { "id": "7640", "type": "Chemicals & Drugs", "text": [ "epidural clonidine" ], "offsets": [ [ 1766, 1784 ] ], "normalized": [] }, { "id": "7641", "type": "Chemicals & Drugs", "text": [ "epidural clonidine" ], "offsets": [ [ 1938, 1956 ] ], "normalized": [] }, { "id": "7642", "type": "", "text": [ "clonidine" ], "offsets": [ [ 90, 99 ] ], "normalized": [] }, { "id": "7643", "type": "", "text": [ "alpha2-adrenoreceptor agonist" ], "offsets": [ [ 60, 89 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7644", "type": "PA", "arg1_id": "7642", "arg2_id": "7643", "normalized": [] } ]

[ { "id": "7647", "type": "title", "text": [ "Clozapine use in children and adolescents." ], "offsets": [ [ 0, 42 ] ] }, { "id": "7648", "type": "abstract", "text": [ "BACKGROUND: Although the role of clozapine is well established for treatment-resistant schizophrenia, it is rarely used in pediatric populations, mainly due to its potentially serious adverse effects. OBJECTIVE: To summarize practical aspects of use of clozapine in treating children with schizophrenia and management of associated adverse effects. METHODS: Available studies in the literature using clozapine in the pediatric population are summarized and the NIMH experience in treating refractory childhood-onset schizophrenia cases with clozapine is discussed. CONCLUSION: Despite a higher incidence of adverse effects in children, clozapine appears to be a uniquely beneficial second-line agent for treating children with refractory schizophrenia." ], "offsets": [ [ 43, 795 ] ] } ]

[ { "id": "7649", "type": "Chemicals & Drugs", "text": [ "Clozapine" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "7650", "type": "Chemicals & Drugs", "text": [ "clozapine" ], "offsets": [ [ 76, 85 ] ], "normalized": [] }, { "id": "7651", "type": "Diseases & Disorders", "text": [ "treatment-resistant schizophrenia" ], "offsets": [ [ 110, 143 ] ], "normalized": [] }, { "id": "7652", "type": "Diseases & Disorders", "text": [ "adverse effects" ], "offsets": [ [ 227, 242 ] ], "normalized": [] }, { "id": "7653", "type": "Chemicals & Drugs", "text": [ "clozapine" ], "offsets": [ [ 296, 305 ] ], "normalized": [] }, { "id": "7654", "type": "Diseases & Disorders", "text": [ "schizophrenia" ], "offsets": [ [ 332, 345 ] ], "normalized": [] }, { "id": "7655", "type": "Diseases & Disorders", "text": [ "adverse effects" ], "offsets": [ [ 375, 390 ] ], "normalized": [] }, { "id": "7656", "type": "Chemicals & Drugs", "text": [ "clozapine" ], "offsets": [ [ 443, 452 ] ], "normalized": [] }, { "id": "7657", "type": "Diseases & Disorders", "text": [ "refractory childhood-onset schizophrenia" ], "offsets": [ [ 532, 572 ] ], "normalized": [] }, { "id": "7658", "type": "Chemicals & Drugs", "text": [ "clozapine" ], "offsets": [ [ 584, 593 ] ], "normalized": [] }, { "id": "7659", "type": "Diseases & Disorders", "text": [ "adverse effects" ], "offsets": [ [ 650, 665 ] ], "normalized": [] }, { "id": "7660", "type": "Chemicals & Drugs", "text": [ "clozapine" ], "offsets": [ [ 679, 688 ] ], "normalized": [] }, { "id": "7661", "type": "Diseases & Disorders", "text": [ "refractory schizophrenia" ], "offsets": [ [ 770, 794 ] ], "normalized": [] }, { "id": "7662", "type": "", "text": [ "clozapine" ], "offsets": [ [ 76, 85 ] ], "normalized": [] }, { "id": "7663", "type": "", "text": [ "treatment-resistant schizophrenia" ], "offsets": [ [ 110, 143 ] ], "normalized": [] }, { "id": "7665", "type": "", "text": [ "clozapine" ], "offsets": [ [ 296, 305 ] ], "normalized": [] }, { "id": "7666", "type": "", "text": [ "schizophrenia" ], "offsets": [ [ 332, 345 ] ], "normalized": [] }, { "id": "7668", "type": "", "text": [ "clozapine" ], "offsets": [ [ 584, 593 ] ], "normalized": [] }, { "id": "7669", "type": "", "text": [ "refractory childhood-onset schizophrenia" ], "offsets": [ [ 532, 572 ] ], "normalized": [] }, { "id": "7671", "type": "", "text": [ "clozapine" ], "offsets": [ [ 679, 688 ] ], "normalized": [] }, { "id": "7672", "type": "", "text": [ "refractory schizophrenia" ], "offsets": [ [ 770, 794 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7664", "type": "PA", "arg1_id": "7662", "arg2_id": "7663", "normalized": [] }, { "id": "7667", "type": "PA", "arg1_id": "7665", "arg2_id": "7666", "normalized": [] }, { "id": "7670", "type": "SA", "arg1_id": "7668", "arg2_id": "7669", "normalized": [] }, { "id": "7673", "type": "PA", "arg1_id": "7671", "arg2_id": "7672", "normalized": [] } ]

[ { "id": "7676", "type": "title", "text": [ "Oritavancin: a new promising agent in the treatment of infections due to Gram-positive pathogens." ], "offsets": [ [ 0, 97 ] ] }, { "id": "7677", "type": "abstract", "text": [ "Nosocomial and community-acquired infections caused by Gram-positive pathogens continue to be a challenge, mainly due to the increasing rates of resistance among Staphylococcus spp. and Enterococcus spp. Oritavancin, a new parenteral semisynthetic glycopeptide, possessing rapid bactericidal action and an antimicrobial spectrum containing all Gram-positive pathogens (streptococci, staphylococci, enterococci--vancomycin-resistant enterococci included--and Clostridia spp.) irrespective of their resistance status to the precursor molecule of vancomycin, is expected to file a new drug application by the first trimester of 2008. Once-daily dosing, good penetration into macrophages, in vitro activity against bacteria embedded in biofilms and low adverse reaction potential are further considered as oritavancin's advantages over existing drugs. While waiting for the results of supplementary Phase III studies to be announced, preliminary reports suggest the new drug will be a welcome addition to the existing antimicrobial armamentarium against Gram-positive cocci." ], "offsets": [ [ 98, 1168 ] ] } ]

[ { "id": "7678", "type": "Chemicals & Drugs", "text": [ "Oritavancin" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "7679", "type": "Diseases & Disorders", "text": [ "infections due to Gram-positive pathogens" ], "offsets": [ [ 55, 96 ] ], "normalized": [] }, { "id": "7680", "type": "Diseases & Disorders", "text": [ "Nosocomial" ], "offsets": [ [ 98, 108 ] ], "normalized": [] }, { "id": "7681", "type": "Diseases & Disorders", "text": [ "community-acquired infections caused by Gram-positive pathogens" ], "offsets": [ [ 113, 176 ] ], "normalized": [] }, { "id": "7682", "type": "Diseases & Disorders", "text": [ "infections" ], "offsets": [ [ 132, 142 ] ], "normalized": [] }, { "id": "7683", "type": "Diseases & Disorders", "text": [ "Staphylococcus" ], "offsets": [ [ 260, 274 ] ], "normalized": [] }, { "id": "7684", "type": "Chemicals & Drugs", "text": [ "spp" ], "offsets": [ [ 275, 278 ] ], "normalized": [] }, { "id": "7685", "type": "Chemicals & Drugs", "text": [ "spp" ], "offsets": [ [ 297, 300 ] ], "normalized": [] }, { "id": "7686", "type": "Chemicals & Drugs", "text": [ "Oritavancin" ], "offsets": [ [ 302, 313 ] ], "normalized": [] }, { "id": "7687", "type": "Chemicals & Drugs", "text": [ "parenteral semisynthetic glycopeptide" ], "offsets": [ [ 321, 358 ] ], "normalized": [] }, { "id": "7688", "type": "Diseases & Disorders", "text": [ "possessing" ], "offsets": [ [ 360, 370 ] ], "normalized": [] }, { "id": "7689", "type": "Diseases & Disorders", "text": [ "staphylococci" ], "offsets": [ [ 481, 494 ] ], "normalized": [] }, { "id": "7690", "type": "Chemicals & Drugs", "text": [ "spp" ], "offsets": [ [ 567, 570 ] ], "normalized": [] }, { "id": "7691", "type": "Chemicals & Drugs", "text": [ "vancomycin" ], "offsets": [ [ 642, 652 ] ], "normalized": [] }, { "id": "7692", "type": "Chemicals & Drugs", "text": [ "oritavancin" ], "offsets": [ [ 900, 911 ] ], "normalized": [] }, { "id": "7693", "type": "", "text": [ "Oritavancin" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "7694", "type": "", "text": [ "infections due to Gram-positive pathogens" ], "offsets": [ [ 55, 96 ] ], "normalized": [] }, { "id": "7696", "type": "", "text": [ "vancomycin" ], "offsets": [ [ 642, 652 ] ], "normalized": [] }, { "id": "7697", "type": "", "text": [ "staphylococci" ], "offsets": [ [ 481, 494 ] ], "normalized": [] }, { "id": "7699", "type": "", "text": [ "vancomycin" ], "offsets": [ [ 642, 652 ] ], "normalized": [] }, { "id": "7700", "type": "", "text": [ "possessing" ], "offsets": [ [ 360, 370 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7695", "type": "PA", "arg1_id": "7693", "arg2_id": "7694", "normalized": [] }, { "id": "7698", "type": "PA", "arg1_id": "7696", "arg2_id": "7697", "normalized": [] }, { "id": "7701", "type": "PA", "arg1_id": "7699", "arg2_id": "7700", "normalized": [] } ]

[ { "id": "7704", "type": "title", "text": [ "Inhibition of P-glycoprotein (ABCB1)- and multidrug resistance-associated protein 1 (ABCC1)-mediated transport by the orally administered inhibitor, CBT-1((R))." ], "offsets": [ [ 0, 160 ] ] }, { "id": "7705", "type": "abstract", "text": [ "Cellular expression of ATP-binding cassette (ABC) transport proteins, such as P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), or ABCG2, is known to confer a drug-resistant phenotype. Thus, the development of effective transporter inhibitors could be of value to cancer treatment. CBT-1 is a bisbenzylisoquinoline plant alkyloid currently in development as a Pgp inhibitor. We characterized its interactions with the three major ABC transporters associated with drug resistance - Pgp, MRP1 and ABCG2 - and compared it to other known inhibitors. CBT-1 completely inhibited rhodamine 123 transport from Pgp-overexpressing cells at a concentration of 1muM. Additionally, 1 microM completely reversed Pgp-mediated resistance to vinblastine, paclitaxel and depsipeptide in SW620 Ad20 cells. CBT-1 was found to compete [(125)I]-IAAP labeling of Pgp with an IC(50) of 0.14 microM, and low concentrations of CBT-1 (<1 microM) stimulated Pgp-mediated ATP hydrolysis. In MRP1-overexpressing cells, 10 microM CBT-1 was found to completely inhibit MRP1-mediated calcein transport. CBT-1 at 25 microM did not have a significant effect on ABCG2-mediated pheophorbide a transport. Serum levels of CBT-1 in samples obtained from eight patients receiving CBT-1 increased intracellular rhodamine 123 levels in CD56+ cells 2.1- to 5.7-fold in an ex vivo assay. CBT-1 is able to inhibit the ABC transporters Pgp and MRP1, making it an attractive candidate for clinical trials in cancers where Pgp and/or MRP1 might be overexpressed. Further clinical studies with CBT-1 are warranted." ], "offsets": [ [ 161, 1745 ] ] } ]

[ { "id": "7706", "type": "Genes & Molecular Sequences", "text": [ "P-glycoprotein" ], "offsets": [ [ 14, 28 ] ], "normalized": [] }, { "id": "7707", "type": "Genes & Molecular Sequences", "text": [ "ABCB1" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "7708", "type": "Genes & Molecular Sequences", "text": [ "multidrug resistance-associated protein" ], "offsets": [ [ 42, 81 ] ], "normalized": [] }, { "id": "7709", "type": "Genes & Molecular Sequences", "text": [ "1" ], "offsets": [ [ 82, 83 ] ], "normalized": [] }, { "id": "7710", "type": "Genes & Molecular Sequences", "text": [ "ABCC1" ], "offsets": [ [ 85, 90 ] ], "normalized": [] }, { "id": "7711", "type": "Chemicals & Drugs", "text": [ "CBT-1((R))" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "7712", "type": "Genes & Molecular Sequences", "text": [ "ATP" ], "offsets": [ [ 184, 187 ] ], "normalized": [] }, { "id": "7713", "type": "Genes & Molecular Sequences", "text": [ "ABC) transport proteins" ], "offsets": [ [ 206, 229 ] ], "normalized": [] }, { "id": "7714", "type": "Chemicals & Drugs", "text": [ "ABC) transport proteins" ], "offsets": [ [ 206, 229 ] ], "normalized": [] }, { "id": "7715", "type": "Genes & Molecular Sequences", "text": [ "P-glycoprotein" ], "offsets": [ [ 239, 253 ] ], "normalized": [] }, { "id": "7716", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 255, 258 ] ], "normalized": [] }, { "id": "7717", "type": "Genes & Molecular Sequences", "text": [ "multidrug resistance-associated protein" ], "offsets": [ [ 261, 300 ] ], "normalized": [] }, { "id": "7718", "type": "Genes & Molecular Sequences", "text": [ "MRP1" ], "offsets": [ [ 302, 306 ] ], "normalized": [] }, { "id": "7719", "type": "Genes & Molecular Sequences", "text": [ "ABCG2" ], "offsets": [ [ 312, 317 ] ], "normalized": [] }, { "id": "7720", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 463, 468 ] ], "normalized": [] }, { "id": "7721", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 463, 468 ] ], "normalized": [] }, { "id": "7722", "type": "Chemicals & Drugs", "text": [ "bisbenzylisoquinoline plant alkyloid" ], "offsets": [ [ 474, 510 ] ], "normalized": [] }, { "id": "7723", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "7724", "type": "Chemicals & Drugs", "text": [ "Pgp" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "7725", "type": "Genes & Molecular Sequences", "text": [ "ABC transporters" ], "offsets": [ [ 611, 627 ] ], "normalized": [] }, { "id": "7726", "type": "Chemicals & Drugs", "text": [ "ABC transporters" ], "offsets": [ [ 611, 627 ] ], "normalized": [] }, { "id": "7727", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 662, 665 ] ], "normalized": [] }, { "id": "7728", "type": "Genes & Molecular Sequences", "text": [ "MRP1" ], "offsets": [ [ 667, 671 ] ], "normalized": [] }, { "id": "7729", "type": "Genes & Molecular Sequences", "text": [ "ABCG2" ], "offsets": [ [ 676, 681 ] ], "normalized": [] }, { "id": "7730", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "7731", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "7732", "type": "Genes & Molecular Sequences", "text": [ "rhodamine 123" ], "offsets": [ [ 754, 767 ] ], "normalized": [] }, { "id": "7733", "type": "Chemicals & Drugs", "text": [ "rhodamine 123" ], "offsets": [ [ 754, 767 ] ], "normalized": [] }, { "id": "7734", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 783, 786 ] ], "normalized": [] }, { "id": "7735", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "7736", "type": "Chemicals & Drugs", "text": [ "vinblastine" ], "offsets": [ [ 906, 917 ] ], "normalized": [] }, { "id": "7737", "type": "Chemicals & Drugs", "text": [ "paclitaxel" ], "offsets": [ [ 919, 929 ] ], "normalized": [] }, { "id": "7738", "type": "Chemicals & Drugs", "text": [ "depsipeptide" ], "offsets": [ [ 934, 946 ] ], "normalized": [] }, { "id": "7739", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "7740", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "7741", "type": "Chemicals & Drugs", "text": [ "[(125)I]-IAAP" ], "offsets": [ [ 995, 1008 ] ], "normalized": [] }, { "id": "7742", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "7743", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 1082, 1087 ] ], "normalized": [] }, { "id": "7744", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 1082, 1087 ] ], "normalized": [] }, { "id": "7745", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 1111, 1114 ] ], "normalized": [] }, { "id": "7746", "type": "Genes & Molecular Sequences", "text": [ "ATP" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [] }, { "id": "7747", "type": "Chemicals & Drugs", "text": [ "ATP" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [] }, { "id": "7748", "type": "Genes & Molecular Sequences", "text": [ "MRP1" ], "offsets": [ [ 1143, 1147 ] ], "normalized": [] }, { "id": "7749", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 1180, 1185 ] ], "normalized": [] }, { "id": "7750", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 1180, 1185 ] ], "normalized": [] }, { "id": "7751", "type": "Genes & Molecular Sequences", "text": [ "MRP1" ], "offsets": [ [ 1218, 1222 ] ], "normalized": [] }, { "id": "7752", "type": "Genes & Molecular Sequences", "text": [ "calcein" ], "offsets": [ [ 1232, 1239 ] ], "normalized": [] }, { "id": "7753", "type": "Chemicals & Drugs", "text": [ "calcein" ], "offsets": [ [ 1232, 1239 ] ], "normalized": [] }, { "id": "7754", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 1251, 1256 ] ], "normalized": [] }, { "id": "7755", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 1251, 1256 ] ], "normalized": [] }, { "id": "7756", "type": "Genes & Molecular Sequences", "text": [ "ABCG2" ], "offsets": [ [ 1307, 1312 ] ], "normalized": [] }, { "id": "7757", "type": "Genes & Molecular Sequences", "text": [ "pheophorbide" ], "offsets": [ [ 1322, 1334 ] ], "normalized": [] }, { "id": "7758", "type": "Chemicals & Drugs", "text": [ "pheophorbide" ], "offsets": [ [ 1322, 1334 ] ], "normalized": [] }, { "id": "7759", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 1364, 1369 ] ], "normalized": [] }, { "id": "7760", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 1364, 1369 ] ], "normalized": [] }, { "id": "7761", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 1420, 1425 ] ], "normalized": [] }, { "id": "7762", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 1420, 1425 ] ], "normalized": [] }, { "id": "7763", "type": "Genes & Molecular Sequences", "text": [ "rhodamine 123" ], "offsets": [ [ 1450, 1463 ] ], "normalized": [] }, { "id": "7764", "type": "Chemicals & Drugs", "text": [ "rhodamine 123" ], "offsets": [ [ 1450, 1463 ] ], "normalized": [] }, { "id": "7765", "type": "Genes & Molecular Sequences", "text": [ "CD56" ], "offsets": [ [ 1474, 1478 ] ], "normalized": [] }, { "id": "7766", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 1524, 1529 ] ], "normalized": [] }, { "id": "7767", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 1524, 1529 ] ], "normalized": [] }, { "id": "7768", "type": "Genes & Molecular Sequences", "text": [ "ABC transporters" ], "offsets": [ [ 1553, 1569 ] ], "normalized": [] }, { "id": "7769", "type": "Chemicals & Drugs", "text": [ "ABC transporters" ], "offsets": [ [ 1553, 1569 ] ], "normalized": [] }, { "id": "7770", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 1570, 1573 ] ], "normalized": [] }, { "id": "7771", "type": "Genes & Molecular Sequences", "text": [ "MRP1" ], "offsets": [ [ 1578, 1582 ] ], "normalized": [] }, { "id": "7772", "type": "Genes & Molecular Sequences", "text": [ "Pgp" ], "offsets": [ [ 1655, 1658 ] ], "normalized": [] }, { "id": "7773", "type": "Genes & Molecular Sequences", "text": [ "MRP1" ], "offsets": [ [ 1666, 1670 ] ], "normalized": [] }, { "id": "7774", "type": "Chemicals & Drugs", "text": [ "CBT-1" ], "offsets": [ [ 1725, 1730 ] ], "normalized": [] }, { "id": "7775", "type": "Genes & Molecular Sequences", "text": [ "CBT-1" ], "offsets": [ [ 1725, 1730 ] ], "normalized": [] }, { "id": "7776", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 463, 468 ] ], "normalized": [] }, { "id": "7777", "type": "", "text": [ "Pgp" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "7779", "type": "", "text": [ "bisbenzylisoquinoline plant alkyloid" ], "offsets": [ [ 474, 510 ] ], "normalized": [] }, { "id": "7780", "type": "", "text": [ "Pgp" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "7782", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "7783", "type": "", "text": [ "rhodamine 123" ], "offsets": [ [ 754, 767 ] ], "normalized": [] }, { "id": "7785", "type": "", "text": [ "vinblastine" ], "offsets": [ [ 906, 917 ] ], "normalized": [] }, { "id": "7786", "type": "", "text": [ "Pgp" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "7788", "type": "", "text": [ "paclitaxel" ], "offsets": [ [ 919, 929 ] ], "normalized": [] }, { "id": "7789", "type": "", "text": [ "Pgp" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "7791", "type": "", "text": [ "depsipeptide" ], "offsets": [ [ 934, 946 ] ], "normalized": [] }, { "id": "7792", "type": "", "text": [ "Pgp" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "7794", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1082, 1087 ] ], "normalized": [] }, { "id": "7795", "type": "", "text": [ "Pgp" ], "offsets": [ [ 1111, 1114 ] ], "normalized": [] }, { "id": "7797", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1082, 1087 ] ], "normalized": [] }, { "id": "7798", "type": "", "text": [ "ATP" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [] }, { "id": "7800", "type": "", "text": [ "[(125)I]-IAAP" ], "offsets": [ [ 995, 1008 ] ], "normalized": [] }, { "id": "7801", "type": "", "text": [ "Pgp" ], "offsets": [ [ 1111, 1114 ] ], "normalized": [] }, { "id": "7803", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1180, 1185 ] ], "normalized": [] }, { "id": "7804", "type": "", "text": [ "MRP1" ], "offsets": [ [ 1218, 1222 ] ], "normalized": [] }, { "id": "7806", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1180, 1185 ] ], "normalized": [] }, { "id": "7807", "type": "", "text": [ "calcein" ], "offsets": [ [ 1232, 1239 ] ], "normalized": [] }, { "id": "7809", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1251, 1256 ] ], "normalized": [] }, { "id": "7810", "type": "", "text": [ "ABCG2" ], "offsets": [ [ 1307, 1312 ] ], "normalized": [] }, { "id": "7812", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1251, 1256 ] ], "normalized": [] }, { "id": "7813", "type": "", "text": [ "pheophorbide" ], "offsets": [ [ 1322, 1334 ] ], "normalized": [] }, { "id": "7815", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1420, 1425 ] ], "normalized": [] }, { "id": "7816", "type": "", "text": [ "rhodamine 123" ], "offsets": [ [ 1450, 1463 ] ], "normalized": [] }, { "id": "7818", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1524, 1529 ] ], "normalized": [] }, { "id": "7819", "type": "", "text": [ "MRP1" ], "offsets": [ [ 1666, 1670 ] ], "normalized": [] }, { "id": "7821", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1524, 1529 ] ], "normalized": [] }, { "id": "7822", "type": "", "text": [ "Pgp" ], "offsets": [ [ 1655, 1658 ] ], "normalized": [] }, { "id": "7824", "type": "", "text": [ "ABC) transport proteins" ], "offsets": [ [ 206, 229 ] ], "normalized": [] }, { "id": "7825", "type": "", "text": [ "MRP1" ], "offsets": [ [ 302, 306 ] ], "normalized": [] }, { "id": "7827", "type": "", "text": [ "ABC) transport proteins" ], "offsets": [ [ 206, 229 ] ], "normalized": [] }, { "id": "7828", "type": "", "text": [ "Pgp" ], "offsets": [ [ 255, 258 ] ], "normalized": [] }, { "id": "7830", "type": "", "text": [ "ABC) transport proteins" ], "offsets": [ [ 206, 229 ] ], "normalized": [] }, { "id": "7831", "type": "", "text": [ "ABCG2" ], "offsets": [ [ 312, 317 ] ], "normalized": [] }, { "id": "7833", "type": "", "text": [ "ABC transporters" ], "offsets": [ [ 611, 627 ] ], "normalized": [] }, { "id": "7834", "type": "", "text": [ "MRP1" ], "offsets": [ [ 667, 671 ] ], "normalized": [] }, { "id": "7836", "type": "", "text": [ "ABC transporters" ], "offsets": [ [ 611, 627 ] ], "normalized": [] }, { "id": "7837", "type": "", "text": [ "Pgp" ], "offsets": [ [ 662, 665 ] ], "normalized": [] }, { "id": "7839", "type": "", "text": [ "ABC transporters" ], "offsets": [ [ 611, 627 ] ], "normalized": [] }, { "id": "7840", "type": "", "text": [ "ABCG2" ], "offsets": [ [ 676, 681 ] ], "normalized": [] }, { "id": "7842", "type": "", "text": [ "ABC transporters" ], "offsets": [ [ 1553, 1569 ] ], "normalized": [] }, { "id": "7843", "type": "", "text": [ "MRP1" ], "offsets": [ [ 1666, 1670 ] ], "normalized": [] }, { "id": "7845", "type": "", "text": [ "ABC transporters" ], "offsets": [ [ 1553, 1569 ] ], "normalized": [] }, { "id": "7846", "type": "", "text": [ "Pgp" ], "offsets": [ [ 1655, 1658 ] ], "normalized": [] }, { "id": "7848", "type": "", "text": [ "ABC transporters" ], "offsets": [ [ 1553, 1569 ] ], "normalized": [] }, { "id": "7849", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1524, 1529 ] ], "normalized": [] }, { "id": "7851", "type": "", "text": [ "CBT-1((R))" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "7852", "type": "", "text": [ "ABCC1" ], "offsets": [ [ 85, 90 ] ], "normalized": [] }, { "id": "7854", "type": "", "text": [ "CBT-1((R))" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "7855", "type": "", "text": [ "ABCB1" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "7857", "type": "", "text": [ "CBT-1((R))" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "7858", "type": "", "text": [ "P-glycoprotein" ], "offsets": [ [ 14, 28 ] ], "normalized": [] }, { "id": "7860", "type": "", "text": [ "CBT-1((R))" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "7861", "type": "", "text": [ "multidrug resistance-associated protein" ], "offsets": [ [ 42, 81 ] ], "normalized": [] }, { "id": "7863", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "7864", "type": "", "text": [ "Pgp" ], "offsets": [ [ 783, 786 ] ], "normalized": [] }, { "id": "7866", "type": "", "text": [ "rhodamine 123" ], "offsets": [ [ 754, 767 ] ], "normalized": [] }, { "id": "7867", "type": "", "text": [ "Pgp" ], "offsets": [ [ 783, 786 ] ], "normalized": [] }, { "id": "7869", "type": "", "text": [ "ATP" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [] }, { "id": "7870", "type": "", "text": [ "Pgp" ], "offsets": [ [ 1111, 1114 ] ], "normalized": [] }, { "id": "7872", "type": "", "text": [ "calcein" ], "offsets": [ [ 1232, 1239 ] ], "normalized": [] }, { "id": "7873", "type": "", "text": [ "MRP1" ], "offsets": [ [ 1143, 1147 ] ], "normalized": [] }, { "id": "7875", "type": "", "text": [ "pheophorbide" ], "offsets": [ [ 1322, 1334 ] ], "normalized": [] }, { "id": "7876", "type": "", "text": [ "ABCG2" ], "offsets": [ [ 1307, 1312 ] ], "normalized": [] }, { "id": "7878", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1420, 1425 ] ], "normalized": [] }, { "id": "7879", "type": "", "text": [ "CD56" ], "offsets": [ [ 1474, 1478 ] ], "normalized": [] }, { "id": "7881", "type": "", "text": [ "rhodamine 123" ], "offsets": [ [ 1450, 1463 ] ], "normalized": [] }, { "id": "7882", "type": "", "text": [ "CD56" ], "offsets": [ [ 1474, 1478 ] ], "normalized": [] }, { "id": "7884", "type": "", "text": [ "CBT-1" ], "offsets": [ [ 1524, 1529 ] ], "normalized": [] }, { "id": "7885", "type": "", "text": [ "ABC transporters" ], "offsets": [ [ 1553, 1569 ] ], "normalized": [] }, { "id": "7887", "type": "", "text": [ "CBT-1((R))" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "7888", "type": "", "text": [ "1" ], "offsets": [ [ 82, 83 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7778", "type": "PA", "arg1_id": "7776", "arg2_id": "7777", "normalized": [] }, { "id": "7781", "type": "PA", "arg1_id": "7779", "arg2_id": "7780", "normalized": [] }, { "id": "7784", "type": "PA", "arg1_id": "7782", "arg2_id": "7783", "normalized": [] }, { "id": "7787", "type": "PA", "arg1_id": "7785", "arg2_id": "7786", "normalized": [] }, { "id": "7790", "type": "PA", "arg1_id": "7788", "arg2_id": "7789", "normalized": [] }, { "id": "7793", "type": "PA", "arg1_id": "7791", "arg2_id": "7792", "normalized": [] }, { "id": "7796", "type": "PA", "arg1_id": "7794", "arg2_id": "7795", "normalized": [] }, { "id": "7799", "type": "PA", "arg1_id": "7797", "arg2_id": "7798", "normalized": [] }, { "id": "7802", "type": "PA", "arg1_id": "7800", "arg2_id": "7801", "normalized": [] }, { "id": "7805", "type": "PA", "arg1_id": "7803", "arg2_id": "7804", "normalized": [] }, { "id": "7808", "type": "PA", "arg1_id": "7806", "arg2_id": "7807", "normalized": [] }, { "id": "7811", "type": "NA", "arg1_id": "7809", "arg2_id": "7810", "normalized": [] }, { "id": "7814", "type": "NA", "arg1_id": "7812", "arg2_id": "7813", "normalized": [] }, { "id": "7817", "type": "PA", "arg1_id": "7815", "arg2_id": "7816", "normalized": [] }, { "id": "7820", "type": "PA", "arg1_id": "7818", "arg2_id": "7819", "normalized": [] }, { "id": "7823", "type": "PA", "arg1_id": "7821", "arg2_id": "7822", "normalized": [] }, { "id": "7826", "type": "PA", "arg1_id": "7824", "arg2_id": "7825", "normalized": [] }, { "id": "7829", "type": "PA", "arg1_id": "7827", "arg2_id": "7828", "normalized": [] }, { "id": "7832", "type": "PA", "arg1_id": "7830", "arg2_id": "7831", "normalized": [] }, { "id": "7835", "type": "PA", "arg1_id": "7833", "arg2_id": "7834", "normalized": [] }, { "id": "7838", "type": "PA", "arg1_id": "7836", "arg2_id": "7837", "normalized": [] }, { "id": "7841", "type": "PA", "arg1_id": "7839", "arg2_id": "7840", "normalized": [] }, { "id": "7844", "type": "PA", "arg1_id": "7842", "arg2_id": "7843", "normalized": [] }, { "id": "7847", "type": "PA", "arg1_id": "7845", "arg2_id": "7846", "normalized": [] }, { "id": "7850", "type": "PA", "arg1_id": "7848", "arg2_id": "7849", "normalized": [] }, { "id": "7853", "type": "PA", "arg1_id": "7851", "arg2_id": "7852", "normalized": [] }, { "id": "7856", "type": "PA", "arg1_id": "7854", "arg2_id": "7855", "normalized": [] }, { "id": "7859", "type": "PA", "arg1_id": "7857", "arg2_id": "7858", "normalized": [] }, { "id": "7862", "type": "PA", "arg1_id": "7860", "arg2_id": "7861", "normalized": [] }, { "id": "7865", "type": "PA", "arg1_id": "7863", "arg2_id": "7864", "normalized": [] }, { "id": "7868", "type": "PA", "arg1_id": "7866", "arg2_id": "7867", "normalized": [] }, { "id": "7871", "type": "PA", "arg1_id": "7869", "arg2_id": "7870", "normalized": [] }, { "id": "7874", "type": "PA", "arg1_id": "7872", "arg2_id": "7873", "normalized": [] }, { "id": "7877", "type": "PA", "arg1_id": "7875", "arg2_id": "7876", "normalized": [] }, { "id": "7880", "type": "PA", "arg1_id": "7878", "arg2_id": "7879", "normalized": [] }, { "id": "7883", "type": "PA", "arg1_id": "7881", "arg2_id": "7882", "normalized": [] }, { "id": "7886", "type": "PA", "arg1_id": "7884", "arg2_id": "7885", "normalized": [] }, { "id": "7889", "type": "PA", "arg1_id": "7887", "arg2_id": "7888", "normalized": [] } ]

[ { "id": "7892", "type": "title", "text": [ "Is serum transthyretin a reliable marker of nutritional status in patients with end-stage renal disease?" ], "offsets": [ [ 0, 104 ] ] }, { "id": "7893", "type": "abstract", "text": [ "OBJECTIVE: To test the value of serum transthyretin (TTR) concentration as a nutritional marker in renal patients. METHODS: The study included 115 renal patients, out of which 35 are on conservative treatment, 50 on hemodialysis and 30 renal transplant recipients, and 31 healthy control subjects. Serum TTR, albumin, transferrin, C-reactive protein (CRP) and alpha1 anti trypsine (AAT) were assessed by immunoturbidimetry, and vitamin A by HPLC. Linear regression models were applied to test the association between serum TTR and body mass index (BMI). RESULTS: Serum TTR concentrations were normal, but serum vitamin A, CRP and AAT concentrations were significantly higher in patients. In renal patients, serum TTR was positively and independently related to BMI and was significantly lower in malnourished than well-nourished patients (367+/-91 vs. 417+/-130 mg/L; p=0.05). The risk of serum TTR<300 mg/L was higher in malnourished patients [OR, 4.82 (1.78-13.2); p=0.001]. CONCLUSION: Serum TTR concentrations were at normal range in renal patients despite evidence of malnutrition and inflammation. However, they were related to BMI and were significantly lowered in malnourished patients. Thus, serum TTR would reflect nutritional status in renal patients. However, the cutoff of malnutrition should be raised to 300 mg/L." ], "offsets": [ [ 105, 1433 ] ] } ]

[ { "id": "7894", "type": "Chemicals & Drugs", "text": [ "transthyretin" ], "offsets": [ [ 9, 22 ] ], "normalized": [] }, { "id": "7895", "type": "Diseases & Disorders", "text": [ "end-stage renal disease" ], "offsets": [ [ 80, 103 ] ], "normalized": [] }, { "id": "7896", "type": "Chemicals & Drugs", "text": [ "transthyretin" ], "offsets": [ [ 143, 156 ] ], "normalized": [] }, { "id": "7897", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 158, 161 ] ], "normalized": [] }, { "id": "7898", "type": "Diseases & Disorders", "text": [ "renal patients" ], "offsets": [ [ 204, 218 ] ], "normalized": [] }, { "id": "7899", "type": "Diseases & Disorders", "text": [ "renal patients" ], "offsets": [ [ 252, 266 ] ], "normalized": [] }, { "id": "7900", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 409, 412 ] ], "normalized": [] }, { "id": "7901", "type": "Chemicals & Drugs", "text": [ "albumin" ], "offsets": [ [ 414, 421 ] ], "normalized": [] }, { "id": "7902", "type": "Chemicals & Drugs", "text": [ "vitamin A" ], "offsets": [ [ 533, 542 ] ], "normalized": [] }, { "id": "7903", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 559, 569 ] ], "normalized": [] }, { "id": "7904", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 628, 631 ] ], "normalized": [] }, { "id": "7905", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 674, 677 ] ], "normalized": [] }, { "id": "7906", "type": "Chemicals & Drugs", "text": [ "vitamin A" ], "offsets": [ [ 716, 725 ] ], "normalized": [] }, { "id": "7907", "type": "Diseases & Disorders", "text": [ "renal patients" ], "offsets": [ [ 796, 810 ] ], "normalized": [] }, { "id": "7908", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 818, 821 ] ], "normalized": [] }, { "id": "7909", "type": "Diseases & Disorders", "text": [ "malnourished" ], "offsets": [ [ 901, 913 ] ], "normalized": [] }, { "id": "7910", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 1000, 1003 ] ], "normalized": [] }, { "id": "7911", "type": "Diseases & Disorders", "text": [ "malnourished" ], "offsets": [ [ 1027, 1039 ] ], "normalized": [] }, { "id": "7912", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 1100, 1103 ] ], "normalized": [] }, { "id": "7913", "type": "Diseases & Disorders", "text": [ "renal patients" ], "offsets": [ [ 1143, 1157 ] ], "normalized": [] }, { "id": "7914", "type": "Diseases & Disorders", "text": [ "malnutrition" ], "offsets": [ [ 1178, 1190 ] ], "normalized": [] }, { "id": "7915", "type": "Diseases & Disorders", "text": [ "inflammation" ], "offsets": [ [ 1195, 1207 ] ], "normalized": [] }, { "id": "7916", "type": "Diseases & Disorders", "text": [ "malnourished" ], "offsets": [ [ 1277, 1289 ] ], "normalized": [] }, { "id": "7917", "type": "Chemicals & Drugs", "text": [ "TTR" ], "offsets": [ [ 1312, 1315 ] ], "normalized": [] }, { "id": "7918", "type": "Diseases & Disorders", "text": [ "renal patients" ], "offsets": [ [ 1352, 1366 ] ], "normalized": [] }, { "id": "7919", "type": "Diseases & Disorders", "text": [ "malnutrition" ], "offsets": [ [ 1391, 1403 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "7922", "type": "title", "text": [ "Docking study yields four novel inhibitors of the protooncogene Pim-1 kinase." ], "offsets": [ [ 0, 77 ] ] }, { "id": "7923", "type": "abstract", "text": [ "To supplement the hits from a high throughput screen, docking was performed against Pim-1 kinase. Glide docking was augmented with a filter to require traditional or aromatic CH..O hydrogen bonds to the kinase hinge. Four diverse actives, of 96 molecules assayed, had K(i) values between 0.091 and 4.5 microM. This gives a 14-fold enrichment over the earlier HTS run, and the two crystal structures solved confirmed the binding modes predicted by docking." ], "offsets": [ [ 78, 533 ] ] } ]

[ { "id": "7924", "type": "Chemicals & Drugs", "text": [ "inhibitors of the protooncogene Pim-1 kinase" ], "offsets": [ [ 32, 76 ] ], "normalized": [] }, { "id": "7925", "type": "Genes & Molecular Sequences", "text": [ "inhibitors of the protooncogene Pim-1 kinase" ], "offsets": [ [ 32, 76 ] ], "normalized": [] }, { "id": "7926", "type": "Genes & Molecular Sequences", "text": [ "Pim-1" ], "offsets": [ [ 64, 69 ] ], "normalized": [] }, { "id": "7927", "type": "Genes & Molecular Sequences", "text": [ "Pim-1 kinase" ], "offsets": [ [ 162, 174 ] ], "normalized": [] }, { "id": "7928", "type": "Genes & Molecular Sequences", "text": [ "Glide" ], "offsets": [ [ 176, 181 ] ], "normalized": [] }, { "id": "7929", "type": "Genes & Molecular Sequences", "text": [ "HTS" ], "offsets": [ [ 437, 440 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "7932", "type": "title", "text": [ "Molluscan shellfish allergy." ], "offsets": [ [ 0, 28 ] ] }, { "id": "7933", "type": "abstract", "text": [ "Food allergies affect approximately 3.5-4.0% of the worldwide population. Immediate-type food allergies are mediated by the production of IgE antibodies to specific proteins that occur naturally in allergenic foods. Symptoms are individually variable ranging from mild rashes and hives to life-threatening anaphylactic shock. Seafood allergies are among the most common types of food allergies on a worldwide basis. Allergies to fish and crustacean shellfish are very common. Molluscan shellfish allergies are well known but do not appear to occur as frequently. Molluscan shellfish allergies have been documented to all classes of mollusks including gastropods (e.g., limpet, abalone), bivalves (e.g., clams, oysters, mussels), and cephalopods (e.g., squid, octopus). Tropomyosin, a major muscle protein, is the only well-recognized allergen in molluscan shellfish. The allergens in oyster (Cra g 1), abalone (Hal m 1), and squid (Tod p 1) have been identified as tropomyosin. Cross-reactivity to tropomyosin from other molluscan shellfish species has been observed with sera from patients allergic to oysters, suggesting that individuals with allergies to molluscan shellfish should avoid eating all species of molluscan shellfish. Cross-reactions with the related tropomyosin allergens in crustacean shellfish may also occur but this is less clearly defined. Occupational allergies have also been described in workers exposed to molluscan shellfish products by the respiratory and/or cutaneous routes. With food allergies, one man's food may truly be another man's poison. Individuals with food allergies react adversely to the ingestion of foods and food ingredients that most consumers can safely ingest (Taylor and Hefle, 2001). The allergens that provoke adverse reactions in susceptible individuals are naturally occurring proteins in the specific foods (Bush and Hefle, 1996). Molluscan shellfish, like virtually all foods that contain protein, can provoke allergic reactions in some individuals." ], "offsets": [ [ 29, 2034 ] ] } ]

[ { "id": "7934", "type": "Diseases & Disorders", "text": [ "Molluscan shellfish allergy" ], "offsets": [ [ 0, 27 ] ], "normalized": [] }, { "id": "7935", "type": "Diseases & Disorders", "text": [ "Food allergies" ], "offsets": [ [ 29, 43 ] ], "normalized": [] }, { "id": "7936", "type": "Diseases & Disorders", "text": [ "food allergies" ], "offsets": [ [ 118, 132 ] ], "normalized": [] }, { "id": "7937", "type": "Diseases & Disorders", "text": [ "Symptoms" ], "offsets": [ [ 245, 253 ] ], "normalized": [] }, { "id": "7938", "type": "Diseases & Disorders", "text": [ "mild rashes" ], "offsets": [ [ 293, 304 ] ], "normalized": [] }, { "id": "7939", "type": "Diseases & Disorders", "text": [ "hives" ], "offsets": [ [ 309, 314 ] ], "normalized": [] }, { "id": "7940", "type": "Diseases & Disorders", "text": [ "anaphylactic shock" ], "offsets": [ [ 335, 353 ] ], "normalized": [] }, { "id": "7941", "type": "Diseases & Disorders", "text": [ "Seafood allergies" ], "offsets": [ [ 355, 372 ] ], "normalized": [] }, { "id": "7942", "type": "Diseases & Disorders", "text": [ "food allergies" ], "offsets": [ [ 408, 422 ] ], "normalized": [] }, { "id": "7943", "type": "Diseases & Disorders", "text": [ "Allergies to fish" ], "offsets": [ [ 445, 462 ] ], "normalized": [] }, { "id": "7944", "type": "Diseases & Disorders", "text": [ "crustacean shellfish" ], "offsets": [ [ 467, 487 ] ], "normalized": [] }, { "id": "7945", "type": "Diseases & Disorders", "text": [ "Molluscan shellfish allergies" ], "offsets": [ [ 505, 534 ] ], "normalized": [] }, { "id": "7946", "type": "Diseases & Disorders", "text": [ "Molluscan shellfish allergies" ], "offsets": [ [ 592, 621 ] ], "normalized": [] }, { "id": "7947", "type": "Chemicals & Drugs", "text": [ "Tropomyosin" ], "offsets": [ [ 798, 809 ] ], "normalized": [] }, { "id": "7948", "type": "Chemicals & Drugs", "text": [ "allergen" ], "offsets": [ [ 863, 871 ] ], "normalized": [] }, { "id": "7949", "type": "Chemicals & Drugs", "text": [ "allergens" ], "offsets": [ [ 900, 909 ] ], "normalized": [] }, { "id": "7950", "type": "Chemicals & Drugs", "text": [ "m" ], "offsets": [ [ 944, 945 ] ], "normalized": [] }, { "id": "7951", "type": "Chemicals & Drugs", "text": [ "tropomyosin" ], "offsets": [ [ 994, 1005 ] ], "normalized": [] }, { "id": "7952", "type": "Chemicals & Drugs", "text": [ "tropomyosin" ], "offsets": [ [ 1027, 1038 ] ], "normalized": [] }, { "id": "7953", "type": "Diseases & Disorders", "text": [ "allergies" ], "offsets": [ [ 1174, 1183 ] ], "normalized": [] }, { "id": "7954", "type": "Chemicals & Drugs", "text": [ "tropomyosin allergens" ], "offsets": [ [ 1296, 1317 ] ], "normalized": [] }, { "id": "7955", "type": "Diseases & Disorders", "text": [ "crustacean shellfish" ], "offsets": [ [ 1321, 1341 ] ], "normalized": [] }, { "id": "7956", "type": "Diseases & Disorders", "text": [ "allergies" ], "offsets": [ [ 1404, 1413 ] ], "normalized": [] }, { "id": "7957", "type": "Diseases & Disorders", "text": [ "food allergies" ], "offsets": [ [ 1539, 1553 ] ], "normalized": [] }, { "id": "7958", "type": "Diseases & Disorders", "text": [ "food allergies" ], "offsets": [ [ 1622, 1636 ] ], "normalized": [] }, { "id": "7959", "type": "Chemicals & Drugs", "text": [ "allergens" ], "offsets": [ [ 1768, 1777 ] ], "normalized": [] }, { "id": "7960", "type": "Diseases & Disorders", "text": [ "allergic reactions" ], "offsets": [ [ 1995, 2013 ] ], "normalized": [] }, { "id": "7961", "type": "", "text": [ "tropomyosin" ], "offsets": [ [ 1027, 1038 ] ], "normalized": [] }, { "id": "7962", "type": "", "text": [ "allergies" ], "offsets": [ [ 1174, 1183 ] ], "normalized": [] }, { "id": "7964", "type": "", "text": [ "tropomyosin allergens" ], "offsets": [ [ 1296, 1317 ] ], "normalized": [] }, { "id": "7965", "type": "", "text": [ "crustacean shellfish" ], "offsets": [ [ 1321, 1341 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7963", "type": "PA", "arg1_id": "7961", "arg2_id": "7962", "normalized": [] }, { "id": "7966", "type": "PA", "arg1_id": "7964", "arg2_id": "7965", "normalized": [] } ]

[ { "id": "7969", "type": "title", "text": [ "Intravascular uptake during fluoroscopically guided cervical interlaminar steroid injection at C6-7: a case report." ], "offsets": [ [ 0, 115 ] ] }, { "id": "7970", "type": "abstract", "text": [ "We report 4 cases of intravascular venous uptake of contrast material during fluoroscopically guided cervical interlaminar epidural steroid injection at the C6-7 level. The blood vessel probably involved is the posterior internal vertebral venous plexus, which drains the interlaminar space and returns blood to the right atrium through the paired vertebral veins and right and left brachiocephalic veins. In all 4 cases, intravascular uptake occurred despite negative aspiration of blood before the contrast material was injected. All patients were successfully injected at the C7-T1 level. We recommend the use of fluoroscopic guidance and the injection of contrast to identify potential placement of the injection needle within the vascular space. Potential complications of intravascular venous uptake of contrast material and steroid solution are discussed." ], "offsets": [ [ 116, 978 ] ] } ]

[ { "id": "7971", "type": "Diseases & Disorders", "text": [ "Intravascular uptake" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "7972", "type": "Chemicals & Drugs", "text": [ "fluoroscopically guided cervical interlaminar steroid injection at C6-7" ], "offsets": [ [ 28, 99 ] ], "normalized": [] }, { "id": "7973", "type": "Chemicals & Drugs", "text": [ "steroid" ], "offsets": [ [ 74, 81 ] ], "normalized": [] }, { "id": "7974", "type": "Diseases & Disorders", "text": [ "intravascular venous uptake" ], "offsets": [ [ 137, 164 ] ], "normalized": [] }, { "id": "7975", "type": "Chemicals & Drugs", "text": [ "contrast material" ], "offsets": [ [ 168, 185 ] ], "normalized": [] }, { "id": "7976", "type": "Chemicals & Drugs", "text": [ "fluoroscopically guided cervical interlaminar epidural steroid injection at the C6-7" ], "offsets": [ [ 193, 277 ] ], "normalized": [] }, { "id": "7977", "type": "Chemicals & Drugs", "text": [ "steroid" ], "offsets": [ [ 248, 255 ] ], "normalized": [] }, { "id": "7978", "type": "Diseases & Disorders", "text": [ "posterior" ], "offsets": [ [ 327, 336 ] ], "normalized": [] }, { "id": "7979", "type": "Diseases & Disorders", "text": [ "intravascular uptake" ], "offsets": [ [ 538, 558 ] ], "normalized": [] }, { "id": "7980", "type": "Diseases & Disorders", "text": [ "aspiration" ], "offsets": [ [ 585, 595 ] ], "normalized": [] }, { "id": "7981", "type": "Chemicals & Drugs", "text": [ "contrast material" ], "offsets": [ [ 616, 633 ] ], "normalized": [] }, { "id": "7982", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 877, 890 ] ], "normalized": [] }, { "id": "7983", "type": "Diseases & Disorders", "text": [ "intravascular venous uptake" ], "offsets": [ [ 894, 921 ] ], "normalized": [] }, { "id": "7984", "type": "Chemicals & Drugs", "text": [ "contrast material" ], "offsets": [ [ 925, 942 ] ], "normalized": [] }, { "id": "7985", "type": "Chemicals & Drugs", "text": [ "steroid" ], "offsets": [ [ 947, 954 ] ], "normalized": [] }, { "id": "7986", "type": "", "text": [ "steroid" ], "offsets": [ [ 248, 255 ] ], "normalized": [] }, { "id": "7987", "type": "", "text": [ "intravascular venous uptake" ], "offsets": [ [ 137, 164 ] ], "normalized": [] }, { "id": "7989", "type": "", "text": [ "steroid" ], "offsets": [ [ 947, 954 ] ], "normalized": [] }, { "id": "7990", "type": "", "text": [ "intravascular venous uptake" ], "offsets": [ [ 894, 921 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7988", "type": "SA", "arg1_id": "7986", "arg2_id": "7987", "normalized": [] }, { "id": "7991", "type": "SA", "arg1_id": "7989", "arg2_id": "7990", "normalized": [] } ]

[ { "id": "7994", "type": "title", "text": [ "Association of ApoE polymorphisms with prevalent hypertension in 1406 older adults: the Bambuí Health Aging Study (BHAS)." ], "offsets": [ [ 0, 122 ] ] }, { "id": "7995", "type": "abstract", "text": [ "Apolipoprotein E (ApoE) polymorphism influences lipid metabolism, but its association with arterial hypertension is controversial. The objective of this study was to examine the association between ApoE polymorphism and prevalent hypertension in a large unselected population of older adults. Participants from the baseline of the Bambuí Health Aging Study whose ApoE genes had been genotyped were selected for this study (N = 1406, aged 60-95 years). These subjects represented 80.7% of the total elderly residents in Bambuí city, MG, Brazil. Hypertension was defined as a systolic blood pressure > or =140 mmHg and/or a diastolic blood pressure > or =90 mmHg, or the use of anti-hypertensive medication. The exposure variable was the ApoE genotype as follows: epsilon3 carriers, epsilon3epsilon3; epsilon2 carriers, epsilon2epsilon2 or epsilon2epsilon3, and epsilon4 carriers, epsilon3epsilon4 or epsilon4epsilon4. Potential confounding variables were age, gender, traditional cardiovascular risk factors, uric acid, and creatinine levels. The prevalence of hypertension was 61.3%. Compared with the epsilon3 homozygotes, neither the epsilon2 nor the epsilon4 carrier status was associated with hypertension (adjusted prevalence ratios = 0.94, 95%CI = 0.83-1.07 and 0.98, 0.89-1.07, respectively). On the other hand, the epsilon2 allele carriers had lower LDL cholesterol levels (P < 0.001) and the epsilon4 carriers had higher LDL cholesterol levels (P = 0.036). This study provides epidemiologic evidence that the ApoE genotype is not associated with prevalent hypertension in old age." ], "offsets": [ [ 123, 1714 ] ] } ]

[ { "id": "7996", "type": "SNP & Sequence variations", "text": [ "ApoE polymorphisms" ], "offsets": [ [ 15, 33 ] ], "normalized": [] }, { "id": "7997", "type": "Genes & Molecular Sequences", "text": [ "ApoE polymorphisms" ], "offsets": [ [ 15, 33 ] ], "normalized": [] }, { "id": "7998", "type": "Diseases & Disorders", "text": [ "prevalent hypertension" ], "offsets": [ [ 39, 61 ] ], "normalized": [] }, { "id": "7999", "type": "Genes & Molecular Sequences", "text": [ " Apolipoprotein " ], "offsets": [ [ 122, 138 ] ], "normalized": [] }, { "id": "8000", "type": "SNP & Sequence variations", "text": [ "(ApoE) polymorphis" ], "offsets": [ [ 140, 158 ] ], "normalized": [] }, { "id": "8001", "type": "Genes & Molecular Sequences", "text": [ "(ApoE) polymorphis" ], "offsets": [ [ 140, 158 ] ], "normalized": [] }, { "id": "8002", "type": "Diseases & Disorders", "text": [ " arterial hypertensio" ], "offsets": [ [ 213, 234 ] ], "normalized": [] }, { "id": "8003", "type": "SNP & Sequence variations", "text": [ " ApoE polymorphis" ], "offsets": [ [ 320, 337 ] ], "normalized": [] }, { "id": "8004", "type": "Genes & Molecular Sequences", "text": [ " ApoE polymorphis" ], "offsets": [ [ 320, 337 ] ], "normalized": [] }, { "id": "8005", "type": "Diseases & Disorders", "text": [ " prevalent hypertensio" ], "offsets": [ [ 342, 364 ] ], "normalized": [] }, { "id": "8006", "type": "Genes & Molecular Sequences", "text": [ "e Ap" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "8007", "type": "Diseases & Disorders", "text": [ "l. Hypertens" ], "offsets": [ [ 666, 678 ] ], "normalized": [] }, { "id": "8008", "type": "Genes & Molecular Sequences", "text": [ "he A" ], "offsets": [ [ 858, 862 ] ], "normalized": [] }, { "id": "8009", "type": "SNP & Sequence variations", "text": [ "s: epsil" ], "offsets": [ [ 884, 892 ] ], "normalized": [] }, { "id": "8010", "type": "SNP & Sequence variations", "text": [ "s, epsilon3epsil" ], "offsets": [ [ 903, 919 ] ], "normalized": [] }, { "id": "8011", "type": "SNP & Sequence variations", "text": [ "3; epsil" ], "offsets": [ [ 921, 929 ] ], "normalized": [] }, { "id": "8012", "type": "SNP & Sequence variations", "text": [ "s, epsilon2epsil" ], "offsets": [ [ 940, 956 ] ], "normalized": [] }, { "id": "8013", "type": "SNP & Sequence variations", "text": [ "or epsilon2epsil" ], "offsets": [ [ 960, 976 ] ], "normalized": [] }, { "id": "8014", "type": "SNP & Sequence variations", "text": [ "nd epsil" ], "offsets": [ [ 982, 990 ] ], "normalized": [] }, { "id": "8015", "type": "SNP & Sequence variations", "text": [ "s, epsilon3epsil" ], "offsets": [ [ 1001, 1017 ] ], "normalized": [] }, { "id": "8016", "type": "SNP & Sequence variations", "text": [ "or epsilon4epsil" ], "offsets": [ [ 1021, 1037 ] ], "normalized": [] }, { "id": "8017", "type": "Diseases & Disorders", "text": [ "al cardiovascular risk fact" ], "offsets": [ [ 1101, 1128 ] ], "normalized": [] }, { "id": "8018", "type": "Diseases & Disorders", "text": [ "of hypertens" ], "offsets": [ [ 1182, 1194 ] ], "normalized": [] }, { "id": "8019", "type": "SNP & Sequence variations", "text": [ "he epsil" ], "offsets": [ [ 1224, 1232 ] ], "normalized": [] }, { "id": "8020", "type": "SNP & Sequence variations", "text": [ "he epsil" ], "offsets": [ [ 1258, 1266 ] ], "normalized": [] }, { "id": "8021", "type": "SNP & Sequence variations", "text": [ "he epsil" ], "offsets": [ [ 1275, 1283 ] ], "normalized": [] }, { "id": "8022", "type": "Diseases & Disorders", "text": [ "th hypertens" ], "offsets": [ [ 1319, 1331 ] ], "normalized": [] }, { "id": "8023", "type": "SNP & Sequence variations", "text": [ "he epsil" ], "offsets": [ [ 1445, 1453 ] ], "normalized": [] }, { "id": "8024", "type": "Genes & Molecular Sequences", "text": [ "er LDL choleste" ], "offsets": [ [ 1480, 1495 ] ], "normalized": [] }, { "id": "8025", "type": "SNP & Sequence variations", "text": [ "he epsil" ], "offsets": [ [ 1523, 1531 ] ], "normalized": [] }, { "id": "8026", "type": "Genes & Molecular Sequences", "text": [ "er LDL choleste" ], "offsets": [ [ 1552, 1567 ] ], "normalized": [] }, { "id": "8027", "type": "Genes & Molecular Sequences", "text": [ "he A" ], "offsets": [ [ 1640, 1644 ] ], "normalized": [] }, { "id": "8028", "type": "Diseases & Disorders", "text": [ "th prevalent hypertens" ], "offsets": [ [ 1677, 1699 ] ], "normalized": [] }, { "id": "8029", "type": "", "text": [ "ApoE polymorphisms" ], "offsets": [ [ 15, 33 ] ], "normalized": [] }, { "id": "8030", "type": "", "text": [ "prevalent hypertension" ], "offsets": [ [ 39, 61 ] ], "normalized": [] }, { "id": "8032", "type": "", "text": [ "(ApoE) polymorphis" ], "offsets": [ [ 140, 158 ] ], "normalized": [] }, { "id": "8033", "type": "", "text": [ " arterial hypertensio" ], "offsets": [ [ 213, 234 ] ], "normalized": [] }, { "id": "8035", "type": "", "text": [ " ApoE polymorphis" ], "offsets": [ [ 320, 337 ] ], "normalized": [] }, { "id": "8036", "type": "", "text": [ " prevalent hypertensio" ], "offsets": [ [ 342, 364 ] ], "normalized": [] }, { "id": "8038", "type": "", "text": [ "he epsil" ], "offsets": [ [ 1258, 1266 ] ], "normalized": [] }, { "id": "8039", "type": "", "text": [ "th hypertens" ], "offsets": [ [ 1319, 1331 ] ], "normalized": [] }, { "id": "8041", "type": "", "text": [ "he epsil" ], "offsets": [ [ 1275, 1283 ] ], "normalized": [] }, { "id": "8042", "type": "", "text": [ "th hypertens" ], "offsets": [ [ 1319, 1331 ] ], "normalized": [] }, { "id": "8044", "type": "", "text": [ "he A" ], "offsets": [ [ 1640, 1644 ] ], "normalized": [] }, { "id": "8045", "type": "", "text": [ "th prevalent hypertens" ], "offsets": [ [ 1677, 1699 ] ], "normalized": [] }, { "id": "8047", "type": "", "text": [ " Apolipoprotein " ], "offsets": [ [ 122, 138 ] ], "normalized": [] }, { "id": "8048", "type": "", "text": [ " arterial hypertensio" ], "offsets": [ [ 213, 234 ] ], "normalized": [] }, { "id": "8050", "type": "", "text": [ "he epsil" ], "offsets": [ [ 1224, 1232 ] ], "normalized": [] }, { "id": "8051", "type": "", "text": [ "th hypertens" ], "offsets": [ [ 1319, 1331 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8031", "type": "SA", "arg1_id": "8029", "arg2_id": "8030", "normalized": [] }, { "id": "8034", "type": "SA", "arg1_id": "8032", "arg2_id": "8033", "normalized": [] }, { "id": "8037", "type": "SA", "arg1_id": "8035", "arg2_id": "8036", "normalized": [] }, { "id": "8040", "type": "NA", "arg1_id": "8038", "arg2_id": "8039", "normalized": [] }, { "id": "8043", "type": "NA", "arg1_id": "8041", "arg2_id": "8042", "normalized": [] }, { "id": "8046", "type": "NA", "arg1_id": "8044", "arg2_id": "8045", "normalized": [] }, { "id": "8049", "type": "PA", "arg1_id": "8047", "arg2_id": "8048", "normalized": [] }, { "id": "8052", "type": "NA", "arg1_id": "8050", "arg2_id": "8051", "normalized": [] } ]

[ { "id": "8055", "type": "title", "text": [ "Intracameral antibiotics: questions for the United States based on prospective studies." ], "offsets": [ [ 0, 87 ] ] }, { "id": "8056", "type": "abstract", "text": [ "Recent prospective studies from Europe suggest the use of intracameral antibiotics for prophylaxis of endophthalmitis, although the studies did not make a comparison with the most common United States prophylaxis techniques. Thus, the European studies as well as the present literature were reviewed in an attempt to place the European studies in perspective with regard to the present U.S. protocol and the available literature. There is no worldwide-established approach to prophylaxis of endophthalmitis. In the absence of a strong evidence-based approach most surgeons use surrogate studies to support their techniques and mold their opinions based on their interpretation of the literature and when they believe organisms causing endophthalmitis enter the eye. The review showed that preoperative topical antibiotics limit the number of bacteria on the ocular surface at surgery and postoperative topical antibiotics are most appropriate to address postoperative inoculation until the wound is sealed (with no tapering). Whereas intracameral antibiotic injection may be an appropriate route of administration to address inoculation occurring at the time of surgery, more research on safety and effectiveness is needed before we expose the millions of eyes having cataract surgery each year. A multipronged approach to limit endophthalmitis risk is also needed, with antibiotics as only part of the strategy." ], "offsets": [ [ 88, 1500 ] ] } ]

[ { "id": "8057", "type": "Chemicals & Drugs", "text": [ "antibiotics" ], "offsets": [ [ 13, 24 ] ], "normalized": [] }, { "id": "8058", "type": "Chemicals & Drugs", "text": [ "antibiotics" ], "offsets": [ [ 159, 170 ] ], "normalized": [] }, { "id": "8059", "type": "Diseases & Disorders", "text": [ "endophthalmitis" ], "offsets": [ [ 190, 205 ] ], "normalized": [] }, { "id": "8060", "type": "Diseases & Disorders", "text": [ "endophthalmitis" ], "offsets": [ [ 579, 594 ] ], "normalized": [] }, { "id": "8061", "type": "Diseases & Disorders", "text": [ "absence" ], "offsets": [ [ 603, 610 ] ], "normalized": [] }, { "id": "8062", "type": "Diseases & Disorders", "text": [ "endophthalmitis" ], "offsets": [ [ 823, 838 ] ], "normalized": [] }, { "id": "8063", "type": "Chemicals & Drugs", "text": [ "antibiotics" ], "offsets": [ [ 898, 909 ] ], "normalized": [] }, { "id": "8064", "type": "Chemicals & Drugs", "text": [ "antibiotics" ], "offsets": [ [ 998, 1009 ] ], "normalized": [] }, { "id": "8065", "type": "Diseases & Disorders", "text": [ "wound" ], "offsets": [ [ 1078, 1083 ] ], "normalized": [] }, { "id": "8066", "type": "Chemicals & Drugs", "text": [ "intracameral antibiotic injection" ], "offsets": [ [ 1122, 1155 ] ], "normalized": [] }, { "id": "8067", "type": "Diseases & Disorders", "text": [ "cataract" ], "offsets": [ [ 1356, 1364 ] ], "normalized": [] }, { "id": "8068", "type": "Diseases & Disorders", "text": [ "endophthalmitis" ], "offsets": [ [ 1417, 1432 ] ], "normalized": [] }, { "id": "8069", "type": "Chemicals & Drugs", "text": [ "antibiotics" ], "offsets": [ [ 1459, 1470 ] ], "normalized": [] }, { "id": "8070", "type": "", "text": [ "antibiotics" ], "offsets": [ [ 159, 170 ] ], "normalized": [] }, { "id": "8071", "type": "", "text": [ "endophthalmitis" ], "offsets": [ [ 190, 205 ] ], "normalized": [] }, { "id": "8073", "type": "", "text": [ "antibiotics" ], "offsets": [ [ 998, 1009 ] ], "normalized": [] }, { "id": "8074", "type": "", "text": [ "wound" ], "offsets": [ [ 1078, 1083 ] ], "normalized": [] }, { "id": "8076", "type": "", "text": [ "intracameral antibiotic injection" ], "offsets": [ [ 1122, 1155 ] ], "normalized": [] }, { "id": "8077", "type": "", "text": [ "cataract" ], "offsets": [ [ 1356, 1364 ] ], "normalized": [] }, { "id": "8079", "type": "", "text": [ "antibiotics" ], "offsets": [ [ 1459, 1470 ] ], "normalized": [] }, { "id": "8080", "type": "", "text": [ "endophthalmitis" ], "offsets": [ [ 1417, 1432 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8072", "type": "SA", "arg1_id": "8070", "arg2_id": "8071", "normalized": [] }, { "id": "8075", "type": "PA", "arg1_id": "8073", "arg2_id": "8074", "normalized": [] }, { "id": "8078", "type": "SA", "arg1_id": "8076", "arg2_id": "8077", "normalized": [] }, { "id": "8081", "type": "PA", "arg1_id": "8079", "arg2_id": "8080", "normalized": [] } ]

[ { "id": "8084", "type": "title", "text": [ "Methods for identifying long-term adverse effects of treatment in patients with eye diseases: the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study." ], "offsets": [ [ 0, 170 ] ] }, { "id": "8085", "type": "abstract", "text": [ "PURPOSE: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. METHODS: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented. RESULTS: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immunosuppressives is ascertained from medical records of approximately 9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over approximately 100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents. CONCLUSIONS: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases." ], "offsets": [ [ 171, 2248 ] ] } ]

[ { "id": "8086", "type": "Diseases & Disorders", "text": [ "adverse effects" ], "offsets": [ [ 34, 49 ] ], "normalized": [] }, { "id": "8087", "type": "Diseases & Disorders", "text": [ "eye diseases" ], "offsets": [ [ 80, 92 ] ], "normalized": [] }, { "id": "8088", "type": "Chemicals & Drugs", "text": [ "Systemic Immunosuppressive Therapy" ], "offsets": [ [ 98, 132 ] ], "normalized": [] }, { "id": "8089", "type": "Diseases & Disorders", "text": [ "Eye Diseases" ], "offsets": [ [ 137, 149 ] ], "normalized": [] }, { "id": "8090", "type": "Diseases & Disorders", "text": [ "immunosuppression" ], "offsets": [ [ 258, 275 ] ], "normalized": [] }, { "id": "8091", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 291, 300 ] ], "normalized": [] }, { "id": "8092", "type": "Diseases & Disorders", "text": [ "fatal malignancy" ], "offsets": [ [ 305, 321 ] ], "normalized": [] }, { "id": "8093", "type": "Chemicals & Drugs", "text": [ "Systemic Immunosuppressive Therapy" ], "offsets": [ [ 369, 403 ] ], "normalized": [] }, { "id": "8094", "type": "Diseases & Disorders", "text": [ "Eye Diseases" ], "offsets": [ [ 408, 420 ] ], "normalized": [] }, { "id": "8095", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 1151, 1160 ] ], "normalized": [] }, { "id": "8096", "type": "Chemicals & Drugs", "text": [ "antimetabolites" ], "offsets": [ [ 1229, 1244 ] ], "normalized": [] }, { "id": "8097", "type": "Chemicals & Drugs", "text": [ "T-cell inhibitors" ], "offsets": [ [ 1246, 1263 ] ], "normalized": [] }, { "id": "8098", "type": "Chemicals & Drugs", "text": [ "alkylating agents" ], "offsets": [ [ 1265, 1282 ] ], "normalized": [] }, { "id": "8099", "type": "Chemicals & Drugs", "text": [ "immunosuppressives" ], "offsets": [ [ 1294, 1312 ] ], "normalized": [] }, { "id": "8100", "type": "Diseases & Disorders", "text": [ "ocular inflammation" ], "offsets": [ [ 1372, 1391 ] ], "normalized": [] }, { "id": "8101", "type": "Diseases & Disorders", "text": [ "Mortality" ], "offsets": [ [ 1447, 1456 ] ], "normalized": [] }, { "id": "8102", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 1476, 1485 ] ], "normalized": [] }, { "id": "8103", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 1696, 1705 ] ], "normalized": [] }, { "id": "8104", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 1776, 1785 ] ], "normalized": [] }, { "id": "8105", "type": "Diseases & Disorders", "text": [ "fatal malignancy" ], "offsets": [ [ 1786, 1802 ] ], "normalized": [] }, { "id": "8106", "type": "Chemicals & Drugs", "text": [ "antimetabolites" ], "offsets": [ [ 1858, 1873 ] ], "normalized": [] }, { "id": "8107", "type": "Chemicals & Drugs", "text": [ "T-cell inhibitors" ], "offsets": [ [ 1887, 1904 ] ], "normalized": [] }, { "id": "8108", "type": "Chemicals & Drugs", "text": [ "alkylating agents" ], "offsets": [ [ 1922, 1939 ] ], "normalized": [] }, { "id": "8109", "type": "Chemicals & Drugs", "text": [ "immunosuppressive drugs" ], "offsets": [ [ 2029, 2052 ] ], "normalized": [] }, { "id": "8110", "type": "Diseases & Disorders", "text": [ "ocular inflammation" ], "offsets": [ [ 2057, 2076 ] ], "normalized": [] }, { "id": "8111", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 2099, 2108 ] ], "normalized": [] }, { "id": "8112", "type": "Diseases & Disorders", "text": [ "fatal cancer" ], "offsets": [ [ 2113, 2125 ] ], "normalized": [] }, { "id": "8113", "type": "Diseases & Disorders", "text": [ "diseases" ], "offsets": [ [ 2239, 2247 ] ], "normalized": [] }, { "id": "8114", "type": "", "text": [ "antimetabolites" ], "offsets": [ [ 1229, 1244 ] ], "normalized": [] }, { "id": "8115", "type": "", "text": [ "ocular inflammation" ], "offsets": [ [ 1372, 1391 ] ], "normalized": [] }, { "id": "8117", "type": "", "text": [ "T-cell inhibitors" ], "offsets": [ [ 1246, 1263 ] ], "normalized": [] }, { "id": "8118", "type": "", "text": [ "ocular inflammation" ], "offsets": [ [ 1372, 1391 ] ], "normalized": [] }, { "id": "8120", "type": "", "text": [ "alkylating agents" ], "offsets": [ [ 1265, 1282 ] ], "normalized": [] }, { "id": "8121", "type": "", "text": [ "ocular inflammation" ], "offsets": [ [ 1372, 1391 ] ], "normalized": [] }, { "id": "8123", "type": "", "text": [ "immunosuppressives" ], "offsets": [ [ 1294, 1312 ] ], "normalized": [] }, { "id": "8124", "type": "", "text": [ "ocular inflammation" ], "offsets": [ [ 1372, 1391 ] ], "normalized": [] }, { "id": "8126", "type": "", "text": [ "antimetabolites" ], "offsets": [ [ 1858, 1873 ] ], "normalized": [] }, { "id": "8127", "type": "", "text": [ "fatal malignancy" ], "offsets": [ [ 1786, 1802 ] ], "normalized": [] }, { "id": "8129", "type": "", "text": [ "T-cell inhibitors" ], "offsets": [ [ 1887, 1904 ] ], "normalized": [] }, { "id": "8130", "type": "", "text": [ "fatal malignancy" ], "offsets": [ [ 1786, 1802 ] ], "normalized": [] }, { "id": "8132", "type": "", "text": [ "alkylating agents" ], "offsets": [ [ 1922, 1939 ] ], "normalized": [] }, { "id": "8133", "type": "", "text": [ "fatal malignancy" ], "offsets": [ [ 1786, 1802 ] ], "normalized": [] }, { "id": "8135", "type": "", "text": [ "immunosuppressive drugs" ], "offsets": [ [ 2029, 2052 ] ], "normalized": [] }, { "id": "8136", "type": "", "text": [ "ocular inflammation" ], "offsets": [ [ 2057, 2076 ] ], "normalized": [] }, { "id": "8138", "type": "", "text": [ "immunosuppressive drugs" ], "offsets": [ [ 2029, 2052 ] ], "normalized": [] }, { "id": "8139", "type": "", "text": [ "fatal cancer" ], "offsets": [ [ 2113, 2125 ] ], "normalized": [] }, { "id": "8141", "type": "", "text": [ "alkylating agents" ], "offsets": [ [ 1922, 1939 ] ], "normalized": [] }, { "id": "8142", "type": "", "text": [ "mortality" ], "offsets": [ [ 1776, 1785 ] ], "normalized": [] }, { "id": "8144", "type": "", "text": [ "T-cell inhibitors" ], "offsets": [ [ 1887, 1904 ] ], "normalized": [] }, { "id": "8145", "type": "", "text": [ "mortality" ], "offsets": [ [ 1776, 1785 ] ], "normalized": [] }, { "id": "8147", "type": "", "text": [ "antimetabolites" ], "offsets": [ [ 1858, 1873 ] ], "normalized": [] }, { "id": "8148", "type": "", "text": [ "mortality" ], "offsets": [ [ 1776, 1785 ] ], "normalized": [] }, { "id": "8150", "type": "", "text": [ "immunosuppressive drugs" ], "offsets": [ [ 2029, 2052 ] ], "normalized": [] }, { "id": "8151", "type": "", "text": [ "mortality" ], "offsets": [ [ 2099, 2108 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8116", "type": "PA", "arg1_id": "8114", "arg2_id": "8115", "normalized": [] }, { "id": "8119", "type": "PA", "arg1_id": "8117", "arg2_id": "8118", "normalized": [] }, { "id": "8122", "type": "PA", "arg1_id": "8120", "arg2_id": "8121", "normalized": [] }, { "id": "8125", "type": "PA", "arg1_id": "8123", "arg2_id": "8124", "normalized": [] }, { "id": "8128", "type": "PA", "arg1_id": "8126", "arg2_id": "8127", "normalized": [] }, { "id": "8131", "type": "PA", "arg1_id": "8129", "arg2_id": "8130", "normalized": [] }, { "id": "8134", "type": "PA", "arg1_id": "8132", "arg2_id": "8133", "normalized": [] }, { "id": "8137", "type": "SA", "arg1_id": "8135", "arg2_id": "8136", "normalized": [] }, { "id": "8140", "type": "SA", "arg1_id": "8138", "arg2_id": "8139", "normalized": [] }, { "id": "8143", "type": "PA", "arg1_id": "8141", "arg2_id": "8142", "normalized": [] }, { "id": "8146", "type": "PA", "arg1_id": "8144", "arg2_id": "8145", "normalized": [] }, { "id": "8149", "type": "PA", "arg1_id": "8147", "arg2_id": "8148", "normalized": [] }, { "id": "8152", "type": "PA", "arg1_id": "8150", "arg2_id": "8151", "normalized": [] } ]

[ { "id": "8155", "type": "title", "text": [ "Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma." ], "offsets": [ [ 0, 168 ] ] }, { "id": "8156", "type": "abstract", "text": [ "AIM: To analyze toxicity, response and outcome of a phase II trial with intensive chemotherapy plus autologous stem-cell transplantation (ASCT) for young patients with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Forty-one patients [30 males and 11 females, median age 47 years] consecutively diagnosed with PTCL received three courses of high-dose cyclophosphamide 2000 mg/m(2)/day, adriamycin 90 mg/m(2)/day, vincristine and prednisone alternating with three courses of etoposide, cisplatin, cytarabine and prednisone. Responders were submitted to ASCT. RESULTS: Sixty-eight percent of patients received the planned treatment. After chemotherapy, 20 patients reached complete response (CR), 4 partial response and 17 failed. ASCT was carried out in 17 of 24 candidates due to lack of mobilization (three cases), toxicity (two), early relapse and patient decision (one each). CR rate after treatment was 51%. With a median follow-up of 3.2 years, 5 of 21 CR patients relapsed and 2 died in CR due to secondary neoplasms. Four-year progression-free survival was 30%. Twenty-two patients have died, with a 4-year overall survival of 39%. International Prognostic Index was the main variable predicting survival. No differences were seen among the 24 candidates according to whether or not they underwent ASCT. CONCLUSION: This intensive regimen resulted in moderate CR rate, with manageable toxicity in PTCL. The contribution of ASCT in preventing relapse is debatable. Novel strategies to increase CR warrant investigation." ], "offsets": [ [ 169, 1704 ] ] } ]

[ { "id": "8157", "type": "Chemicals & Drugs", "text": [ "Intensive chemotherapy" ], "offsets": [ [ 0, 22 ] ], "normalized": [] }, { "id": "8158", "type": "Chemicals & Drugs", "text": [ "high-dose CHOP" ], "offsets": [ [ 24, 38 ] ], "normalized": [] }, { "id": "8159", "type": "Chemicals & Drugs", "text": [ "ESHAP" ], "offsets": [ [ 39, 44 ] ], "normalized": [] }, { "id": "8160", "type": "Diseases & Disorders", "text": [ "peripheral T-cell lymphoma" ], "offsets": [ [ 141, 167 ] ], "normalized": [] }, { "id": "8161", "type": "Chemicals & Drugs", "text": [ "intensive chemotherapy" ], "offsets": [ [ 241, 263 ] ], "normalized": [] }, { "id": "8162", "type": "Diseases & Disorders", "text": [ "peripheral T-cell lymphoma" ], "offsets": [ [ 337, 363 ] ], "normalized": [] }, { "id": "8163", "type": "Diseases & Disorders", "text": [ "PTCL" ], "offsets": [ [ 365, 369 ] ], "normalized": [] }, { "id": "8164", "type": "Diseases & Disorders", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8165", "type": "Chemicals & Drugs", "text": [ "high-dose cyclophosphamide" ], "offsets": [ [ 520, 546 ] ], "normalized": [] }, { "id": "8166", "type": "Chemicals & Drugs", "text": [ "adriamycin" ], "offsets": [ [ 565, 575 ] ], "normalized": [] }, { "id": "8167", "type": "Chemicals & Drugs", "text": [ "vincristine" ], "offsets": [ [ 592, 603 ] ], "normalized": [] }, { "id": "8168", "type": "Chemicals & Drugs", "text": [ "prednisone" ], "offsets": [ [ 608, 618 ] ], "normalized": [] }, { "id": "8169", "type": "Chemicals & Drugs", "text": [ "etoposide" ], "offsets": [ [ 653, 662 ] ], "normalized": [] }, { "id": "8170", "type": "Chemicals & Drugs", "text": [ "cisplatin" ], "offsets": [ [ 664, 673 ] ], "normalized": [] }, { "id": "8171", "type": "Chemicals & Drugs", "text": [ "cytarabine" ], "offsets": [ [ 675, 685 ] ], "normalized": [] }, { "id": "8172", "type": "Chemicals & Drugs", "text": [ "prednisone" ], "offsets": [ [ 690, 700 ] ], "normalized": [] }, { "id": "8173", "type": "Diseases & Disorders", "text": [ "relapse" ], "offsets": [ [ 1017, 1024 ] ], "normalized": [] }, { "id": "8174", "type": "Diseases & Disorders", "text": [ "relapsed" ], "offsets": [ [ 1149, 1157 ] ], "normalized": [] }, { "id": "8175", "type": "Diseases & Disorders", "text": [ "secondary neoplasms" ], "offsets": [ [ 1182, 1201 ] ], "normalized": [] }, { "id": "8176", "type": "Chemicals & Drugs", "text": [ "intensive regimen" ], "offsets": [ [ 1507, 1524 ] ], "normalized": [] }, { "id": "8177", "type": "Diseases & Disorders", "text": [ "PTCL" ], "offsets": [ [ 1583, 1587 ] ], "normalized": [] }, { "id": "8178", "type": "Diseases & Disorders", "text": [ "relapse" ], "offsets": [ [ 1628, 1635 ] ], "normalized": [] }, { "id": "8179", "type": "", "text": [ "adriamycin" ], "offsets": [ [ 565, 575 ] ], "normalized": [] }, { "id": "8180", "type": "", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8182", "type": "", "text": [ "vincristine" ], "offsets": [ [ 592, 603 ] ], "normalized": [] }, { "id": "8183", "type": "", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8185", "type": "", "text": [ "prednisone" ], "offsets": [ [ 690, 700 ] ], "normalized": [] }, { "id": "8186", "type": "", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8188", "type": "", "text": [ "etoposide" ], "offsets": [ [ 653, 662 ] ], "normalized": [] }, { "id": "8189", "type": "", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8191", "type": "", "text": [ "cisplatin" ], "offsets": [ [ 664, 673 ] ], "normalized": [] }, { "id": "8192", "type": "", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8194", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 675, 685 ] ], "normalized": [] }, { "id": "8195", "type": "", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8197", "type": "", "text": [ "high-dose cyclophosphamide" ], "offsets": [ [ 520, 546 ] ], "normalized": [] }, { "id": "8198", "type": "", "text": [ "PTCL" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "8200", "type": "", "text": [ "intensive regimen" ], "offsets": [ [ 1507, 1524 ] ], "normalized": [] }, { "id": "8201", "type": "", "text": [ "PTCL" ], "offsets": [ [ 1583, 1587 ] ], "normalized": [] }, { "id": "8203", "type": "", "text": [ "Intensive chemotherapy" ], "offsets": [ [ 0, 22 ] ], "normalized": [] }, { "id": "8204", "type": "", "text": [ "peripheral T-cell lymphoma" ], "offsets": [ [ 141, 167 ] ], "normalized": [] }, { "id": "8206", "type": "", "text": [ "high-dose CHOP" ], "offsets": [ [ 24, 38 ] ], "normalized": [] }, { "id": "8207", "type": "", "text": [ "peripheral T-cell lymphoma" ], "offsets": [ [ 141, 167 ] ], "normalized": [] }, { "id": "8209", "type": "", "text": [ "intensive chemotherapy" ], "offsets": [ [ 241, 263 ] ], "normalized": [] }, { "id": "8210", "type": "", "text": [ "PTCL" ], "offsets": [ [ 365, 369 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8181", "type": "PA", "arg1_id": "8179", "arg2_id": "8180", "normalized": [] }, { "id": "8184", "type": "PA", "arg1_id": "8182", "arg2_id": "8183", "normalized": [] }, { "id": "8187", "type": "PA", "arg1_id": "8185", "arg2_id": "8186", "normalized": [] }, { "id": "8190", "type": "PA", "arg1_id": "8188", "arg2_id": "8189", "normalized": [] }, { "id": "8193", "type": "PA", "arg1_id": "8191", "arg2_id": "8192", "normalized": [] }, { "id": "8196", "type": "PA", "arg1_id": "8194", "arg2_id": "8195", "normalized": [] }, { "id": "8199", "type": "PA", "arg1_id": "8197", "arg2_id": "8198", "normalized": [] }, { "id": "8202", "type": "PA", "arg1_id": "8200", "arg2_id": "8201", "normalized": [] }, { "id": "8205", "type": "PA", "arg1_id": "8203", "arg2_id": "8204", "normalized": [] }, { "id": "8208", "type": "PA", "arg1_id": "8206", "arg2_id": "8207", "normalized": [] }, { "id": "8211", "type": "PA", "arg1_id": "8209", "arg2_id": "8210", "normalized": [] } ]

[ { "id": "8214", "type": "title", "text": [ "IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple sclerosis." ], "offsets": [ [ 0, 88 ] ] }, { "id": "8215", "type": "abstract", "text": [ "Different research groups have extensively studied the associations of cytokine gene polymorphisms in different diseases. The role of cytokines gene polymorphisms in multiple sclerosis (MS), as a chronic Immune-mediated neurodegenerative disease, has been previously reported in the various populations. For determining pro-inflammatory cytokine gene polymorphisms, 100 relapsing remitting multiple sclerosis (RRMS) Iranian patients and 140 normal individuals as control enrolled in this study. DNA of each sample was extracted by a modified salting out method. Cytokine single gene nucleotide polymorphisms including IL-1alpha -889, IL-1beta (-511 and +3962), IL-1R pst1 1970, IL-1RA mspal 11100, and TNF-alpha (-308 and -238) were determined by using the PCR-SSP method. The results of our data indicate the decrease in frequency of IL-1alpha TC-889 genotype (p=0.002), IL-1beta TC +3962 genotype (p=0.004), IL-1R T pst1 1970 allele (p= 0.0001), IL-1 RA TC Mspa1 11100 genotype (p=0.009), TNF-alpha A-308 allele (p=0.0002) and AG genotype (p=0.00001) in the patients group versus normal subjects. On the other hand the frequency of IL-1alpha TT -889 genotype (p=0.028), IL-1R C pst1 1970 allele (p=0.0001) and CC genotype (p=0.00006), TNFalpha G -308 allele (p=0.0002) and GG genotype (p=0.000001) decreased significantly in the patients versus normal subjects.These results suggest that polymorphic variations of these pro-inflammatory cytokines may play an important role in susceptibility of Iranian multiple sclerosis patients." ], "offsets": [ [ 89, 1622 ] ] } ]

[ { "id": "8216", "type": "SNP & Sequence variations", "text": [ "IL-1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "8217", "type": "Genes & Molecular Sequences", "text": [ "IL-1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "8218", "type": "SNP & Sequence variations", "text": [ "IL-1R" ], "offsets": [ [ 6, 11 ] ], "normalized": [] }, { "id": "8219", "type": "Genes & Molecular Sequences", "text": [ "IL-1R" ], "offsets": [ [ 6, 11 ] ], "normalized": [] }, { "id": "8220", "type": "SNP & Sequence variations", "text": [ "TNFalpha gene polymorphisms" ], "offsets": [ [ 16, 43 ] ], "normalized": [] }, { "id": "8221", "type": "Genes & Molecular Sequences", "text": [ "TNFalpha gene polymorphisms" ], "offsets": [ [ 16, 43 ] ], "normalized": [] }, { "id": "8222", "type": "Diseases & Disorders", "text": [ "multiple sclerosis" ], "offsets": [ [ 69, 87 ] ], "normalized": [] }, { "id": "8223", "type": "SNP & Sequence variations", "text": [ "cytokine gene polymorphisms" ], "offsets": [ [ 160, 187 ] ], "normalized": [] }, { "id": "8224", "type": "Genes & Molecular Sequences", "text": [ "cytokine gene polymorphisms" ], "offsets": [ [ 160, 187 ] ], "normalized": [] }, { "id": "8225", "type": "Diseases & Disorders", "text": [ "diseases" ], "offsets": [ [ 201, 209 ] ], "normalized": [] }, { "id": "8226", "type": "SNP & Sequence variations", "text": [ "cytokines gene polymorphisms" ], "offsets": [ [ 223, 251 ] ], "normalized": [] }, { "id": "8227", "type": "Diseases & Disorders", "text": [ "multiple sclerosis" ], "offsets": [ [ 255, 273 ] ], "normalized": [] }, { "id": "8228", "type": "Diseases & Disorders", "text": [ "MS" ], "offsets": [ [ 275, 277 ] ], "normalized": [] }, { "id": "8229", "type": "Diseases & Disorders", "text": [ "chronic Immune-mediated neurodegenerative disease" ], "offsets": [ [ 285, 334 ] ], "normalized": [] }, { "id": "8230", "type": "SNP & Sequence variations", "text": [ "cytokine gene polymorphisms" ], "offsets": [ [ 426, 453 ] ], "normalized": [] }, { "id": "8231", "type": "Genes & Molecular Sequences", "text": [ "cytokine gene polymorphisms" ], "offsets": [ [ 426, 453 ] ], "normalized": [] }, { "id": "8232", "type": "Diseases & Disorders", "text": [ "relapsing remitting multiple sclerosis" ], "offsets": [ [ 459, 497 ] ], "normalized": [] }, { "id": "8233", "type": "Diseases & Disorders", "text": [ "RRMS" ], "offsets": [ [ 499, 503 ] ], "normalized": [] }, { "id": "8234", "type": "Genes & Molecular Sequences", "text": [ "Cytokine" ], "offsets": [ [ 651, 659 ] ], "normalized": [] }, { "id": "8235", "type": "SNP & Sequence variations", "text": [ "IL-1alpha -889" ], "offsets": [ [ 707, 721 ] ], "normalized": [] }, { "id": "8236", "type": "Genes & Molecular Sequences", "text": [ "IL-1alpha -889" ], "offsets": [ [ 707, 721 ] ], "normalized": [] }, { "id": "8237", "type": "SNP & Sequence variations", "text": [ "IL-1beta (-511" ], "offsets": [ [ 723, 737 ] ], "normalized": [] }, { "id": "8238", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta (-511" ], "offsets": [ [ 723, 737 ] ], "normalized": [] }, { "id": "8239", "type": "SNP & Sequence variations", "text": [ "+3962" ], "offsets": [ [ 742, 747 ] ], "normalized": [] }, { "id": "8240", "type": "SNP & Sequence variations", "text": [ "IL-1R pst1 1970" ], "offsets": [ [ 750, 765 ] ], "normalized": [] }, { "id": "8241", "type": "Genes & Molecular Sequences", "text": [ "IL-1R pst1 1970" ], "offsets": [ [ 750, 765 ] ], "normalized": [] }, { "id": "8242", "type": "Genes & Molecular Sequences", "text": [ "pst1" ], "offsets": [ [ 756, 760 ] ], "normalized": [] }, { "id": "8243", "type": "SNP & Sequence variations", "text": [ "pst1" ], "offsets": [ [ 756, 760 ] ], "normalized": [] }, { "id": "8244", "type": "SNP & Sequence variations", "text": [ "IL-1RA mspal 11100" ], "offsets": [ [ 767, 785 ] ], "normalized": [] }, { "id": "8245", "type": "Genes & Molecular Sequences", "text": [ "IL-1RA mspal 11100" ], "offsets": [ [ 767, 785 ] ], "normalized": [] }, { "id": "8246", "type": "SNP & Sequence variations", "text": [ "TNF-alpha (-308" ], "offsets": [ [ 791, 806 ] ], "normalized": [] }, { "id": "8247", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha (-308" ], "offsets": [ [ 791, 806 ] ], "normalized": [] }, { "id": "8248", "type": "SNP & Sequence variations", "text": [ "-238" ], "offsets": [ [ 811, 815 ] ], "normalized": [] }, { "id": "8249", "type": "SNP & Sequence variations", "text": [ "IL-1alpha TC-889" ], "offsets": [ [ 924, 940 ] ], "normalized": [] }, { "id": "8250", "type": "Genes & Molecular Sequences", "text": [ "IL-1alpha TC-889" ], "offsets": [ [ 924, 940 ] ], "normalized": [] }, { "id": "8251", "type": "SNP & Sequence variations", "text": [ "IL-1beta TC +3962" ], "offsets": [ [ 961, 978 ] ], "normalized": [] }, { "id": "8252", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta TC +3962" ], "offsets": [ [ 961, 978 ] ], "normalized": [] }, { "id": "8253", "type": "SNP & Sequence variations", "text": [ "IL-1R T pst1 1970 allele" ], "offsets": [ [ 999, 1023 ] ], "normalized": [] }, { "id": "8254", "type": "Genes & Molecular Sequences", "text": [ "IL-1R T pst1 1970 allele" ], "offsets": [ [ 999, 1023 ] ], "normalized": [] }, { "id": "8255", "type": "Genes & Molecular Sequences", "text": [ "pst1" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [] }, { "id": "8256", "type": "SNP & Sequence variations", "text": [ "pst1" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [] }, { "id": "8257", "type": "SNP & Sequence variations", "text": [ "IL-1 RA TC Mspa1 11100" ], "offsets": [ [ 1037, 1059 ] ], "normalized": [] }, { "id": "8258", "type": "Genes & Molecular Sequences", "text": [ "IL-1 RA TC Mspa1 11100" ], "offsets": [ [ 1037, 1059 ] ], "normalized": [] }, { "id": "8259", "type": "SNP & Sequence variations", "text": [ "TNF-alpha A-308 allele" ], "offsets": [ [ 1080, 1102 ] ], "normalized": [] }, { "id": "8260", "type": "Genes & Molecular Sequences", "text": [ "TNF-alpha A-308 allele" ], "offsets": [ [ 1080, 1102 ] ], "normalized": [] }, { "id": "8261", "type": "SNP & Sequence variations", "text": [ "A-308" ], "offsets": [ [ 1090, 1095 ] ], "normalized": [] }, { "id": "8262", "type": "SNP & Sequence variations", "text": [ "AG" ], "offsets": [ [ 1118, 1120 ] ], "normalized": [] }, { "id": "8263", "type": "SNP & Sequence variations", "text": [ "IL-1alpha TT -889" ], "offsets": [ [ 1223, 1240 ] ], "normalized": [] }, { "id": "8264", "type": "Genes & Molecular Sequences", "text": [ "IL-1alpha TT -889" ], "offsets": [ [ 1223, 1240 ] ], "normalized": [] }, { "id": "8265", "type": "SNP & Sequence variations", "text": [ "IL-1R C pst1 1970 allele" ], "offsets": [ [ 1261, 1285 ] ], "normalized": [] }, { "id": "8266", "type": "Genes & Molecular Sequences", "text": [ "IL-1R C pst1 1970 allele" ], "offsets": [ [ 1261, 1285 ] ], "normalized": [] }, { "id": "8267", "type": "Genes & Molecular Sequences", "text": [ "pst1" ], "offsets": [ [ 1269, 1273 ] ], "normalized": [] }, { "id": "8268", "type": "SNP & Sequence variations", "text": [ "pst1" ], "offsets": [ [ 1269, 1273 ] ], "normalized": [] }, { "id": "8269", "type": "SNP & Sequence variations", "text": [ "CC" ], "offsets": [ [ 1301, 1303 ] ], "normalized": [] }, { "id": "8270", "type": "SNP & Sequence variations", "text": [ "TNFalpha G -308 allele" ], "offsets": [ [ 1326, 1348 ] ], "normalized": [] }, { "id": "8271", "type": "Genes & Molecular Sequences", "text": [ "TNFalpha G -308 allele" ], "offsets": [ [ 1326, 1348 ] ], "normalized": [] }, { "id": "8272", "type": "SNP & Sequence variations", "text": [ "G -308" ], "offsets": [ [ 1335, 1341 ] ], "normalized": [] }, { "id": "8273", "type": "SNP & Sequence variations", "text": [ "GG" ], "offsets": [ [ 1364, 1366 ] ], "normalized": [] }, { "id": "8274", "type": "Genes & Molecular Sequences", "text": [ "pro-inflammatory cytokines" ], "offsets": [ [ 1511, 1537 ] ], "normalized": [] }, { "id": "8275", "type": "Diseases & Disorders", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] }, { "id": "8276", "type": "", "text": [ "pro-inflammatory cytokines" ], "offsets": [ [ 1511, 1537 ] ], "normalized": [] }, { "id": "8277", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] }, { "id": "8279", "type": "", "text": [ "IL-1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "8280", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 69, 87 ] ], "normalized": [] }, { "id": "8282", "type": "", "text": [ "TNFalpha gene polymorphisms" ], "offsets": [ [ 16, 43 ] ], "normalized": [] }, { "id": "8283", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 69, 87 ] ], "normalized": [] }, { "id": "8285", "type": "", "text": [ "TNFalpha G -308 allele" ], "offsets": [ [ 1326, 1348 ] ], "normalized": [] }, { "id": "8286", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] }, { "id": "8288", "type": "", "text": [ "pst1" ], "offsets": [ [ 1269, 1273 ] ], "normalized": [] }, { "id": "8289", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] }, { "id": "8291", "type": "", "text": [ "IL-1R" ], "offsets": [ [ 6, 11 ] ], "normalized": [] }, { "id": "8292", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 69, 87 ] ], "normalized": [] }, { "id": "8294", "type": "", "text": [ "cytokine gene polymorphisms" ], "offsets": [ [ 426, 453 ] ], "normalized": [] }, { "id": "8295", "type": "", "text": [ "relapsing remitting multiple sclerosis" ], "offsets": [ [ 459, 497 ] ], "normalized": [] }, { "id": "8297", "type": "", "text": [ "cytokine gene polymorphisms" ], "offsets": [ [ 426, 453 ] ], "normalized": [] }, { "id": "8298", "type": "", "text": [ "RRMS" ], "offsets": [ [ 499, 503 ] ], "normalized": [] }, { "id": "8300", "type": "", "text": [ "IL-1R C pst1 1970 allele" ], "offsets": [ [ 1261, 1285 ] ], "normalized": [] }, { "id": "8301", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] }, { "id": "8303", "type": "", "text": [ "IL-1alpha TT -889" ], "offsets": [ [ 1223, 1240 ] ], "normalized": [] }, { "id": "8304", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] }, { "id": "8306", "type": "", "text": [ "G -308" ], "offsets": [ [ 1335, 1341 ] ], "normalized": [] }, { "id": "8307", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] }, { "id": "8309", "type": "", "text": [ "GG" ], "offsets": [ [ 1364, 1366 ] ], "normalized": [] }, { "id": "8310", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 1594, 1612 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8278", "type": "SA", "arg1_id": "8276", "arg2_id": "8277", "normalized": [] }, { "id": "8281", "type": "PA", "arg1_id": "8279", "arg2_id": "8280", "normalized": [] }, { "id": "8284", "type": "PA", "arg1_id": "8282", "arg2_id": "8283", "normalized": [] }, { "id": "8287", "type": "PA", "arg1_id": "8285", "arg2_id": "8286", "normalized": [] }, { "id": "8290", "type": "PA", "arg1_id": "8288", "arg2_id": "8289", "normalized": [] }, { "id": "8293", "type": "SA", "arg1_id": "8291", "arg2_id": "8292", "normalized": [] }, { "id": "8296", "type": "SA", "arg1_id": "8294", "arg2_id": "8295", "normalized": [] }, { "id": "8299", "type": "SA", "arg1_id": "8297", "arg2_id": "8298", "normalized": [] }, { "id": "8302", "type": "PA", "arg1_id": "8300", "arg2_id": "8301", "normalized": [] }, { "id": "8305", "type": "PA", "arg1_id": "8303", "arg2_id": "8304", "normalized": [] }, { "id": "8308", "type": "PA", "arg1_id": "8306", "arg2_id": "8307", "normalized": [] }, { "id": "8311", "type": "PA", "arg1_id": "8309", "arg2_id": "8310", "normalized": [] } ]

[ { "id": "8314", "type": "title", "text": [ "Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor." ], "offsets": [ [ 0, 218 ] ] }, { "id": "8315", "type": "abstract", "text": [ "Neuropeptide S (NPS) has been shown to modulate arousal, sleep wakefulness, anxiety-like behavior, and feeding after central administration of the peptide agonist to mice or rats. We report here the chemical synthesis and pharmacological characterization of SHA 66 (3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid benzylamide) and SHA 68 (3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide), two closely related bicyclic piperazines with antagonistic properties at the NPS receptor (NPSR). The compounds block NPS-induced Ca2+ mobilization, and SHA 68 shows displaceable binding to NPSR in the nanomolar range. The antagonistic activity of SHA 68 seems to be specific because it does not affect signaling at 14 unrelated G protein-coupled receptors. Analysis of pharmacokinetic parameters of SHA 68 demonstrates that the compound reaches pharmacologically relevant levels in plasma and brain after i.p. administration. Furthermore, peripheral administration of SHA 68 in mice (50 mg/kg i.p.) is able to antagonize NPS-induced horizontal and vertical activity as well as stereotypic behavior. Therefore, SHA 68 could be a useful tool to characterize physiological functions and pharmacological parameters of the NPS system in vitro and in vivo." ], "offsets": [ [ 219, 1526 ] ] } ]

[ { "id": "8316", "type": "Chemicals & Drugs", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide" ], "offsets": [ [ 62, 153 ] ], "normalized": [] }, { "id": "8317", "type": "Chemicals & Drugs", "text": [ "SHA 68" ], "offsets": [ [ 155, 161 ] ], "normalized": [] }, { "id": "8318", "type": "Genes & Molecular Sequences", "text": [ "neuropeptide S receptor" ], "offsets": [ [ 194, 217 ] ], "normalized": [] }, { "id": "8319", "type": "Genes & Molecular Sequences", "text": [ "Neuropeptide S" ], "offsets": [ [ 219, 233 ] ], "normalized": [] }, { "id": "8320", "type": "Genes & Molecular Sequences", "text": [ "NPS" ], "offsets": [ [ 235, 238 ] ], "normalized": [] }, { "id": "8321", "type": "Chemicals & Drugs", "text": [ "SHA 66" ], "offsets": [ [ 477, 483 ] ], "normalized": [] }, { "id": "8322", "type": "Chemicals & Drugs", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid benzylamide" ], "offsets": [ [ 485, 567 ] ], "normalized": [] }, { "id": "8323", "type": "Chemicals & Drugs", "text": [ "SHA 68" ], "offsets": [ [ 573, 579 ] ], "normalized": [] }, { "id": "8324", "type": "Chemicals & Drugs", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide" ], "offsets": [ [ 581, 672 ] ], "normalized": [] }, { "id": "8325", "type": "Genes & Molecular Sequences", "text": [ "NPS receptor" ], "offsets": [ [ 752, 764 ] ], "normalized": [] }, { "id": "8326", "type": "Genes & Molecular Sequences", "text": [ "NPSR" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "8327", "type": "Genes & Molecular Sequences", "text": [ "NPS" ], "offsets": [ [ 793, 796 ] ], "normalized": [] }, { "id": "8328", "type": "Chemicals & Drugs", "text": [ "SHA 68" ], "offsets": [ [ 828, 834 ] ], "normalized": [] }, { "id": "8329", "type": "Genes & Molecular Sequences", "text": [ "NPSR" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "8330", "type": "Chemicals & Drugs", "text": [ "SHA 68" ], "offsets": [ [ 923, 929 ] ], "normalized": [] }, { "id": "8331", "type": "Genes & Molecular Sequences", "text": [ "G protein-coupled receptors" ], "offsets": [ [ 1004, 1031 ] ], "normalized": [] }, { "id": "8332", "type": "Chemicals & Drugs", "text": [ "SHA 68" ], "offsets": [ [ 1075, 1081 ] ], "normalized": [] }, { "id": "8333", "type": "Chemicals & Drugs", "text": [ "SHA 68" ], "offsets": [ [ 1244, 1250 ] ], "normalized": [] }, { "id": "8334", "type": "Genes & Molecular Sequences", "text": [ "NPS" ], "offsets": [ [ 1297, 1300 ] ], "normalized": [] }, { "id": "8335", "type": "Chemicals & Drugs", "text": [ "SHA 68" ], "offsets": [ [ 1386, 1392 ] ], "normalized": [] }, { "id": "8336", "type": "Genes & Molecular Sequences", "text": [ "NPS" ], "offsets": [ [ 1494, 1497 ] ], "normalized": [] }, { "id": "8337", "type": "", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide" ], "offsets": [ [ 62, 153 ] ], "normalized": [] }, { "id": "8338", "type": "", "text": [ "neuropeptide S receptor" ], "offsets": [ [ 194, 217 ] ], "normalized": [] }, { "id": "8340", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 155, 161 ] ], "normalized": [] }, { "id": "8341", "type": "", "text": [ "neuropeptide S receptor" ], "offsets": [ [ 194, 217 ] ], "normalized": [] }, { "id": "8343", "type": "", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide" ], "offsets": [ [ 581, 672 ] ], "normalized": [] }, { "id": "8344", "type": "", "text": [ "NPSR" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "8346", "type": "", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide" ], "offsets": [ [ 581, 672 ] ], "normalized": [] }, { "id": "8347", "type": "", "text": [ "NPS receptor" ], "offsets": [ [ 752, 764 ] ], "normalized": [] }, { "id": "8349", "type": "", "text": [ "SHA 66" ], "offsets": [ [ 477, 483 ] ], "normalized": [] }, { "id": "8350", "type": "", "text": [ "NPSR" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "8352", "type": "", "text": [ "SHA 66" ], "offsets": [ [ 477, 483 ] ], "normalized": [] }, { "id": "8353", "type": "", "text": [ "NPS receptor" ], "offsets": [ [ 752, 764 ] ], "normalized": [] }, { "id": "8355", "type": "", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid benzylamide" ], "offsets": [ [ 485, 567 ] ], "normalized": [] }, { "id": "8356", "type": "", "text": [ "NPSR" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "8358", "type": "", "text": [ "3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid benzylamide" ], "offsets": [ [ 485, 567 ] ], "normalized": [] }, { "id": "8359", "type": "", "text": [ "NPS receptor" ], "offsets": [ [ 752, 764 ] ], "normalized": [] }, { "id": "8361", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 573, 579 ] ], "normalized": [] }, { "id": "8362", "type": "", "text": [ "NPSR" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "8364", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 573, 579 ] ], "normalized": [] }, { "id": "8365", "type": "", "text": [ "NPS receptor" ], "offsets": [ [ 752, 764 ] ], "normalized": [] }, { "id": "8367", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 828, 834 ] ], "normalized": [] }, { "id": "8368", "type": "", "text": [ "NPSR" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "8370", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 1244, 1250 ] ], "normalized": [] }, { "id": "8371", "type": "", "text": [ "NPS" ], "offsets": [ [ 1297, 1300 ] ], "normalized": [] }, { "id": "8373", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 1386, 1392 ] ], "normalized": [] }, { "id": "8374", "type": "", "text": [ "NPS" ], "offsets": [ [ 1494, 1497 ] ], "normalized": [] }, { "id": "8376", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 828, 834 ] ], "normalized": [] }, { "id": "8377", "type": "", "text": [ "NPS" ], "offsets": [ [ 793, 796 ] ], "normalized": [] }, { "id": "8379", "type": "", "text": [ "SHA 68" ], "offsets": [ [ 923, 929 ] ], "normalized": [] }, { "id": "8380", "type": "", "text": [ "G protein-coupled receptors" ], "offsets": [ [ 1004, 1031 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8339", "type": "PA", "arg1_id": "8337", "arg2_id": "8338", "normalized": [] }, { "id": "8342", "type": "PA", "arg1_id": "8340", "arg2_id": "8341", "normalized": [] }, { "id": "8345", "type": "PA", "arg1_id": "8343", "arg2_id": "8344", "normalized": [] }, { "id": "8348", "type": "PA", "arg1_id": "8346", "arg2_id": "8347", "normalized": [] }, { "id": "8351", "type": "PA", "arg1_id": "8349", "arg2_id": "8350", "normalized": [] }, { "id": "8354", "type": "PA", "arg1_id": "8352", "arg2_id": "8353", "normalized": [] }, { "id": "8357", "type": "PA", "arg1_id": "8355", "arg2_id": "8356", "normalized": [] }, { "id": "8360", "type": "PA", "arg1_id": "8358", "arg2_id": "8359", "normalized": [] }, { "id": "8363", "type": "PA", "arg1_id": "8361", "arg2_id": "8362", "normalized": [] }, { "id": "8366", "type": "PA", "arg1_id": "8364", "arg2_id": "8365", "normalized": [] }, { "id": "8369", "type": "PA", "arg1_id": "8367", "arg2_id": "8368", "normalized": [] }, { "id": "8372", "type": "PA", "arg1_id": "8370", "arg2_id": "8371", "normalized": [] }, { "id": "8375", "type": "PA", "arg1_id": "8373", "arg2_id": "8374", "normalized": [] }, { "id": "8378", "type": "PA", "arg1_id": "8376", "arg2_id": "8377", "normalized": [] }, { "id": "8381", "type": "NA", "arg1_id": "8379", "arg2_id": "8380", "normalized": [] } ]

[ { "id": "8384", "type": "title", "text": [ "Acute myeloid leukaemia blast cells with a tyrosine kinase domain mutation of FLT3 are less sensitive to lestaurtinib than those with a FLT3 internal tandem duplication." ], "offsets": [ [ 0, 169 ] ] }, { "id": "8385", "type": "abstract", "text": [ "FLT3 tyrosine kinase domain mutations (FLT3/TKDs) are associated with a favourable prognosis in acute myeloid leukaemia (AML), unlike FLT3 internal tandem duplications (FLT3/ITDs) that have a poor prognosis. Whilst FLT3/ITD+ cells are more susceptible to the cytotoxic effects of FLT3 inhibitors than wild type (WT) cells, the sensitivity of FLT3/TKD+ cells to therapeutic agents is unclear, as is the importance of the mutant level. We therefore studied the effect of cytarabine and the FLT3 inhibitor lestaurtinib, either alone or in combination, on in vitro survival of blast cells from 36 cases of AML (14 FLT3/WT, 11 FLT3/ITD+ and 11 FLT3/TKD+). All three groups showed similar sensitivity to the cytotoxic effects of cytarabine but FLT3/ITD mutant level was inversely correlated with cytarabine cytotoxicity (P = 0.04) whereas FLT3/TKD mutant level had no impact. FLT3/TKD+ cells showed a similar response to lestaurtinib as FLT3/WT cells, whereas FLT3/ITD+ cells were more sensitive (P = 0.004). There was no correlation between mutant level and lestaurtinib sensitivity for either FLT3/ITD+ or FLT3/TKD+ cells. Synergistic cytotoxicity of lestaurtinib plus cytarabine was demonstrated in all three groups. These results suggest that FLT3/TKD+ and FLT3/WT cases should not be differentiated when considering patients for treatment with FLT3 inhibitors." ], "offsets": [ [ 170, 1529 ] ] } ]

[ { "id": "8386", "type": "Chemicals & Drugs", "text": [ "blast" ], "offsets": [ [ 24, 29 ] ], "normalized": [] }, { "id": "8387", "type": "SNP & Sequence variations", "text": [ "tyrosine kinase domain mutation of FLT3" ], "offsets": [ [ 43, 82 ] ], "normalized": [] }, { "id": "8388", "type": "Genes & Molecular Sequences", "text": [ "tyrosine kinase domain mutation of FLT3" ], "offsets": [ [ 43, 82 ] ], "normalized": [] }, { "id": "8389", "type": "Chemicals & Drugs", "text": [ "lestaurtinib" ], "offsets": [ [ 105, 117 ] ], "normalized": [] }, { "id": "8390", "type": "SNP & Sequence variations", "text": [ "FLT3 internal tandem duplication" ], "offsets": [ [ 136, 168 ] ], "normalized": [] }, { "id": "8391", "type": "Genes & Molecular Sequences", "text": [ "FLT3 internal tandem duplication" ], "offsets": [ [ 136, 168 ] ], "normalized": [] }, { "id": "8392", "type": "SNP & Sequence variations", "text": [ "FLT3 tyrosine kinase domain mutations" ], "offsets": [ [ 170, 207 ] ], "normalized": [] }, { "id": "8393", "type": "Genes & Molecular Sequences", "text": [ "FLT3 tyrosine kinase domain mutations" ], "offsets": [ [ 170, 207 ] ], "normalized": [] }, { "id": "8394", "type": "SNP & Sequence variations", "text": [ "FLT3/TKDs" ], "offsets": [ [ 209, 218 ] ], "normalized": [] }, { "id": "8395", "type": "Genes & Molecular Sequences", "text": [ "FLT3/TKDs" ], "offsets": [ [ 209, 218 ] ], "normalized": [] }, { "id": "8396", "type": "SNP & Sequence variations", "text": [ "FLT3 internal tandem duplications" ], "offsets": [ [ 304, 337 ] ], "normalized": [] }, { "id": "8397", "type": "Genes & Molecular Sequences", "text": [ "FLT3 internal tandem duplications" ], "offsets": [ [ 304, 337 ] ], "normalized": [] }, { "id": "8398", "type": "SNP & Sequence variations", "text": [ "FLT3/ITDs" ], "offsets": [ [ 339, 348 ] ], "normalized": [] }, { "id": "8399", "type": "Genes & Molecular Sequences", "text": [ "FLT3/ITDs" ], "offsets": [ [ 339, 348 ] ], "normalized": [] }, { "id": "8400", "type": "SNP & Sequence variations", "text": [ "FLT3/ITD+" ], "offsets": [ [ 385, 394 ] ], "normalized": [] }, { "id": "8401", "type": "Genes & Molecular Sequences", "text": [ "FLT3/ITD+" ], "offsets": [ [ 385, 394 ] ], "normalized": [] }, { "id": "8402", "type": "SNP & Sequence variations", "text": [ "ITD" ], "offsets": [ [ 390, 393 ] ], "normalized": [] }, { "id": "8403", "type": "Chemicals & Drugs", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 450, 465 ] ], "normalized": [] }, { "id": "8404", "type": "Genes & Molecular Sequences", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 450, 465 ] ], "normalized": [] }, { "id": "8405", "type": "SNP & Sequence variations", "text": [ "WT" ], "offsets": [ [ 482, 484 ] ], "normalized": [] }, { "id": "8406", "type": "SNP & Sequence variations", "text": [ "FLT3/TKD+" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "8407", "type": "Genes & Molecular Sequences", "text": [ "FLT3/TKD+" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "8408", "type": "Chemicals & Drugs", "text": [ "cytarabine" ], "offsets": [ [ 639, 649 ] ], "normalized": [] }, { "id": "8409", "type": "Chemicals & Drugs", "text": [ "FLT3 inhibitor" ], "offsets": [ [ 658, 672 ] ], "normalized": [] }, { "id": "8410", "type": "Genes & Molecular Sequences", "text": [ "FLT3 inhibitor" ], "offsets": [ [ 658, 672 ] ], "normalized": [] }, { "id": "8411", "type": "Chemicals & Drugs", "text": [ "lestaurtinib" ], "offsets": [ [ 673, 685 ] ], "normalized": [] }, { "id": "8412", "type": "Chemicals & Drugs", "text": [ "blast" ], "offsets": [ [ 743, 748 ] ], "normalized": [] }, { "id": "8413", "type": "SNP & Sequence variations", "text": [ "FLT3/WT" ], "offsets": [ [ 780, 787 ] ], "normalized": [] }, { "id": "8414", "type": "Genes & Molecular Sequences", "text": [ "FLT3/WT" ], "offsets": [ [ 780, 787 ] ], "normalized": [] }, { "id": "8415", "type": "SNP & Sequence variations", "text": [ "FLT3/ITD+" ], "offsets": [ [ 792, 801 ] ], "normalized": [] }, { "id": "8416", "type": "Genes & Molecular Sequences", "text": [ "FLT3/ITD+" ], "offsets": [ [ 792, 801 ] ], "normalized": [] }, { "id": "8417", "type": "SNP & Sequence variations", "text": [ "ITD" ], "offsets": [ [ 797, 800 ] ], "normalized": [] }, { "id": "8418", "type": "SNP & Sequence variations", "text": [ "FLT3/TKD+" ], "offsets": [ [ 809, 818 ] ], "normalized": [] }, { "id": "8419", "type": "Genes & Molecular Sequences", "text": [ "FLT3/TKD+" ], "offsets": [ [ 809, 818 ] ], "normalized": [] }, { "id": "8420", "type": "Chemicals & Drugs", "text": [ "cytarabine" ], "offsets": [ [ 893, 903 ] ], "normalized": [] }, { "id": "8421", "type": "SNP & Sequence variations", "text": [ "FLT3/ITD" ], "offsets": [ [ 908, 916 ] ], "normalized": [] }, { "id": "8422", "type": "Genes & Molecular Sequences", "text": [ "FLT3/ITD" ], "offsets": [ [ 908, 916 ] ], "normalized": [] }, { "id": "8423", "type": "Chemicals & Drugs", "text": [ "cytarabine" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "8424", "type": "SNP & Sequence variations", "text": [ "FLT3/TKD" ], "offsets": [ [ 1003, 1011 ] ], "normalized": [] }, { "id": "8425", "type": "Genes & Molecular Sequences", "text": [ "FLT3/TKD" ], "offsets": [ [ 1003, 1011 ] ], "normalized": [] }, { "id": "8426", "type": "SNP & Sequence variations", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1040, 1049 ] ], "normalized": [] }, { "id": "8427", "type": "Genes & Molecular Sequences", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1040, 1049 ] ], "normalized": [] }, { "id": "8428", "type": "Chemicals & Drugs", "text": [ "lestaurtinib" ], "offsets": [ [ 1085, 1097 ] ], "normalized": [] }, { "id": "8429", "type": "SNP & Sequence variations", "text": [ "FLT3/WT" ], "offsets": [ [ 1101, 1108 ] ], "normalized": [] }, { "id": "8430", "type": "Genes & Molecular Sequences", "text": [ "FLT3/WT" ], "offsets": [ [ 1101, 1108 ] ], "normalized": [] }, { "id": "8431", "type": "SNP & Sequence variations", "text": [ "FLT3/ITD+" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "8432", "type": "Genes & Molecular Sequences", "text": [ "FLT3/ITD+" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "8433", "type": "SNP & Sequence variations", "text": [ "ITD" ], "offsets": [ [ 1129, 1132 ] ], "normalized": [] }, { "id": "8434", "type": "Chemicals & Drugs", "text": [ "lestaurtinib" ], "offsets": [ [ 1223, 1235 ] ], "normalized": [] }, { "id": "8435", "type": "SNP & Sequence variations", "text": [ "FLT3/ITD+" ], "offsets": [ [ 1259, 1268 ] ], "normalized": [] }, { "id": "8436", "type": "Genes & Molecular Sequences", "text": [ "FLT3/ITD+" ], "offsets": [ [ 1259, 1268 ] ], "normalized": [] }, { "id": "8437", "type": "SNP & Sequence variations", "text": [ "ITD" ], "offsets": [ [ 1264, 1267 ] ], "normalized": [] }, { "id": "8438", "type": "SNP & Sequence variations", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1272, 1281 ] ], "normalized": [] }, { "id": "8439", "type": "Genes & Molecular Sequences", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1272, 1281 ] ], "normalized": [] }, { "id": "8440", "type": "Chemicals & Drugs", "text": [ "lestaurtinib" ], "offsets": [ [ 1317, 1329 ] ], "normalized": [] }, { "id": "8441", "type": "Chemicals & Drugs", "text": [ "cytarabine" ], "offsets": [ [ 1335, 1345 ] ], "normalized": [] }, { "id": "8442", "type": "SNP & Sequence variations", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1411, 1420 ] ], "normalized": [] }, { "id": "8443", "type": "Genes & Molecular Sequences", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1411, 1420 ] ], "normalized": [] }, { "id": "8444", "type": "SNP & Sequence variations", "text": [ "FLT3/WT" ], "offsets": [ [ 1425, 1432 ] ], "normalized": [] }, { "id": "8445", "type": "Genes & Molecular Sequences", "text": [ "FLT3/WT" ], "offsets": [ [ 1425, 1432 ] ], "normalized": [] }, { "id": "8446", "type": "Chemicals & Drugs", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 1513, 1528 ] ], "normalized": [] }, { "id": "8447", "type": "Genes & Molecular Sequences", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 1513, 1528 ] ], "normalized": [] }, { "id": "8448", "type": "", "text": [ "tyrosine kinase domain mutation of FLT3" ], "offsets": [ [ 43, 82 ] ], "normalized": [] }, { "id": "8449", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 105, 117 ] ], "normalized": [] }, { "id": "8451", "type": "", "text": [ "FLT3 internal tandem duplication" ], "offsets": [ [ 136, 168 ] ], "normalized": [] }, { "id": "8452", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 105, 117 ] ], "normalized": [] }, { "id": "8454", "type": "", "text": [ "WT" ], "offsets": [ [ 482, 484 ] ], "normalized": [] }, { "id": "8455", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 450, 465 ] ], "normalized": [] }, { "id": "8457", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "8458", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 450, 465 ] ], "normalized": [] }, { "id": "8460", "type": "", "text": [ "FLT3/ITD+" ], "offsets": [ [ 385, 394 ] ], "normalized": [] }, { "id": "8461", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 450, 465 ] ], "normalized": [] }, { "id": "8463", "type": "", "text": [ "FLT3/ITD" ], "offsets": [ [ 908, 916 ] ], "normalized": [] }, { "id": "8464", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "8466", "type": "", "text": [ "FLT3/TKD" ], "offsets": [ [ 1003, 1011 ] ], "normalized": [] }, { "id": "8467", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "8469", "type": "", "text": [ "FLT3/WT" ], "offsets": [ [ 1101, 1108 ] ], "normalized": [] }, { "id": "8470", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 1085, 1097 ] ], "normalized": [] }, { "id": "8472", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1040, 1049 ] ], "normalized": [] }, { "id": "8473", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 1085, 1097 ] ], "normalized": [] }, { "id": "8475", "type": "", "text": [ "FLT3/ITD+" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "8476", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 1085, 1097 ] ], "normalized": [] }, { "id": "8478", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1272, 1281 ] ], "normalized": [] }, { "id": "8479", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 1223, 1235 ] ], "normalized": [] }, { "id": "8481", "type": "", "text": [ "FLT3/ITD+" ], "offsets": [ [ 1259, 1268 ] ], "normalized": [] }, { "id": "8482", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 1223, 1235 ] ], "normalized": [] }, { "id": "8484", "type": "", "text": [ "blast" ], "offsets": [ [ 24, 29 ] ], "normalized": [] }, { "id": "8485", "type": "", "text": [ "FLT3 internal tandem duplication" ], "offsets": [ [ 136, 168 ] ], "normalized": [] }, { "id": "8487", "type": "", "text": [ "blast" ], "offsets": [ [ 743, 748 ] ], "normalized": [] }, { "id": "8488", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 809, 818 ] ], "normalized": [] }, { "id": "8490", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 639, 649 ] ], "normalized": [] }, { "id": "8491", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 809, 818 ] ], "normalized": [] }, { "id": "8493", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "8494", "type": "", "text": [ "FLT3/TKD" ], "offsets": [ [ 1003, 1011 ] ], "normalized": [] }, { "id": "8496", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 105, 117 ] ], "normalized": [] }, { "id": "8497", "type": "", "text": [ "FLT3 internal tandem duplication" ], "offsets": [ [ 136, 168 ] ], "normalized": [] }, { "id": "8499", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 639, 649 ] ], "normalized": [] }, { "id": "8500", "type": "", "text": [ "FLT3 inhibitor" ], "offsets": [ [ 658, 672 ] ], "normalized": [] }, { "id": "8502", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 673, 685 ] ], "normalized": [] }, { "id": "8503", "type": "", "text": [ "FLT3 inhibitor" ], "offsets": [ [ 658, 672 ] ], "normalized": [] }, { "id": "8505", "type": "", "text": [ "FLT3/WT" ], "offsets": [ [ 780, 787 ] ], "normalized": [] }, { "id": "8506", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 639, 649 ] ], "normalized": [] }, { "id": "8508", "type": "", "text": [ "FLT3/WT" ], "offsets": [ [ 780, 787 ] ], "normalized": [] }, { "id": "8509", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 673, 685 ] ], "normalized": [] }, { "id": "8511", "type": "", "text": [ "FLT3/ITD+" ], "offsets": [ [ 792, 801 ] ], "normalized": [] }, { "id": "8512", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 639, 649 ] ], "normalized": [] }, { "id": "8514", "type": "", "text": [ "FLT3/ITD+" ], "offsets": [ [ 792, 801 ] ], "normalized": [] }, { "id": "8515", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 673, 685 ] ], "normalized": [] }, { "id": "8517", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 809, 818 ] ], "normalized": [] }, { "id": "8518", "type": "", "text": [ "cytarabine" ], "offsets": [ [ 639, 649 ] ], "normalized": [] }, { "id": "8520", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 809, 818 ] ], "normalized": [] }, { "id": "8521", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 673, 685 ] ], "normalized": [] }, { "id": "8523", "type": "", "text": [ "FLT3/WT" ], "offsets": [ [ 1425, 1432 ] ], "normalized": [] }, { "id": "8524", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 1513, 1528 ] ], "normalized": [] }, { "id": "8526", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1411, 1420 ] ], "normalized": [] }, { "id": "8527", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 1513, 1528 ] ], "normalized": [] }, { "id": "8529", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 450, 465 ] ], "normalized": [] }, { "id": "8530", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "8532", "type": "", "text": [ "ITD" ], "offsets": [ [ 390, 393 ] ], "normalized": [] }, { "id": "8533", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 450, 465 ] ], "normalized": [] }, { "id": "8535", "type": "", "text": [ "ITD" ], "offsets": [ [ 1129, 1132 ] ], "normalized": [] }, { "id": "8536", "type": "", "text": [ "lestaurtinib" ], "offsets": [ [ 1085, 1097 ] ], "normalized": [] }, { "id": "8538", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 1513, 1528 ] ], "normalized": [] }, { "id": "8539", "type": "", "text": [ "FLT3/WT" ], "offsets": [ [ 1425, 1432 ] ], "normalized": [] }, { "id": "8541", "type": "", "text": [ "FLT3/TKD+" ], "offsets": [ [ 1411, 1420 ] ], "normalized": [] }, { "id": "8542", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 1513, 1528 ] ], "normalized": [] }, { "id": "8544", "type": "", "text": [ "FLT3/WT" ], "offsets": [ [ 1425, 1432 ] ], "normalized": [] }, { "id": "8545", "type": "", "text": [ "FLT3 inhibitors" ], "offsets": [ [ 1513, 1528 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8450", "type": "PA", "arg1_id": "8448", "arg2_id": "8449", "normalized": [] }, { "id": "8453", "type": "PA", "arg1_id": "8451", "arg2_id": "8452", "normalized": [] }, { "id": "8456", "type": "PA", "arg1_id": "8454", "arg2_id": "8455", "normalized": [] }, { "id": "8459", "type": "SA", "arg1_id": "8457", "arg2_id": "8458", "normalized": [] }, { "id": "8462", "type": "PA", "arg1_id": "8460", "arg2_id": "8461", "normalized": [] }, { "id": "8465", "type": "PA", "arg1_id": "8463", "arg2_id": "8464", "normalized": [] }, { "id": "8468", "type": "NA", "arg1_id": "8466", "arg2_id": "8467", "normalized": [] }, { "id": "8471", "type": "PA", "arg1_id": "8469", "arg2_id": "8470", "normalized": [] }, { "id": "8474", "type": "PA", "arg1_id": "8472", "arg2_id": "8473", "normalized": [] }, { "id": "8477", "type": "PA", "arg1_id": "8475", "arg2_id": "8476", "normalized": [] }, { "id": "8480", "type": "NA", "arg1_id": "8478", "arg2_id": "8479", "normalized": [] }, { "id": "8483", "type": "NA", "arg1_id": "8481", "arg2_id": "8482", "normalized": [] }, { "id": "8486", "type": "PA", "arg1_id": "8484", "arg2_id": "8485", "normalized": [] }, { "id": "8489", "type": "PA", "arg1_id": "8487", "arg2_id": "8488", "normalized": [] }, { "id": "8492", "type": "PA", "arg1_id": "8490", "arg2_id": "8491", "normalized": [] }, { "id": "8495", "type": "PA", "arg1_id": "8493", "arg2_id": "8494", "normalized": [] }, { "id": "8498", "type": "PA", "arg1_id": "8496", "arg2_id": "8497", "normalized": [] }, { "id": "8501", "type": "PA", "arg1_id": "8499", "arg2_id": "8500", "normalized": [] }, { "id": "8504", "type": "PA", "arg1_id": "8502", "arg2_id": "8503", "normalized": [] }, { "id": "8507", "type": "SA", "arg1_id": "8505", "arg2_id": "8506", "normalized": [] }, { "id": "8510", "type": "SA", "arg1_id": "8508", "arg2_id": "8509", "normalized": [] }, { "id": "8513", "type": "SA", "arg1_id": "8511", "arg2_id": "8512", "normalized": [] }, { "id": "8516", "type": "SA", "arg1_id": "8514", "arg2_id": "8515", "normalized": [] }, { "id": "8519", "type": "SA", "arg1_id": "8517", "arg2_id": "8518", "normalized": [] }, { "id": "8522", "type": "SA", "arg1_id": "8520", "arg2_id": "8521", "normalized": [] }, { "id": "8525", "type": "NA", "arg1_id": "8523", "arg2_id": "8524", "normalized": [] }, { "id": "8528", "type": "NA", "arg1_id": "8526", "arg2_id": "8527", "normalized": [] }, { "id": "8531", "type": "PA", "arg1_id": "8529", "arg2_id": "8530", "normalized": [] }, { "id": "8534", "type": "PA", "arg1_id": "8532", "arg2_id": "8533", "normalized": [] }, { "id": "8537", "type": "PA", "arg1_id": "8535", "arg2_id": "8536", "normalized": [] }, { "id": "8540", "type": "PA", "arg1_id": "8538", "arg2_id": "8539", "normalized": [] }, { "id": "8543", "type": "PA", "arg1_id": "8541", "arg2_id": "8542", "normalized": [] }, { "id": "8546", "type": "PA", "arg1_id": "8544", "arg2_id": "8545", "normalized": [] } ]

[ { "id": "8549", "type": "title", "text": [ "Inhaled corticosteroids during pregnancy: a review of methodologic issues." ], "offsets": [ [ 0, 74 ] ] }, { "id": "8550", "type": "abstract", "text": [ "BACKGROUND: There is evidence in the literature that inhaled corticosteroids (ICSs) are safe for pregnant women with asthma and their infants. Although this is useful information about ICS use during pregnancy, some articles must be viewed cautiously because of lack of power and adjustment for potentially important confounding variables. OBJECTIVE: To summarize evidence on the potential effects of ICSs to treat asthma in pregnant mothers and their children with particular focus on study power. METHODS: Studies published before September 1, 2007, and focusing mainly on ICS use for asthma treatment during pregnancy were researched in Pubmed and the Cochrane Library. Post hoc power calculations were completed using data reported in the published articles. RESULTS: Twenty-three studies that evaluated the associations between ICS use during pregnancy and maternal and/or perinatal outcomes were retained. Only six studies on the association between ICS use and maternal outcomes reported significant results; five studies found significant associations between ICS use and perinatal outcomes. Regarding non-significant results, two studies on maternal outcomes and seven studies on perinatal outcomes had a power higher than 80% to detect a relative risk of 1.5 or a mean birth weight difference of 500 g. CONCLUSION: While there currently is some degree of evidence to support the safety of ICS use during pregnancy, this review highlights the limited statistical power of several studies published in this area." ], "offsets": [ [ 75, 1595 ] ] } ]

[ { "id": "8551", "type": "Chemicals & Drugs", "text": [ "Inhaled corticosteroids" ], "offsets": [ [ 0, 23 ] ], "normalized": [] }, { "id": "8552", "type": "Chemicals & Drugs", "text": [ "inhaled corticosteroids" ], "offsets": [ [ 128, 151 ] ], "normalized": [] }, { "id": "8553", "type": "Chemicals & Drugs", "text": [ "ICSs" ], "offsets": [ [ 153, 157 ] ], "normalized": [] }, { "id": "8554", "type": "Diseases & Disorders", "text": [ "ICSs" ], "offsets": [ [ 153, 157 ] ], "normalized": [] }, { "id": "8555", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 192, 198 ] ], "normalized": [] }, { "id": "8556", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 260, 263 ] ], "normalized": [] }, { "id": "8557", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 260, 263 ] ], "normalized": [] }, { "id": "8558", "type": "Chemicals & Drugs", "text": [ "ICSs" ], "offsets": [ [ 476, 480 ] ], "normalized": [] }, { "id": "8559", "type": "Diseases & Disorders", "text": [ "ICSs" ], "offsets": [ [ 476, 480 ] ], "normalized": [] }, { "id": "8560", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 490, 496 ] ], "normalized": [] }, { "id": "8561", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "8562", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "8563", "type": "Diseases & Disorders", "text": [ "asthma" ], "offsets": [ [ 662, 668 ] ], "normalized": [] }, { "id": "8564", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "8565", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "8566", "type": "Diseases & Disorders", "text": [ "perinatal outcomes" ], "offsets": [ [ 953, 971 ] ], "normalized": [] }, { "id": "8567", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 1031, 1034 ] ], "normalized": [] }, { "id": "8568", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 1031, 1034 ] ], "normalized": [] }, { "id": "8569", "type": "Diseases & Disorders", "text": [ "maternal outcomes" ], "offsets": [ [ 1043, 1060 ] ], "normalized": [] }, { "id": "8570", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 1143, 1146 ] ], "normalized": [] }, { "id": "8571", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 1143, 1146 ] ], "normalized": [] }, { "id": "8572", "type": "Diseases & Disorders", "text": [ "perinatal outcomes" ], "offsets": [ [ 1155, 1173 ] ], "normalized": [] }, { "id": "8573", "type": "Diseases & Disorders", "text": [ "maternal outcomes" ], "offsets": [ [ 1225, 1242 ] ], "normalized": [] }, { "id": "8574", "type": "Diseases & Disorders", "text": [ "perinatal outcomes" ], "offsets": [ [ 1264, 1282 ] ], "normalized": [] }, { "id": "8575", "type": "Chemicals & Drugs", "text": [ "ICS" ], "offsets": [ [ 1474, 1477 ] ], "normalized": [] }, { "id": "8576", "type": "Diseases & Disorders", "text": [ "ICS" ], "offsets": [ [ 1474, 1477 ] ], "normalized": [] }, { "id": "8577", "type": "", "text": [ "ICSs" ], "offsets": [ [ 153, 157 ] ], "normalized": [] }, { "id": "8578", "type": "", "text": [ "asthma" ], "offsets": [ [ 192, 198 ] ], "normalized": [] }, { "id": "8580", "type": "", "text": [ "inhaled corticosteroids" ], "offsets": [ [ 128, 151 ] ], "normalized": [] }, { "id": "8581", "type": "", "text": [ "asthma" ], "offsets": [ [ 192, 198 ] ], "normalized": [] }, { "id": "8583", "type": "", "text": [ "ICSs" ], "offsets": [ [ 476, 480 ] ], "normalized": [] }, { "id": "8584", "type": "", "text": [ "asthma" ], "offsets": [ [ 490, 496 ] ], "normalized": [] }, { "id": "8586", "type": "", "text": [ "ICS" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "8587", "type": "", "text": [ "asthma" ], "offsets": [ [ 662, 668 ] ], "normalized": [] }, { "id": "8589", "type": "", "text": [ "ICS" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "8590", "type": "", "text": [ "perinatal outcomes" ], "offsets": [ [ 953, 971 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8579", "type": "PA", "arg1_id": "8577", "arg2_id": "8578", "normalized": [] }, { "id": "8582", "type": "PA", "arg1_id": "8580", "arg2_id": "8581", "normalized": [] }, { "id": "8585", "type": "PA", "arg1_id": "8583", "arg2_id": "8584", "normalized": [] }, { "id": "8588", "type": "PA", "arg1_id": "8586", "arg2_id": "8587", "normalized": [] }, { "id": "8591", "type": "PA", "arg1_id": "8589", "arg2_id": "8590", "normalized": [] } ]

[ { "id": "8594", "type": "title", "text": [ "Overall and relapse-free survival in oropharyngeal and hypopharyngeal squamous cell carcinoma are associated with genotypes of T393C polymorphism of the GNAS1 gene." ], "offsets": [ [ 0, 164 ] ] }, { "id": "8595", "type": "abstract", "text": [ "PURPOSE: In previous studies, we have shown that the T allele of a specific single-nucleotide polymorphism (SNP) in the Galphas gene (T393C) correlates with increased Galphas expression and hence apoptosis. The T allele was associated with a favorable outcome in a variety of human cancers, e.g., carcinoma of the urinary bladder, kidney, and colorectum. EXPERIMENTAL DESIGN: The prognostic value of the T393C SNP was evaluated in an unselected series of patients treated with curative intent for oropharyngeal and hypopharyngeal squamous cell carcinomas, including all tumor stages with different therapeutic regimens. Genotype analysis was done using DNA from paraffin-embedded tissue samples from 202 patients (162 men, 40 women) with a median follow-up of 38 months (1-133 months). The various genotypes were correlated with relapse-free and overall survival. RESULTS: GNAS1 393C homozygous patients displayed a higher risk for disease progression than T393 homozygous patients (hazard ratio CC versus TT, 1.9; 95% confidence interval, 1.1-3.2; P = 0.019). The same genotype effect was observed for overall survival with CC genotypes at higher risk for death compared with TT genotypes (hazard ratio, 1.7; 95% confidence interval, 1.1-2.9; P = 0.015). Multivariate analysis showed that, besides American Joint Committee on Cancer stage, tumor localization, and gender, the T393C polymorphism was an independent prognostic factor for disease progression and death. CONCLUSION: The T393C SNP could be considered as a genetic marker to predict the clinical course of patients suffering from oropharyngeal and hypopharyngeal cancer." ], "offsets": [ [ 165, 1797 ] ] } ]

[ { "id": "8596", "type": "Diseases & Disorders", "text": [ "relapse" ], "offsets": [ [ 12, 19 ] ], "normalized": [] }, { "id": "8597", "type": "Diseases & Disorders", "text": [ "oropharyngeal" ], "offsets": [ [ 37, 50 ] ], "normalized": [] }, { "id": "8598", "type": "Diseases & Disorders", "text": [ "hypopharyngeal squamous cell carcinoma" ], "offsets": [ [ 55, 93 ] ], "normalized": [] }, { "id": "8599", "type": "SNP & Sequence variations", "text": [ "T393C polymorphism of the GNAS1" ], "offsets": [ [ 127, 158 ] ], "normalized": [] }, { "id": "8600", "type": "Genes & Molecular Sequences", "text": [ "T393C polymorphism of the GNAS1" ], "offsets": [ [ 127, 158 ] ], "normalized": [] }, { "id": "8601", "type": "SNP & Sequence variations", "text": [ "T allele" ], "offsets": [ [ 218, 226 ] ], "normalized": [] }, { "id": "8602", "type": "Genes & Molecular Sequences", "text": [ "Galphas" ], "offsets": [ [ 285, 292 ] ], "normalized": [] }, { "id": "8603", "type": "SNP & Sequence variations", "text": [ "T393C" ], "offsets": [ [ 299, 304 ] ], "normalized": [] }, { "id": "8604", "type": "Genes & Molecular Sequences", "text": [ "Galphas" ], "offsets": [ [ 332, 339 ] ], "normalized": [] }, { "id": "8605", "type": "SNP & Sequence variations", "text": [ "T allele" ], "offsets": [ [ 376, 384 ] ], "normalized": [] }, { "id": "8606", "type": "Diseases & Disorders", "text": [ "cancers" ], "offsets": [ [ 447, 454 ] ], "normalized": [] }, { "id": "8607", "type": "Diseases & Disorders", "text": [ "carcinoma of the urinary bladder" ], "offsets": [ [ 462, 494 ] ], "normalized": [] }, { "id": "8608", "type": "Diseases & Disorders", "text": [ "kidney" ], "offsets": [ [ 496, 502 ] ], "normalized": [] }, { "id": "8609", "type": "Diseases & Disorders", "text": [ "colorectum" ], "offsets": [ [ 508, 518 ] ], "normalized": [] }, { "id": "8610", "type": "SNP & Sequence variations", "text": [ "T393C" ], "offsets": [ [ 569, 574 ] ], "normalized": [] }, { "id": "8611", "type": "Diseases & Disorders", "text": [ "oropharyngeal" ], "offsets": [ [ 662, 675 ] ], "normalized": [] }, { "id": "8612", "type": "Diseases & Disorders", "text": [ "hypopharyngeal squamous cell carcinomas" ], "offsets": [ [ 680, 719 ] ], "normalized": [] }, { "id": "8613", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 735, 740 ] ], "normalized": [] }, { "id": "8614", "type": "Diseases & Disorders", "text": [ "relapse" ], "offsets": [ [ 994, 1001 ] ], "normalized": [] }, { "id": "8615", "type": "SNP & Sequence variations", "text": [ "GNAS1 393C homozygous" ], "offsets": [ [ 1038, 1059 ] ], "normalized": [] }, { "id": "8616", "type": "Genes & Molecular Sequences", "text": [ "GNAS1 393C homozygous" ], "offsets": [ [ 1038, 1059 ] ], "normalized": [] }, { "id": "8617", "type": "SNP & Sequence variations", "text": [ "393C" ], "offsets": [ [ 1044, 1048 ] ], "normalized": [] }, { "id": "8618", "type": "Diseases & Disorders", "text": [ "disease progression" ], "offsets": [ [ 1097, 1116 ] ], "normalized": [] }, { "id": "8619", "type": "SNP & Sequence variations", "text": [ "T393 homozygous" ], "offsets": [ [ 1122, 1137 ] ], "normalized": [] }, { "id": "8620", "type": "SNP & Sequence variations", "text": [ "CC" ], "offsets": [ [ 1161, 1163 ] ], "normalized": [] }, { "id": "8621", "type": "SNP & Sequence variations", "text": [ "TT" ], "offsets": [ [ 1171, 1173 ] ], "normalized": [] }, { "id": "8622", "type": "SNP & Sequence variations", "text": [ "CC" ], "offsets": [ [ 1290, 1292 ] ], "normalized": [] }, { "id": "8623", "type": "Diseases & Disorders", "text": [ "death" ], "offsets": [ [ 1322, 1327 ] ], "normalized": [] }, { "id": "8624", "type": "SNP & Sequence variations", "text": [ "TT" ], "offsets": [ [ 1342, 1344 ] ], "normalized": [] }, { "id": "8625", "type": "Diseases & Disorders", "text": [ "Cancer" ], "offsets": [ [ 1492, 1498 ] ], "normalized": [] }, { "id": "8626", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 1506, 1511 ] ], "normalized": [] }, { "id": "8627", "type": "SNP & Sequence variations", "text": [ "T393C" ], "offsets": [ [ 1542, 1547 ] ], "normalized": [] }, { "id": "8628", "type": "Diseases & Disorders", "text": [ "disease progression" ], "offsets": [ [ 1602, 1621 ] ], "normalized": [] }, { "id": "8629", "type": "Diseases & Disorders", "text": [ "death" ], "offsets": [ [ 1626, 1631 ] ], "normalized": [] }, { "id": "8630", "type": "SNP & Sequence variations", "text": [ "T393C" ], "offsets": [ [ 1649, 1654 ] ], "normalized": [] }, { "id": "8631", "type": "Diseases & Disorders", "text": [ "suffering" ], "offsets": [ [ 1742, 1751 ] ], "normalized": [] }, { "id": "8632", "type": "Diseases & Disorders", "text": [ "oropharyngeal" ], "offsets": [ [ 1757, 1770 ] ], "normalized": [] }, { "id": "8633", "type": "Diseases & Disorders", "text": [ "hypopharyngeal cancer" ], "offsets": [ [ 1775, 1796 ] ], "normalized": [] }, { "id": "8634", "type": "", "text": [ "T393C polymorphism of the GNAS1" ], "offsets": [ [ 127, 158 ] ], "normalized": [] }, { "id": "8635", "type": "", "text": [ "hypopharyngeal squamous cell carcinoma" ], "offsets": [ [ 55, 93 ] ], "normalized": [] }, { "id": "8637", "type": "", "text": [ "T393C polymorphism of the GNAS1" ], "offsets": [ [ 127, 158 ] ], "normalized": [] }, { "id": "8638", "type": "", "text": [ "oropharyngeal" ], "offsets": [ [ 37, 50 ] ], "normalized": [] }, { "id": "8640", "type": "", "text": [ "T allele" ], "offsets": [ [ 376, 384 ] ], "normalized": [] }, { "id": "8641", "type": "", "text": [ "carcinoma of the urinary bladder" ], "offsets": [ [ 462, 494 ] ], "normalized": [] }, { "id": "8643", "type": "", "text": [ "T allele" ], "offsets": [ [ 376, 384 ] ], "normalized": [] }, { "id": "8644", "type": "", "text": [ "kidney" ], "offsets": [ [ 496, 502 ] ], "normalized": [] }, { "id": "8646", "type": "", "text": [ "T allele" ], "offsets": [ [ 376, 384 ] ], "normalized": [] }, { "id": "8647", "type": "", "text": [ "colorectum" ], "offsets": [ [ 508, 518 ] ], "normalized": [] }, { "id": "8649", "type": "", "text": [ "T allele" ], "offsets": [ [ 376, 384 ] ], "normalized": [] }, { "id": "8650", "type": "", "text": [ "cancers" ], "offsets": [ [ 447, 454 ] ], "normalized": [] }, { "id": "8652", "type": "", "text": [ "CC" ], "offsets": [ [ 1290, 1292 ] ], "normalized": [] }, { "id": "8653", "type": "", "text": [ "death" ], "offsets": [ [ 1322, 1327 ] ], "normalized": [] }, { "id": "8655", "type": "", "text": [ "TT" ], "offsets": [ [ 1342, 1344 ] ], "normalized": [] }, { "id": "8656", "type": "", "text": [ "death" ], "offsets": [ [ 1322, 1327 ] ], "normalized": [] }, { "id": "8658", "type": "", "text": [ "T393C" ], "offsets": [ [ 1542, 1547 ] ], "normalized": [] }, { "id": "8659", "type": "", "text": [ "death" ], "offsets": [ [ 1626, 1631 ] ], "normalized": [] }, { "id": "8661", "type": "", "text": [ "T393C" ], "offsets": [ [ 1649, 1654 ] ], "normalized": [] }, { "id": "8662", "type": "", "text": [ "hypopharyngeal cancer" ], "offsets": [ [ 1775, 1796 ] ], "normalized": [] }, { "id": "8664", "type": "", "text": [ "T393C" ], "offsets": [ [ 1649, 1654 ] ], "normalized": [] }, { "id": "8665", "type": "", "text": [ "oropharyngeal" ], "offsets": [ [ 1757, 1770 ] ], "normalized": [] }, { "id": "8667", "type": "", "text": [ "T393C polymorphism of the GNAS1" ], "offsets": [ [ 127, 158 ] ], "normalized": [] }, { "id": "8668", "type": "", "text": [ "relapse" ], "offsets": [ [ 12, 19 ] ], "normalized": [] }, { "id": "8670", "type": "", "text": [ "GNAS1 393C homozygous" ], "offsets": [ [ 1038, 1059 ] ], "normalized": [] }, { "id": "8671", "type": "", "text": [ "disease progression" ], "offsets": [ [ 1097, 1116 ] ], "normalized": [] }, { "id": "8673", "type": "", "text": [ "T393C" ], "offsets": [ [ 569, 574 ] ], "normalized": [] }, { "id": "8674", "type": "", "text": [ "oropharyngeal" ], "offsets": [ [ 662, 675 ] ], "normalized": [] } ]

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[ { "id": "8636", "type": "PA", "arg1_id": "8634", "arg2_id": "8635", "normalized": [] }, { "id": "8639", "type": "PA", "arg1_id": "8637", "arg2_id": "8638", "normalized": [] }, { "id": "8642", "type": "PA", "arg1_id": "8640", "arg2_id": "8641", "normalized": [] }, { "id": "8645", "type": "PA", "arg1_id": "8643", "arg2_id": "8644", "normalized": [] }, { "id": "8648", "type": "PA", "arg1_id": "8646", "arg2_id": "8647", "normalized": [] }, { "id": "8651", "type": "PA", "arg1_id": "8649", "arg2_id": "8650", "normalized": [] }, { "id": "8654", "type": "PA", "arg1_id": "8652", "arg2_id": "8653", "normalized": [] }, { "id": "8657", "type": "PA", "arg1_id": "8655", "arg2_id": "8656", "normalized": [] }, { "id": "8660", "type": "PA", "arg1_id": "8658", "arg2_id": "8659", "normalized": [] }, { "id": "8663", "type": "PA", "arg1_id": "8661", "arg2_id": "8662", "normalized": [] }, { "id": "8666", "type": "PA", "arg1_id": "8664", "arg2_id": "8665", "normalized": [] }, { "id": "8669", "type": "PA", "arg1_id": "8667", "arg2_id": "8668", "normalized": [] }, { "id": "8672", "type": "PA", "arg1_id": "8670", "arg2_id": "8671", "normalized": [] }, { "id": "8675", "type": "SA", "arg1_id": "8673", "arg2_id": "8674", "normalized": [] } ]

[ { "id": "8678", "type": "title", "text": [ "Surface expression of Hsp70B' in response to proteasome inhibition in human colon cells." ], "offsets": [ [ 0, 88 ] ] }, { "id": "8679", "type": "abstract", "text": [ "Hsp70B' was expressed on the surface of HT-29 and CRL-1809 but not SW-480 human colon cell lines in response to proteasome inhibition as detected using flow cytometry. Surface expression was not detected under non-stress conditions nor was heat shock an inducer of surface expression in the three cell lines tested. Phylogenetic analysis indicated that the Hsp70B' protein sequence was most closely related to another major inducible human Hsp70, Hsp72. Hsp70B' appeared to be recently diverged, as homologs for Hsp70B' have not been found in rodents. Hsp72 and Hsp70B' shared 100% amino acid sequence identity in their predicted peptide-binding regions suggesting that they bind the same peptide substrates, perhaps in extracellular antigen presentation. Amino acid sequence differences were concentrated in the lid regions and the C-terminal domains raising the possibility that Hsp72 and Hsp70B' bind different co-chaperones or cell surface receptors." ], "offsets": [ [ 89, 1043 ] ] } ]

[ { "id": "8680", "type": "Genes & Molecular Sequences", "text": [ "Hsp70B'" ], "offsets": [ [ 22, 29 ] ], "normalized": [] }, { "id": "8681", "type": "Genes & Molecular Sequences", "text": [ "proteasome" ], "offsets": [ [ 45, 55 ] ], "normalized": [] }, { "id": "8682", "type": "Genes & Molecular Sequences", "text": [ "Hsp70B'" ], "offsets": [ [ 89, 96 ] ], "normalized": [] }, { "id": "8683", "type": "Genes & Molecular Sequences", "text": [ "proteasome" ], "offsets": [ [ 201, 211 ] ], "normalized": [] }, { "id": "8684", "type": "Genes & Molecular Sequences", "text": [ "Hsp70B'" ], "offsets": [ [ 446, 453 ] ], "normalized": [] }, { "id": "8685", "type": "Genes & Molecular Sequences", "text": [ "Hsp70" ], "offsets": [ [ 529, 534 ] ], "normalized": [] }, { "id": "8686", "type": "Genes & Molecular Sequences", "text": [ "Hsp72" ], "offsets": [ [ 536, 541 ] ], "normalized": [] }, { "id": "8687", "type": "Genes & Molecular Sequences", "text": [ "Hsp70B'" ], "offsets": [ [ 543, 550 ] ], "normalized": [] }, { "id": "8688", "type": "Genes & Molecular Sequences", "text": [ "Hsp70B'" ], "offsets": [ [ 601, 608 ] ], "normalized": [] }, { "id": "8689", "type": "Genes & Molecular Sequences", "text": [ "Hsp72" ], "offsets": [ [ 641, 646 ] ], "normalized": [] }, { "id": "8690", "type": "Genes & Molecular Sequences", "text": [ "Hsp70B'" ], "offsets": [ [ 651, 658 ] ], "normalized": [] }, { "id": "8691", "type": "Genes & Molecular Sequences", "text": [ "Hsp72" ], "offsets": [ [ 970, 975 ] ], "normalized": [] }, { "id": "8692", "type": "Genes & Molecular Sequences", "text": [ "Hsp70B'" ], "offsets": [ [ 980, 987 ] ], "normalized": [] } ]

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[ { "id": "8695", "type": "title", "text": [ "Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome." ], "offsets": [ [ 0, 141 ] ] }, { "id": "8696", "type": "abstract", "text": [ "BACKGROUND: In men with prostate cancer, gonadotropin-releasing hormone (GnRH) agonists increase fat mass, decrease insulin sensitivity, and increase triglycerides, features that are shared with metabolic syndrome. To the authors' knowledge, however, less is known regarding the effects of GnRH agonists on other attributes of the metabolic syndrome. METHODS: In an open-label prospective study, 26 men with recurrent or locally advanced prostate cancer were treated with leuprolide for 12 months. Outcomes included changes in blood pressure, body composition, lipids, adipocytokines, and C-reactive protein. RESULTS: The mean weight, body mass index, and waist circumference increased significantly from baseline to Month 12 (P < .001 for each comparison). Fat mass increased by 11.2% +/- 1.5% (P < .001) and the percentage lean body mass decreased by 3.6% +/- 0.5% (P < .001). The total abdominal fat area increased by 16.5% +/- 2.6% (P < .001), with the accumulation of subcutaneous fat accounting for 94% of the observed increase. The waist-to-hip ratio and blood pressure did not change significantly. Serum high-density lipoprotein (HDL) cholesterol concentrations increased significantly (P = .002). Serum adiponectin levels increased by 36.4 +/- 5.9% from baseline to Month 3 and remained significantly elevated through Month 12 (P < .001). Resistin and C-reactive protein levels did not change significantly. CONCLUSIONS: The term metabolic syndrome does not appear to adequately describe the effects of GnRH agonists in men with prostate cancer. In contrast to the metabolic syndrome, GnRH agonists increase subcutaneous fat mass, HDL cholesterol, and adiponectin, and do not alter the waist-to-hip ratio, blood pressure, or C-reactive protein level.CI - (c) 2008 American Cancer Society." ], "offsets": [ [ 142, 1940 ] ] } ]

[ { "id": "8697", "type": "Chemicals & Drugs", "text": [ "gonadotropin-releasing hormone agonist" ], "offsets": [ [ 25, 63 ] ], "normalized": [] }, { "id": "8698", "type": "Chemicals & Drugs", "text": [ "gonadotropin-releasing hormone" ], "offsets": [ [ 183, 213 ] ], "normalized": [] }, { "id": "8699", "type": "Chemicals & Drugs", "text": [ "GnRH) agonists" ], "offsets": [ [ 215, 229 ] ], "normalized": [] }, { "id": "8700", "type": "Genes & Molecular Sequences", "text": [ "insulin" ], "offsets": [ [ 258, 265 ] ], "normalized": [] }, { "id": "8701", "type": "Chemicals & Drugs", "text": [ "GnRH agonists" ], "offsets": [ [ 432, 445 ] ], "normalized": [] }, { "id": "8702", "type": "Chemicals & Drugs", "text": [ "leuprolide" ], "offsets": [ [ 614, 624 ] ], "normalized": [] }, { "id": "8703", "type": "Genes & Molecular Sequences", "text": [ "lipids" ], "offsets": [ [ 703, 709 ] ], "normalized": [] }, { "id": "8704", "type": "Genes & Molecular Sequences", "text": [ "adipocytokines" ], "offsets": [ [ 711, 725 ] ], "normalized": [] }, { "id": "8705", "type": "Genes & Molecular Sequences", "text": [ "C-reactive protein" ], "offsets": [ [ 731, 749 ] ], "normalized": [] }, { "id": "8706", "type": "Genes & Molecular Sequences", "text": [ "high-density lipoprotein" ], "offsets": [ [ 1255, 1279 ] ], "normalized": [] }, { "id": "8707", "type": "Genes & Molecular Sequences", "text": [ "HDL) cholesterol" ], "offsets": [ [ 1281, 1297 ] ], "normalized": [] }, { "id": "8708", "type": "Genes & Molecular Sequences", "text": [ "adiponectin" ], "offsets": [ [ 1355, 1366 ] ], "normalized": [] }, { "id": "8709", "type": "Genes & Molecular Sequences", "text": [ "Resistin" ], "offsets": [ [ 1491, 1499 ] ], "normalized": [] }, { "id": "8710", "type": "Genes & Molecular Sequences", "text": [ "C-reactive protein" ], "offsets": [ [ 1504, 1522 ] ], "normalized": [] }, { "id": "8711", "type": "Chemicals & Drugs", "text": [ "GnRH agonists" ], "offsets": [ [ 1655, 1668 ] ], "normalized": [] }, { "id": "8712", "type": "Chemicals & Drugs", "text": [ "GnRH agonists" ], "offsets": [ [ 1737, 1750 ] ], "normalized": [] }, { "id": "8713", "type": "Genes & Molecular Sequences", "text": [ "HDL cholesterol" ], "offsets": [ [ 1783, 1798 ] ], "normalized": [] }, { "id": "8714", "type": "Genes & Molecular Sequences", "text": [ "adiponectin" ], "offsets": [ [ 1804, 1815 ] ], "normalized": [] }, { "id": "8715", "type": "Genes & Molecular Sequences", "text": [ "C-reactive protein" ], "offsets": [ [ 1877, 1895 ] ], "normalized": [] }, { "id": "8716", "type": "", "text": [ "gonadotropin-releasing hormone" ], "offsets": [ [ 183, 213 ] ], "normalized": [] }, { "id": "8717", "type": "", "text": [ "insulin" ], "offsets": [ [ 258, 265 ] ], "normalized": [] }, { "id": "8719", "type": "", "text": [ "GnRH) agonists" ], "offsets": [ [ 215, 229 ] ], "normalized": [] }, { "id": "8720", "type": "", "text": [ "insulin" ], "offsets": [ [ 258, 265 ] ], "normalized": [] }, { "id": "8722", "type": "", "text": [ "GnRH agonists" ], "offsets": [ [ 1737, 1750 ] ], "normalized": [] }, { "id": "8723", "type": "", "text": [ "C-reactive protein" ], "offsets": [ [ 1877, 1895 ] ], "normalized": [] }, { "id": "8725", "type": "", "text": [ "GnRH agonists" ], "offsets": [ [ 1737, 1750 ] ], "normalized": [] }, { "id": "8726", "type": "", "text": [ "adiponectin" ], "offsets": [ [ 1804, 1815 ] ], "normalized": [] }, { "id": "8728", "type": "", "text": [ "GnRH agonists" ], "offsets": [ [ 1737, 1750 ] ], "normalized": [] }, { "id": "8729", "type": "", "text": [ "HDL cholesterol" ], "offsets": [ [ 1783, 1798 ] ], "normalized": [] } ]

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[ { "id": "8718", "type": "PA", "arg1_id": "8716", "arg2_id": "8717", "normalized": [] }, { "id": "8721", "type": "PA", "arg1_id": "8719", "arg2_id": "8720", "normalized": [] }, { "id": "8724", "type": "NA", "arg1_id": "8722", "arg2_id": "8723", "normalized": [] }, { "id": "8727", "type": "PA", "arg1_id": "8725", "arg2_id": "8726", "normalized": [] }, { "id": "8730", "type": "PA", "arg1_id": "8728", "arg2_id": "8729", "normalized": [] } ]

[ { "id": "8733", "type": "title", "text": [ "Postoperative anemia and quality of life after primary hip arthroplasty in patients over 65 years old." ], "offsets": [ [ 0, 102 ] ] }, { "id": "8734", "type": "abstract", "text": [ "BACKGROUND: It is uncertain whether anemia in elderly patients after primary hip arthroplasty has an effect on their quality of life. METHODS: We conducted a prospective observational study over 3 mo to investigate the association between discharge hemoglobin levels and subjective experience of quality of life at 2 mo postoperatively in patients aged over 65 yr who were scheduled for primary hip arthroplasty. Quality of life was measured preoperatively and at 2 mo postoperatively using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Anemia (FACT-Anemia) subscale. Pearson correlation coefficients between change in SF-36 and FACT-Anemia subscale scores (from preoperatively to 2 mo postoperatively) and hemoglobin on Day 8 were calculated. RESULTS: Eighty-seven patients were included in the study. Data were available at 2 mo postoperatively from 79 of these patients. The correlation between Day 8 postoperative hemoglobin and change in SF-36 was 0.49 (P < 0.0005) and change in FACT-Anemia subscale score was 0.46 (P = < 0.0005). The correlation was not significantly changed after adjusting for advancing age, presence of significant cardiovascular disease, or whether the patient was transfused. CONCLUSIONS: We found a positive correlation between hemoglobin levels on discharge and change in quality of life scores from preoperatively to 2 mo postoperatively in patients over 65 yr old after primary hip arthroplasty." ], "offsets": [ [ 103, 1601 ] ] } ]

[ { "id": "8735", "type": "Diseases & Disorders", "text": [ "anemia" ], "offsets": [ [ 14, 20 ] ], "normalized": [] }, { "id": "8736", "type": "Diseases & Disorders", "text": [ "anemia" ], "offsets": [ [ 139, 145 ] ], "normalized": [] }, { "id": "8737", "type": "Diseases & Disorders", "text": [ "mo" ], "offsets": [ [ 300, 302 ] ], "normalized": [] }, { "id": "8738", "type": "Diseases & Disorders", "text": [ "subjective" ], "offsets": [ [ 374, 384 ] ], "normalized": [] }, { "id": "8739", "type": "Diseases & Disorders", "text": [ "mo" ], "offsets": [ [ 420, 422 ] ], "normalized": [] }, { "id": "8740", "type": "Diseases & Disorders", "text": [ "mo" ], "offsets": [ [ 569, 571 ] ], "normalized": [] }, { "id": "8741", "type": "Diseases & Disorders", "text": [ "Cancer" ], "offsets": [ [ 695, 701 ] ], "normalized": [] }, { "id": "8742", "type": "Diseases & Disorders", "text": [ "Anemia" ], "offsets": [ [ 710, 716 ] ], "normalized": [] }, { "id": "8743", "type": "Diseases & Disorders", "text": [ "Anemia" ], "offsets": [ [ 723, 729 ] ], "normalized": [] }, { "id": "8744", "type": "Diseases & Disorders", "text": [ "Anemia" ], "offsets": [ [ 807, 813 ] ], "normalized": [] }, { "id": "8745", "type": "Diseases & Disorders", "text": [ "mo" ], "offsets": [ [ 856, 858 ] ], "normalized": [] }, { "id": "8746", "type": "Diseases & Disorders", "text": [ "mo" ], "offsets": [ [ 1001, 1003 ] ], "normalized": [] }, { "id": "8747", "type": "Diseases & Disorders", "text": [ "Anemia" ], "offsets": [ [ 1163, 1169 ] ], "normalized": [] }, { "id": "8748", "type": "Diseases & Disorders", "text": [ "cardiovascular disease" ], "offsets": [ [ 1315, 1337 ] ], "normalized": [] }, { "id": "8749", "type": "Diseases & Disorders", "text": [ "mo" ], "offsets": [ [ 1524, 1526 ] ], "normalized": [] } ]

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[]

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[ { "id": "8752", "type": "title", "text": [ "Hypofractionated accelerated radiotherapy using concomitant intensity-modulated radiotherapy boost technique for localized high-risk prostate cancer: acute toxicity results." ], "offsets": [ [ 0, 173 ] ] }, { "id": "8753", "type": "abstract", "text": [ "PURPOSE: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. METHODS AND MATERIALS: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >or=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. RESULTS: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. CONCLUSION: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity." ], "offsets": [ [ 174, 2006 ] ] } ]

[ { "id": "8754", "type": "Chemicals & Drugs", "text": [ "radiotherapy" ], "offsets": [ [ 29, 41 ] ], "normalized": [] }, { "id": "8755", "type": "Chemicals & Drugs", "text": [ "radiotherapy" ], "offsets": [ [ 80, 92 ] ], "normalized": [] }, { "id": "8756", "type": "Diseases & Disorders", "text": [ "high-risk prostate cancer" ], "offsets": [ [ 123, 148 ] ], "normalized": [] }, { "id": "8757", "type": "Chemicals & Drugs", "text": [ "radiotherapy" ], "offsets": [ [ 248, 260 ] ], "normalized": [] }, { "id": "8758", "type": "Chemicals & Drugs", "text": [ "RT" ], "offsets": [ [ 262, 264 ] ], "normalized": [] }, { "id": "8759", "type": "Chemicals & Drugs", "text": [ "RT" ], "offsets": [ [ 306, 308 ] ], "normalized": [] }, { "id": "8760", "type": "Diseases & Disorders", "text": [ "high-risk prostate cancer" ], "offsets": [ [ 373, 398 ] ], "normalized": [] }, { "id": "8761", "type": "Diseases & Disorders", "text": [ "prostate cancer" ], "offsets": [ [ 550, 565 ] ], "normalized": [] }, { "id": "8762", "type": "Chemicals & Drugs", "text": [ "T3" ], "offsets": [ [ 627, 629 ] ], "normalized": [] }, { "id": "8763", "type": "Chemicals & Drugs", "text": [ "radiotherapy" ], "offsets": [ [ 851, 863 ] ], "normalized": [] }, { "id": "8764", "type": "Chemicals & Drugs", "text": [ "RT" ], "offsets": [ [ 1220, 1222 ] ], "normalized": [] }, { "id": "8765", "type": "Diseases & Disorders", "text": [ "genitourinary and gastrointestinal toxicities" ], "offsets": [ [ 1389, 1434 ] ], "normalized": [] }, { "id": "8766", "type": "Chemicals & Drugs", "text": [ "RT" ], "offsets": [ [ 1454, 1456 ] ], "normalized": [] }, { "id": "8767", "type": "Diseases & Disorders", "text": [ "genitourinary toxicity" ], "offsets": [ [ 1541, 1563 ] ], "normalized": [] }, { "id": "8768", "type": "Diseases & Disorders", "text": [ "urinary incontinence" ], "offsets": [ [ 1580, 1600 ] ], "normalized": [] }, { "id": "8769", "type": "Diseases & Disorders", "text": [ "urinary frequency/urgency" ], "offsets": [ [ 1610, 1635 ] ], "normalized": [] }, { "id": "8770", "type": "Diseases & Disorders", "text": [ "urinary retention" ], "offsets": [ [ 1649, 1666 ] ], "normalized": [] }, { "id": "8771", "type": "Diseases & Disorders", "text": [ "genitourinary toxicity" ], "offsets": [ [ 1765, 1787 ] ], "normalized": [] }, { "id": "8772", "type": "Chemicals & Drugs", "text": [ "RT" ], "offsets": [ [ 1883, 1885 ] ], "normalized": [] }, { "id": "8773", "type": "Chemicals & Drugs", "text": [ "RT" ], "offsets": [ [ 1925, 1927 ] ], "normalized": [] }, { "id": "8774", "type": "", "text": [ "radiotherapy" ], "offsets": [ [ 80, 92 ] ], "normalized": [] }, { "id": "8775", "type": "", "text": [ "high-risk prostate cancer" ], "offsets": [ [ 123, 148 ] ], "normalized": [] }, { "id": "8777", "type": "", "text": [ "T3" ], "offsets": [ [ 627, 629 ] ], "normalized": [] }, { "id": "8778", "type": "", "text": [ "prostate cancer" ], "offsets": [ [ 550, 565 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8776", "type": "PA", "arg1_id": "8774", "arg2_id": "8775", "normalized": [] }, { "id": "8779", "type": "PA", "arg1_id": "8777", "arg2_id": "8778", "normalized": [] } ]

[ { "id": "8782", "type": "title", "text": [ "Case-control study of the role of the Gitelman's syndrome gene in essential hypertension." ], "offsets": [ [ 0, 89 ] ] }, { "id": "8783", "type": "abstract", "text": [ "BACKGROUND: Gitelman's syndrome is an inherited tubular disorder characterized by sodium wasting, low blood pressure, secondary hyperaldosteronism, metabolic alkalosis, hypokalemia, hypomagnesemia of renal origin, and hypocalciuria. The majority of patients with this syndrome carry inactivating mutations in the SLC12A3 gene encoding the thiazide-sensitive Na (+)-Cl (-) cotransporter (NCC) located in the distal convoluted tubule, which is involved in renal sodium reabsorption. This suggests that the SLC12A3 gene is involved in mediation of blood pressure levels. The aim of the present study was to investigate relationships between single nucleotide polymorphisms (SNPs) in the human SLC12A3 gene and essential hypertension (EH) in Japanese. METHOD: We selected 3 SNPs in the human SLC12A3 gene (T180K, A569V, L849H), and performed a case-control study of 315 EH patients and 305 normotensive (NT) individuals. RESULTS: There was no significant difference in overall distribution of genotypes or alleles of any of the SNPs between the EH and NT groups. CONCLUSION: We conclude that the causal gene of Gitelman's syndrome is not involved in determining blood pressure levels." ], "offsets": [ [ 90, 1270 ] ] } ]

[ { "id": "8784", "type": "Genes & Molecular Sequences", "text": [ "Gitelman's syndrome gene" ], "offsets": [ [ 38, 62 ] ], "normalized": [] }, { "id": "8785", "type": "Diseases & Disorders", "text": [ "Gitelman's syndrome gene" ], "offsets": [ [ 38, 62 ] ], "normalized": [] }, { "id": "8786", "type": "Diseases & Disorders", "text": [ "essential hypertension" ], "offsets": [ [ 66, 88 ] ], "normalized": [] }, { "id": "8787", "type": "Diseases & Disorders", "text": [ "Gitelman's syndrome" ], "offsets": [ [ 102, 121 ] ], "normalized": [] }, { "id": "8788", "type": "Diseases & Disorders", "text": [ "disorder" ], "offsets": [ [ 146, 154 ] ], "normalized": [] }, { "id": "8789", "type": "Diseases & Disorders", "text": [ "wasting" ], "offsets": [ [ 179, 186 ] ], "normalized": [] }, { "id": "8790", "type": "Diseases & Disorders", "text": [ "secondary hyperaldosteronism" ], "offsets": [ [ 208, 236 ] ], "normalized": [] }, { "id": "8791", "type": "Diseases & Disorders", "text": [ "metabolic alkalosis" ], "offsets": [ [ 238, 257 ] ], "normalized": [] }, { "id": "8792", "type": "Diseases & Disorders", "text": [ "hypokalemia" ], "offsets": [ [ 259, 270 ] ], "normalized": [] }, { "id": "8793", "type": "Diseases & Disorders", "text": [ "hypomagnesemia of renal origin" ], "offsets": [ [ 272, 302 ] ], "normalized": [] }, { "id": "8794", "type": "Diseases & Disorders", "text": [ "hypocalciuria" ], "offsets": [ [ 308, 321 ] ], "normalized": [] }, { "id": "8795", "type": "Diseases & Disorders", "text": [ "syndrome" ], "offsets": [ [ 358, 366 ] ], "normalized": [] }, { "id": "8796", "type": "SNP & Sequence variations", "text": [ "mutations in the SLC12A3" ], "offsets": [ [ 386, 410 ] ], "normalized": [] }, { "id": "8797", "type": "Diseases & Disorders", "text": [ "mutations in the SLC12A3" ], "offsets": [ [ 386, 410 ] ], "normalized": [] }, { "id": "8798", "type": "Genes & Molecular Sequences", "text": [ "mutations in the SLC12A3" ], "offsets": [ [ 386, 410 ] ], "normalized": [] }, { "id": "8799", "type": "Genes & Molecular Sequences", "text": [ "thiazide-sensitive Na (+)-Cl (-) cotransporter" ], "offsets": [ [ 429, 475 ] ], "normalized": [] }, { "id": "8800", "type": "Genes & Molecular Sequences", "text": [ "NCC" ], "offsets": [ [ 477, 480 ] ], "normalized": [] }, { "id": "8801", "type": "Genes & Molecular Sequences", "text": [ "SLC12A3" ], "offsets": [ [ 594, 601 ] ], "normalized": [] }, { "id": "8802", "type": "SNP & Sequence variations", "text": [ "SNPs) in the human SLC12A3" ], "offsets": [ [ 761, 787 ] ], "normalized": [] }, { "id": "8803", "type": "Genes & Molecular Sequences", "text": [ "SNPs) in the human SLC12A3" ], "offsets": [ [ 761, 787 ] ], "normalized": [] }, { "id": "8804", "type": "Diseases & Disorders", "text": [ "essential hypertension" ], "offsets": [ [ 797, 819 ] ], "normalized": [] }, { "id": "8805", "type": "Diseases & Disorders", "text": [ "EH" ], "offsets": [ [ 821, 823 ] ], "normalized": [] }, { "id": "8806", "type": "Genes & Molecular Sequences", "text": [ "SLC12A3" ], "offsets": [ [ 878, 885 ] ], "normalized": [] }, { "id": "8807", "type": "SNP & Sequence variations", "text": [ "T180K" ], "offsets": [ [ 892, 897 ] ], "normalized": [] }, { "id": "8808", "type": "SNP & Sequence variations", "text": [ "A569V" ], "offsets": [ [ 899, 904 ] ], "normalized": [] }, { "id": "8809", "type": "SNP & Sequence variations", "text": [ "L849H" ], "offsets": [ [ 906, 911 ] ], "normalized": [] }, { "id": "8810", "type": "Diseases & Disorders", "text": [ "EH" ], "offsets": [ [ 956, 958 ] ], "normalized": [] }, { "id": "8811", "type": "Diseases & Disorders", "text": [ "EH" ], "offsets": [ [ 1131, 1133 ] ], "normalized": [] }, { "id": "8812", "type": "Diseases & Disorders", "text": [ "Gitelman's syndrome" ], "offsets": [ [ 1197, 1216 ] ], "normalized": [] }, { "id": "8813", "type": "", "text": [ "NCC" ], "offsets": [ [ 477, 480 ] ], "normalized": [] }, { "id": "8814", "type": "", "text": [ "syndrome" ], "offsets": [ [ 358, 366 ] ], "normalized": [] }, { "id": "8816", "type": "", "text": [ "NCC" ], "offsets": [ [ 477, 480 ] ], "normalized": [] }, { "id": "8817", "type": "", "text": [ "mutations in the SLC12A3" ], "offsets": [ [ 386, 410 ] ], "normalized": [] }, { "id": "8819", "type": "", "text": [ "SNPs) in the human SLC12A3" ], "offsets": [ [ 761, 787 ] ], "normalized": [] }, { "id": "8820", "type": "", "text": [ "essential hypertension" ], "offsets": [ [ 797, 819 ] ], "normalized": [] }, { "id": "8822", "type": "", "text": [ "SNPs) in the human SLC12A3" ], "offsets": [ [ 761, 787 ] ], "normalized": [] }, { "id": "8823", "type": "", "text": [ "EH" ], "offsets": [ [ 821, 823 ] ], "normalized": [] }, { "id": "8825", "type": "", "text": [ "SLC12A3" ], "offsets": [ [ 878, 885 ] ], "normalized": [] }, { "id": "8826", "type": "", "text": [ "EH" ], "offsets": [ [ 956, 958 ] ], "normalized": [] }, { "id": "8828", "type": "", "text": [ "T180K" ], "offsets": [ [ 892, 897 ] ], "normalized": [] }, { "id": "8829", "type": "", "text": [ "EH" ], "offsets": [ [ 956, 958 ] ], "normalized": [] }, { "id": "8831", "type": "", "text": [ "A569V" ], "offsets": [ [ 899, 904 ] ], "normalized": [] }, { "id": "8832", "type": "", "text": [ "EH" ], "offsets": [ [ 956, 958 ] ], "normalized": [] }, { "id": "8834", "type": "", "text": [ "L849H" ], "offsets": [ [ 906, 911 ] ], "normalized": [] }, { "id": "8835", "type": "", "text": [ "EH" ], "offsets": [ [ 956, 958 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8815", "type": "PA", "arg1_id": "8813", "arg2_id": "8814", "normalized": [] }, { "id": "8818", "type": "PA", "arg1_id": "8816", "arg2_id": "8817", "normalized": [] }, { "id": "8821", "type": "PA", "arg1_id": "8819", "arg2_id": "8820", "normalized": [] }, { "id": "8824", "type": "SA", "arg1_id": "8822", "arg2_id": "8823", "normalized": [] }, { "id": "8827", "type": "SA", "arg1_id": "8825", "arg2_id": "8826", "normalized": [] }, { "id": "8830", "type": "SA", "arg1_id": "8828", "arg2_id": "8829", "normalized": [] }, { "id": "8833", "type": "SA", "arg1_id": "8831", "arg2_id": "8832", "normalized": [] }, { "id": "8836", "type": "SA", "arg1_id": "8834", "arg2_id": "8835", "normalized": [] } ]

[ { "id": "8839", "type": "title", "text": [ "Selective cytotoxicity of indomethacin and indomethacin ethyl ester-loaded nanocapsules against glioma cell lines: an in vitro study." ], "offsets": [ [ 0, 133 ] ] }, { "id": "8840", "type": "abstract", "text": [ "Gliomas are the most common and devastating tumors of the central nervous system. Several studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. Biodegradable nanoparticulate systems have received considerable attention as potential drug delivery vehicles. The aim of this study was to evaluate the effects of indomethacin-loaded nanocapsules and indomethacin ethyl ester-loaded nanocapsules on glioma cell lines. In addition, the effect of these formulations on normal neural tissue was also evaluated. In order to investigate this, glioma cell lines (U138-MG and C6) and hippocampal organotypic cultures were used. The main finding of the present study is that indomethacin-loaded nanocapsules formulation was more potent than a solution of indomethacin in decreasing the viability and cell proliferation of glioma lines. Indomethacin and indomethacin ethyl ester associated together in the same nanocapsule formulation caused a synergic effect decreasing glioma cell proliferation. In addition, when the glioma cells were exposed to 25 microM of indomethacin-loaded nanocapsules or indomethacin ethyl ester-loaded nanocapsules, a necrotic cell death was observed. Interestingly, 5 microM of indomethacin-loaded nanocapsules was able to cause an antiproliferative effect without promoting necrosis in glioma cells. Another important finding was that the cytotoxic effect induced by 25 microM or 50 microM of indomethacin-loaded nanocapsules or indomethacin ethyl ester-loaded nanocapsules, in glioma cells was not observed in the organotypic cultures, indicating selective cytotoxicity of those formulations for tumoral cells. Further investigations using in vivo glioma model should be helpful to confirm the distinct effects of indomethacin-loaded nanocapsules and indomethacin ethyl ester-loaded nanocapsules, in normal versus tumoral cells." ], "offsets": [ [ 134, 2032 ] ] } ]

[ { "id": "8841", "type": "Diseases & Disorders", "text": [ "cytotoxicity" ], "offsets": [ [ 10, 22 ] ], "normalized": [] }, { "id": "8842", "type": "Chemicals & Drugs", "text": [ "indomethacin" ], "offsets": [ [ 26, 38 ] ], "normalized": [] }, { "id": "8843", "type": "Chemicals & Drugs", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 43, 87 ] ], "normalized": [] }, { "id": "8844", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 96, 102 ] ], "normalized": [] }, { "id": "8845", "type": "Diseases & Disorders", "text": [ "Gliomas" ], "offsets": [ [ 134, 141 ] ], "normalized": [] }, { "id": "8846", "type": "Diseases & Disorders", "text": [ "tumors of the central nervous system" ], "offsets": [ [ 178, 214 ] ], "normalized": [] }, { "id": "8847", "type": "Chemicals & Drugs", "text": [ "nonsteroidal anti-inflammatory drugs" ], "offsets": [ [ 252, 288 ] ], "normalized": [] }, { "id": "8848", "type": "Chemicals & Drugs", "text": [ "NSAIDs" ], "offsets": [ [ 290, 296 ] ], "normalized": [] }, { "id": "8849", "type": "Chemicals & Drugs", "text": [ "anticancer agents" ], "offsets": [ [ 312, 329 ] ], "normalized": [] }, { "id": "8850", "type": "Chemicals & Drugs", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 496, 528 ] ], "normalized": [] }, { "id": "8851", "type": "Chemicals & Drugs", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 533, 577 ] ], "normalized": [] }, { "id": "8852", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 581, 587 ] ], "normalized": [] }, { "id": "8853", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 720, 726 ] ], "normalized": [] }, { "id": "8854", "type": "Chemicals & Drugs", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 849, 881 ] ], "normalized": [] }, { "id": "8855", "type": "Chemicals & Drugs", "text": [ "solution of indomethacin" ], "offsets": [ [ 917, 941 ] ], "normalized": [] }, { "id": "8856", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 996, 1002 ] ], "normalized": [] }, { "id": "8857", "type": "Chemicals & Drugs", "text": [ "Indomethacin" ], "offsets": [ [ 1010, 1022 ] ], "normalized": [] }, { "id": "8858", "type": "Chemicals & Drugs", "text": [ "indomethacin ethyl ester" ], "offsets": [ [ 1027, 1051 ] ], "normalized": [] }, { "id": "8859", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "8860", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 1193, 1199 ] ], "normalized": [] }, { "id": "8861", "type": "Chemicals & Drugs", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1235, 1267 ] ], "normalized": [] }, { "id": "8862", "type": "Chemicals & Drugs", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1271, 1315 ] ], "normalized": [] }, { "id": "8863", "type": "Diseases & Disorders", "text": [ "necrotic" ], "offsets": [ [ 1319, 1327 ] ], "normalized": [] }, { "id": "8864", "type": "Chemicals & Drugs", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1380, 1412 ] ], "normalized": [] }, { "id": "8865", "type": "Diseases & Disorders", "text": [ "necrosis" ], "offsets": [ [ 1477, 1485 ] ], "normalized": [] }, { "id": "8866", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 1489, 1495 ] ], "normalized": [] }, { "id": "8867", "type": "Chemicals & Drugs", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1596, 1628 ] ], "normalized": [] }, { "id": "8868", "type": "Chemicals & Drugs", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1632, 1676 ] ], "normalized": [] }, { "id": "8869", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 1681, 1687 ] ], "normalized": [] }, { "id": "8870", "type": "Diseases & Disorders", "text": [ "cytotoxicity" ], "offsets": [ [ 1761, 1773 ] ], "normalized": [] }, { "id": "8871", "type": "Diseases & Disorders", "text": [ "glioma" ], "offsets": [ [ 1852, 1858 ] ], "normalized": [] }, { "id": "8872", "type": "Chemicals & Drugs", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1918, 1950 ] ], "normalized": [] }, { "id": "8873", "type": "Chemicals & Drugs", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1955, 1999 ] ], "normalized": [] }, { "id": "8874", "type": "", "text": [ "indomethacin" ], "offsets": [ [ 26, 38 ] ], "normalized": [] }, { "id": "8875", "type": "", "text": [ "glioma" ], "offsets": [ [ 96, 102 ] ], "normalized": [] }, { "id": "8877", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 43, 87 ] ], "normalized": [] }, { "id": "8878", "type": "", "text": [ "glioma" ], "offsets": [ [ 96, 102 ] ], "normalized": [] }, { "id": "8880", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 533, 577 ] ], "normalized": [] }, { "id": "8881", "type": "", "text": [ "glioma" ], "offsets": [ [ 581, 587 ] ], "normalized": [] }, { "id": "8883", "type": "", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 496, 528 ] ], "normalized": [] }, { "id": "8884", "type": "", "text": [ "glioma" ], "offsets": [ [ 581, 587 ] ], "normalized": [] }, { "id": "8886", "type": "", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 849, 881 ] ], "normalized": [] }, { "id": "8887", "type": "", "text": [ "glioma" ], "offsets": [ [ 996, 1002 ] ], "normalized": [] }, { "id": "8889", "type": "", "text": [ "solution of indomethacin" ], "offsets": [ [ 917, 941 ] ], "normalized": [] }, { "id": "8890", "type": "", "text": [ "glioma" ], "offsets": [ [ 996, 1002 ] ], "normalized": [] }, { "id": "8892", "type": "", "text": [ "Indomethacin" ], "offsets": [ [ 1010, 1022 ] ], "normalized": [] }, { "id": "8893", "type": "", "text": [ "glioma" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "8895", "type": "", "text": [ "indomethacin ethyl ester" ], "offsets": [ [ 1027, 1051 ] ], "normalized": [] }, { "id": "8896", "type": "", "text": [ "glioma" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "8898", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1271, 1315 ] ], "normalized": [] }, { "id": "8899", "type": "", "text": [ "glioma" ], "offsets": [ [ 1193, 1199 ] ], "normalized": [] }, { "id": "8901", "type": "", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1235, 1267 ] ], "normalized": [] }, { "id": "8902", "type": "", "text": [ "glioma" ], "offsets": [ [ 1193, 1199 ] ], "normalized": [] }, { "id": "8904", "type": "", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1380, 1412 ] ], "normalized": [] }, { "id": "8905", "type": "", "text": [ "glioma" ], "offsets": [ [ 1489, 1495 ] ], "normalized": [] }, { "id": "8907", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1632, 1676 ] ], "normalized": [] }, { "id": "8908", "type": "", "text": [ "glioma" ], "offsets": [ [ 1681, 1687 ] ], "normalized": [] }, { "id": "8910", "type": "", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1596, 1628 ] ], "normalized": [] }, { "id": "8911", "type": "", "text": [ "glioma" ], "offsets": [ [ 1681, 1687 ] ], "normalized": [] }, { "id": "8913", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1955, 1999 ] ], "normalized": [] }, { "id": "8914", "type": "", "text": [ "glioma" ], "offsets": [ [ 1852, 1858 ] ], "normalized": [] }, { "id": "8916", "type": "", "text": [ "indomethacin-loaded nanocapsules" ], "offsets": [ [ 1918, 1950 ] ], "normalized": [] }, { "id": "8917", "type": "", "text": [ "glioma" ], "offsets": [ [ 1852, 1858 ] ], "normalized": [] }, { "id": "8919", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 43, 87 ] ], "normalized": [] }, { "id": "8920", "type": "", "text": [ "cytotoxicity" ], "offsets": [ [ 10, 22 ] ], "normalized": [] }, { "id": "8922", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1271, 1315 ] ], "normalized": [] }, { "id": "8923", "type": "", "text": [ "necrotic" ], "offsets": [ [ 1319, 1327 ] ], "normalized": [] }, { "id": "8925", "type": "", "text": [ "indomethacin ethyl ester-loaded nanocapsules" ], "offsets": [ [ 1632, 1676 ] ], "normalized": [] }, { "id": "8926", "type": "", "text": [ "cytotoxicity" ], "offsets": [ [ 1761, 1773 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8876", "type": "PA", "arg1_id": "8874", "arg2_id": "8875", "normalized": [] }, { "id": "8879", "type": "PA", "arg1_id": "8877", "arg2_id": "8878", "normalized": [] }, { "id": "8882", "type": "PA", "arg1_id": "8880", "arg2_id": "8881", "normalized": [] }, { "id": "8885", "type": "PA", "arg1_id": "8883", "arg2_id": "8884", "normalized": [] }, { "id": "8888", "type": "PA", "arg1_id": "8886", "arg2_id": "8887", "normalized": [] }, { "id": "8891", "type": "PA", "arg1_id": "8889", "arg2_id": "8890", "normalized": [] }, { "id": "8894", "type": "PA", "arg1_id": "8892", "arg2_id": "8893", "normalized": [] }, { "id": "8897", "type": "PA", "arg1_id": "8895", "arg2_id": "8896", "normalized": [] }, { "id": "8900", "type": "PA", "arg1_id": "8898", "arg2_id": "8899", "normalized": [] }, { "id": "8903", "type": "PA", "arg1_id": "8901", "arg2_id": "8902", "normalized": [] }, { "id": "8906", "type": "PA", "arg1_id": "8904", "arg2_id": "8905", "normalized": [] }, { "id": "8909", "type": "PA", "arg1_id": "8907", "arg2_id": "8908", "normalized": [] }, { "id": "8912", "type": "PA", "arg1_id": "8910", "arg2_id": "8911", "normalized": [] }, { "id": "8915", "type": "PA", "arg1_id": "8913", "arg2_id": "8914", "normalized": [] }, { "id": "8918", "type": "PA", "arg1_id": "8916", "arg2_id": "8917", "normalized": [] }, { "id": "8921", "type": "PA", "arg1_id": "8919", "arg2_id": "8920", "normalized": [] }, { "id": "8924", "type": "PA", "arg1_id": "8922", "arg2_id": "8923", "normalized": [] }, { "id": "8927", "type": "PA", "arg1_id": "8925", "arg2_id": "8926", "normalized": [] } ]

[ { "id": "8930", "type": "title", "text": [ "Both preoperative perinuclear antineutrophil cytoplasmic antibody and anti-CBir1 expression in ulcerative colitis patients influence pouchitis development after ileal pouch-anal anastomosis." ], "offsets": [ [ 0, 190 ] ] }, { "id": "8931", "type": "abstract", "text": [ "BACKGROUND & AIMS: Acute pouchitis (AP) and chronic pouchitis (CP) are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. The aim of this study was to assess associations of preoperative perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-CBir1 flagellin on AP or CP development. METHODS: Patients were assessed prospectively for clinically and endoscopically proven AP (antibiotic responsive) or CP (antibiotic-dependent or refractory to antibiotic therapy). Sera from 238 patients were analyzed for ANCA and anti-CBir1 using an enzyme-linked immunosorbent assay. pANCA(+) patients were substratified into high-level (>100 EU/mL) and low-level (<100 EU/mL) groups. RESULTS: After a median follow-up period of 47 months, 72 patients (30%) developed pouchitis. Pouchitis developed in 36% of pANCA(+) patients versus 16% of pANCA(-) patients (P = .005), 46% of anti-CBir1(+) patients versus 26% of anti-CBir1(-) patients (P = .02), and 54% of 35 pANCA(+)/anti-CBir1(+) patients versus 31% of 136 pANCA(+)/anti-CBir1(-) patients (P = .02). AP developed in 37 pANCA(+) patients (22%) versus 6 pANCA(-) patients (9%) (P = .02), and 12 anti-CBir1(+) patients (26%) versus 31 anti-CBir1(-) patients (16%) (P = .1). Although AP was not influenced by pANCA level, AP was seen in 38% of low-level pANCA(+)/anti-CBir1(+) patients versus 18% low-level pANCA(+)/anti-CBir1(-) patients (P = .03). CP was seen in 29% of high-level pANCA(+) patients versus 11% of low-level pANCA(+) patients (P = .03). CONCLUSIONS: Both pANCA and anti-CBir1 expression are associated with pouchitis after IPAA. Anti-CBir1 increases the incidence of AP only in patients who have low-level pANCA expression, and increases the incidence of CP only in patients who have high-level pANCA expression. Diverse patterns of reactivity to microbial antigens may manifest as different forms of pouchitis after IPAA." ], "offsets": [ [ 191, 2098 ] ] } ]

[ { "id": "8932", "type": "Diseases & Disorders", "text": [ "ulcerative colitis" ], "offsets": [ [ 95, 113 ] ], "normalized": [] }, { "id": "8933", "type": "Diseases & Disorders", "text": [ "pouchitis" ], "offsets": [ [ 133, 142 ] ], "normalized": [] }, { "id": "8934", "type": "Diseases & Disorders", "text": [ "ileal pouch-anal anastomosis" ], "offsets": [ [ 161, 189 ] ], "normalized": [] }, { "id": "8935", "type": "Diseases & Disorders", "text": [ "Acute pouchitis" ], "offsets": [ [ 210, 225 ] ], "normalized": [] }, { "id": "8936", "type": "Diseases & Disorders", "text": [ "AP" ], "offsets": [ [ 227, 229 ] ], "normalized": [] }, { "id": "8937", "type": "Diseases & Disorders", "text": [ "chronic pouchitis" ], "offsets": [ [ 235, 252 ] ], "normalized": [] }, { "id": "8938", "type": "Diseases & Disorders", "text": [ "CP" ], "offsets": [ [ 254, 256 ] ], "normalized": [] }, { "id": "8939", "type": "Chemicals & Drugs", "text": [ "CP" ], "offsets": [ [ 254, 256 ] ], "normalized": [] }, { "id": "8940", "type": "Diseases & Disorders", "text": [ "ileal pouch-anal anastomosis" ], "offsets": [ [ 275, 303 ] ], "normalized": [] }, { "id": "8941", "type": "Diseases & Disorders", "text": [ "IPAA" ], "offsets": [ [ 305, 309 ] ], "normalized": [] }, { "id": "8942", "type": "Diseases & Disorders", "text": [ "ulcerative colitis" ], "offsets": [ [ 315, 333 ] ], "normalized": [] }, { "id": "8943", "type": "Diseases & Disorders", "text": [ "AP" ], "offsets": [ [ 484, 486 ] ], "normalized": [] }, { "id": "8944", "type": "Diseases & Disorders", "text": [ "CP" ], "offsets": [ [ 490, 492 ] ], "normalized": [] }, { "id": "8945", "type": "Chemicals & Drugs", "text": [ "CP" ], "offsets": [ [ 490, 492 ] ], "normalized": [] }, { "id": "8946", "type": "Diseases & Disorders", "text": [ "AP" ], "offsets": [ [ 593, 595 ] ], "normalized": [] }, { "id": "8947", "type": "Chemicals & Drugs", "text": [ "antibiotic" ], "offsets": [ [ 597, 607 ] ], "normalized": [] }, { "id": "8948", "type": "Diseases & Disorders", "text": [ "CP" ], "offsets": [ [ 623, 625 ] ], "normalized": [] }, { "id": "8949", "type": "Chemicals & Drugs", "text": [ "CP" ], "offsets": [ [ 623, 625 ] ], "normalized": [] }, { "id": "8950", "type": "Chemicals & Drugs", "text": [ "antibiotic" ], "offsets": [ [ 627, 637 ] ], "normalized": [] }, { "id": "8951", "type": "Chemicals & Drugs", "text": [ "antibiotic" ], "offsets": [ [ 665, 675 ] ], "normalized": [] }, { "id": "8952", "type": "Diseases & Disorders", "text": [ "pouchitis" ], "offsets": [ [ 975, 984 ] ], "normalized": [] }, { "id": "8953", "type": "Diseases & Disorders", "text": [ "Pouchitis" ], "offsets": [ [ 986, 995 ] ], "normalized": [] }, { "id": "8954", "type": "Diseases & Disorders", "text": [ "AP" ], "offsets": [ [ 1263, 1265 ] ], "normalized": [] }, { "id": "8955", "type": "Diseases & Disorders", "text": [ "AP" ], "offsets": [ [ 1443, 1445 ] ], "normalized": [] }, { "id": "8956", "type": "Diseases & Disorders", "text": [ "AP" ], "offsets": [ [ 1481, 1483 ] ], "normalized": [] }, { "id": "8957", "type": "Diseases & Disorders", "text": [ "CP" ], "offsets": [ [ 1609, 1611 ] ], "normalized": [] }, { "id": "8958", "type": "Chemicals & Drugs", "text": [ "CP" ], "offsets": [ [ 1609, 1611 ] ], "normalized": [] }, { "id": "8959", "type": "Diseases & Disorders", "text": [ "pouchitis" ], "offsets": [ [ 1783, 1792 ] ], "normalized": [] }, { "id": "8960", "type": "Diseases & Disorders", "text": [ "IPAA" ], "offsets": [ [ 1799, 1803 ] ], "normalized": [] }, { "id": "8961", "type": "Diseases & Disorders", "text": [ "AP" ], "offsets": [ [ 1843, 1845 ] ], "normalized": [] }, { "id": "8962", "type": "Diseases & Disorders", "text": [ "CP" ], "offsets": [ [ 1931, 1933 ] ], "normalized": [] }, { "id": "8963", "type": "Chemicals & Drugs", "text": [ "CP" ], "offsets": [ [ 1931, 1933 ] ], "normalized": [] }, { "id": "8964", "type": "Diseases & Disorders", "text": [ "pouchitis" ], "offsets": [ [ 2077, 2086 ] ], "normalized": [] }, { "id": "8965", "type": "Diseases & Disorders", "text": [ "IPAA" ], "offsets": [ [ 2093, 2097 ] ], "normalized": [] }, { "id": "8966", "type": "", "text": [ "CP" ], "offsets": [ [ 254, 256 ] ], "normalized": [] }, { "id": "8967", "type": "", "text": [ "ulcerative colitis" ], "offsets": [ [ 315, 333 ] ], "normalized": [] }, { "id": "8969", "type": "", "text": [ "CP" ], "offsets": [ [ 254, 256 ] ], "normalized": [] }, { "id": "8970", "type": "", "text": [ "chronic pouchitis" ], "offsets": [ [ 235, 252 ] ], "normalized": [] }, { "id": "8972", "type": "", "text": [ "CP" ], "offsets": [ [ 254, 256 ] ], "normalized": [] }, { "id": "8973", "type": "", "text": [ "ileal pouch-anal anastomosis" ], "offsets": [ [ 275, 303 ] ], "normalized": [] } ]

[]

[]

[ { "id": "8968", "type": "PA", "arg1_id": "8966", "arg2_id": "8967", "normalized": [] }, { "id": "8971", "type": "PA", "arg1_id": "8969", "arg2_id": "8970", "normalized": [] }, { "id": "8974", "type": "PA", "arg1_id": "8972", "arg2_id": "8973", "normalized": [] } ]

[ { "id": "8977", "type": "title", "text": [ "The cyclin-dependent kinase inhibitor flavopiridol potentiates the effects of topoisomerase I poisons by suppressing Rad51 expression in a p53-dependent manner." ], "offsets": [ [ 0, 160 ] ] }, { "id": "8978", "type": "abstract", "text": [ "The results of a phase I clinical trial of the topoisomerase I (Topo I) poison CPT-11 followed by the cyclin-dependent kinase inhibitor flavopiridol in patients with advanced solid tumors indicate that patients whose tumors were wild-type, but not mutant, for p53 obtained the most clinical benefit from this combination therapy. We elected to elucidate the mechanistic basis for this effect in isogenic-paired HCT116 colon cancer cells that were either wild-type (+/+) or null (-/-) for p53. With the combination therapy of SN-38 (the active metabolite of CPT-11) followed by flavopiridol, the induction of apoptosis was 5-fold greater in the p53+/+ cells compared with the p53-/- cells. This sequential treatment induced phosphorylation of p53 at Ser(15), which interacted with Rad51, a DNA repair protein involved in homologous recombination. Rad51 bound to p53-Ser(15) within the first 5 hours of combination therapy, and then was transcriptionally suppressed at 24 hours by flavopiridol only in p53+/+ cells. Microarray analysis also revealed suppression of Rad51 in a p53-dependent manner. Depletion of Rad51 by small interfering RNA (siRNA) sensitized both p53+/+ and p53-/- cells to SN-38-induced apoptosis with increase of gamma H2AX, a marker of DNA damage. Conversely, overexpression of Rad51 rescued p53+/+ cells from SN-->F-induced apoptosis. Because flavopiridol inhibits Cdk9, we found that inhibition of Cdk9 by DRB or by siRNA could recapitulate the flavopiridol effects, with suppression of Rad51 and induction of apoptosis only in p53+/+ cells. In conclusion, after DNA damage by Topo I poisons, flavopiridol targets homologous recombination through a p53-dependent down-regulation of Rad51, resulting in enhancement of apoptosis." ], "offsets": [ [ 161, 1910 ] ] } ]

[ { "id": "8979", "type": "Genes & Molecular Sequences", "text": [ "topoisomerase I" ], "offsets": [ [ 78, 93 ] ], "normalized": [] }, { "id": "8980", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 117, 122 ] ], "normalized": [] }, { "id": "8981", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 139, 142 ] ], "normalized": [] }, { "id": "8982", "type": "Genes & Molecular Sequences", "text": [ "topoisomerase I" ], "offsets": [ [ 208, 223 ] ], "normalized": [] }, { "id": "8983", "type": "Genes & Molecular Sequences", "text": [ "Topo I" ], "offsets": [ [ 225, 231 ] ], "normalized": [] }, { "id": "8984", "type": "Diseases & Disorders", "text": [ "solid tumors" ], "offsets": [ [ 336, 348 ] ], "normalized": [] }, { "id": "8985", "type": "Diseases & Disorders", "text": [ "tumors" ], "offsets": [ [ 378, 384 ] ], "normalized": [] }, { "id": "8986", "type": "Diseases & Disorders", "text": [ "mutant" ], "offsets": [ [ 409, 415 ] ], "normalized": [] }, { "id": "8987", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 421, 424 ] ], "normalized": [] }, { "id": "8988", "type": "Diseases & Disorders", "text": [ "colon cancer" ], "offsets": [ [ 579, 591 ] ], "normalized": [] }, { "id": "8989", "type": "SNP & Sequence variations", "text": [ "wild-type (+/+)" ], "offsets": [ [ 615, 630 ] ], "normalized": [] }, { "id": "8990", "type": "SNP & Sequence variations", "text": [ "null (-/-) for p53" ], "offsets": [ [ 634, 652 ] ], "normalized": [] }, { "id": "8991", "type": "Genes & Molecular Sequences", "text": [ "null (-/-) for p53" ], "offsets": [ [ 634, 652 ] ], "normalized": [] }, { "id": "8992", "type": "SNP & Sequence variations", "text": [ "p53+/+" ], "offsets": [ [ 805, 811 ] ], "normalized": [] }, { "id": "8993", "type": "Genes & Molecular Sequences", "text": [ "p53+/+" ], "offsets": [ [ 805, 811 ] ], "normalized": [] }, { "id": "8994", "type": "SNP & Sequence variations", "text": [ "p53-/-" ], "offsets": [ [ 836, 842 ] ], "normalized": [] }, { "id": "8995", "type": "Genes & Molecular Sequences", "text": [ "p53-/-" ], "offsets": [ [ 836, 842 ] ], "normalized": [] }, { "id": "8996", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 903, 906 ] ], "normalized": [] }, { "id": "8997", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 941, 946 ] ], "normalized": [] }, { "id": "8998", "type": "Genes & Molecular Sequences", "text": [ "DNA repair protein" ], "offsets": [ [ 950, 968 ] ], "normalized": [] }, { "id": "8999", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 1007, 1012 ] ], "normalized": [] }, { "id": "9000", "type": "Genes & Molecular Sequences", "text": [ "p53-Ser(15)" ], "offsets": [ [ 1022, 1033 ] ], "normalized": [] }, { "id": "9001", "type": "SNP & Sequence variations", "text": [ "p53+/+" ], "offsets": [ [ 1161, 1167 ] ], "normalized": [] }, { "id": "9002", "type": "Genes & Molecular Sequences", "text": [ "p53+/+" ], "offsets": [ [ 1161, 1167 ] ], "normalized": [] }, { "id": "9003", "type": "Diseases & Disorders", "text": [ "suppression" ], "offsets": [ [ 1209, 1220 ] ], "normalized": [] }, { "id": "9004", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 1224, 1229 ] ], "normalized": [] }, { "id": "9005", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 1235, 1238 ] ], "normalized": [] }, { "id": "9006", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 1270, 1275 ] ], "normalized": [] }, { "id": "9007", "type": "SNP & Sequence variations", "text": [ "p53+/+" ], "offsets": [ [ 1325, 1331 ] ], "normalized": [] }, { "id": "9008", "type": "Genes & Molecular Sequences", "text": [ "p53+/+" ], "offsets": [ [ 1325, 1331 ] ], "normalized": [] }, { "id": "9009", "type": "SNP & Sequence variations", "text": [ "p53-/-" ], "offsets": [ [ 1336, 1342 ] ], "normalized": [] }, { "id": "9010", "type": "Genes & Molecular Sequences", "text": [ "p53-/-" ], "offsets": [ [ 1336, 1342 ] ], "normalized": [] }, { "id": "9011", "type": "Genes & Molecular Sequences", "text": [ "H2AX" ], "offsets": [ [ 1399, 1403 ] ], "normalized": [] }, { "id": "9012", "type": "Diseases & Disorders", "text": [ "DNA damage" ], "offsets": [ [ 1417, 1427 ] ], "normalized": [] }, { "id": "9013", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 1459, 1464 ] ], "normalized": [] }, { "id": "9014", "type": "SNP & Sequence variations", "text": [ "p53+/+" ], "offsets": [ [ 1473, 1479 ] ], "normalized": [] }, { "id": "9015", "type": "Genes & Molecular Sequences", "text": [ "p53+/+" ], "offsets": [ [ 1473, 1479 ] ], "normalized": [] }, { "id": "9016", "type": "Genes & Molecular Sequences", "text": [ "Cdk9" ], "offsets": [ [ 1547, 1551 ] ], "normalized": [] }, { "id": "9017", "type": "Genes & Molecular Sequences", "text": [ "Cdk9" ], "offsets": [ [ 1581, 1585 ] ], "normalized": [] }, { "id": "9018", "type": "Diseases & Disorders", "text": [ "suppression" ], "offsets": [ [ 1655, 1666 ] ], "normalized": [] }, { "id": "9019", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 1670, 1675 ] ], "normalized": [] }, { "id": "9020", "type": "SNP & Sequence variations", "text": [ "p53+/+" ], "offsets": [ [ 1711, 1717 ] ], "normalized": [] }, { "id": "9021", "type": "Genes & Molecular Sequences", "text": [ "p53+/+" ], "offsets": [ [ 1711, 1717 ] ], "normalized": [] }, { "id": "9022", "type": "Diseases & Disorders", "text": [ "DNA damage" ], "offsets": [ [ 1746, 1756 ] ], "normalized": [] }, { "id": "9023", "type": "Genes & Molecular Sequences", "text": [ "Topo I" ], "offsets": [ [ 1760, 1766 ] ], "normalized": [] }, { "id": "9024", "type": "Genes & Molecular Sequences", "text": [ "p53" ], "offsets": [ [ 1832, 1835 ] ], "normalized": [] }, { "id": "9025", "type": "Genes & Molecular Sequences", "text": [ "Rad51" ], "offsets": [ [ 1865, 1870 ] ], "normalized": [] }, { "id": "9026", "type": "", "text": [ "p53" ], "offsets": [ [ 421, 424 ] ], "normalized": [] }, { "id": "9027", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 336, 348 ] ], "normalized": [] }, { "id": "9029", "type": "", "text": [ "p53" ], "offsets": [ [ 421, 424 ] ], "normalized": [] }, { "id": "9030", "type": "", "text": [ "tumors" ], "offsets": [ [ 378, 384 ] ], "normalized": [] }, { "id": "9032", "type": "", "text": [ "p53" ], "offsets": [ [ 421, 424 ] ], "normalized": [] }, { "id": "9033", "type": "", "text": [ "mutant" ], "offsets": [ [ 409, 415 ] ], "normalized": [] }, { "id": "9035", "type": "", "text": [ "null (-/-) for p53" ], "offsets": [ [ 634, 652 ] ], "normalized": [] }, { "id": "9036", "type": "", "text": [ "colon cancer" ], "offsets": [ [ 579, 591 ] ], "normalized": [] }, { "id": "9038", "type": "", "text": [ "Rad51" ], "offsets": [ [ 1224, 1229 ] ], "normalized": [] }, { "id": "9039", "type": "", "text": [ "suppression" ], "offsets": [ [ 1209, 1220 ] ], "normalized": [] }, { "id": "9041", "type": "", "text": [ "p53" ], "offsets": [ [ 1235, 1238 ] ], "normalized": [] }, { "id": "9042", "type": "", "text": [ "suppression" ], "offsets": [ [ 1209, 1220 ] ], "normalized": [] }, { "id": "9044", "type": "", "text": [ "Rad51" ], "offsets": [ [ 1270, 1275 ] ], "normalized": [] }, { "id": "9045", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 1417, 1427 ] ], "normalized": [] }, { "id": "9047", "type": "", "text": [ "H2AX" ], "offsets": [ [ 1399, 1403 ] ], "normalized": [] }, { "id": "9048", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 1417, 1427 ] ], "normalized": [] }, { "id": "9050", "type": "", "text": [ "Rad51" ], "offsets": [ [ 1670, 1675 ] ], "normalized": [] }, { "id": "9051", "type": "", "text": [ "suppression" ], "offsets": [ [ 1655, 1666 ] ], "normalized": [] }, { "id": "9053", "type": "", "text": [ "Cdk9" ], "offsets": [ [ 1581, 1585 ] ], "normalized": [] }, { "id": "9054", "type": "", "text": [ "suppression" ], "offsets": [ [ 1655, 1666 ] ], "normalized": [] }, { "id": "9056", "type": "", "text": [ "Rad51" ], "offsets": [ [ 1865, 1870 ] ], "normalized": [] }, { "id": "9057", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 1746, 1756 ] ], "normalized": [] }, { "id": "9059", "type": "", "text": [ "p53" ], "offsets": [ [ 1832, 1835 ] ], "normalized": [] }, { "id": "9060", "type": "", "text": [ "DNA damage" ], "offsets": [ [ 1746, 1756 ] ], "normalized": [] }, { "id": "9062", "type": "", "text": [ "topoisomerase I" ], "offsets": [ [ 208, 223 ] ], "normalized": [] }, { "id": "9063", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 336, 348 ] ], "normalized": [] }, { "id": "9065", "type": "", "text": [ "Topo I" ], "offsets": [ [ 225, 231 ] ], "normalized": [] }, { "id": "9066", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 336, 348 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9028", "type": "PA", "arg1_id": "9026", "arg2_id": "9027", "normalized": [] }, { "id": "9031", "type": "PA", "arg1_id": "9029", "arg2_id": "9030", "normalized": [] }, { "id": "9034", "type": "PA", "arg1_id": "9032", "arg2_id": "9033", "normalized": [] }, { "id": "9037", "type": "PA", "arg1_id": "9035", "arg2_id": "9036", "normalized": [] }, { "id": "9040", "type": "PA", "arg1_id": "9038", "arg2_id": "9039", "normalized": [] }, { "id": "9043", "type": "PA", "arg1_id": "9041", "arg2_id": "9042", "normalized": [] }, { "id": "9046", "type": "PA", "arg1_id": "9044", "arg2_id": "9045", "normalized": [] }, { "id": "9049", "type": "PA", "arg1_id": "9047", "arg2_id": "9048", "normalized": [] }, { "id": "9052", "type": "PA", "arg1_id": "9050", "arg2_id": "9051", "normalized": [] }, { "id": "9055", "type": "PA", "arg1_id": "9053", "arg2_id": "9054", "normalized": [] }, { "id": "9058", "type": "PA", "arg1_id": "9056", "arg2_id": "9057", "normalized": [] }, { "id": "9061", "type": "PA", "arg1_id": "9059", "arg2_id": "9060", "normalized": [] }, { "id": "9064", "type": "PA", "arg1_id": "9062", "arg2_id": "9063", "normalized": [] }, { "id": "9067", "type": "PA", "arg1_id": "9065", "arg2_id": "9066", "normalized": [] } ]

[ { "id": "9070", "type": "title", "text": [ "Oral surgery in a child with a prosthetic aortic valve and pulmonary artery stent at risk for thromboembolism." ], "offsets": [ [ 0, 110 ] ] }, { "id": "9071", "type": "abstract", "text": [ "Children with prosthetic cardiac valves and other invasive mechanical devices that direct blood flow require anticoagulant medication for prevention of thrombosis. Dental surgery for these children has historically consisted of decreasing and/or discontinuing the oral anticoagulant and instituting heparin therapy prior to the planned dental procedure, which can result in thromboembolism and increased morbidity and mortality. This case report demonstrates that oral anticoagulation need not be decreased or discontinued prior to extraction of multiple carious primary teeth in a child at risk for thromboembolism." ], "offsets": [ [ 111, 727 ] ] } ]

[ { "id": "9072", "type": "Diseases & Disorders", "text": [ "artery" ], "offsets": [ [ 69, 75 ] ], "normalized": [] }, { "id": "9073", "type": "Diseases & Disorders", "text": [ "thromboembolism" ], "offsets": [ [ 94, 109 ] ], "normalized": [] }, { "id": "9074", "type": "Chemicals & Drugs", "text": [ "anticoagulant" ], "offsets": [ [ 220, 233 ] ], "normalized": [] }, { "id": "9075", "type": "Diseases & Disorders", "text": [ "thrombosis" ], "offsets": [ [ 263, 273 ] ], "normalized": [] }, { "id": "9076", "type": "Chemicals & Drugs", "text": [ "anticoagulant" ], "offsets": [ [ 380, 393 ] ], "normalized": [] }, { "id": "9077", "type": "Chemicals & Drugs", "text": [ "heparin" ], "offsets": [ [ 410, 417 ] ], "normalized": [] }, { "id": "9078", "type": "Diseases & Disorders", "text": [ "thromboembolism" ], "offsets": [ [ 485, 500 ] ], "normalized": [] }, { "id": "9079", "type": "Diseases & Disorders", "text": [ "mortality" ], "offsets": [ [ 529, 538 ] ], "normalized": [] }, { "id": "9080", "type": "Chemicals & Drugs", "text": [ "oral anticoagulation" ], "offsets": [ [ 575, 595 ] ], "normalized": [] }, { "id": "9081", "type": "Diseases & Disorders", "text": [ "thromboembolism" ], "offsets": [ [ 711, 726 ] ], "normalized": [] }, { "id": "9082", "type": "", "text": [ "anticoagulant" ], "offsets": [ [ 220, 233 ] ], "normalized": [] }, { "id": "9083", "type": "", "text": [ "thrombosis" ], "offsets": [ [ 263, 273 ] ], "normalized": [] }, { "id": "9085", "type": "", "text": [ "oral anticoagulation" ], "offsets": [ [ 575, 595 ] ], "normalized": [] }, { "id": "9086", "type": "", "text": [ "thromboembolism" ], "offsets": [ [ 711, 726 ] ], "normalized": [] }, { "id": "9088", "type": "", "text": [ "heparin" ], "offsets": [ [ 410, 417 ] ], "normalized": [] }, { "id": "9089", "type": "", "text": [ "thromboembolism" ], "offsets": [ [ 485, 500 ] ], "normalized": [] }, { "id": "9091", "type": "", "text": [ "anticoagulant" ], "offsets": [ [ 380, 393 ] ], "normalized": [] }, { "id": "9092", "type": "", "text": [ "thromboembolism" ], "offsets": [ [ 485, 500 ] ], "normalized": [] }, { "id": "9094", "type": "", "text": [ "heparin" ], "offsets": [ [ 410, 417 ] ], "normalized": [] }, { "id": "9095", "type": "", "text": [ "mortality" ], "offsets": [ [ 529, 538 ] ], "normalized": [] }, { "id": "9097", "type": "", "text": [ "anticoagulant" ], "offsets": [ [ 380, 393 ] ], "normalized": [] }, { "id": "9098", "type": "", "text": [ "mortality" ], "offsets": [ [ 529, 538 ] ], "normalized": [] }, { "id": "9100", "type": "", "text": [ "oral anticoagulation" ], "offsets": [ [ 575, 595 ] ], "normalized": [] }, { "id": "9101", "type": "", "text": [ "thromboembolism" ], "offsets": [ [ 711, 726 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9084", "type": "PA", "arg1_id": "9082", "arg2_id": "9083", "normalized": [] }, { "id": "9087", "type": "NA", "arg1_id": "9085", "arg2_id": "9086", "normalized": [] }, { "id": "9090", "type": "PA", "arg1_id": "9088", "arg2_id": "9089", "normalized": [] }, { "id": "9093", "type": "PA", "arg1_id": "9091", "arg2_id": "9092", "normalized": [] }, { "id": "9096", "type": "PA", "arg1_id": "9094", "arg2_id": "9095", "normalized": [] }, { "id": "9099", "type": "PA", "arg1_id": "9097", "arg2_id": "9098", "normalized": [] }, { "id": "9102", "type": "PA", "arg1_id": "9100", "arg2_id": "9101", "normalized": [] } ]

[ { "id": "9105", "type": "title", "text": [ "Adherence to the immunomodulatory drugs for multiple sclerosis: contrasting factors affect stopping drug and missing doses." ], "offsets": [ [ 0, 123 ] ] }, { "id": "9106", "type": "abstract", "text": [ "BACKGROUND: Long-term immunomodulatory drug (IMD) treatment is now common in multiple sclerosis (MS). However, predictors of adherence are not well understood; past studies lacked lifestyle factors such as alcohol use and predictors of missed doses have not been evaluated. We examined both levels of non-adherence-stopping IMD and missing doses. METHODS: This longitudinal prospective study followed a population-based cohort (n = 199) of definite MS patients in Southern Tasmania (January 2002 to April 2005, source population 226 559) every 6 months. Baseline factors (demographic, clinical, psychological and cognitive) affecting adherence were examined by logistic regression and a longitudinal analysis (generalized estimating equation (GEE)). RESULTS: Of the 97 patients taking an IMD (mean follow-up = 2.4 years), 73% (71/97) missed doses, with 1 in 10 missing > 10 doses in any 6-month period. Missed doses were positively associated with alcohol amount consumed per session (p = 0.008). A history of missed doses predicted future missed doses (p < 0.0005). Over one-quarter (27/97) stopped their current IMD, which was associated with lower education levels (p = 0.032) and previous relapses (p = 0.05). No cognitive or psychological test predicted adherence. CONCLUSIONS: There were few strong predictors of missed doses, although people with MS consuming more alcoholic drinks per session are at a higher risk of missing doses. Divergent factors influenced the two levels of non-adherence indicating the need for a multifaceted approach to improving IMD adherence. In addition, missed doses should be assessed and incorporated into clinical trial design and clinical practice as poor adherers could impact on clinical outcomes." ], "offsets": [ [ 124, 1863 ] ] } ]

[ { "id": "9107", "type": "Chemicals & Drugs", "text": [ "immunomodulatory drugs" ], "offsets": [ [ 17, 39 ] ], "normalized": [] }, { "id": "9108", "type": "Diseases & Disorders", "text": [ "multiple sclerosis" ], "offsets": [ [ 44, 62 ] ], "normalized": [] }, { "id": "9109", "type": "Chemicals & Drugs", "text": [ "Long-term immunomodulatory drug" ], "offsets": [ [ 136, 167 ] ], "normalized": [] }, { "id": "9110", "type": "Chemicals & Drugs", "text": [ "IMD" ], "offsets": [ [ 169, 172 ] ], "normalized": [] }, { "id": "9111", "type": "Diseases & Disorders", "text": [ "multiple sclerosis" ], "offsets": [ [ 201, 219 ] ], "normalized": [] }, { "id": "9112", "type": "Diseases & Disorders", "text": [ "MS" ], "offsets": [ [ 221, 223 ] ], "normalized": [] }, { "id": "9113", "type": "Chemicals & Drugs", "text": [ "IMD" ], "offsets": [ [ 448, 451 ] ], "normalized": [] }, { "id": "9114", "type": "Diseases & Disorders", "text": [ "MS" ], "offsets": [ [ 573, 575 ] ], "normalized": [] }, { "id": "9115", "type": "Diseases & Disorders", "text": [ "regression" ], "offsets": [ [ 794, 804 ] ], "normalized": [] }, { "id": "9116", "type": "Chemicals & Drugs", "text": [ "IMD" ], "offsets": [ [ 912, 915 ] ], "normalized": [] }, { "id": "9117", "type": "Chemicals & Drugs", "text": [ "alcohol" ], "offsets": [ [ 1072, 1079 ] ], "normalized": [] }, { "id": "9118", "type": "Chemicals & Drugs", "text": [ "IMD" ], "offsets": [ [ 1238, 1241 ] ], "normalized": [] }, { "id": "9119", "type": "Diseases & Disorders", "text": [ "relapses" ], "offsets": [ [ 1317, 1325 ] ], "normalized": [] }, { "id": "9120", "type": "Diseases & Disorders", "text": [ "MS" ], "offsets": [ [ 1478, 1480 ] ], "normalized": [] }, { "id": "9121", "type": "Diseases & Disorders", "text": [ "drinks" ], "offsets": [ [ 1506, 1512 ] ], "normalized": [] }, { "id": "9122", "type": "Chemicals & Drugs", "text": [ "IMD" ], "offsets": [ [ 1686, 1689 ] ], "normalized": [] }, { "id": "9123", "type": "", "text": [ "immunomodulatory drugs" ], "offsets": [ [ 17, 39 ] ], "normalized": [] }, { "id": "9124", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 44, 62 ] ], "normalized": [] }, { "id": "9126", "type": "", "text": [ "Long-term immunomodulatory drug" ], "offsets": [ [ 136, 167 ] ], "normalized": [] }, { "id": "9127", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 201, 219 ] ], "normalized": [] }, { "id": "9129", "type": "", "text": [ "Long-term immunomodulatory drug" ], "offsets": [ [ 136, 167 ] ], "normalized": [] }, { "id": "9130", "type": "", "text": [ "MS" ], "offsets": [ [ 221, 223 ] ], "normalized": [] }, { "id": "9132", "type": "", "text": [ "IMD" ], "offsets": [ [ 169, 172 ] ], "normalized": [] }, { "id": "9133", "type": "", "text": [ "multiple sclerosis" ], "offsets": [ [ 201, 219 ] ], "normalized": [] }, { "id": "9135", "type": "", "text": [ "IMD" ], "offsets": [ [ 169, 172 ] ], "normalized": [] }, { "id": "9136", "type": "", "text": [ "MS" ], "offsets": [ [ 221, 223 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9125", "type": "PA", "arg1_id": "9123", "arg2_id": "9124", "normalized": [] }, { "id": "9128", "type": "PA", "arg1_id": "9126", "arg2_id": "9127", "normalized": [] }, { "id": "9131", "type": "PA", "arg1_id": "9129", "arg2_id": "9130", "normalized": [] }, { "id": "9134", "type": "PA", "arg1_id": "9132", "arg2_id": "9133", "normalized": [] }, { "id": "9137", "type": "PA", "arg1_id": "9135", "arg2_id": "9136", "normalized": [] } ]

[ { "id": "9140", "type": "title", "text": [ "Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study." ], "offsets": [ [ 0, 109 ] ] }, { "id": "9141", "type": "abstract", "text": [ "BACKGROUND: Patients with an early response to neoadjuvant chemotherapy have chemosensitive tumors and a high probability for a pathological complete response at surgery. The relationship between extended chemotherapy and pathological complete response at surgery was investigated in a clinical trial. METHODS: Untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2), doxorubicin at 50 mg/m(2), and cyclophosphamide at 500 mg/m(2) (TAC). Those whose tumor size decreased by 50% or more by sonographic measurement (ie, reduction in the product of the two largest perpendicular diameters by at least 50%) were classified as responders and randomly assigned to receive four or six more cycles of TAC, for a total of six or eight TAC cycles. The primary aim was to increase the rate of a pathological complete response (defined as no invasive or in situ residual tumor masses in the breast and lymph nodes) from 20% to 26%. Sonographic response rates and rates of breast-conserving surgery and adverse effects were also assessed. All statistical tests were two-sided. RESULTS: Of the 2090 patients in the GeparTrio trial, 1390 (66.5%) were randomly assigned as responders after two initial TAC cycles to receive an additional four (n = 704) or six (n = 686) TAC cycles. Rates of pathological complete response were not statistically significantly different between the arms (21.0% with six TAC cycles and 23.5% with eight TAC cycles; difference = 2.5%, 95% confidence interval [CI] = -1.8% to 6.8%; P = .27). More clinical (48.2% vs 52.9%, difference = 4.7%; 95% CI = -0.55% to 9.95%; P = .08) and sonographic (22.6% vs 27.6%, difference = 5%; 95% CI = 0.45% to 9.55%; P = .033) complete responses at surgery were observed with eight TAC cycles than with six TAC cycles. The rate of breast-conserving surgery was similar in both arms (67.5% vs 68.5%, respectively, P = .68). Grade 3 or 4 leukopenia and edema and various grade 1 or 2 adverse events were more frequent in patients receiving eight TAC cycles than in those receiving six cycles. CONCLUSION: Patients receiving eight TAC cycles had statistically significantly higher sonographic response rates but not pathological complete response rates than those receiving six TAC cycles. However, they also had more toxic effects. So far, eight cycles of TAC cannot be recommended for the whole group of patients responding to two initial cycles of TAC." ], "offsets": [ [ 110, 2541 ] ] } ]

[ { "id": "9142", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 24, 36 ] ], "normalized": [] }, { "id": "9143", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 57, 70 ] ], "normalized": [] }, { "id": "9144", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 169, 181 ] ], "normalized": [] }, { "id": "9145", "type": "Diseases & Disorders", "text": [ "tumors" ], "offsets": [ [ 202, 208 ] ], "normalized": [] }, { "id": "9146", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 315, 327 ] ], "normalized": [] }, { "id": "9147", "type": "Diseases & Disorders", "text": [ "breast cancer" ], "offsets": [ [ 431, 444 ] ], "normalized": [] }, { "id": "9148", "type": "Chemicals & Drugs", "text": [ "docetaxel" ], "offsets": [ [ 484, 493 ] ], "normalized": [] }, { "id": "9149", "type": "Chemicals & Drugs", "text": [ "doxorubicin" ], "offsets": [ [ 509, 520 ] ], "normalized": [] }, { "id": "9150", "type": "Chemicals & Drugs", "text": [ "cyclophosphamide" ], "offsets": [ [ 540, 556 ] ], "normalized": [] }, { "id": "9151", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 573, 576 ] ], "normalized": [] }, { "id": "9152", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 591, 596 ] ], "normalized": [] }, { "id": "9153", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 834, 837 ] ], "normalized": [] }, { "id": "9154", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 867, 870 ] ], "normalized": [] }, { "id": "9155", "type": "Diseases & Disorders", "text": [ "residual tumor masses" ], "offsets": [ [ 991, 1012 ] ], "normalized": [] }, { "id": "9156", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 1000, 1005 ] ], "normalized": [] }, { "id": "9157", "type": "Diseases & Disorders", "text": [ "adverse effects" ], "offsets": [ [ 1131, 1146 ] ], "normalized": [] }, { "id": "9158", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 1327, 1330 ] ], "normalized": [] }, { "id": "9159", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 1395, 1398 ] ], "normalized": [] }, { "id": "9160", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 1527, 1530 ] ], "normalized": [] }, { "id": "9161", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 1559, 1562 ] ], "normalized": [] }, { "id": "9162", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 1871, 1874 ] ], "normalized": [] }, { "id": "9163", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 1896, 1899 ] ], "normalized": [] }, { "id": "9164", "type": "Diseases & Disorders", "text": [ "Grade 3" ], "offsets": [ [ 2012, 2019 ] ], "normalized": [] }, { "id": "9165", "type": "Diseases & Disorders", "text": [ "4 leukopenia" ], "offsets": [ [ 2023, 2035 ] ], "normalized": [] }, { "id": "9166", "type": "Diseases & Disorders", "text": [ "edema" ], "offsets": [ [ 2040, 2045 ] ], "normalized": [] }, { "id": "9167", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 2133, 2136 ] ], "normalized": [] }, { "id": "9168", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 2217, 2220 ] ], "normalized": [] }, { "id": "9169", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 2364, 2367 ] ], "normalized": [] }, { "id": "9170", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 2443, 2446 ] ], "normalized": [] }, { "id": "9171", "type": "Chemicals & Drugs", "text": [ "TAC" ], "offsets": [ [ 2537, 2540 ] ], "normalized": [] }, { "id": "9172", "type": "", "text": [ "TAC" ], "offsets": [ [ 2133, 2136 ] ], "normalized": [] }, { "id": "9173", "type": "", "text": [ "edema" ], "offsets": [ [ 2040, 2045 ] ], "normalized": [] }, { "id": "9175", "type": "", "text": [ "TAC" ], "offsets": [ [ 2133, 2136 ] ], "normalized": [] }, { "id": "9176", "type": "", "text": [ "Grade 3" ], "offsets": [ [ 2012, 2019 ] ], "normalized": [] }, { "id": "9178", "type": "", "text": [ "TAC" ], "offsets": [ [ 2133, 2136 ] ], "normalized": [] }, { "id": "9179", "type": "", "text": [ "4 leukopenia" ], "offsets": [ [ 2023, 2035 ] ], "normalized": [] }, { "id": "9181", "type": "", "text": [ "TAC" ], "offsets": [ [ 573, 576 ] ], "normalized": [] }, { "id": "9182", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 431, 444 ] ], "normalized": [] }, { "id": "9184", "type": "", "text": [ "docetaxel" ], "offsets": [ [ 484, 493 ] ], "normalized": [] }, { "id": "9185", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 431, 444 ] ], "normalized": [] }, { "id": "9187", "type": "", "text": [ "doxorubicin" ], "offsets": [ [ 509, 520 ] ], "normalized": [] }, { "id": "9188", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 431, 444 ] ], "normalized": [] }, { "id": "9190", "type": "", "text": [ "cyclophosphamide" ], "offsets": [ [ 540, 556 ] ], "normalized": [] }, { "id": "9191", "type": "", "text": [ "breast cancer" ], "offsets": [ [ 431, 444 ] ], "normalized": [] }, { "id": "9193", "type": "", "text": [ "TAC" ], "offsets": [ [ 867, 870 ] ], "normalized": [] }, { "id": "9194", "type": "", "text": [ "tumor" ], "offsets": [ [ 591, 596 ] ], "normalized": [] }, { "id": "9196", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 169, 181 ] ], "normalized": [] }, { "id": "9197", "type": "", "text": [ "tumors" ], "offsets": [ [ 202, 208 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9174", "type": "PA", "arg1_id": "9172", "arg2_id": "9173", "normalized": [] }, { "id": "9177", "type": "PA", "arg1_id": "9175", "arg2_id": "9176", "normalized": [] }, { "id": "9180", "type": "PA", "arg1_id": "9178", "arg2_id": "9179", "normalized": [] }, { "id": "9183", "type": "PA", "arg1_id": "9181", "arg2_id": "9182", "normalized": [] }, { "id": "9186", "type": "PA", "arg1_id": "9184", "arg2_id": "9185", "normalized": [] }, { "id": "9189", "type": "PA", "arg1_id": "9187", "arg2_id": "9188", "normalized": [] }, { "id": "9192", "type": "PA", "arg1_id": "9190", "arg2_id": "9191", "normalized": [] }, { "id": "9195", "type": "PA", "arg1_id": "9193", "arg2_id": "9194", "normalized": [] }, { "id": "9198", "type": "PA", "arg1_id": "9196", "arg2_id": "9197", "normalized": [] } ]

[ { "id": "9201", "type": "title", "text": [ "Hepatitis C virus genotypes: clinical relevance and therapeutic implications." ], "offsets": [ [ 0, 77 ] ] }, { "id": "9202", "type": "abstract", "text": [ "The incidence of hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) has been increasing in several countries including Taiwan. There are six main genotypes, each of which contains closely related subtypes. Molecular epidemiological studies have shown marked differences in the genotype distribution by geographical region and between patient groups. HCV genotype 1 may play a role in the development of HCC, although some studies have argued against this. A sustained virological response secondary to interferon monotherapy or interferon/ribavirin combination therapy may reduce the risk of HCC and improve survival in chronic hepatitis C patients. The HCV genotypes are associated with therapeutic response. Rapid virological response is also a predictor of therapeutic response. Although viral characteristics have consistently been shown to be important predictors of treatment response, identification of additional host immune and genetic factors involved in determining the outcome of antiviral therapy is necessary. Newly developed bio-techniques (microarray, proteomes, bioinformatics), drugs, and treatment strategies may elucidate the pathogenesis and improve the therapeutic response in HCV infection." ], "offsets": [ [ 78, 1304 ] ] } ]

[ { "id": "9203", "type": "Diseases & Disorders", "text": [ "Hepatitis C" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "9204", "type": "Genes & Molecular Sequences", "text": [ "Hepatitis C" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "9205", "type": "Diseases & Disorders", "text": [ "virus" ], "offsets": [ [ 12, 17 ] ], "normalized": [] }, { "id": "9206", "type": "Diseases & Disorders", "text": [ "hepatitis C" ], "offsets": [ [ 95, 106 ] ], "normalized": [] }, { "id": "9207", "type": "Diseases & Disorders", "text": [ "virus" ], "offsets": [ [ 107, 112 ] ], "normalized": [] }, { "id": "9208", "type": "Diseases & Disorders", "text": [ "HCV" ], "offsets": [ [ 114, 117 ] ], "normalized": [] }, { "id": "9209", "type": "Diseases & Disorders", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 128, 152 ] ], "normalized": [] }, { "id": "9210", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 154, 157 ] ], "normalized": [] }, { "id": "9211", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 154, 157 ] ], "normalized": [] }, { "id": "9212", "type": "Genes & Molecular Sequences", "text": [ "HCV genotype 1" ], "offsets": [ [ 441, 455 ] ], "normalized": [] }, { "id": "9213", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 494, 497 ] ], "normalized": [] }, { "id": "9214", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 494, 497 ] ], "normalized": [] }, { "id": "9215", "type": "Diseases & Disorders", "text": [ "secondary" ], "offsets": [ [ 580, 589 ] ], "normalized": [] }, { "id": "9216", "type": "Diseases & Disorders", "text": [ "HCC" ], "offsets": [ [ 683, 686 ] ], "normalized": [] }, { "id": "9217", "type": "Genes & Molecular Sequences", "text": [ "HCC" ], "offsets": [ [ 683, 686 ] ], "normalized": [] }, { "id": "9218", "type": "Diseases & Disorders", "text": [ "chronic hepatitis C" ], "offsets": [ [ 711, 730 ] ], "normalized": [] }, { "id": "9219", "type": "Genes & Molecular Sequences", "text": [ "HCV genotypes" ], "offsets": [ [ 745, 758 ] ], "normalized": [] }, { "id": "9220", "type": "Diseases & Disorders", "text": [ "pathogenesis" ], "offsets": [ [ 1237, 1249 ] ], "normalized": [] }, { "id": "9221", "type": "Diseases & Disorders", "text": [ "HCV infection" ], "offsets": [ [ 1290, 1303 ] ], "normalized": [] }, { "id": "9222", "type": "", "text": [ "HCC" ], "offsets": [ [ 154, 157 ] ], "normalized": [] }, { "id": "9223", "type": "", "text": [ "hepatitis C" ], "offsets": [ [ 95, 106 ] ], "normalized": [] }, { "id": "9225", "type": "", "text": [ "HCC" ], "offsets": [ [ 154, 157 ] ], "normalized": [] }, { "id": "9226", "type": "", "text": [ "virus" ], "offsets": [ [ 107, 112 ] ], "normalized": [] }, { "id": "9228", "type": "", "text": [ "HCC" ], "offsets": [ [ 154, 157 ] ], "normalized": [] }, { "id": "9229", "type": "", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 128, 152 ] ], "normalized": [] }, { "id": "9231", "type": "", "text": [ "HCC" ], "offsets": [ [ 683, 686 ] ], "normalized": [] }, { "id": "9232", "type": "", "text": [ "chronic hepatitis C" ], "offsets": [ [ 711, 730 ] ], "normalized": [] }, { "id": "9234", "type": "", "text": [ "HCC" ], "offsets": [ [ 683, 686 ] ], "normalized": [] }, { "id": "9235", "type": "", "text": [ "secondary" ], "offsets": [ [ 580, 589 ] ], "normalized": [] }, { "id": "9237", "type": "", "text": [ "HCV genotype 1" ], "offsets": [ [ 441, 455 ] ], "normalized": [] }, { "id": "9238", "type": "", "text": [ "HCC" ], "offsets": [ [ 494, 497 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9224", "type": "PA", "arg1_id": "9222", "arg2_id": "9223", "normalized": [] }, { "id": "9227", "type": "PA", "arg1_id": "9225", "arg2_id": "9226", "normalized": [] }, { "id": "9230", "type": "PA", "arg1_id": "9228", "arg2_id": "9229", "normalized": [] }, { "id": "9233", "type": "PA", "arg1_id": "9231", "arg2_id": "9232", "normalized": [] }, { "id": "9236", "type": "PA", "arg1_id": "9234", "arg2_id": "9235", "normalized": [] }, { "id": "9239", "type": "SA", "arg1_id": "9237", "arg2_id": "9238", "normalized": [] } ]

[ { "id": "9242", "type": "title", "text": [ "Changing patterns in HIV reverse transcriptase resistance mutations after availability of tenofovir." ], "offsets": [ [ 0, 100 ] ] }, { "id": "9243", "type": "abstract", "text": [ "Assessment of 1177 human immunodeficiency virus (HIV) resistance genotypes at an HIV/AIDS clinic showed a decrease in the incidence of the K65R mutation, from 15.2% of isolates during the period 2002-2004 to 2.7% of isolates during the period 2005-2006 (P < .001), despite elevated and stable rates of tenofovir use. A reduction in the rate of coadministration of didanosine (from 41.6% of patients in 2004 to 0.8% of patients in 2006; P < .001) largely explained this observation." ], "offsets": [ [ 101, 582 ] ] } ]

[ { "id": "9244", "type": "SNP & Sequence variations", "text": [ "HIV reverse transcriptase resistance mutations" ], "offsets": [ [ 21, 67 ] ], "normalized": [] }, { "id": "9245", "type": "Genes & Molecular Sequences", "text": [ "HIV reverse transcriptase resistance mutations" ], "offsets": [ [ 21, 67 ] ], "normalized": [] }, { "id": "9246", "type": "Chemicals & Drugs", "text": [ "tenofovir" ], "offsets": [ [ 90, 99 ] ], "normalized": [] }, { "id": "9247", "type": "SNP & Sequence variations", "text": [ "K65R mutation" ], "offsets": [ [ 240, 253 ] ], "normalized": [] }, { "id": "9248", "type": "Chemicals & Drugs", "text": [ "tenofovir" ], "offsets": [ [ 403, 412 ] ], "normalized": [] }, { "id": "9249", "type": "Chemicals & Drugs", "text": [ "didanosine" ], "offsets": [ [ 465, 475 ] ], "normalized": [] }, { "id": "9250", "type": "", "text": [ "K65R mutation" ], "offsets": [ [ 240, 253 ] ], "normalized": [] }, { "id": "9251", "type": "", "text": [ "tenofovir" ], "offsets": [ [ 403, 412 ] ], "normalized": [] }, { "id": "9253", "type": "", "text": [ "tenofovir" ], "offsets": [ [ 90, 99 ] ], "normalized": [] }, { "id": "9254", "type": "", "text": [ "HIV reverse transcriptase resistance mutations" ], "offsets": [ [ 21, 67 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9252", "type": "PA", "arg1_id": "9250", "arg2_id": "9251", "normalized": [] }, { "id": "9255", "type": "PA", "arg1_id": "9253", "arg2_id": "9254", "normalized": [] } ]

[ { "id": "9258", "type": "title", "text": [ "Intra-articular lidocaine versus intravenous meperidine/diazepam in anterior shoulder dislocation: a randomised clinical trial." ], "offsets": [ [ 0, 127 ] ] }, { "id": "9259", "type": "abstract", "text": [ "BACKGROUND: Anterior shoulder dislocation is one of the most common complaints of patients referred to emergency departments. Intravenous opiates and benzodiazepines are traditionally prescribed in order to relieve the pain in this group of patients; however, complications always pose a problem. OBJECTIVE: To compare the pain relief and complications following intra-articular lidocaine and intravenous meperidine/diazepam in patients with anterior shoulder dislocation. METHODS: 48 patients with non-habitual traumatic anterior dislocation of the glenohumoral joint admitted to Imam Khomeini hospital emergency department were enrolled in this randomised clinical trial. They were divided into two groups: one group of patients received intra-articular lidocaine 1%, while the other received intravenous meperidine and diazepam. Closed reduction using the countertraction-traction method was performed by a single person in all the patients. Utilising a 100 mm visual analogue scale, each patient's pain was recorded before injection, before reduction, and after reduction. RESULTS: Mean pain (mm) recorded before injection, before reduction, and after reduction in the intra-articular lidocaine group was 84.3 (95% confidence interval (CI) 79.8 to 88.8), 52.6 (95% CI 45.2 to 60.1), and 27.3 (95% CI 19.9 to 34.7), respectively. The corresponding rates in the intravenous meperidine/diazepam group were 83.2 (95% CI 79.2 to 87.2), 57.9 (95% CI 53.8 to 62.0), and 23.9 (95% CI 18.9 to 28.8), respectively. Both groups demonstrated a similar significant decline in pain after injection (p<0.005). No severe complications were reported in either of the groups. CONCLUSION: Intra-articular injection of lidocaine before closed reduction of anterior shoulder dislocation produces the same pain relief as intravenous meperidine and diazepam." ], "offsets": [ [ 128, 1967 ] ] } ]

[ { "id": "9260", "type": "Chemicals & Drugs", "text": [ "Intra-articular lidocaine" ], "offsets": [ [ 0, 25 ] ], "normalized": [] }, { "id": "9261", "type": "Chemicals & Drugs", "text": [ "intravenous meperidine" ], "offsets": [ [ 33, 55 ] ], "normalized": [] }, { "id": "9262", "type": "Chemicals & Drugs", "text": [ "diazepam" ], "offsets": [ [ 56, 64 ] ], "normalized": [] }, { "id": "9263", "type": "Diseases & Disorders", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 68, 97 ] ], "normalized": [] }, { "id": "9264", "type": "Diseases & Disorders", "text": [ "Anterior shoulder dislocation" ], "offsets": [ [ 140, 169 ] ], "normalized": [] }, { "id": "9265", "type": "Chemicals & Drugs", "text": [ "Intravenous opiates" ], "offsets": [ [ 254, 273 ] ], "normalized": [] }, { "id": "9266", "type": "Diseases & Disorders", "text": [ "Intravenous opiates" ], "offsets": [ [ 254, 273 ] ], "normalized": [] }, { "id": "9267", "type": "Chemicals & Drugs", "text": [ "benzodiazepines" ], "offsets": [ [ 278, 293 ] ], "normalized": [] }, { "id": "9268", "type": "Diseases & Disorders", "text": [ "pain" ], "offsets": [ [ 347, 351 ] ], "normalized": [] }, { "id": "9269", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 388, 401 ] ], "normalized": [] }, { "id": "9270", "type": "Diseases & Disorders", "text": [ "pain" ], "offsets": [ [ 451, 455 ] ], "normalized": [] }, { "id": "9271", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 467, 480 ] ], "normalized": [] }, { "id": "9272", "type": "Chemicals & Drugs", "text": [ "intra-articular lidocaine" ], "offsets": [ [ 491, 516 ] ], "normalized": [] }, { "id": "9273", "type": "Chemicals & Drugs", "text": [ "intravenous meperidine" ], "offsets": [ [ 521, 543 ] ], "normalized": [] }, { "id": "9274", "type": "Chemicals & Drugs", "text": [ "diazepam" ], "offsets": [ [ 544, 552 ] ], "normalized": [] }, { "id": "9275", "type": "Diseases & Disorders", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 570, 599 ] ], "normalized": [] }, { "id": "9276", "type": "Diseases & Disorders", "text": [ "non-habitual traumatic anterior dislocation of the glenohumoral joint" ], "offsets": [ [ 627, 696 ] ], "normalized": [] }, { "id": "9277", "type": "Diseases & Disorders", "text": [ "dislocation" ], "offsets": [ [ 659, 670 ] ], "normalized": [] }, { "id": "9278", "type": "Chemicals & Drugs", "text": [ "intra-articular lidocaine" ], "offsets": [ [ 868, 893 ] ], "normalized": [] }, { "id": "9279", "type": "Chemicals & Drugs", "text": [ "intravenous meperidine" ], "offsets": [ [ 923, 945 ] ], "normalized": [] }, { "id": "9280", "type": "Chemicals & Drugs", "text": [ "diazepam" ], "offsets": [ [ 950, 958 ] ], "normalized": [] }, { "id": "9281", "type": "Diseases & Disorders", "text": [ "pain" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "9282", "type": "Diseases & Disorders", "text": [ "pain" ], "offsets": [ [ 1219, 1223 ] ], "normalized": [] }, { "id": "9283", "type": "Chemicals & Drugs", "text": [ "intra-articular lidocaine" ], "offsets": [ [ 1301, 1326 ] ], "normalized": [] }, { "id": "9284", "type": "Chemicals & Drugs", "text": [ "intravenous meperidine" ], "offsets": [ [ 1492, 1514 ] ], "normalized": [] }, { "id": "9285", "type": "Chemicals & Drugs", "text": [ "diazepam" ], "offsets": [ [ 1515, 1523 ] ], "normalized": [] }, { "id": "9286", "type": "Diseases & Disorders", "text": [ "pain" ], "offsets": [ [ 1695, 1699 ] ], "normalized": [] }, { "id": "9287", "type": "Chemicals & Drugs", "text": [ "No" ], "offsets": [ [ 1727, 1729 ] ], "normalized": [] }, { "id": "9288", "type": "Diseases & Disorders", "text": [ "complications" ], "offsets": [ [ 1737, 1750 ] ], "normalized": [] }, { "id": "9289", "type": "Chemicals & Drugs", "text": [ "Intra-articular injection of lidocaine" ], "offsets": [ [ 1802, 1840 ] ], "normalized": [] }, { "id": "9290", "type": "Diseases & Disorders", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 1868, 1897 ] ], "normalized": [] }, { "id": "9291", "type": "Diseases & Disorders", "text": [ "pain" ], "offsets": [ [ 1916, 1920 ] ], "normalized": [] }, { "id": "9292", "type": "Chemicals & Drugs", "text": [ "intravenous meperidine" ], "offsets": [ [ 1931, 1953 ] ], "normalized": [] }, { "id": "9293", "type": "Chemicals & Drugs", "text": [ "diazepam" ], "offsets": [ [ 1958, 1966 ] ], "normalized": [] }, { "id": "9294", "type": "", "text": [ "intravenous meperidine" ], "offsets": [ [ 1931, 1953 ] ], "normalized": [] }, { "id": "9295", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 1868, 1897 ] ], "normalized": [] }, { "id": "9297", "type": "", "text": [ "diazepam" ], "offsets": [ [ 1958, 1966 ] ], "normalized": [] }, { "id": "9298", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 1868, 1897 ] ], "normalized": [] }, { "id": "9300", "type": "", "text": [ "Intra-articular injection of lidocaine" ], "offsets": [ [ 1802, 1840 ] ], "normalized": [] }, { "id": "9301", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 1868, 1897 ] ], "normalized": [] }, { "id": "9303", "type": "", "text": [ "intra-articular lidocaine" ], "offsets": [ [ 1301, 1326 ] ], "normalized": [] }, { "id": "9304", "type": "", "text": [ "pain" ], "offsets": [ [ 1219, 1223 ] ], "normalized": [] }, { "id": "9306", "type": "", "text": [ "Intra-articular injection of lidocaine" ], "offsets": [ [ 1802, 1840 ] ], "normalized": [] }, { "id": "9307", "type": "", "text": [ "pain" ], "offsets": [ [ 1916, 1920 ] ], "normalized": [] }, { "id": "9309", "type": "", "text": [ "intravenous meperidine" ], "offsets": [ [ 1931, 1953 ] ], "normalized": [] }, { "id": "9310", "type": "", "text": [ "pain" ], "offsets": [ [ 1916, 1920 ] ], "normalized": [] }, { "id": "9312", "type": "", "text": [ "diazepam" ], "offsets": [ [ 1958, 1966 ] ], "normalized": [] }, { "id": "9313", "type": "", "text": [ "pain" ], "offsets": [ [ 1916, 1920 ] ], "normalized": [] }, { "id": "9315", "type": "", "text": [ "Intra-articular lidocaine" ], "offsets": [ [ 0, 25 ] ], "normalized": [] }, { "id": "9316", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 68, 97 ] ], "normalized": [] }, { "id": "9318", "type": "", "text": [ "intravenous meperidine" ], "offsets": [ [ 33, 55 ] ], "normalized": [] }, { "id": "9319", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 68, 97 ] ], "normalized": [] }, { "id": "9321", "type": "", "text": [ "diazepam" ], "offsets": [ [ 56, 64 ] ], "normalized": [] }, { "id": "9322", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 68, 97 ] ], "normalized": [] }, { "id": "9324", "type": "", "text": [ "intra-articular lidocaine" ], "offsets": [ [ 491, 516 ] ], "normalized": [] }, { "id": "9325", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 570, 599 ] ], "normalized": [] }, { "id": "9327", "type": "", "text": [ "intra-articular lidocaine" ], "offsets": [ [ 491, 516 ] ], "normalized": [] }, { "id": "9328", "type": "", "text": [ "pain" ], "offsets": [ [ 451, 455 ] ], "normalized": [] }, { "id": "9330", "type": "", "text": [ "intra-articular lidocaine" ], "offsets": [ [ 491, 516 ] ], "normalized": [] }, { "id": "9331", "type": "", "text": [ "complications" ], "offsets": [ [ 467, 480 ] ], "normalized": [] }, { "id": "9333", "type": "", "text": [ "intravenous meperidine" ], "offsets": [ [ 521, 543 ] ], "normalized": [] }, { "id": "9334", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 570, 599 ] ], "normalized": [] }, { "id": "9336", "type": "", "text": [ "intravenous meperidine" ], "offsets": [ [ 521, 543 ] ], "normalized": [] }, { "id": "9337", "type": "", "text": [ "pain" ], "offsets": [ [ 451, 455 ] ], "normalized": [] }, { "id": "9339", "type": "", "text": [ "intravenous meperidine" ], "offsets": [ [ 521, 543 ] ], "normalized": [] }, { "id": "9340", "type": "", "text": [ "complications" ], "offsets": [ [ 467, 480 ] ], "normalized": [] }, { "id": "9342", "type": "", "text": [ "diazepam" ], "offsets": [ [ 544, 552 ] ], "normalized": [] }, { "id": "9343", "type": "", "text": [ "anterior shoulder dislocation" ], "offsets": [ [ 570, 599 ] ], "normalized": [] }, { "id": "9345", "type": "", "text": [ "diazepam" ], "offsets": [ [ 544, 552 ] ], "normalized": [] }, { "id": "9346", "type": "", "text": [ "pain" ], "offsets": [ [ 451, 455 ] ], "normalized": [] }, { "id": "9348", "type": "", "text": [ "diazepam" ], "offsets": [ [ 544, 552 ] ], "normalized": [] }, { "id": "9349", "type": "", "text": [ "complications" ], "offsets": [ [ 467, 480 ] ], "normalized": [] }, { "id": "9351", "type": "", "text": [ "Intravenous opiates" ], "offsets": [ [ 254, 273 ] ], "normalized": [] }, { "id": "9352", "type": "", "text": [ "pain" ], "offsets": [ [ 347, 351 ] ], "normalized": [] }, { "id": "9354", "type": "", "text": [ "benzodiazepines" ], "offsets": [ [ 278, 293 ] ], "normalized": [] }, { "id": "9355", "type": "", "text": [ "pain" ], "offsets": [ [ 347, 351 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9296", "type": "PA", "arg1_id": "9294", "arg2_id": "9295", "normalized": [] }, { "id": "9299", "type": "PA", "arg1_id": "9297", "arg2_id": "9298", "normalized": [] }, { "id": "9302", "type": "PA", "arg1_id": "9300", "arg2_id": "9301", "normalized": [] }, { "id": "9305", "type": "PA", "arg1_id": "9303", "arg2_id": "9304", "normalized": [] }, { "id": "9308", "type": "PA", "arg1_id": "9306", "arg2_id": "9307", "normalized": [] }, { "id": "9311", "type": "PA", "arg1_id": "9309", "arg2_id": "9310", "normalized": [] }, { "id": "9314", "type": "PA", "arg1_id": "9312", "arg2_id": "9313", "normalized": [] }, { "id": "9317", "type": "PA", "arg1_id": "9315", "arg2_id": "9316", "normalized": [] }, { "id": "9320", "type": "PA", "arg1_id": "9318", "arg2_id": "9319", "normalized": [] }, { "id": "9323", "type": "PA", "arg1_id": "9321", "arg2_id": "9322", "normalized": [] }, { "id": "9326", "type": "PA", "arg1_id": "9324", "arg2_id": "9325", "normalized": [] }, { "id": "9329", "type": "PA", "arg1_id": "9327", "arg2_id": "9328", "normalized": [] }, { "id": "9332", "type": "PA", "arg1_id": "9330", "arg2_id": "9331", "normalized": [] }, { "id": "9335", "type": "PA", "arg1_id": "9333", "arg2_id": "9334", "normalized": [] }, { "id": "9338", "type": "PA", "arg1_id": "9336", "arg2_id": "9337", "normalized": [] }, { "id": "9341", "type": "PA", "arg1_id": "9339", "arg2_id": "9340", "normalized": [] }, { "id": "9344", "type": "PA", "arg1_id": "9342", "arg2_id": "9343", "normalized": [] }, { "id": "9347", "type": "PA", "arg1_id": "9345", "arg2_id": "9346", "normalized": [] }, { "id": "9350", "type": "PA", "arg1_id": "9348", "arg2_id": "9349", "normalized": [] }, { "id": "9353", "type": "PA", "arg1_id": "9351", "arg2_id": "9352", "normalized": [] }, { "id": "9356", "type": "PA", "arg1_id": "9354", "arg2_id": "9355", "normalized": [] } ]

[ { "id": "9359", "type": "title", "text": [ "MEK inhibition induces caspases activation, differentiation blockade and PML/RARalpha degradation in acute promyelocytic leukaemia." ], "offsets": [ [ 0, 131 ] ] }, { "id": "9360", "type": "abstract", "text": [ "The hallmark of acute promyelocytic leukaemia (APL) is the reciprocal translocation t(15;17), which leads to the expression of the promyelocytic leukaemia/retinoic acid receptor alpha (PML/RARalpha) fusion protein and a cell differentiation blockade at the promyelocytic stage. PML/RARalpha is directly targeted by all-trans-retinoic acid (ATRA), which degrades the oncoprotein and induces complete remission of malignancies. The aberrant function of PML/RARalpha, together with the constitutive activation of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) signalling pathway, regulates the ability of haematopoietic cells to proliferate, differentiate, and escape from apoptotic episodes. The role of the MEK/ERK pathway in PML/RARalpha expression, differentiation, proliferation and apoptosis in APL cells was analysed using specific MEK inhibitors. The blockade of MEK/ERK pathway resulted in caspase-dependent degradation of PML/RARalpha, and attenuation of the cell differentiation induction. To our knowledge, this is the first report to show that PML/RARalpha was suppressed by MEK/ERK inhibition, through a mechanism dependent on caspase activation. ATRA co-operated with MEK inhibitor to increase degradation of PML/RARalpha and exhibited a convergence point in caspase activation with MEK inhibitors. Taken together, our data suggest a new role of MEK/ERK pathway in the pathogenesis of APL, thus supporting the use of MEK/ERK inhibitors as an efficient therapeutic strategy for this haematological malignancy." ], "offsets": [ [ 132, 1683 ] ] } ]

[ { "id": "9361", "type": "Genes & Molecular Sequences", "text": [ "MEK" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "9362", "type": "Genes & Molecular Sequences", "text": [ "caspases" ], "offsets": [ [ 23, 31 ] ], "normalized": [] }, { "id": "9363", "type": "Genes & Molecular Sequences", "text": [ "PML/RARalpha" ], "offsets": [ [ 73, 85 ] ], "normalized": [] }, { "id": "9364", "type": "Genes & Molecular Sequences", "text": [ "APL" ], "offsets": [ [ 179, 182 ] ], "normalized": [] }, { "id": "9365", "type": "SNP & Sequence variations", "text": [ "reciprocal translocation t(15;17)" ], "offsets": [ [ 191, 224 ] ], "normalized": [] }, { "id": "9366", "type": "Genes & Molecular Sequences", "text": [ "promyelocytic leukaemia/retinoic acid receptor alpha" ], "offsets": [ [ 263, 315 ] ], "normalized": [] }, { "id": "9367", "type": "Genes & Molecular Sequences", "text": [ "(PML/RARalpha) fusion protein" ], "offsets": [ [ 316, 345 ] ], "normalized": [] }, { "id": "9368", "type": "Genes & Molecular Sequences", "text": [ "PML" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "9369", "type": "Genes & Molecular Sequences", "text": [ "PML/RARalpha" ], "offsets": [ [ 410, 422 ] ], "normalized": [] }, { "id": "9370", "type": "Chemicals & Drugs", "text": [ "all-trans-retinoic acid" ], "offsets": [ [ 447, 470 ] ], "normalized": [] }, { "id": "9371", "type": "Chemicals & Drugs", "text": [ "ATRA" ], "offsets": [ [ 472, 476 ] ], "normalized": [] }, { "id": "9372", "type": "Genes & Molecular Sequences", "text": [ "PML/RARalpha" ], "offsets": [ [ 583, 595 ] ], "normalized": [] }, { "id": "9373", "type": "Genes & Molecular Sequences", "text": [ "mitogen-activated protein/extracellular signal-regulated kinase" ], "offsets": [ [ 646, 709 ] ], "normalized": [] }, { "id": "9374", "type": "Genes & Molecular Sequences", "text": [ "MEK/ERK" ], "offsets": [ [ 711, 718 ] ], "normalized": [] }, { "id": "9375", "type": "Chemicals & Drugs", "text": [ "MEK/ERK" ], "offsets": [ [ 711, 718 ] ], "normalized": [] }, { "id": "9376", "type": "Genes & Molecular Sequences", "text": [ "MEK/ERK" ], "offsets": [ [ 869, 876 ] ], "normalized": [] }, { "id": "9377", "type": "Chemicals & Drugs", "text": [ "MEK/ERK" ], "offsets": [ [ 869, 876 ] ], "normalized": [] }, { "id": "9378", "type": "Genes & Molecular Sequences", "text": [ "PML/RARalpha" ], "offsets": [ [ 888, 900 ] ], "normalized": [] }, { "id": "9379", "type": "Genes & Molecular Sequences", "text": [ "APL" ], "offsets": [ [ 961, 964 ] ], "normalized": [] }, { "id": "9380", "type": "Chemicals & Drugs", "text": [ "MEK inhibitors" ], "offsets": [ [ 999, 1013 ] ], "normalized": [] }, { "id": "9381", "type": "Genes & Molecular Sequences", "text": [ "MEK inhibitors" ], "offsets": [ [ 999, 1013 ] ], "normalized": [] }, { "id": "9382", "type": "Genes & Molecular Sequences", "text": [ "MEK/ERK" ], "offsets": [ [ 1031, 1038 ] ], "normalized": [] }, { "id": "9383", "type": "Chemicals & Drugs", "text": [ "MEK/ERK" ], "offsets": [ [ 1031, 1038 ] ], "normalized": [] }, { "id": "9384", "type": "Genes & Molecular Sequences", "text": [ "caspase" ], "offsets": [ [ 1059, 1066 ] ], "normalized": [] }, { "id": "9385", "type": "Genes & Molecular Sequences", "text": [ "PML/RARalpha" ], "offsets": [ [ 1092, 1104 ] ], "normalized": [] }, { "id": "9386", "type": "Genes & Molecular Sequences", "text": [ "PML/RARalpha" ], "offsets": [ [ 1217, 1229 ] ], "normalized": [] }, { "id": "9387", "type": "Genes & Molecular Sequences", "text": [ "MEK/ERK" ], "offsets": [ [ 1248, 1255 ] ], "normalized": [] }, { "id": "9388", "type": "Chemicals & Drugs", "text": [ "MEK/ERK" ], "offsets": [ [ 1248, 1255 ] ], "normalized": [] }, { "id": "9389", "type": "Genes & Molecular Sequences", "text": [ "caspase" ], "offsets": [ [ 1301, 1308 ] ], "normalized": [] }, { "id": "9390", "type": "Chemicals & Drugs", "text": [ "ATRA" ], "offsets": [ [ 1321, 1325 ] ], "normalized": [] }, { "id": "9391", "type": "Chemicals & Drugs", "text": [ "MEK inhibitor" ], "offsets": [ [ 1343, 1356 ] ], "normalized": [] }, { "id": "9392", "type": "Genes & Molecular Sequences", "text": [ "MEK inhibitor" ], "offsets": [ [ 1343, 1356 ] ], "normalized": [] }, { "id": "9393", "type": "Genes & Molecular Sequences", "text": [ "PML/RARalpha" ], "offsets": [ [ 1384, 1396 ] ], "normalized": [] }, { "id": "9394", "type": "Genes & Molecular Sequences", "text": [ "caspase" ], "offsets": [ [ 1434, 1441 ] ], "normalized": [] }, { "id": "9395", "type": "Chemicals & Drugs", "text": [ "MEK inhibitors" ], "offsets": [ [ 1458, 1472 ] ], "normalized": [] }, { "id": "9396", "type": "Genes & Molecular Sequences", "text": [ "MEK inhibitors" ], "offsets": [ [ 1458, 1472 ] ], "normalized": [] }, { "id": "9397", "type": "Genes & Molecular Sequences", "text": [ "MEK/ERK" ], "offsets": [ [ 1521, 1528 ] ], "normalized": [] }, { "id": "9398", "type": "Chemicals & Drugs", "text": [ "MEK/ERK" ], "offsets": [ [ 1521, 1528 ] ], "normalized": [] }, { "id": "9399", "type": "Genes & Molecular Sequences", "text": [ "APL" ], "offsets": [ [ 1560, 1563 ] ], "normalized": [] }, { "id": "9400", "type": "Chemicals & Drugs", "text": [ "MEK/ERK inhibitors" ], "offsets": [ [ 1592, 1610 ] ], "normalized": [] }, { "id": "9401", "type": "Genes & Molecular Sequences", "text": [ "MEK/ERK inhibitors" ], "offsets": [ [ 1592, 1610 ] ], "normalized": [] }, { "id": "9402", "type": "", "text": [ "ATRA" ], "offsets": [ [ 472, 476 ] ], "normalized": [] }, { "id": "9403", "type": "", "text": [ "PML/RARalpha" ], "offsets": [ [ 410, 422 ] ], "normalized": [] }, { "id": "9405", "type": "", "text": [ "ATRA" ], "offsets": [ [ 1321, 1325 ] ], "normalized": [] }, { "id": "9406", "type": "", "text": [ "PML/RARalpha" ], "offsets": [ [ 1384, 1396 ] ], "normalized": [] }, { "id": "9408", "type": "", "text": [ "ATRA" ], "offsets": [ [ 1321, 1325 ] ], "normalized": [] }, { "id": "9409", "type": "", "text": [ "caspase" ], "offsets": [ [ 1434, 1441 ] ], "normalized": [] }, { "id": "9411", "type": "", "text": [ "MEK inhibitors" ], "offsets": [ [ 1458, 1472 ] ], "normalized": [] }, { "id": "9412", "type": "", "text": [ "PML/RARalpha" ], "offsets": [ [ 1384, 1396 ] ], "normalized": [] }, { "id": "9414", "type": "", "text": [ "MEK inhibitors" ], "offsets": [ [ 1458, 1472 ] ], "normalized": [] }, { "id": "9415", "type": "", "text": [ "caspase" ], "offsets": [ [ 1434, 1441 ] ], "normalized": [] }, { "id": "9417", "type": "", "text": [ "MEK inhibitor" ], "offsets": [ [ 1343, 1356 ] ], "normalized": [] }, { "id": "9418", "type": "", "text": [ "PML/RARalpha" ], "offsets": [ [ 1384, 1396 ] ], "normalized": [] }, { "id": "9420", "type": "", "text": [ "MEK inhibitor" ], "offsets": [ [ 1343, 1356 ] ], "normalized": [] }, { "id": "9421", "type": "", "text": [ "caspase" ], "offsets": [ [ 1434, 1441 ] ], "normalized": [] }, { "id": "9423", "type": "", "text": [ "MEK/ERK inhibitors" ], "offsets": [ [ 1592, 1610 ] ], "normalized": [] }, { "id": "9424", "type": "", "text": [ "MEK/ERK" ], "offsets": [ [ 1521, 1528 ] ], "normalized": [] }, { "id": "9426", "type": "", "text": [ "ATRA" ], "offsets": [ [ 1321, 1325 ] ], "normalized": [] }, { "id": "9427", "type": "", "text": [ "MEK inhibitors" ], "offsets": [ [ 1458, 1472 ] ], "normalized": [] }, { "id": "9429", "type": "", "text": [ "MEK/ERK" ], "offsets": [ [ 1031, 1038 ] ], "normalized": [] }, { "id": "9430", "type": "", "text": [ "PML/RARalpha" ], "offsets": [ [ 1092, 1104 ] ], "normalized": [] }, { "id": "9432", "type": "", "text": [ "MEK/ERK" ], "offsets": [ [ 1248, 1255 ] ], "normalized": [] }, { "id": "9433", "type": "", "text": [ "PML/RARalpha" ], "offsets": [ [ 1217, 1229 ] ], "normalized": [] } ]

[]

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[ { "id": "9404", "type": "PA", "arg1_id": "9402", "arg2_id": "9403", "normalized": [] }, { "id": "9407", "type": "PA", "arg1_id": "9405", "arg2_id": "9406", "normalized": [] }, { "id": "9410", "type": "PA", "arg1_id": "9408", "arg2_id": "9409", "normalized": [] }, { "id": "9413", "type": "PA", "arg1_id": "9411", "arg2_id": "9412", "normalized": [] }, { "id": "9416", "type": "PA", "arg1_id": "9414", "arg2_id": "9415", "normalized": [] }, { "id": "9419", "type": "PA", "arg1_id": "9417", "arg2_id": "9418", "normalized": [] }, { "id": "9422", "type": "PA", "arg1_id": "9420", "arg2_id": "9421", "normalized": [] }, { "id": "9425", "type": "PA", "arg1_id": "9423", "arg2_id": "9424", "normalized": [] }, { "id": "9428", "type": "PA", "arg1_id": "9426", "arg2_id": "9427", "normalized": [] }, { "id": "9431", "type": "PA", "arg1_id": "9429", "arg2_id": "9430", "normalized": [] }, { "id": "9434", "type": "PA", "arg1_id": "9432", "arg2_id": "9433", "normalized": [] } ]

[ { "id": "9437", "type": "title", "text": [ "Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference." ], "offsets": [ [ 0, 124 ] ] }, { "id": "9438", "type": "abstract", "text": [ "BACKGROUND: Methyl-CpG binding domain protein 1 (MBD1), a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas. METHODS: In this study, we established a MBD1-knock-down pancreatic cancer cell line (BxPC-3) using stable RNA interference, to compare the proteomic changes between control and MBD1-knock-down cells using two-dimensional gel electrophoresis and mass spectrometry. RESULTS: We identified five proteins that were up-regulated and nine proteins that were down-regulated. Most of the identified proteins are involved in tumorigenesis, some are prognostic biomarkers for human malignant tumors. CONCLUSION: Our data suggest that these differential proteins may be associated with the function of MBD1, and provide some insight into the functional mechanism of MBD1 in the development of pancreatic cancer." ], "offsets": [ [ 125, 1072 ] ] } ]

[ { "id": "9439", "type": "Genes & Molecular Sequences", "text": [ "MBD1" ], "offsets": [ [ 81, 85 ] ], "normalized": [] }, { "id": "9440", "type": "Genes & Molecular Sequences", "text": [ "Methyl-CpG binding domain protein 1" ], "offsets": [ [ 137, 172 ] ], "normalized": [] }, { "id": "9441", "type": "Genes & Molecular Sequences", "text": [ "MBD1" ], "offsets": [ [ 174, 178 ] ], "normalized": [] }, { "id": "9442", "type": "Genes & Molecular Sequences", "text": [ "tumor" ], "offsets": [ [ 252, 257 ] ], "normalized": [] }, { "id": "9443", "type": "Genes & Molecular Sequences", "text": [ "MBD1" ], "offsets": [ [ 316, 320 ] ], "normalized": [] }, { "id": "9444", "type": "Genes & Molecular Sequences", "text": [ "MBD1" ], "offsets": [ [ 412, 416 ] ], "normalized": [] }, { "id": "9445", "type": "Genes & Molecular Sequences", "text": [ "pancreatic cancer" ], "offsets": [ [ 428, 445 ] ], "normalized": [] }, { "id": "9446", "type": "Genes & Molecular Sequences", "text": [ "BxPC-3" ], "offsets": [ [ 457, 463 ] ], "normalized": [] }, { "id": "9447", "type": "Genes & Molecular Sequences", "text": [ "MBD1" ], "offsets": [ [ 549, 553 ] ], "normalized": [] }, { "id": "9448", "type": "Genes & Molecular Sequences", "text": [ "MBD1" ], "offsets": [ [ 963, 967 ] ], "normalized": [] }, { "id": "9449", "type": "Genes & Molecular Sequences", "text": [ "MBD1" ], "offsets": [ [ 1027, 1031 ] ], "normalized": [] } ]

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[ { "id": "9452", "type": "title", "text": [ "MS4A12 is a colon-selective store-operated calcium channel promoting malignant cell processes." ], "offsets": [ [ 0, 94 ] ] }, { "id": "9453", "type": "abstract", "text": [ "Using a data mining approach for the discovery of new targets for antibody therapy of colon cancer, we identified MS4A12, a sequence homologue of CD20. We show that MS4A12 is a cell surface protein. Expression analysis and immunohistochemistry revealed MS4A12 to be a colonic epithelial cell lineage gene confined to the apical membrane of colonocytes with strict transcriptional repression in all other normal tissue types. Expression is maintained upon malignant transformation in 63% of colon cancers. Ca(2+) flux analyses disclosed that MS4A12 is a novel component of store-operated Ca(2+) entry in intestinal cells. Using RNAi-mediated gene silencing, we show that loss of MS4A12 in LoVo colon cancer cells attenuates epidermal growth factor receptor-mediated effects. In particular, proliferation, cell motility, and chemotactic invasion of cells are significantly impaired. Cancer cells expressing MS4A12, in contrast, are sensitized and respond to lower concentrations of epidermal growth factor. In summary, these findings have implications for both the physiology of colonic epithelium as well as for the biology and treatment of colon cancer." ], "offsets": [ [ 95, 1248 ] ] } ]

[ { "id": "9454", "type": "Genes & Molecular Sequences", "text": [ "MS4A12" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "9455", "type": "Chemicals & Drugs", "text": [ "calcium" ], "offsets": [ [ 43, 50 ] ], "normalized": [] }, { "id": "9456", "type": "Genes & Molecular Sequences", "text": [ "MS4A12" ], "offsets": [ [ 209, 215 ] ], "normalized": [] }, { "id": "9457", "type": "Genes & Molecular Sequences", "text": [ "CD20" ], "offsets": [ [ 241, 245 ] ], "normalized": [] }, { "id": "9458", "type": "Genes & Molecular Sequences", "text": [ "MS4A12" ], "offsets": [ [ 260, 266 ] ], "normalized": [] }, { "id": "9459", "type": "Genes & Molecular Sequences", "text": [ "MS4A12" ], "offsets": [ [ 348, 354 ] ], "normalized": [] }, { "id": "9460", "type": "Chemicals & Drugs", "text": [ "Ca(2+)" ], "offsets": [ [ 600, 606 ] ], "normalized": [] }, { "id": "9461", "type": "Genes & Molecular Sequences", "text": [ "MS4A12" ], "offsets": [ [ 636, 642 ] ], "normalized": [] }, { "id": "9462", "type": "Chemicals & Drugs", "text": [ "Ca(2+)" ], "offsets": [ [ 682, 688 ] ], "normalized": [] }, { "id": "9463", "type": "Genes & Molecular Sequences", "text": [ "MS4A12" ], "offsets": [ [ 773, 779 ] ], "normalized": [] }, { "id": "9464", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor receptor" ], "offsets": [ [ 818, 850 ] ], "normalized": [] }, { "id": "9465", "type": "Genes & Molecular Sequences", "text": [ "MS4A12" ], "offsets": [ [ 1000, 1006 ] ], "normalized": [] }, { "id": "9466", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor" ], "offsets": [ [ 1075, 1098 ] ], "normalized": [] }, { "id": "9467", "type": "", "text": [ "calcium" ], "offsets": [ [ 43, 50 ] ], "normalized": [] }, { "id": "9468", "type": "", "text": [ "MS4A12" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "9470", "type": "", "text": [ "Ca(2+)" ], "offsets": [ [ 682, 688 ] ], "normalized": [] }, { "id": "9471", "type": "", "text": [ "MS4A12" ], "offsets": [ [ 636, 642 ] ], "normalized": [] }, { "id": "9473", "type": "", "text": [ "MS4A12" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "9474", "type": "", "text": [ "malignant" ], "offsets": [ [ 69, 78 ] ], "normalized": [] }, { "id": "9476", "type": "", "text": [ "MS4A12" ], "offsets": [ [ 209, 215 ] ], "normalized": [] }, { "id": "9477", "type": "", "text": [ "colon cancer" ], "offsets": [ [ 181, 193 ] ], "normalized": [] }, { "id": "9479", "type": "", "text": [ "CD20" ], "offsets": [ [ 241, 245 ] ], "normalized": [] }, { "id": "9480", "type": "", "text": [ "colon cancer" ], "offsets": [ [ 181, 193 ] ], "normalized": [] }, { "id": "9482", "type": "", "text": [ "MS4A12" ], "offsets": [ [ 773, 779 ] ], "normalized": [] }, { "id": "9483", "type": "", "text": [ "colon cancer" ], "offsets": [ [ 788, 800 ] ], "normalized": [] }, { "id": "9485", "type": "", "text": [ "epidermal growth factor receptor" ], "offsets": [ [ 818, 850 ] ], "normalized": [] }, { "id": "9486", "type": "", "text": [ "colon cancer" ], "offsets": [ [ 788, 800 ] ], "normalized": [] }, { "id": "9488", "type": "", "text": [ "MS4A12" ], "offsets": [ [ 1000, 1006 ] ], "normalized": [] }, { "id": "9489", "type": "", "text": [ "Cancer" ], "offsets": [ [ 976, 982 ] ], "normalized": [] }, { "id": "9491", "type": "", "text": [ "epidermal growth factor" ], "offsets": [ [ 1075, 1098 ] ], "normalized": [] }, { "id": "9492", "type": "", "text": [ "Cancer" ], "offsets": [ [ 976, 982 ] ], "normalized": [] } ]

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[ { "id": "9469", "type": "PA", "arg1_id": "9467", "arg2_id": "9468", "normalized": [] }, { "id": "9472", "type": "PA", "arg1_id": "9470", "arg2_id": "9471", "normalized": [] }, { "id": "9475", "type": "PA", "arg1_id": "9473", "arg2_id": "9474", "normalized": [] }, { "id": "9478", "type": "PA", "arg1_id": "9476", "arg2_id": "9477", "normalized": [] }, { "id": "9481", "type": "PA", "arg1_id": "9479", "arg2_id": "9480", "normalized": [] }, { "id": "9484", "type": "PA", "arg1_id": "9482", "arg2_id": "9483", "normalized": [] }, { "id": "9487", "type": "PA", "arg1_id": "9485", "arg2_id": "9486", "normalized": [] }, { "id": "9490", "type": "PA", "arg1_id": "9488", "arg2_id": "9489", "normalized": [] }, { "id": "9493", "type": "PA", "arg1_id": "9491", "arg2_id": "9492", "normalized": [] } ]

[ { "id": "9496", "type": "title", "text": [ "5-aminosalicylic acid inhibits colitis-associated colorectal dysplasias in the mouse model of azoxymethane/dextran sulfate sodium-induced colitis." ], "offsets": [ [ 0, 146 ] ] }, { "id": "9497", "type": "abstract", "text": [ "BACKGROUND: The impact of the antiinflammatory agent 5-aminosalicylic acid (5-ASA) on the risk for colitis-associated colorectal cancer remains controversial. The chemopreventive activity of 5-ASA was evaluated in the Swiss Webster model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated neoplasia. METHODS: Mice were injected with AOM (7.4 mg/kg i.p.) and randomized to receive either vehicle or 5-ASA (75, 150, and 225 mg/kg) for the remainder of the study. DSS treatment began at 9 weeks of age and continued for 3 cycles. At the time of sacrifice (18 weeks of age), the entire colon and rectum were processed for histopathologic examination. RESULTS: An inverse trend was observed between dose and multiplicity of colonic dysplasias in all drug-treated groups (P = 0.03), with animals receiving 75 mg/kg 5-ASA exhibiting 56% of the number of dysplasias of the AOM/DSS controls (mean +/- SEM: 7.6 +/- 1.4 and 13.6 +/- 2.7, respectively). Administration of 75 mg/kg 5-ASA decreased both the mean multiplicity of flat dysplasias (1.8 +/- 0.4 for drug-treated versus 5.6 +/- 1.2 for AOM/DSS control) and the burden of polypoid dysplasias (tumor burden: 6.7 +/- 2.7 for drug-treated versus 14.9 +/- 3.9 units for AOM/DSS controls) significantly (P = 0.002 and 0.04, respectively). Inflammation was least severe in the 75 mg/kg group, which exhibited the fewest number of colorectal tumors. CONCLUSIONS: These data suggest that low-dose 5-ASA may be efficacious in preventing colitis-associated dysplasias and provide strong support for optimizing this therapy for the prevention of colonic neoplasms in patients with ulcerative colitis." ], "offsets": [ [ 147, 1810 ] ] } ]

[ { "id": "9498", "type": "Chemicals & Drugs", "text": [ "5-aminosalicylic acid" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "9499", "type": "Diseases & Disorders", "text": [ "colitis-associated colorectal dysplasias" ], "offsets": [ [ 31, 71 ] ], "normalized": [] }, { "id": "9500", "type": "Chemicals & Drugs", "text": [ "azoxymethane" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "9501", "type": "Chemicals & Drugs", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 107, 129 ] ], "normalized": [] }, { "id": "9502", "type": "Diseases & Disorders", "text": [ "colitis" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "9503", "type": "Chemicals & Drugs", "text": [ "5-aminosalicylic acid" ], "offsets": [ [ 200, 221 ] ], "normalized": [] }, { "id": "9504", "type": "Chemicals & Drugs", "text": [ "5-ASA" ], "offsets": [ [ 223, 228 ] ], "normalized": [] }, { "id": "9505", "type": "Diseases & Disorders", "text": [ "colitis-associated colorectal cancer" ], "offsets": [ [ 246, 282 ] ], "normalized": [] }, { "id": "9506", "type": "Chemicals & Drugs", "text": [ "5-ASA" ], "offsets": [ [ 338, 343 ] ], "normalized": [] }, { "id": "9507", "type": "Chemicals & Drugs", "text": [ "azoxymethane" ], "offsets": [ [ 388, 400 ] ], "normalized": [] }, { "id": "9508", "type": "Chemicals & Drugs", "text": [ "AOM" ], "offsets": [ [ 402, 405 ] ], "normalized": [] }, { "id": "9509", "type": "Diseases & Disorders", "text": [ "AOM" ], "offsets": [ [ 402, 405 ] ], "normalized": [] }, { "id": "9510", "type": "Chemicals & Drugs", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 407, 429 ] ], "normalized": [] }, { "id": "9511", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 431, 434 ] ], "normalized": [] }, { "id": "9512", "type": "Diseases & Disorders", "text": [ "DSS" ], "offsets": [ [ 431, 434 ] ], "normalized": [] }, { "id": "9513", "type": "Diseases & Disorders", "text": [ "colitis-associated neoplasia" ], "offsets": [ [ 444, 472 ] ], "normalized": [] }, { "id": "9514", "type": "Chemicals & Drugs", "text": [ "AOM" ], "offsets": [ [ 507, 510 ] ], "normalized": [] }, { "id": "9515", "type": "Diseases & Disorders", "text": [ "AOM" ], "offsets": [ [ 507, 510 ] ], "normalized": [] }, { "id": "9516", "type": "Chemicals & Drugs", "text": [ "5-ASA" ], "offsets": [ [ 572, 577 ] ], "normalized": [] }, { "id": "9517", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 635, 638 ] ], "normalized": [] }, { "id": "9518", "type": "Diseases & Disorders", "text": [ "DSS" ], "offsets": [ [ 635, 638 ] ], "normalized": [] }, { "id": "9519", "type": "Diseases & Disorders", "text": [ "colonic dysplasias" ], "offsets": [ [ 893, 911 ] ], "normalized": [] }, { "id": "9520", "type": "Chemicals & Drugs", "text": [ "5-ASA" ], "offsets": [ [ 983, 988 ] ], "normalized": [] }, { "id": "9521", "type": "Diseases & Disorders", "text": [ "dysplasias" ], "offsets": [ [ 1021, 1031 ] ], "normalized": [] }, { "id": "9522", "type": "Chemicals & Drugs", "text": [ "AOM" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "9523", "type": "Diseases & Disorders", "text": [ "AOM" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "9524", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1043, 1046 ] ], "normalized": [] }, { "id": "9525", "type": "Diseases & Disorders", "text": [ "DSS" ], "offsets": [ [ 1043, 1046 ] ], "normalized": [] }, { "id": "9526", "type": "Diseases & Disorders", "text": [ "SEM" ], "offsets": [ [ 1066, 1069 ] ], "normalized": [] }, { "id": "9527", "type": "Chemicals & Drugs", "text": [ "5-ASA" ], "offsets": [ [ 1143, 1148 ] ], "normalized": [] }, { "id": "9528", "type": "Diseases & Disorders", "text": [ "flat dysplasias" ], "offsets": [ [ 1189, 1204 ] ], "normalized": [] }, { "id": "9529", "type": "Chemicals & Drugs", "text": [ "AOM" ], "offsets": [ [ 1258, 1261 ] ], "normalized": [] }, { "id": "9530", "type": "Diseases & Disorders", "text": [ "AOM" ], "offsets": [ [ 1258, 1261 ] ], "normalized": [] }, { "id": "9531", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1262, 1265 ] ], "normalized": [] }, { "id": "9532", "type": "Diseases & Disorders", "text": [ "DSS" ], "offsets": [ [ 1262, 1265 ] ], "normalized": [] }, { "id": "9533", "type": "Diseases & Disorders", "text": [ "polypoid dysplasias" ], "offsets": [ [ 1293, 1312 ] ], "normalized": [] }, { "id": "9534", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "9535", "type": "Chemicals & Drugs", "text": [ "AOM" ], "offsets": [ [ 1387, 1390 ] ], "normalized": [] }, { "id": "9536", "type": "Diseases & Disorders", "text": [ "AOM" ], "offsets": [ [ 1387, 1390 ] ], "normalized": [] }, { "id": "9537", "type": "Chemicals & Drugs", "text": [ "DSS" ], "offsets": [ [ 1391, 1394 ] ], "normalized": [] }, { "id": "9538", "type": "Diseases & Disorders", "text": [ "DSS" ], "offsets": [ [ 1391, 1394 ] ], "normalized": [] }, { "id": "9539", "type": "Diseases & Disorders", "text": [ "Inflammation" ], "offsets": [ [ 1455, 1467 ] ], "normalized": [] }, { "id": "9540", "type": "Diseases & Disorders", "text": [ "colorectal tumors" ], "offsets": [ [ 1545, 1562 ] ], "normalized": [] }, { "id": "9541", "type": "Chemicals & Drugs", "text": [ "low-dose 5-ASA" ], "offsets": [ [ 1601, 1615 ] ], "normalized": [] }, { "id": "9542", "type": "Diseases & Disorders", "text": [ "colitis-associated dysplasias" ], "offsets": [ [ 1649, 1678 ] ], "normalized": [] }, { "id": "9543", "type": "Diseases & Disorders", "text": [ "colonic neoplasms" ], "offsets": [ [ 1756, 1773 ] ], "normalized": [] }, { "id": "9544", "type": "Diseases & Disorders", "text": [ "ulcerative colitis" ], "offsets": [ [ 1791, 1809 ] ], "normalized": [] }, { "id": "9545", "type": "", "text": [ "5-aminosalicylic acid" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "9546", "type": "", "text": [ "colitis-associated colorectal dysplasias" ], "offsets": [ [ 31, 71 ] ], "normalized": [] }, { "id": "9548", "type": "", "text": [ "azoxymethane" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "9549", "type": "", "text": [ "colitis" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "9551", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 107, 129 ] ], "normalized": [] }, { "id": "9552", "type": "", "text": [ "colitis" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "9554", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 223, 228 ] ], "normalized": [] }, { "id": "9555", "type": "", "text": [ "colitis-associated colorectal cancer" ], "offsets": [ [ 246, 282 ] ], "normalized": [] }, { "id": "9557", "type": "", "text": [ "azoxymethane" ], "offsets": [ [ 388, 400 ] ], "normalized": [] }, { "id": "9558", "type": "", "text": [ "colitis-associated neoplasia" ], "offsets": [ [ 444, 472 ] ], "normalized": [] }, { "id": "9560", "type": "", "text": [ "AOM" ], "offsets": [ [ 402, 405 ] ], "normalized": [] }, { "id": "9561", "type": "", "text": [ "colitis-associated neoplasia" ], "offsets": [ [ 444, 472 ] ], "normalized": [] }, { "id": "9563", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 407, 429 ] ], "normalized": [] }, { "id": "9564", "type": "", "text": [ "colitis-associated neoplasia" ], "offsets": [ [ 444, 472 ] ], "normalized": [] }, { "id": "9566", "type": "", "text": [ "DSS" ], "offsets": [ [ 431, 434 ] ], "normalized": [] }, { "id": "9567", "type": "", "text": [ "colitis-associated neoplasia" ], "offsets": [ [ 444, 472 ] ], "normalized": [] }, { "id": "9569", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 983, 988 ] ], "normalized": [] }, { "id": "9570", "type": "", "text": [ "colonic dysplasias" ], "offsets": [ [ 893, 911 ] ], "normalized": [] }, { "id": "9572", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 983, 988 ] ], "normalized": [] }, { "id": "9573", "type": "", "text": [ "dysplasias" ], "offsets": [ [ 1021, 1031 ] ], "normalized": [] }, { "id": "9575", "type": "", "text": [ "AOM" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "9576", "type": "", "text": [ "colonic dysplasias" ], "offsets": [ [ 893, 911 ] ], "normalized": [] }, { "id": "9578", "type": "", "text": [ "AOM" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "9579", "type": "", "text": [ "dysplasias" ], "offsets": [ [ 1021, 1031 ] ], "normalized": [] }, { "id": "9581", "type": "", "text": [ "DSS" ], "offsets": [ [ 1043, 1046 ] ], "normalized": [] }, { "id": "9582", "type": "", "text": [ "colonic dysplasias" ], "offsets": [ [ 893, 911 ] ], "normalized": [] }, { "id": "9584", "type": "", "text": [ "DSS" ], "offsets": [ [ 1043, 1046 ] ], "normalized": [] }, { "id": "9585", "type": "", "text": [ "dysplasias" ], "offsets": [ [ 1021, 1031 ] ], "normalized": [] }, { "id": "9587", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 1143, 1148 ] ], "normalized": [] }, { "id": "9588", "type": "", "text": [ "tumor" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "9590", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 1143, 1148 ] ], "normalized": [] }, { "id": "9591", "type": "", "text": [ "flat dysplasias" ], "offsets": [ [ 1189, 1204 ] ], "normalized": [] }, { "id": "9593", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 1143, 1148 ] ], "normalized": [] }, { "id": "9594", "type": "", "text": [ "polypoid dysplasias" ], "offsets": [ [ 1293, 1312 ] ], "normalized": [] }, { "id": "9596", "type": "", "text": [ "low-dose 5-ASA" ], "offsets": [ [ 1601, 1615 ] ], "normalized": [] }, { "id": "9597", "type": "", "text": [ "colonic neoplasms" ], "offsets": [ [ 1756, 1773 ] ], "normalized": [] }, { "id": "9599", "type": "", "text": [ "low-dose 5-ASA" ], "offsets": [ [ 1601, 1615 ] ], "normalized": [] }, { "id": "9600", "type": "", "text": [ "ulcerative colitis" ], "offsets": [ [ 1791, 1809 ] ], "normalized": [] }, { "id": "9602", "type": "", "text": [ "low-dose 5-ASA" ], "offsets": [ [ 1601, 1615 ] ], "normalized": [] }, { "id": "9603", "type": "", "text": [ "colitis-associated dysplasias" ], "offsets": [ [ 1649, 1678 ] ], "normalized": [] }, { "id": "9605", "type": "", "text": [ "dextran sulfate sodium" ], "offsets": [ [ 107, 129 ] ], "normalized": [] }, { "id": "9606", "type": "", "text": [ "colitis-associated colorectal dysplasias" ], "offsets": [ [ 31, 71 ] ], "normalized": [] }, { "id": "9608", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 338, 343 ] ], "normalized": [] }, { "id": "9609", "type": "", "text": [ "colitis-associated neoplasia" ], "offsets": [ [ 444, 472 ] ], "normalized": [] }, { "id": "9611", "type": "", "text": [ "5-ASA" ], "offsets": [ [ 983, 988 ] ], "normalized": [] }, { "id": "9612", "type": "", "text": [ "SEM" ], "offsets": [ [ 1066, 1069 ] ], "normalized": [] }, { "id": "9614", "type": "", "text": [ "azoxymethane" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "9615", "type": "", "text": [ "colitis-associated colorectal dysplasias" ], "offsets": [ [ 31, 71 ] ], "normalized": [] }, { "id": "9617", "type": "", "text": [ "AOM" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "9618", "type": "", "text": [ "SEM" ], "offsets": [ [ 1066, 1069 ] ], "normalized": [] }, { "id": "9620", "type": "", "text": [ "DSS" ], "offsets": [ [ 1043, 1046 ] ], "normalized": [] }, { "id": "9621", "type": "", "text": [ "SEM" ], "offsets": [ [ 1066, 1069 ] ], "normalized": [] }, { "id": "9623", "type": "", "text": [ "AOM" ], "offsets": [ [ 1387, 1390 ] ], "normalized": [] }, { "id": "9624", "type": "", "text": [ "tumor" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "9626", "type": "", "text": [ "AOM" ], "offsets": [ [ 1387, 1390 ] ], "normalized": [] }, { "id": "9627", "type": "", "text": [ "flat dysplasias" ], "offsets": [ [ 1189, 1204 ] ], "normalized": [] }, { "id": "9629", "type": "", "text": [ "AOM" ], "offsets": [ [ 1387, 1390 ] ], "normalized": [] }, { "id": "9630", "type": "", "text": [ "polypoid dysplasias" ], "offsets": [ [ 1293, 1312 ] ], "normalized": [] }, { "id": "9632", "type": "", "text": [ "DSS" ], "offsets": [ [ 1391, 1394 ] ], "normalized": [] }, { "id": "9633", "type": "", "text": [ "tumor" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "9635", "type": "", "text": [ "DSS" ], "offsets": [ [ 1391, 1394 ] ], "normalized": [] }, { "id": "9636", "type": "", "text": [ "flat dysplasias" ], "offsets": [ [ 1189, 1204 ] ], "normalized": [] }, { "id": "9638", "type": "", "text": [ "DSS" ], "offsets": [ [ 1391, 1394 ] ], "normalized": [] }, { "id": "9639", "type": "", "text": [ "polypoid dysplasias" ], "offsets": [ [ 1293, 1312 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9547", "type": "PA", "arg1_id": "9545", "arg2_id": "9546", "normalized": [] }, { "id": "9550", "type": "PA", "arg1_id": "9548", "arg2_id": "9549", "normalized": [] }, { "id": "9553", "type": "PA", "arg1_id": "9551", "arg2_id": "9552", "normalized": [] }, { "id": "9556", "type": "SA", "arg1_id": "9554", "arg2_id": "9555", "normalized": [] }, { "id": "9559", "type": "PA", "arg1_id": "9557", "arg2_id": "9558", "normalized": [] }, { "id": "9562", "type": "PA", "arg1_id": "9560", "arg2_id": "9561", "normalized": [] }, { "id": "9565", "type": "PA", "arg1_id": "9563", "arg2_id": "9564", "normalized": [] }, { "id": "9568", "type": "PA", "arg1_id": "9566", "arg2_id": "9567", "normalized": [] }, { "id": "9571", "type": "PA", "arg1_id": "9569", "arg2_id": "9570", "normalized": [] }, { "id": "9574", "type": "PA", "arg1_id": "9572", "arg2_id": "9573", "normalized": [] }, { "id": "9577", "type": "PA", "arg1_id": "9575", "arg2_id": "9576", "normalized": [] }, { "id": "9580", "type": "PA", "arg1_id": "9578", "arg2_id": "9579", "normalized": [] }, { "id": "9583", "type": "PA", "arg1_id": "9581", "arg2_id": "9582", "normalized": [] }, { "id": "9586", "type": "PA", "arg1_id": "9584", "arg2_id": "9585", "normalized": [] }, { "id": "9589", "type": "PA", "arg1_id": "9587", "arg2_id": "9588", "normalized": [] }, { "id": "9592", "type": "PA", "arg1_id": "9590", "arg2_id": "9591", "normalized": [] }, { "id": "9595", "type": "PA", "arg1_id": "9593", "arg2_id": "9594", "normalized": [] }, { "id": "9598", "type": "SA", "arg1_id": "9596", "arg2_id": "9597", "normalized": [] }, { "id": "9601", "type": "SA", "arg1_id": "9599", "arg2_id": "9600", "normalized": [] }, { "id": "9604", "type": "SA", "arg1_id": "9602", "arg2_id": "9603", "normalized": [] }, { "id": "9607", "type": "PA", "arg1_id": "9605", "arg2_id": "9606", "normalized": [] }, { "id": "9610", "type": "PA", "arg1_id": "9608", "arg2_id": "9609", "normalized": [] }, { "id": "9613", "type": "PA", "arg1_id": "9611", "arg2_id": "9612", "normalized": [] }, { "id": "9616", "type": "PA", "arg1_id": "9614", "arg2_id": "9615", "normalized": [] }, { "id": "9619", "type": "PA", "arg1_id": "9617", "arg2_id": "9618", "normalized": [] }, { "id": "9622", "type": "PA", "arg1_id": "9620", "arg2_id": "9621", "normalized": [] }, { "id": "9625", "type": "PA", "arg1_id": "9623", "arg2_id": "9624", "normalized": [] }, { "id": "9628", "type": "PA", "arg1_id": "9626", "arg2_id": "9627", "normalized": [] }, { "id": "9631", "type": "PA", "arg1_id": "9629", "arg2_id": "9630", "normalized": [] }, { "id": "9634", "type": "PA", "arg1_id": "9632", "arg2_id": "9633", "normalized": [] }, { "id": "9637", "type": "PA", "arg1_id": "9635", "arg2_id": "9636", "normalized": [] }, { "id": "9640", "type": "PA", "arg1_id": "9638", "arg2_id": "9639", "normalized": [] } ]

[ { "id": "9643", "type": "title", "text": [ "IL23R haplotypes provide a large population attributable risk for Crohn's disease." ], "offsets": [ [ 0, 82 ] ] }, { "id": "9644", "type": "abstract", "text": [ "BACKGROUND: The IL-23 pathway plays a pivotal role in the development of chronic mucosal inflammation seen in the inflammatory bowel diseases. Multiple studies have now established the contribution of the interleukin 23 receptor gene (IL23R) to Crohn's disease (CD) risk in general and of the IL23R R381Q variant in particular. The aim of this work was to estimate the total contribution of this gene to CD risk test using a haplotype approach. METHODS: In all, 763 CD subjects and 254 controls were genotyped for single nucleotide polymorphisms in the IL23R gene using Illumina and ABI methods. Haplotypes were assigned using PHASEv2 and tested for association with CD by chi-square and permutation. RESULTS: Haplotypes with both increased and decreased risk for CD were observed in 2 of the 4 observed blocks (Block 2 H1: 55.4% control, 64% CD, P = 0.019; H2: 64.5% control, 54.4% CD, P = 0.006; Block 3 H1: 55.8% control, 64.4% CD, P = 0.013; H2: 47.0% control, 36.6% CD, P = 0.001). The population attributable risk for these haplotypes was substantially larger than that estimated for the IL23R R381Q variant (Block 2 H1 and block 3 H1 approximately 20%, compared with approximately 4% for Block 3 H6, containing the variant). CONCLUSIONS: These observations suggest that IL23R makes a substantial contribution to CD susceptibility, larger than that estimated from the population frequency of the R381Q variant. These observations also support the expectation that finding \"hits\" from genomewide association studies will be but an important chapter in the story of unraveling the genetic contribution to CD, rather than the final chapter that brings clarity to all the plot twists of a complicated story." ], "offsets": [ [ 83, 1792 ] ] } ]

[ { "id": "9645", "type": "SNP & Sequence variations", "text": [ "IL23R haplotypes" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "9646", "type": "Genes & Molecular Sequences", "text": [ "IL23R haplotypes" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "9647", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 66, 81 ] ], "normalized": [] }, { "id": "9648", "type": "Genes & Molecular Sequences", "text": [ "IL-23" ], "offsets": [ [ 99, 104 ] ], "normalized": [] }, { "id": "9649", "type": "Diseases & Disorders", "text": [ "chronic mucosal inflammation" ], "offsets": [ [ 156, 184 ] ], "normalized": [] }, { "id": "9650", "type": "Diseases & Disorders", "text": [ "inflammatory bowel diseases" ], "offsets": [ [ 197, 224 ] ], "normalized": [] }, { "id": "9651", "type": "Genes & Molecular Sequences", "text": [ "interleukin 23 receptor" ], "offsets": [ [ 288, 311 ] ], "normalized": [] }, { "id": "9652", "type": "Genes & Molecular Sequences", "text": [ "IL23R" ], "offsets": [ [ 318, 323 ] ], "normalized": [] }, { "id": "9653", "type": "Diseases & Disorders", "text": [ "Crohn's disease" ], "offsets": [ [ 328, 343 ] ], "normalized": [] }, { "id": "9654", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 345, 347 ] ], "normalized": [] }, { "id": "9655", "type": "SNP & Sequence variations", "text": [ "IL23R R381Q" ], "offsets": [ [ 376, 387 ] ], "normalized": [] }, { "id": "9656", "type": "Genes & Molecular Sequences", "text": [ "IL23R R381Q" ], "offsets": [ [ 376, 387 ] ], "normalized": [] }, { "id": "9657", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 487, 489 ] ], "normalized": [] }, { "id": "9658", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 549, 551 ] ], "normalized": [] }, { "id": "9659", "type": "Genes & Molecular Sequences", "text": [ "IL23R" ], "offsets": [ [ 636, 641 ] ], "normalized": [] }, { "id": "9660", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 750, 752 ] ], "normalized": [] }, { "id": "9661", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 847, 849 ] ], "normalized": [] }, { "id": "9662", "type": "Diseases & Disorders", "text": [ "blocks" ], "offsets": [ [ 887, 893 ] ], "normalized": [] }, { "id": "9663", "type": "Diseases & Disorders", "text": [ "Block" ], "offsets": [ [ 895, 900 ] ], "normalized": [] }, { "id": "9664", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 926, 928 ] ], "normalized": [] }, { "id": "9665", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 966, 968 ] ], "normalized": [] }, { "id": "9666", "type": "Diseases & Disorders", "text": [ "Block" ], "offsets": [ [ 981, 986 ] ], "normalized": [] }, { "id": "9667", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1014, 1016 ] ], "normalized": [] }, { "id": "9668", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1054, 1056 ] ], "normalized": [] }, { "id": "9669", "type": "SNP & Sequence variations", "text": [ "IL23R R381Q" ], "offsets": [ [ 1177, 1188 ] ], "normalized": [] }, { "id": "9670", "type": "Genes & Molecular Sequences", "text": [ "IL23R R381Q" ], "offsets": [ [ 1177, 1188 ] ], "normalized": [] }, { "id": "9671", "type": "Diseases & Disorders", "text": [ "Block" ], "offsets": [ [ 1198, 1203 ] ], "normalized": [] }, { "id": "9672", "type": "Diseases & Disorders", "text": [ "block" ], "offsets": [ [ 1213, 1218 ] ], "normalized": [] }, { "id": "9673", "type": "Diseases & Disorders", "text": [ "Block" ], "offsets": [ [ 1278, 1283 ] ], "normalized": [] }, { "id": "9674", "type": "Genes & Molecular Sequences", "text": [ "IL23R" ], "offsets": [ [ 1360, 1365 ] ], "normalized": [] }, { "id": "9675", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1402, 1404 ] ], "normalized": [] }, { "id": "9676", "type": "SNP & Sequence variations", "text": [ "R381Q" ], "offsets": [ [ 1485, 1490 ] ], "normalized": [] }, { "id": "9677", "type": "Diseases & Disorders", "text": [ "CD" ], "offsets": [ [ 1692, 1694 ] ], "normalized": [] }, { "id": "9678", "type": "Diseases & Disorders", "text": [ "twists" ], "offsets": [ [ 1762, 1768 ] ], "normalized": [] }, { "id": "9679", "type": "", "text": [ "IL23R haplotypes" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "9680", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 66, 81 ] ], "normalized": [] }, { "id": "9682", "type": "", "text": [ "IL-23" ], "offsets": [ [ 99, 104 ] ], "normalized": [] }, { "id": "9683", "type": "", "text": [ "chronic mucosal inflammation" ], "offsets": [ [ 156, 184 ] ], "normalized": [] }, { "id": "9685", "type": "", "text": [ "IL23R" ], "offsets": [ [ 318, 323 ] ], "normalized": [] }, { "id": "9686", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 328, 343 ] ], "normalized": [] }, { "id": "9688", "type": "", "text": [ "IL23R" ], "offsets": [ [ 318, 323 ] ], "normalized": [] }, { "id": "9689", "type": "", "text": [ "CD" ], "offsets": [ [ 345, 347 ] ], "normalized": [] }, { "id": "9691", "type": "", "text": [ "IL23R R381Q" ], "offsets": [ [ 376, 387 ] ], "normalized": [] }, { "id": "9692", "type": "", "text": [ "Crohn's disease" ], "offsets": [ [ 328, 343 ] ], "normalized": [] }, { "id": "9694", "type": "", "text": [ "IL23R R381Q" ], "offsets": [ [ 376, 387 ] ], "normalized": [] }, { "id": "9695", "type": "", "text": [ "CD" ], "offsets": [ [ 345, 347 ] ], "normalized": [] }, { "id": "9697", "type": "", "text": [ "IL23R" ], "offsets": [ [ 636, 641 ] ], "normalized": [] }, { "id": "9698", "type": "", "text": [ "CD" ], "offsets": [ [ 549, 551 ] ], "normalized": [] }, { "id": "9700", "type": "", "text": [ "IL23R" ], "offsets": [ [ 1360, 1365 ] ], "normalized": [] }, { "id": "9701", "type": "", "text": [ "CD" ], "offsets": [ [ 1402, 1404 ] ], "normalized": [] }, { "id": "9703", "type": "", "text": [ "R381Q" ], "offsets": [ [ 1485, 1490 ] ], "normalized": [] }, { "id": "9704", "type": "", "text": [ "CD" ], "offsets": [ [ 1402, 1404 ] ], "normalized": [] }, { "id": "9706", "type": "", "text": [ "IL-23" ], "offsets": [ [ 99, 104 ] ], "normalized": [] }, { "id": "9707", "type": "", "text": [ "inflammatory bowel diseases" ], "offsets": [ [ 197, 224 ] ], "normalized": [] }, { "id": "9709", "type": "", "text": [ "IL23R R381Q" ], "offsets": [ [ 1177, 1188 ] ], "normalized": [] }, { "id": "9710", "type": "", "text": [ "Block" ], "offsets": [ [ 1278, 1283 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9681", "type": "SA", "arg1_id": "9679", "arg2_id": "9680", "normalized": [] }, { "id": "9684", "type": "PA", "arg1_id": "9682", "arg2_id": "9683", "normalized": [] }, { "id": "9687", "type": "PA", "arg1_id": "9685", "arg2_id": "9686", "normalized": [] }, { "id": "9690", "type": "PA", "arg1_id": "9688", "arg2_id": "9689", "normalized": [] }, { "id": "9693", "type": "PA", "arg1_id": "9691", "arg2_id": "9692", "normalized": [] }, { "id": "9696", "type": "PA", "arg1_id": "9694", "arg2_id": "9695", "normalized": [] }, { "id": "9699", "type": "PA", "arg1_id": "9697", "arg2_id": "9698", "normalized": [] }, { "id": "9702", "type": "SA", "arg1_id": "9700", "arg2_id": "9701", "normalized": [] }, { "id": "9705", "type": "SA", "arg1_id": "9703", "arg2_id": "9704", "normalized": [] }, { "id": "9708", "type": "PA", "arg1_id": "9706", "arg2_id": "9707", "normalized": [] }, { "id": "9711", "type": "PA", "arg1_id": "9709", "arg2_id": "9710", "normalized": [] } ]

[ { "id": "9714", "type": "title", "text": [ "Three new BLM gene mutations associated with Bloom syndrome." ], "offsets": [ [ 0, 60 ] ] }, { "id": "9715", "type": "abstract", "text": [ "Bloom's syndrome (BS) is a rare autosomal recessive disease predisposing patients to all types of cancers affecting the general population. BS cells display a high level of genetic instability, including a 10-fold increase in the rate of sister chromatid exchanges, currently the only objective criterion for BS diagnosis. We have developed a method for screening the BLM gene for mutations based on direct genomic DNA sequencing. A questionnaire based on clinical information, cytogenetic features, and family history was addressed to physicians prescribing BS genetic screening, with the aim of confirming or guiding diagnosis. We report here four BLM gene mutations, three of which have not been described before. Three of the mutations are frameshift mutations, and the fourth is a nonsense mutation. All these mutations introduce a stop codon, and may therefore be considered to have deleterious biological effect. This approach should make it possible to identify new mutations and to correlate them with clinical information." ], "offsets": [ [ 61, 1093 ] ] } ]

[ { "id": "9716", "type": "SNP & Sequence variations", "text": [ "BLM gene mutations" ], "offsets": [ [ 10, 28 ] ], "normalized": [] }, { "id": "9717", "type": "Genes & Molecular Sequences", "text": [ "BLM gene mutations" ], "offsets": [ [ 10, 28 ] ], "normalized": [] }, { "id": "9718", "type": "Diseases & Disorders", "text": [ "BLM gene mutations" ], "offsets": [ [ 10, 28 ] ], "normalized": [] }, { "id": "9719", "type": "Diseases & Disorders", "text": [ "Bloom syndrome" ], "offsets": [ [ 45, 59 ] ], "normalized": [] }, { "id": "9720", "type": "Genes & Molecular Sequences", "text": [ "Bloom syndrome" ], "offsets": [ [ 45, 59 ] ], "normalized": [] }, { "id": "9721", "type": "Diseases & Disorders", "text": [ "Bloom's syndrome" ], "offsets": [ [ 61, 77 ] ], "normalized": [] }, { "id": "9722", "type": "Diseases & Disorders", "text": [ "BS" ], "offsets": [ [ 79, 81 ] ], "normalized": [] }, { "id": "9723", "type": "Diseases & Disorders", "text": [ "disease" ], "offsets": [ [ 113, 120 ] ], "normalized": [] }, { "id": "9724", "type": "Diseases & Disorders", "text": [ "cancers" ], "offsets": [ [ 159, 166 ] ], "normalized": [] }, { "id": "9725", "type": "Diseases & Disorders", "text": [ "BS" ], "offsets": [ [ 201, 203 ] ], "normalized": [] }, { "id": "9726", "type": "SNP & Sequence variations", "text": [ "sister chromatid exchanges" ], "offsets": [ [ 299, 325 ] ], "normalized": [] }, { "id": "9727", "type": "Diseases & Disorders", "text": [ "BS" ], "offsets": [ [ 370, 372 ] ], "normalized": [] }, { "id": "9728", "type": "Genes & Molecular Sequences", "text": [ "BLM" ], "offsets": [ [ 429, 432 ] ], "normalized": [] }, { "id": "9729", "type": "Diseases & Disorders", "text": [ "BLM" ], "offsets": [ [ 429, 432 ] ], "normalized": [] }, { "id": "9730", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 442, 451 ] ], "normalized": [] }, { "id": "9731", "type": "Diseases & Disorders", "text": [ "BS" ], "offsets": [ [ 620, 622 ] ], "normalized": [] }, { "id": "9732", "type": "SNP & Sequence variations", "text": [ "BLM gene mutations" ], "offsets": [ [ 711, 729 ] ], "normalized": [] }, { "id": "9733", "type": "Genes & Molecular Sequences", "text": [ "BLM gene mutations" ], "offsets": [ [ 711, 729 ] ], "normalized": [] }, { "id": "9734", "type": "Diseases & Disorders", "text": [ "BLM gene mutations" ], "offsets": [ [ 711, 729 ] ], "normalized": [] }, { "id": "9735", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 791, 800 ] ], "normalized": [] }, { "id": "9736", "type": "SNP & Sequence variations", "text": [ "frameshift mutations" ], "offsets": [ [ 805, 825 ] ], "normalized": [] }, { "id": "9737", "type": "Diseases & Disorders", "text": [ "frameshift mutations" ], "offsets": [ [ 805, 825 ] ], "normalized": [] }, { "id": "9738", "type": "SNP & Sequence variations", "text": [ "nonsense mutation" ], "offsets": [ [ 847, 864 ] ], "normalized": [] }, { "id": "9739", "type": "Diseases & Disorders", "text": [ "nonsense mutation" ], "offsets": [ [ 847, 864 ] ], "normalized": [] }, { "id": "9740", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 876, 885 ] ], "normalized": [] }, { "id": "9741", "type": "Diseases & Disorders", "text": [ "mutations" ], "offsets": [ [ 1035, 1044 ] ], "normalized": [] }, { "id": "9742", "type": "", "text": [ "BLM gene mutations" ], "offsets": [ [ 10, 28 ] ], "normalized": [] }, { "id": "9743", "type": "", "text": [ "Bloom syndrome" ], "offsets": [ [ 45, 59 ] ], "normalized": [] }, { "id": "9745", "type": "", "text": [ "sister chromatid exchanges" ], "offsets": [ [ 299, 325 ] ], "normalized": [] }, { "id": "9746", "type": "", "text": [ "BS" ], "offsets": [ [ 370, 372 ] ], "normalized": [] }, { "id": "9748", "type": "", "text": [ "Bloom syndrome" ], "offsets": [ [ 45, 59 ] ], "normalized": [] }, { "id": "9749", "type": "", "text": [ "BLM gene mutations" ], "offsets": [ [ 10, 28 ] ], "normalized": [] }, { "id": "9751", "type": "", "text": [ "BLM" ], "offsets": [ [ 429, 432 ] ], "normalized": [] }, { "id": "9752", "type": "", "text": [ "mutations" ], "offsets": [ [ 442, 451 ] ], "normalized": [] }, { "id": "9754", "type": "", "text": [ "BLM gene mutations" ], "offsets": [ [ 711, 729 ] ], "normalized": [] }, { "id": "9755", "type": "", "text": [ "BLM gene mutations" ], "offsets": [ [ 711, 729 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9744", "type": "SA", "arg1_id": "9742", "arg2_id": "9743", "normalized": [] }, { "id": "9747", "type": "PA", "arg1_id": "9745", "arg2_id": "9746", "normalized": [] }, { "id": "9750", "type": "PA", "arg1_id": "9748", "arg2_id": "9749", "normalized": [] }, { "id": "9753", "type": "PA", "arg1_id": "9751", "arg2_id": "9752", "normalized": [] }, { "id": "9756", "type": "PA", "arg1_id": "9754", "arg2_id": "9755", "normalized": [] } ]

[ { "id": "9759", "type": "title", "text": [ "GPx2 counteracts" ], "offsets": [ [ 0, 16 ] ] }, { "id": "9760", "type": "abstract", "text": [ "GPx2, the gastrointestinal glutathione peroxidase, is a selenoprotein predominantly expressed in the intestine. An anti-inflammatory and anticarcinogenic potential has been inferred from the development of colitis and intestinal cancer in GPx1 and GPx2 double knockout mice. Further, induction by Nrf2 activators classifies GPx2 as a protective enzyme. In contrast, enhanced COX-2 expression is consistently associated with inflammation. The antagonistic roles and an intriguing co-localization of GPx2 and COX-2 prompted us to investigate their possible mutual regulation. Both enzymes were upregulated in tissues of patients with colorectal cancer and colitis, and co-localized in the endoplasmic reticulum. A stable knockdown of GPx2 in HT-29 cells by siRNA resulted in a high basal and IL-1-induced expression of COX-2 and mPGES-1, enzymes required for the production of the pro-inflammatory PGE(2). Accordingly, si-GPx2 cells released high concentrations of PGE(2). Observed effects were specific for GPx2, since COX-2 and mPGES-1 expression was not affected by selenium-deprivation which resulted in the disappearance of GPx1. It is concluded that GPx2 by compartmentalized removal of hydroperoxides silences COX-2 activity and suppresses PGE(2)-dependent COX-2 expression. Thus, GPx2 may prevent undue responses to inflammatory stimuli and, in consequence, inflammation-driven initiation of carcinogenesis." ], "offsets": [ [ 17, 1430 ] ] } ]

[ { "id": "9761", "type": "Genes & Molecular Sequences", "text": [ "GPx2" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "9762", "type": "Genes & Molecular Sequences", "text": [ "GPx2" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "9763", "type": "Genes & Molecular Sequences", "text": [ "utath" ], "offsets": [ [ 46, 51 ] ], "normalized": [] }, { "id": "9764", "type": "Genes & Molecular Sequences", "text": [ "peroxid" ], "offsets": [ [ 56, 63 ] ], "normalized": [] }, { "id": "9765", "type": "Diseases & Disorders", "text": [ "in predomina" ], "offsets": [ [ 84, 96 ] ], "normalized": [] }, { "id": "9766", "type": "Genes & Molecular Sequences", "text": [ "ress" ], "offsets": [ [ 104, 108 ] ], "normalized": [] }, { "id": "9767", "type": "Genes & Molecular Sequences", "text": [ "the intestine. An anti-inflammatory and" ], "offsets": [ [ 114, 153 ] ], "normalized": [] }, { "id": "9768", "type": "Genes & Molecular Sequences", "text": [ "rcinogenic po" ], "offsets": [ [ 160, 173 ] ], "normalized": [] }, { "id": "9769", "type": "Diseases & Disorders", "text": [ " by Nrf" ], "offsets": [ [ 310, 317 ] ], "normalized": [] }, { "id": "9770", "type": "Diseases & Disorders", "text": [ "ivators classifie" ], "offsets": [ [ 322, 339 ] ], "normalized": [] }, { "id": "9771", "type": "Genes & Molecular Sequences", "text": [ "x2 a" ], "offsets": [ [ 343, 347 ] ], "normalized": [] }, { "id": "9772", "type": "Genes & Molecular Sequences", "text": [ "rote" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "9773", "type": "Genes & Molecular Sequences", "text": [ "ress" ], "offsets": [ [ 401, 405 ] ], "normalized": [] }, { "id": "9774", "type": "Genes & Molecular Sequences", "text": [ "ocia" ], "offsets": [ [ 428, 432 ] ], "normalized": [] }, { "id": "9775", "type": "Genes & Molecular Sequences", "text": [ "nd an" ], "offsets": [ [ 479, 484 ] ], "normalized": [] }, { "id": "9776", "type": "Diseases & Disorders", "text": [ "2 prompted u" ], "offsets": [ [ 528, 540 ] ], "normalized": [] }, { "id": "9777", "type": "Genes & Molecular Sequences", "text": [ "s we" ], "offsets": [ [ 602, 606 ] ], "normalized": [] }, { "id": "9778", "type": "Genes & Molecular Sequences", "text": [ "regul" ], "offsets": [ [ 611, 616 ] ], "normalized": [] }, { "id": "9779", "type": "Diseases & Disorders", "text": [ "knockdown of GPx2" ], "offsets": [ [ 736, 753 ] ], "normalized": [] }, { "id": "9780", "type": "Diseases & Disorders", "text": [ "T-29 ce" ], "offsets": [ [ 758, 765 ] ], "normalized": [] }, { "id": "9781", "type": "Genes & Molecular Sequences", "text": [ "X-2 " ], "offsets": [ [ 836, 840 ] ], "normalized": [] }, { "id": "9782", "type": "Genes & Molecular Sequences", "text": [ "e pr" ], "offsets": [ [ 894, 898 ] ], "normalized": [] }, { "id": "9783", "type": "Genes & Molecular Sequences", "text": [ "Accor" ], "offsets": [ [ 921, 926 ] ], "normalized": [] }, { "id": "9784", "type": "Genes & Molecular Sequences", "text": [ "y, si-G" ], "offsets": [ [ 931, 938 ] ], "normalized": [] }, { "id": "9785", "type": "Genes & Molecular Sequences", "text": [ "ects w" ], "offsets": [ [ 1000, 1006 ] ], "normalized": [] }, { "id": "9786", "type": "Genes & Molecular Sequences", "text": [ "Px2," ], "offsets": [ [ 1024, 1028 ] ], "normalized": [] }, { "id": "9787", "type": "Genes & Molecular Sequences", "text": [ " not a" ], "offsets": [ [ 1067, 1073 ] ], "normalized": [] }, { "id": "9788", "type": "Genes & Molecular Sequences", "text": [ " res" ], "offsets": [ [ 1110, 1114 ] ], "normalized": [] }, { "id": "9789", "type": "Genes & Molecular Sequences", "text": [ " the " ], "offsets": [ [ 1122, 1127 ] ], "normalized": [] }, { "id": "9790", "type": "Genes & Molecular Sequences", "text": [ "pearanc" ], "offsets": [ [ 1132, 1139 ] ], "normalized": [] }, { "id": "9791", "type": "Genes & Molecular Sequences", "text": [ " COX" ], "offsets": [ [ 1231, 1235 ] ], "normalized": [] }, { "id": "9792", "type": "Genes & Molecular Sequences", "text": [ "ses " ], "offsets": [ [ 1258, 1262 ] ], "normalized": [] }, { "id": "9793", "type": "Diseases & Disorders", "text": [ "y preven" ], "offsets": [ [ 1310, 1318 ] ], "normalized": [] }, { "id": "9794", "type": "Genes & Molecular Sequences", "text": [ " undu" ], "offsets": [ [ 1319, 1324 ] ], "normalized": [] }, { "id": "9795", "type": "Genes & Molecular Sequences", "text": [ "ry sti" ], "offsets": [ [ 1349, 1355 ] ], "normalized": [] }, { "id": "9796", "type": "Genes & Molecular Sequences", "text": [ "n con" ], "offsets": [ [ 1366, 1371 ] ], "normalized": [] }, { "id": "9797", "type": "Genes & Molecular Sequences", "text": [ "ion-" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "9798", "type": "Diseases & Disorders", "text": [ "" ], "offsets": [ [ 1502, 1516 ] ], "normalized": [] }, { "id": "9799", "type": "", "text": [ "rote" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "9800", "type": "", "text": [ " by Nrf" ], "offsets": [ [ 310, 317 ] ], "normalized": [] }, { "id": "9802", "type": "", "text": [ "rote" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "9803", "type": "", "text": [ "ivators classifie" ], "offsets": [ [ 322, 339 ] ], "normalized": [] }, { "id": "9805", "type": "", "text": [ "x2 a" ], "offsets": [ [ 343, 347 ] ], "normalized": [] }, { "id": "9806", "type": "", "text": [ " by Nrf" ], "offsets": [ [ 310, 317 ] ], "normalized": [] }, { "id": "9808", "type": "", "text": [ "x2 a" ], "offsets": [ [ 343, 347 ] ], "normalized": [] }, { "id": "9809", "type": "", "text": [ "ivators classifie" ], "offsets": [ [ 322, 339 ] ], "normalized": [] }, { "id": "9811", "type": "", "text": [ "nd an" ], "offsets": [ [ 479, 484 ] ], "normalized": [] }, { "id": "9812", "type": "", "text": [ "2 prompted u" ], "offsets": [ [ 528, 540 ] ], "normalized": [] }, { "id": "9814", "type": "", "text": [ "ion-" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "9815", "type": "", "text": [ "" ], "offsets": [ [ 1502, 1516 ] ], "normalized": [] }, { "id": "9817", "type": "", "text": [ "GPx2" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "9818", "type": "", "text": [ "in predomina" ], "offsets": [ [ 84, 96 ] ], "normalized": [] }, { "id": "9820", "type": "", "text": [ "GPx2" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "9821", "type": "", "text": [ "in predomina" ], "offsets": [ [ 84, 96 ] ], "normalized": [] }, { "id": "9823", "type": "", "text": [ "utath" ], "offsets": [ [ 46, 51 ] ], "normalized": [] }, { "id": "9824", "type": "", "text": [ "in predomina" ], "offsets": [ [ 84, 96 ] ], "normalized": [] }, { "id": "9826", "type": "", "text": [ "peroxid" ], "offsets": [ [ 56, 63 ] ], "normalized": [] }, { "id": "9827", "type": "", "text": [ "in predomina" ], "offsets": [ [ 84, 96 ] ], "normalized": [] }, { "id": "9829", "type": "", "text": [ "ses " ], "offsets": [ [ 1258, 1262 ] ], "normalized": [] }, { "id": "9830", "type": "", "text": [ "y preven" ], "offsets": [ [ 1310, 1318 ] ], "normalized": [] }, { "id": "9832", "type": "", "text": [ "n con" ], "offsets": [ [ 1366, 1371 ] ], "normalized": [] }, { "id": "9833", "type": "", "text": [ "y preven" ], "offsets": [ [ 1310, 1318 ] ], "normalized": [] } ]

[]

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[ { "id": "9801", "type": "PA", "arg1_id": "9799", "arg2_id": "9800", "normalized": [] }, { "id": "9804", "type": "PA", "arg1_id": "9802", "arg2_id": "9803", "normalized": [] }, { "id": "9807", "type": "PA", "arg1_id": "9805", "arg2_id": "9806", "normalized": [] }, { "id": "9810", "type": "PA", "arg1_id": "9808", "arg2_id": "9809", "normalized": [] }, { "id": "9813", "type": "PA", "arg1_id": "9811", "arg2_id": "9812", "normalized": [] }, { "id": "9816", "type": "SA", "arg1_id": "9814", "arg2_id": "9815", "normalized": [] }, { "id": "9819", "type": "PA", "arg1_id": "9817", "arg2_id": "9818", "normalized": [] }, { "id": "9822", "type": "PA", "arg1_id": "9820", "arg2_id": "9821", "normalized": [] }, { "id": "9825", "type": "PA", "arg1_id": "9823", "arg2_id": "9824", "normalized": [] }, { "id": "9828", "type": "PA", "arg1_id": "9826", "arg2_id": "9827", "normalized": [] }, { "id": "9831", "type": "PA", "arg1_id": "9829", "arg2_id": "9830", "normalized": [] }, { "id": "9834", "type": "PA", "arg1_id": "9832", "arg2_id": "9833", "normalized": [] } ]

[ { "id": "9837", "type": "title", "text": [ "Role of Stat3 in suppressing anti-tumor immunity." ], "offsets": [ [ 0, 49 ] ] }, { "id": "9838", "type": "abstract", "text": [ "Recent evidence suggests that what sustains a tumor's survival and proliferation can also subvert the immune system from its defense role. As a point of convergence for numerous oncogenic signaling pathways, Stat3 is constitutively activated in diverse human cancer cells. Activated Stat3 not only upregulates genes crucial for survival, proliferation, angiogenesis, and metastasis but also promotes expression of immune suppressive factors while inhibiting Th1 immunostimulatory molecules. By virtue of its ability to promote expression of many factors that activate Stat3 in diverse cells, Stat3 allows malignant and immune cells resonate, forming close partnership for tumor immune evasion, tumor progression, and resistance to therapies." ], "offsets": [ [ 50, 791 ] ] } ]

[ { "id": "9839", "type": "Genes & Molecular Sequences", "text": [ "Stat3" ], "offsets": [ [ 8, 13 ] ], "normalized": [] }, { "id": "9840", "type": "Genes & Molecular Sequences", "text": [ "Stat3" ], "offsets": [ [ 258, 263 ] ], "normalized": [] }, { "id": "9841", "type": "Genes & Molecular Sequences", "text": [ "Stat3" ], "offsets": [ [ 333, 338 ] ], "normalized": [] }, { "id": "9842", "type": "Genes & Molecular Sequences", "text": [ "Th1" ], "offsets": [ [ 508, 511 ] ], "normalized": [] }, { "id": "9843", "type": "Genes & Molecular Sequences", "text": [ "Stat3" ], "offsets": [ [ 618, 623 ] ], "normalized": [] }, { "id": "9844", "type": "Genes & Molecular Sequences", "text": [ "Stat3" ], "offsets": [ [ 642, 647 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "9847", "type": "title", "text": [ "Rivaroxaban, an oral direct factor Xa inhibitor." ], "offsets": [ [ 0, 48 ] ] }, { "id": "9848", "type": "abstract", "text": [ "Rivaroxaban is a small molecule, direct Factor Xa inhibitor and may be a potentially attractive alternative to vitamin K antagonists. Rivaroxaban is being investigated for the prevention and treatment of venous and arterial thrombosis. A broad search of Medline, clinicaltrials.gov and the annual proceedings of the American Society of Hematology and the International Society on Thrombosis and Hemostasis was conducted. This review addresses the findings of this systematic search, including the need for new oral anticoagulants, the development and pharmacology of rivaroxaban, and the results of completed as well as ongoing trials with rivaroxaban. At present, the safety and efficacy of rivaroxaban for the prophylaxis and treatment of venous thromboembolism has been evaluated in Phase II and Phase III trials involving over 24,000 patients. Additionally, rivaroxaban is being evaluated for the treatment of pulmonary embolism, secondary prevention after acute coronary syndromes and the prevention of stroke and non-central nervous system embolism in patients with non-valvular atrial fibrillation. The drug may have its greatest impact in providing a much-needed and attractive alternative to warfarin. Further data (especially large Phase III trials) are required." ], "offsets": [ [ 49, 1322 ] ] } ]

[ { "id": "9849", "type": "Chemicals & Drugs", "text": [ "Rivaroxaban" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "9850", "type": "Chemicals & Drugs", "text": [ "direct factor Xa inhibitor" ], "offsets": [ [ 21, 47 ] ], "normalized": [] }, { "id": "9851", "type": "Genes & Molecular Sequences", "text": [ "factor Xa" ], "offsets": [ [ 28, 37 ] ], "normalized": [] }, { "id": "9852", "type": "Chemicals & Drugs", "text": [ "Rivaroxaban" ], "offsets": [ [ 49, 60 ] ], "normalized": [] }, { "id": "9853", "type": "Chemicals & Drugs", "text": [ "direct Factor Xa inhibitor" ], "offsets": [ [ 82, 108 ] ], "normalized": [] }, { "id": "9854", "type": "Genes & Molecular Sequences", "text": [ "Factor Xa" ], "offsets": [ [ 89, 98 ] ], "normalized": [] }, { "id": "9855", "type": "Chemicals & Drugs", "text": [ "vitamin K antagonists" ], "offsets": [ [ 160, 181 ] ], "normalized": [] }, { "id": "9856", "type": "Chemicals & Drugs", "text": [ "Rivaroxaban" ], "offsets": [ [ 183, 194 ] ], "normalized": [] }, { "id": "9857", "type": "Chemicals & Drugs", "text": [ "oral anticoagulants" ], "offsets": [ [ 559, 578 ] ], "normalized": [] }, { "id": "9858", "type": "Chemicals & Drugs", "text": [ "rivaroxaban" ], "offsets": [ [ 616, 627 ] ], "normalized": [] }, { "id": "9859", "type": "Chemicals & Drugs", "text": [ "rivaroxaban" ], "offsets": [ [ 689, 700 ] ], "normalized": [] }, { "id": "9860", "type": "Chemicals & Drugs", "text": [ "rivaroxaban" ], "offsets": [ [ 741, 752 ] ], "normalized": [] }, { "id": "9861", "type": "Chemicals & Drugs", "text": [ "rivaroxaban" ], "offsets": [ [ 911, 922 ] ], "normalized": [] }, { "id": "9862", "type": "Chemicals & Drugs", "text": [ "warfarin" ], "offsets": [ [ 1250, 1258 ] ], "normalized": [] }, { "id": "9863", "type": "", "text": [ "Rivaroxaban" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "9864", "type": "", "text": [ "factor Xa" ], "offsets": [ [ 28, 37 ] ], "normalized": [] }, { "id": "9866", "type": "", "text": [ "vitamin K antagonists" ], "offsets": [ [ 160, 181 ] ], "normalized": [] }, { "id": "9867", "type": "", "text": [ "Factor Xa" ], "offsets": [ [ 89, 98 ] ], "normalized": [] }, { "id": "9869", "type": "", "text": [ "Rivaroxaban" ], "offsets": [ [ 49, 60 ] ], "normalized": [] }, { "id": "9870", "type": "", "text": [ "Factor Xa" ], "offsets": [ [ 89, 98 ] ], "normalized": [] }, { "id": "9872", "type": "", "text": [ "Rivaroxaban" ], "offsets": [ [ 183, 194 ] ], "normalized": [] }, { "id": "9873", "type": "", "text": [ "arterial thrombosis" ], "offsets": [ [ 264, 283 ] ], "normalized": [] }, { "id": "9875", "type": "", "text": [ "rivaroxaban" ], "offsets": [ [ 741, 752 ] ], "normalized": [] }, { "id": "9876", "type": "", "text": [ "venous thromboembolism" ], "offsets": [ [ 790, 812 ] ], "normalized": [] }, { "id": "9878", "type": "", "text": [ "rivaroxaban" ], "offsets": [ [ 911, 922 ] ], "normalized": [] }, { "id": "9879", "type": "", "text": [ "pulmonary embolism" ], "offsets": [ [ 963, 981 ] ], "normalized": [] }, { "id": "9881", "type": "", "text": [ "rivaroxaban" ], "offsets": [ [ 911, 922 ] ], "normalized": [] }, { "id": "9882", "type": "", "text": [ "acute coronary syndromes" ], "offsets": [ [ 1010, 1034 ] ], "normalized": [] }, { "id": "9884", "type": "", "text": [ "rivaroxaban" ], "offsets": [ [ 911, 922 ] ], "normalized": [] }, { "id": "9885", "type": "", "text": [ "stroke" ], "offsets": [ [ 1057, 1063 ] ], "normalized": [] }, { "id": "9887", "type": "", "text": [ "rivaroxaban" ], "offsets": [ [ 911, 922 ] ], "normalized": [] }, { "id": "9888", "type": "", "text": [ "atrial fibrillation" ], "offsets": [ [ 1134, 1153 ] ], "normalized": [] }, { "id": "9890", "type": "", "text": [ "rivaroxaban" ], "offsets": [ [ 911, 922 ] ], "normalized": [] }, { "id": "9891", "type": "", "text": [ "embolism" ], "offsets": [ [ 1095, 1103 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9865", "type": "PA", "arg1_id": "9863", "arg2_id": "9864", "normalized": [] }, { "id": "9868", "type": "PA", "arg1_id": "9866", "arg2_id": "9867", "normalized": [] }, { "id": "9871", "type": "PA", "arg1_id": "9869", "arg2_id": "9870", "normalized": [] }, { "id": "9874", "type": "PA", "arg1_id": "9872", "arg2_id": "9873", "normalized": [] }, { "id": "9877", "type": "PA", "arg1_id": "9875", "arg2_id": "9876", "normalized": [] }, { "id": "9880", "type": "PA", "arg1_id": "9878", "arg2_id": "9879", "normalized": [] }, { "id": "9883", "type": "PA", "arg1_id": "9881", "arg2_id": "9882", "normalized": [] }, { "id": "9886", "type": "PA", "arg1_id": "9884", "arg2_id": "9885", "normalized": [] }, { "id": "9889", "type": "PA", "arg1_id": "9887", "arg2_id": "9888", "normalized": [] }, { "id": "9892", "type": "PA", "arg1_id": "9890", "arg2_id": "9891", "normalized": [] } ]

[ { "id": "9895", "type": "title", "text": [ "The impact of ovarian stimulation with recombinant FSH in combination with GnRH antagonist on the endometrial transcriptome in the window of implantation." ], "offsets": [ [ 0, 154 ] ] }, { "id": "9896", "type": "abstract", "text": [ "The aim of this prospective paired cohort study is to elucidate the impact of ovarian stimulation with recombinant follicle-stimulating hormone in combination with gonadotropin-releasing hormone antagonist on the endometrial transcriptome. Oocyte donors underwent endometrial biopsy during the implantation window of the nonstimulated cycle and following ovarian stimulation with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonist but no luteal progesterone supplementation (n = 4). Microarray analysis showed 142 genes to be significantly upregulated and 98 significantly downregulated. Significantly upregulated genes included those sequencing for the chemokine ligand CXCL 13, the Dickkopf homolog, steroidogenic acute regulatory protein, and homeobox C6. Also upregulated were genes inhibited by progesterone, such as insulin-like growth factor binding protein 5. In conclusion, ovarian stimulation with follicle-stimulating hormone and gonadotropin-releasing hormone antagonist dysregulates the expression of many genes involved in cell adhesion, T-cell receptor signaling, and regulation of signal transduction. These data suggest that dysregulation of the endometrial transcriptome in the stimulated cycle is not fully attributable to supraphysiological sex steroid levels at the folliculo-luteal transition." ], "offsets": [ [ 155, 1506 ] ] } ]

[ { "id": "9897", "type": "Chemicals & Drugs", "text": [ "recombinant FSH" ], "offsets": [ [ 39, 54 ] ], "normalized": [] }, { "id": "9898", "type": "Chemicals & Drugs", "text": [ "GnRH antagonist" ], "offsets": [ [ 75, 90 ] ], "normalized": [] }, { "id": "9899", "type": "Genes & Molecular Sequences", "text": [ "endometrial transcriptome" ], "offsets": [ [ 98, 123 ] ], "normalized": [] }, { "id": "9900", "type": "Chemicals & Drugs", "text": [ "recombinant follicle-stimulating hormone" ], "offsets": [ [ 258, 298 ] ], "normalized": [] }, { "id": "9901", "type": "Chemicals & Drugs", "text": [ "gonadotropin-releasing hormone antagonist" ], "offsets": [ [ 319, 360 ] ], "normalized": [] }, { "id": "9902", "type": "Genes & Molecular Sequences", "text": [ "endometrial transcriptome" ], "offsets": [ [ 368, 393 ] ], "normalized": [] }, { "id": "9903", "type": "Chemicals & Drugs", "text": [ "recombinant follicle-stimulating hormone" ], "offsets": [ [ 535, 575 ] ], "normalized": [] }, { "id": "9904", "type": "Chemicals & Drugs", "text": [ "gonadotropin-releasing hormone antagonist" ], "offsets": [ [ 580, 621 ] ], "normalized": [] }, { "id": "9905", "type": "Chemicals & Drugs", "text": [ "luteal progesterone" ], "offsets": [ [ 629, 648 ] ], "normalized": [] }, { "id": "9906", "type": "Chemicals & Drugs", "text": [ "chemokine ligand" ], "offsets": [ [ 845, 861 ] ], "normalized": [] }, { "id": "9907", "type": "Chemicals & Drugs", "text": [ "CXCL 13" ], "offsets": [ [ 862, 869 ] ], "normalized": [] }, { "id": "9908", "type": "Genes & Molecular Sequences", "text": [ "CXCL 13" ], "offsets": [ [ 862, 869 ] ], "normalized": [] }, { "id": "9909", "type": "Genes & Molecular Sequences", "text": [ "Dickkopf homolog, steroidogenic acute regulatory protein" ], "offsets": [ [ 875, 931 ] ], "normalized": [] }, { "id": "9910", "type": "Genes & Molecular Sequences", "text": [ "homeobox C6" ], "offsets": [ [ 937, 948 ] ], "normalized": [] }, { "id": "9911", "type": "Chemicals & Drugs", "text": [ "progesterone" ], "offsets": [ [ 991, 1003 ] ], "normalized": [] }, { "id": "9912", "type": "Genes & Molecular Sequences", "text": [ "insulin-like growth factor binding protein 5" ], "offsets": [ [ 1013, 1057 ] ], "normalized": [] }, { "id": "9913", "type": "Chemicals & Drugs", "text": [ "follicle-stimulating hormone" ], "offsets": [ [ 1099, 1127 ] ], "normalized": [] }, { "id": "9914", "type": "Chemicals & Drugs", "text": [ "gonadotropin-releasing hormone antagonist" ], "offsets": [ [ 1132, 1173 ] ], "normalized": [] }, { "id": "9915", "type": "Genes & Molecular Sequences", "text": [ "endometrial transcriptome" ], "offsets": [ [ 1354, 1379 ] ], "normalized": [] }, { "id": "9916", "type": "Genes & Molecular Sequences", "text": [ "sex steroid" ], "offsets": [ [ 1452, 1463 ] ], "normalized": [] }, { "id": "9917", "type": "", "text": [ "CXCL 13" ], "offsets": [ [ 862, 869 ] ], "normalized": [] }, { "id": "9918", "type": "", "text": [ "homeobox C6" ], "offsets": [ [ 937, 948 ] ], "normalized": [] }, { "id": "9920", "type": "", "text": [ "CXCL 13" ], "offsets": [ [ 862, 869 ] ], "normalized": [] }, { "id": "9921", "type": "", "text": [ "Dickkopf homolog, steroidogenic acute regulatory protein" ], "offsets": [ [ 875, 931 ] ], "normalized": [] }, { "id": "9923", "type": "", "text": [ "chemokine ligand" ], "offsets": [ [ 845, 861 ] ], "normalized": [] }, { "id": "9924", "type": "", "text": [ "homeobox C6" ], "offsets": [ [ 937, 948 ] ], "normalized": [] }, { "id": "9926", "type": "", "text": [ "chemokine ligand" ], "offsets": [ [ 845, 861 ] ], "normalized": [] }, { "id": "9927", "type": "", "text": [ "Dickkopf homolog, steroidogenic acute regulatory protein" ], "offsets": [ [ 875, 931 ] ], "normalized": [] }, { "id": "9929", "type": "", "text": [ "progesterone" ], "offsets": [ [ 991, 1003 ] ], "normalized": [] }, { "id": "9930", "type": "", "text": [ "insulin-like growth factor binding protein 5" ], "offsets": [ [ 1013, 1057 ] ], "normalized": [] } ]

[]

[]

[ { "id": "9919", "type": "PA", "arg1_id": "9917", "arg2_id": "9918", "normalized": [] }, { "id": "9922", "type": "PA", "arg1_id": "9920", "arg2_id": "9921", "normalized": [] }, { "id": "9925", "type": "PA", "arg1_id": "9923", "arg2_id": "9924", "normalized": [] }, { "id": "9928", "type": "PA", "arg1_id": "9926", "arg2_id": "9927", "normalized": [] }, { "id": "9931", "type": "PA", "arg1_id": "9929", "arg2_id": "9930", "normalized": [] } ]

[ { "id": "9934", "type": "title", "text": [ "Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays." ], "offsets": [ [ 0, 169 ] ] }, { "id": "9935", "type": "abstract", "text": [ "BACKGROUND: We undertook a genome wide single nucleotide polymorphism analysis of a spectrum of patients with myelodysplastic syndrome del(5q) in order to investigate whether additional genomic abnormalities occur. Single nucleotide polymorphism array analysis has been shown to detect not only gene deletions but also regions of uniparental disomy that can pinpoint particular regions for mutation analysis. DESIGN AND METHODS: We studied 42 cases of myelodysplastic syndrome with del(5q), comprising 21 patients with 5q- syndrome and 21 with del(5q) (not 5q- syndrome), and 45 healthy controls by genome wide single nucleotide polymorphism analysis with the 50K Affymetrix single nucleotide polymorphism arrays. RESULTS: The del(5q) was characterized in all cases. The commonly deleted region of the 5q- syndrome extends between the genes SH3TC2 (proximal boundary) and GLRA1 (distal boundary) and measures 2.9 Mb. Copy number changes in addition to the del(5q) were observed in 10 of 21 patients with del(5q) myelodysplastic syndrome but in none of the patients with the 5q- syndrome. A total of 63 regions of uniparental disomy greater than 2 Mb were detected in 40 of 42 patients, dispersed on 18/23 chromosomes. In the 5q- syndrome group 31 regions of uniparental disomy were identified in 19 of 21 patients, the largest one being 7.6 Mb. All 21 patients with del(5q) myelodysplastic syndrome had uniparental disomy; in total 32 regions of uniparental disomy were identified in the 21 patients, including six regions of uniparental disomy > 10 Mb. Eight recurrent regions of uniparental disomy were observed among the 42 patients. For eight patients we had T-cell DNA as a germline control and four recurrent regions of uniparental disomy were identified that were present only in the neutrophil and not T-cell DNA. One small region of uniparental disomy at 10p12.31-p12.2 was observed in four patients with the 5q- syndrome. CONCLUSIONS: This study shows that regions of uniparental disomy greater than 2 Mb are found in the 5q-syndrome and del(5q) myelodysplastic syndrome, although large regions of uniparental disomy (>10 Mb) are only found in the latter group. The recurrent regions of uniparental disomy may indicate the position of novel leukemia-associated genes." ], "offsets": [ [ 170, 2447 ] ] } ]

[ { "id": "9936", "type": "Genes & Molecular Sequences", "text": [ "copy number" ], "offsets": [ [ 24, 35 ] ], "normalized": [] }, { "id": "9937", "type": "Genes & Molecular Sequences", "text": [ "loss of heterozygosity" ], "offsets": [ [ 48, 70 ] ], "normalized": [] }, { "id": "9938", "type": "Diseases & Disorders", "text": [ "myelodysplastic syndrome" ], "offsets": [ [ 74, 98 ] ], "normalized": [] }, { "id": "9939", "type": "Diseases & Disorders", "text": [ "del(5q)" ], "offsets": [ [ 104, 111 ] ], "normalized": [] }, { "id": "9940", "type": "SNP & Sequence variations", "text": [ "del(5q)" ], "offsets": [ [ 104, 111 ] ], "normalized": [] }, { "id": "9941", "type": "Genes & Molecular Sequences", "text": [ "del(5q)" ], "offsets": [ [ 104, 111 ] ], "normalized": [] }, { "id": "9942", "type": "Diseases & Disorders", "text": [ "myelodysplastic syndrome del(5q)" ], "offsets": [ [ 280, 312 ] ], "normalized": [] }, { "id": "9943", "type": "SNP & Sequence variations", "text": [ "del(5q" ], "offsets": [ [ 305, 311 ] ], "normalized": [] }, { "id": "9944", "type": "Diseases & Disorders", "text": [ "abnormalities" ], "offsets": [ [ 364, 377 ] ], "normalized": [] }, { "id": "9945", "type": "Diseases & Disorders", "text": [ "gene deletions" ], "offsets": [ [ 465, 479 ] ], "normalized": [] }, { "id": "9946", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 500, 518 ] ], "normalized": [] }, { "id": "9947", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 500, 518 ] ], "normalized": [] }, { "id": "9948", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 560, 568 ] ], "normalized": [] }, { "id": "9949", "type": "Diseases & Disorders", "text": [ "myelodysplastic syndrome" ], "offsets": [ [ 622, 646 ] ], "normalized": [] }, { "id": "9950", "type": "Diseases & Disorders", "text": [ "del(5q)" ], "offsets": [ [ 652, 659 ] ], "normalized": [] }, { "id": "9951", "type": "SNP & Sequence variations", "text": [ "del(5q)" ], "offsets": [ [ 652, 659 ] ], "normalized": [] }, { "id": "9952", "type": "Genes & Molecular Sequences", "text": [ "del(5q)" ], "offsets": [ [ 652, 659 ] ], "normalized": [] }, { "id": "9953", "type": "Diseases & Disorders", "text": [ "5q- syndrome" ], "offsets": [ [ 689, 701 ] ], "normalized": [] }, { "id": "9954", "type": "Diseases & Disorders", "text": [ "del(5q)" ], "offsets": [ [ 714, 721 ] ], "normalized": [] }, { "id": "9955", "type": "SNP & Sequence variations", "text": [ "del(5q)" ], "offsets": [ [ 714, 721 ] ], "normalized": [] }, { "id": "9956", "type": "Genes & Molecular Sequences", "text": [ "del(5q)" ], "offsets": [ [ 714, 721 ] ], "normalized": [] }, { "id": "9957", "type": "Diseases & Disorders", "text": [ "5q- syndrome" ], "offsets": [ [ 727, 739 ] ], "normalized": [] }, { "id": "9958", "type": "Diseases & Disorders", "text": [ "del(5q)" ], "offsets": [ [ 897, 904 ] ], "normalized": [] }, { "id": "9959", "type": "SNP & Sequence variations", "text": [ "del(5q)" ], "offsets": [ [ 897, 904 ] ], "normalized": [] }, { "id": "9960", "type": "Genes & Molecular Sequences", "text": [ "del(5q)" ], "offsets": [ [ 897, 904 ] ], "normalized": [] }, { "id": "9961", "type": "Diseases & Disorders", "text": [ "5q- syndrome" ], "offsets": [ [ 972, 984 ] ], "normalized": [] }, { "id": "9962", "type": "Genes & Molecular Sequences", "text": [ "SH3TC2" ], "offsets": [ [ 1011, 1017 ] ], "normalized": [] }, { "id": "9963", "type": "Genes & Molecular Sequences", "text": [ "GLRA1" ], "offsets": [ [ 1042, 1047 ] ], "normalized": [] }, { "id": "9964", "type": "Genes & Molecular Sequences", "text": [ "Copy number" ], "offsets": [ [ 1087, 1098 ] ], "normalized": [] }, { "id": "9965", "type": "Diseases & Disorders", "text": [ "del(5q)" ], "offsets": [ [ 1126, 1133 ] ], "normalized": [] }, { "id": "9966", "type": "SNP & Sequence variations", "text": [ "del(5q)" ], "offsets": [ [ 1126, 1133 ] ], "normalized": [] }, { "id": "9967", "type": "Genes & Molecular Sequences", "text": [ "del(5q)" ], "offsets": [ [ 1126, 1133 ] ], "normalized": [] }, { "id": "9968", "type": "Diseases & Disorders", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1174, 1206 ] ], "normalized": [] }, { "id": "9969", "type": "SNP & Sequence variations", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1174, 1206 ] ], "normalized": [] }, { "id": "9970", "type": "Diseases & Disorders", "text": [ "5q- syndrome" ], "offsets": [ [ 1244, 1256 ] ], "normalized": [] }, { "id": "9971", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 1283, 1301 ] ], "normalized": [] }, { "id": "9972", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 1283, 1301 ] ], "normalized": [] }, { "id": "9973", "type": "Diseases & Disorders", "text": [ "5q- syndrome" ], "offsets": [ [ 1395, 1407 ] ], "normalized": [] }, { "id": "9974", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 1428, 1446 ] ], "normalized": [] }, { "id": "9975", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 1428, 1446 ] ], "normalized": [] }, { "id": "9976", "type": "Diseases & Disorders", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1536, 1568 ] ], "normalized": [] }, { "id": "9977", "type": "SNP & Sequence variations", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1536, 1568 ] ], "normalized": [] }, { "id": "9978", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 1573, 1591 ] ], "normalized": [] }, { "id": "9979", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 1573, 1591 ] ], "normalized": [] }, { "id": "9980", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 1616, 1634 ] ], "normalized": [] }, { "id": "9981", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 1616, 1634 ] ], "normalized": [] }, { "id": "9982", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 1696, 1714 ] ], "normalized": [] }, { "id": "9983", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 1696, 1714 ] ], "normalized": [] }, { "id": "9984", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 1751, 1769 ] ], "normalized": [] }, { "id": "9985", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 1751, 1769 ] ], "normalized": [] }, { "id": "9986", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 1896, 1914 ] ], "normalized": [] }, { "id": "9987", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 1896, 1914 ] ], "normalized": [] }, { "id": "9988", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 2012, 2030 ] ], "normalized": [] }, { "id": "9989", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 2012, 2030 ] ], "normalized": [] }, { "id": "9990", "type": "SNP & Sequence variations", "text": [ "10p12.31-p12.2" ], "offsets": [ [ 2034, 2048 ] ], "normalized": [] }, { "id": "9991", "type": "Diseases & Disorders", "text": [ "5q- syndrome" ], "offsets": [ [ 2088, 2100 ] ], "normalized": [] }, { "id": "9992", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 2148, 2166 ] ], "normalized": [] }, { "id": "9993", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 2148, 2166 ] ], "normalized": [] }, { "id": "9994", "type": "Diseases & Disorders", "text": [ "5q-syndrome" ], "offsets": [ [ 2202, 2213 ] ], "normalized": [] }, { "id": "9995", "type": "Diseases & Disorders", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 2218, 2250 ] ], "normalized": [] }, { "id": "9996", "type": "SNP & Sequence variations", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 2218, 2250 ] ], "normalized": [] }, { "id": "9997", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 2278, 2296 ] ], "normalized": [] }, { "id": "9998", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 2278, 2296 ] ], "normalized": [] }, { "id": "9999", "type": "Diseases & Disorders", "text": [ "uniparental disomy" ], "offsets": [ [ 2367, 2385 ] ], "normalized": [] }, { "id": "10000", "type": "Genes & Molecular Sequences", "text": [ "uniparental disomy" ], "offsets": [ [ 2367, 2385 ] ], "normalized": [] }, { "id": "10001", "type": "Diseases & Disorders", "text": [ "leukemia" ], "offsets": [ [ 2421, 2429 ] ], "normalized": [] }, { "id": "10002", "type": "", "text": [ "SH3TC2" ], "offsets": [ [ 1011, 1017 ] ], "normalized": [] }, { "id": "10003", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 972, 984 ] ], "normalized": [] }, { "id": "10005", "type": "", "text": [ "GLRA1" ], "offsets": [ [ 1042, 1047 ] ], "normalized": [] }, { "id": "10006", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 972, 984 ] ], "normalized": [] }, { "id": "10008", "type": "", "text": [ "del(5q)" ], "offsets": [ [ 104, 111 ] ], "normalized": [] }, { "id": "10009", "type": "", "text": [ "myelodysplastic syndrome" ], "offsets": [ [ 74, 98 ] ], "normalized": [] }, { "id": "10011", "type": "", "text": [ "del(5q" ], "offsets": [ [ 305, 311 ] ], "normalized": [] }, { "id": "10012", "type": "", "text": [ "myelodysplastic syndrome del(5q)" ], "offsets": [ [ 280, 312 ] ], "normalized": [] }, { "id": "10014", "type": "", "text": [ "del(5q)" ], "offsets": [ [ 714, 721 ] ], "normalized": [] }, { "id": "10015", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 727, 739 ] ], "normalized": [] }, { "id": "10017", "type": "", "text": [ "del(5q)" ], "offsets": [ [ 714, 721 ] ], "normalized": [] }, { "id": "10018", "type": "", "text": [ "myelodysplastic syndrome" ], "offsets": [ [ 622, 646 ] ], "normalized": [] }, { "id": "10020", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1174, 1206 ] ], "normalized": [] }, { "id": "10021", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 1244, 1256 ] ], "normalized": [] }, { "id": "10023", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1174, 1206 ] ], "normalized": [] }, { "id": "10024", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1174, 1206 ] ], "normalized": [] }, { "id": "10026", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1536, 1568 ] ], "normalized": [] }, { "id": "10027", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1536, 1568 ] ], "normalized": [] }, { "id": "10029", "type": "", "text": [ "10p12.31-p12.2" ], "offsets": [ [ 2034, 2048 ] ], "normalized": [] }, { "id": "10030", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 2088, 2100 ] ], "normalized": [] }, { "id": "10032", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 2218, 2250 ] ], "normalized": [] }, { "id": "10033", "type": "", "text": [ "5q-syndrome" ], "offsets": [ [ 2202, 2213 ] ], "normalized": [] }, { "id": "10035", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 2218, 2250 ] ], "normalized": [] }, { "id": "10036", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 2218, 2250 ] ], "normalized": [] }, { "id": "10038", "type": "", "text": [ "Copy number" ], "offsets": [ [ 1087, 1098 ] ], "normalized": [] }, { "id": "10039", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 1244, 1256 ] ], "normalized": [] }, { "id": "10041", "type": "", "text": [ "Copy number" ], "offsets": [ [ 1087, 1098 ] ], "normalized": [] }, { "id": "10042", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1174, 1206 ] ], "normalized": [] }, { "id": "10044", "type": "", "text": [ "del(5q)" ], "offsets": [ [ 1126, 1133 ] ], "normalized": [] }, { "id": "10045", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 1244, 1256 ] ], "normalized": [] }, { "id": "10047", "type": "", "text": [ "del(5q)" ], "offsets": [ [ 1126, 1133 ] ], "normalized": [] }, { "id": "10048", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1174, 1206 ] ], "normalized": [] }, { "id": "10050", "type": "", "text": [ "uniparental disomy" ], "offsets": [ [ 1428, 1446 ] ], "normalized": [] }, { "id": "10051", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 1395, 1407 ] ], "normalized": [] }, { "id": "10053", "type": "", "text": [ "uniparental disomy" ], "offsets": [ [ 1696, 1714 ] ], "normalized": [] }, { "id": "10054", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 1536, 1568 ] ], "normalized": [] }, { "id": "10056", "type": "", "text": [ "uniparental disomy" ], "offsets": [ [ 2012, 2030 ] ], "normalized": [] }, { "id": "10057", "type": "", "text": [ "5q- syndrome" ], "offsets": [ [ 2088, 2100 ] ], "normalized": [] }, { "id": "10059", "type": "", "text": [ "uniparental disomy" ], "offsets": [ [ 2278, 2296 ] ], "normalized": [] }, { "id": "10060", "type": "", "text": [ "5q-syndrome" ], "offsets": [ [ 2202, 2213 ] ], "normalized": [] }, { "id": "10062", "type": "", "text": [ "uniparental disomy" ], "offsets": [ [ 2278, 2296 ] ], "normalized": [] }, { "id": "10063", "type": "", "text": [ "del(5q) myelodysplastic syndrome" ], "offsets": [ [ 2218, 2250 ] ], "normalized": [] }, { "id": "10065", "type": "", "text": [ "uniparental disomy" ], "offsets": [ [ 2367, 2385 ] ], "normalized": [] }, { "id": "10066", "type": "", "text": [ "leukemia" ], "offsets": [ [ 2421, 2429 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10004", "type": "PA", "arg1_id": "10002", "arg2_id": "10003", "normalized": [] }, { "id": "10007", "type": "PA", "arg1_id": "10005", "arg2_id": "10006", "normalized": [] }, { "id": "10010", "type": "PA", "arg1_id": "10008", "arg2_id": "10009", "normalized": [] }, { "id": "10013", "type": "SA", "arg1_id": "10011", "arg2_id": "10012", "normalized": [] }, { "id": "10016", "type": "PA", "arg1_id": "10014", "arg2_id": "10015", "normalized": [] }, { "id": "10019", "type": "PA", "arg1_id": "10017", "arg2_id": "10018", "normalized": [] }, { "id": "10022", "type": "PA", "arg1_id": "10020", "arg2_id": "10021", "normalized": [] }, { "id": "10025", "type": "PA", "arg1_id": "10023", "arg2_id": "10024", "normalized": [] }, { "id": "10028", "type": "PA", "arg1_id": "10026", "arg2_id": "10027", "normalized": [] }, { "id": "10031", "type": "PA", "arg1_id": "10029", "arg2_id": "10030", "normalized": [] }, { "id": "10034", "type": "PA", "arg1_id": "10032", "arg2_id": "10033", "normalized": [] }, { "id": "10037", "type": "PA", "arg1_id": "10035", "arg2_id": "10036", "normalized": [] }, { "id": "10040", "type": "NA", "arg1_id": "10038", "arg2_id": "10039", "normalized": [] }, { "id": "10043", "type": "PA", "arg1_id": "10041", "arg2_id": "10042", "normalized": [] }, { "id": "10046", "type": "NA", "arg1_id": "10044", "arg2_id": "10045", "normalized": [] }, { "id": "10049", "type": "PA", "arg1_id": "10047", "arg2_id": "10048", "normalized": [] }, { "id": "10052", "type": "PA", "arg1_id": "10050", "arg2_id": "10051", "normalized": [] }, { "id": "10055", "type": "PA", "arg1_id": "10053", "arg2_id": "10054", "normalized": [] }, { "id": "10058", "type": "PA", "arg1_id": "10056", "arg2_id": "10057", "normalized": [] }, { "id": "10061", "type": "PA", "arg1_id": "10059", "arg2_id": "10060", "normalized": [] }, { "id": "10064", "type": "PA", "arg1_id": "10062", "arg2_id": "10063", "normalized": [] }, { "id": "10067", "type": "SA", "arg1_id": "10065", "arg2_id": "10066", "normalized": [] } ]

[ { "id": "10070", "type": "title", "text": [ "Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate." ], "offsets": [ [ 0, 107 ] ] }, { "id": "10071", "type": "abstract", "text": [ "OBJECTIVE: To determine cancer risk in a cohort of 459 rheumatoid arthritis (RA) patients treated with methotrexate in community practice. METHODS: All RA patients who started methotrexate prior to June 1986 and were attending 1 of 6 rheumatologists were studied. Demographic data were matched to the State Cancer Registry to identify all malignancies (except nonmelanoma skin cancer) for 1983-1998, and to the National Death Index to identify all deaths to the end of 1999. Followup started on the date when methotrexate was started and ended either on the last confirmed date on which the patient was seen by the rheumatologist or at death. Standardized incidence ratios (SIRs) were calculated using state population cancer rates stratified by sex, age (in 5-year groups), and calendar year. RESULTS: There were 4,145 person-years of followup (average 9.3 years). Eighty-seven malignancies were identified (14 before, 64 during, and 9 after the followup period). There was an estimated 50% excess risk of malignancy among methotrexate-exposed RA patients relative to the general population (SIR 1.5, 95% confidence interval [95% CI] 1.2-1.9), with a 3-fold increase in melanoma (SIR 3.0, 95% CI 1.2-6.2), a 5-fold increase in non-Hodgkin's lymphoma (SIR 5.1, 95% CI 2.2-10.0), and an almost 3-fold increase in lung cancer (SIR 2.9, 95% CI 1.6-4.8). CONCLUSION: Compared with the general population, methotrexate-treated RA patients have an increased incidence of melanoma, non-Hodgkin's lymphoma, and lung cancer. There may be a role for regular skin cancer screening for all RA patients, particularly those receiving immunosuppressive therapy." ], "offsets": [ [ 108, 1754 ] ] } ]

[ { "id": "10072", "type": "Diseases & Disorders", "text": [ "melanoma" ], "offsets": [ [ 13, 21 ] ], "normalized": [] }, { "id": "10073", "type": "Diseases & Disorders", "text": [ "malignancies" ], "offsets": [ [ 32, 44 ] ], "normalized": [] }, { "id": "10074", "type": "Diseases & Disorders", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 51, 71 ] ], "normalized": [] }, { "id": "10075", "type": "Chemicals & Drugs", "text": [ "methotrexate" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "10076", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 132, 138 ] ], "normalized": [] }, { "id": "10077", "type": "Diseases & Disorders", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 163, 183 ] ], "normalized": [] }, { "id": "10078", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 185, 187 ] ], "normalized": [] }, { "id": "10079", "type": "Chemicals & Drugs", "text": [ "methotrexate" ], "offsets": [ [ 211, 223 ] ], "normalized": [] }, { "id": "10080", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 260, 262 ] ], "normalized": [] }, { "id": "10081", "type": "Chemicals & Drugs", "text": [ "methotrexate" ], "offsets": [ [ 284, 296 ] ], "normalized": [] }, { "id": "10082", "type": "Diseases & Disorders", "text": [ "Cancer" ], "offsets": [ [ 415, 421 ] ], "normalized": [] }, { "id": "10083", "type": "Diseases & Disorders", "text": [ "malignancies" ], "offsets": [ [ 447, 459 ] ], "normalized": [] }, { "id": "10084", "type": "Diseases & Disorders", "text": [ "nonmelanoma skin cancer" ], "offsets": [ [ 468, 491 ] ], "normalized": [] }, { "id": "10085", "type": "Diseases & Disorders", "text": [ "deaths" ], "offsets": [ [ 556, 562 ] ], "normalized": [] }, { "id": "10086", "type": "Chemicals & Drugs", "text": [ "methotrexate" ], "offsets": [ [ 617, 629 ] ], "normalized": [] }, { "id": "10087", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 827, 833 ] ], "normalized": [] }, { "id": "10088", "type": "Diseases & Disorders", "text": [ "malignancies" ], "offsets": [ [ 987, 999 ] ], "normalized": [] }, { "id": "10089", "type": "Diseases & Disorders", "text": [ "malignancy" ], "offsets": [ [ 1115, 1125 ] ], "normalized": [] }, { "id": "10090", "type": "Chemicals & Drugs", "text": [ "methotrexate" ], "offsets": [ [ 1132, 1144 ] ], "normalized": [] }, { "id": "10091", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 1153, 1155 ] ], "normalized": [] }, { "id": "10092", "type": "Diseases & Disorders", "text": [ "melanoma" ], "offsets": [ [ 1279, 1287 ] ], "normalized": [] }, { "id": "10093", "type": "Diseases & Disorders", "text": [ "non-Hodgkin's lymphoma" ], "offsets": [ [ 1336, 1358 ] ], "normalized": [] }, { "id": "10094", "type": "Diseases & Disorders", "text": [ "lung cancer" ], "offsets": [ [ 1420, 1431 ] ], "normalized": [] }, { "id": "10095", "type": "Chemicals & Drugs", "text": [ "methotrexate" ], "offsets": [ [ 1509, 1521 ] ], "normalized": [] }, { "id": "10096", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 1530, 1532 ] ], "normalized": [] }, { "id": "10097", "type": "Diseases & Disorders", "text": [ "melanoma" ], "offsets": [ [ 1573, 1581 ] ], "normalized": [] }, { "id": "10098", "type": "Diseases & Disorders", "text": [ "non-Hodgkin's lymphoma" ], "offsets": [ [ 1583, 1605 ] ], "normalized": [] }, { "id": "10099", "type": "Diseases & Disorders", "text": [ "lung cancer" ], "offsets": [ [ 1611, 1622 ] ], "normalized": [] }, { "id": "10100", "type": "Diseases & Disorders", "text": [ "skin cancer" ], "offsets": [ [ 1656, 1667 ] ], "normalized": [] }, { "id": "10101", "type": "Diseases & Disorders", "text": [ "RA" ], "offsets": [ [ 1686, 1688 ] ], "normalized": [] }, { "id": "10102", "type": "Chemicals & Drugs", "text": [ "immunosuppressive therapy" ], "offsets": [ [ 1728, 1753 ] ], "normalized": [] }, { "id": "10103", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "10104", "type": "", "text": [ "melanoma" ], "offsets": [ [ 13, 21 ] ], "normalized": [] }, { "id": "10106", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "10107", "type": "", "text": [ "malignancies" ], "offsets": [ [ 32, 44 ] ], "normalized": [] }, { "id": "10109", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "10110", "type": "", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 51, 71 ] ], "normalized": [] }, { "id": "10112", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 211, 223 ] ], "normalized": [] }, { "id": "10113", "type": "", "text": [ "cancer" ], "offsets": [ [ 132, 138 ] ], "normalized": [] }, { "id": "10115", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 211, 223 ] ], "normalized": [] }, { "id": "10116", "type": "", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 163, 183 ] ], "normalized": [] }, { "id": "10118", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 211, 223 ] ], "normalized": [] }, { "id": "10119", "type": "", "text": [ "RA" ], "offsets": [ [ 185, 187 ] ], "normalized": [] }, { "id": "10121", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 284, 296 ] ], "normalized": [] }, { "id": "10122", "type": "", "text": [ "RA" ], "offsets": [ [ 260, 262 ] ], "normalized": [] }, { "id": "10124", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1132, 1144 ] ], "normalized": [] }, { "id": "10125", "type": "", "text": [ "melanoma" ], "offsets": [ [ 1279, 1287 ] ], "normalized": [] }, { "id": "10127", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1132, 1144 ] ], "normalized": [] }, { "id": "10128", "type": "", "text": [ "malignancy" ], "offsets": [ [ 1115, 1125 ] ], "normalized": [] }, { "id": "10130", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1132, 1144 ] ], "normalized": [] }, { "id": "10131", "type": "", "text": [ "non-Hodgkin's lymphoma" ], "offsets": [ [ 1336, 1358 ] ], "normalized": [] }, { "id": "10133", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1132, 1144 ] ], "normalized": [] }, { "id": "10134", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 1420, 1431 ] ], "normalized": [] }, { "id": "10136", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1132, 1144 ] ], "normalized": [] }, { "id": "10137", "type": "", "text": [ "RA" ], "offsets": [ [ 1153, 1155 ] ], "normalized": [] }, { "id": "10139", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1509, 1521 ] ], "normalized": [] }, { "id": "10140", "type": "", "text": [ "melanoma" ], "offsets": [ [ 1573, 1581 ] ], "normalized": [] }, { "id": "10142", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1509, 1521 ] ], "normalized": [] }, { "id": "10143", "type": "", "text": [ "non-Hodgkin's lymphoma" ], "offsets": [ [ 1583, 1605 ] ], "normalized": [] }, { "id": "10145", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1509, 1521 ] ], "normalized": [] }, { "id": "10146", "type": "", "text": [ "lung cancer" ], "offsets": [ [ 1611, 1622 ] ], "normalized": [] }, { "id": "10148", "type": "", "text": [ "methotrexate" ], "offsets": [ [ 1509, 1521 ] ], "normalized": [] }, { "id": "10149", "type": "", "text": [ "RA" ], "offsets": [ [ 1530, 1532 ] ], "normalized": [] }, { "id": "10151", "type": "", "text": [ "immunosuppressive therapy" ], "offsets": [ [ 1728, 1753 ] ], "normalized": [] }, { "id": "10152", "type": "", "text": [ "skin cancer" ], "offsets": [ [ 1656, 1667 ] ], "normalized": [] }, { "id": "10154", "type": "", "text": [ "immunosuppressive therapy" ], "offsets": [ [ 1728, 1753 ] ], "normalized": [] }, { "id": "10155", "type": "", "text": [ "RA" ], "offsets": [ [ 1686, 1688 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10105", "type": "PA", "arg1_id": "10103", "arg2_id": "10104", "normalized": [] }, { "id": "10108", "type": "PA", "arg1_id": "10106", "arg2_id": "10107", "normalized": [] }, { "id": "10111", "type": "PA", "arg1_id": "10109", "arg2_id": "10110", "normalized": [] }, { "id": "10114", "type": "PA", "arg1_id": "10112", "arg2_id": "10113", "normalized": [] }, { "id": "10117", "type": "PA", "arg1_id": "10115", "arg2_id": "10116", "normalized": [] }, { "id": "10120", "type": "PA", "arg1_id": "10118", "arg2_id": "10119", "normalized": [] }, { "id": "10123", "type": "PA", "arg1_id": "10121", "arg2_id": "10122", "normalized": [] }, { "id": "10126", "type": "PA", "arg1_id": "10124", "arg2_id": "10125", "normalized": [] }, { "id": "10129", "type": "PA", "arg1_id": "10127", "arg2_id": "10128", "normalized": [] }, { "id": "10132", "type": "PA", "arg1_id": "10130", "arg2_id": "10131", "normalized": [] }, { "id": "10135", "type": "PA", "arg1_id": "10133", "arg2_id": "10134", "normalized": [] }, { "id": "10138", "type": "PA", "arg1_id": "10136", "arg2_id": "10137", "normalized": [] }, { "id": "10141", "type": "PA", "arg1_id": "10139", "arg2_id": "10140", "normalized": [] }, { "id": "10144", "type": "PA", "arg1_id": "10142", "arg2_id": "10143", "normalized": [] }, { "id": "10147", "type": "PA", "arg1_id": "10145", "arg2_id": "10146", "normalized": [] }, { "id": "10150", "type": "PA", "arg1_id": "10148", "arg2_id": "10149", "normalized": [] }, { "id": "10153", "type": "PA", "arg1_id": "10151", "arg2_id": "10152", "normalized": [] }, { "id": "10156", "type": "PA", "arg1_id": "10154", "arg2_id": "10155", "normalized": [] } ]

[ { "id": "10159", "type": "title", "text": [ "Detection and surveillance of waterborne protozoan parasites." ], "offsets": [ [ 0, 61 ] ] }, { "id": "10160", "type": "abstract", "text": [ "The majority of the world's population still live without access to healthy water and the contamination of drinking water with protozoan pathogens poses a serious threat to millions of people in the developing world. Even in the developed world periodic outbreaks of diarrhoeal diseases are caused by the protozoan parasites Cryptosporidium sp., Giardia duodenalis and Entamoeba histolytica. Thus, surveillance of drinking water is imperative to minimize such contaminations and ensure continuous supplies of healthy water world-wide. This article reviews the progress in technology for detection and surveillance of these important waterborne parasites." ], "offsets": [ [ 62, 716 ] ] } ]

[ { "id": "10161", "type": "Diseases & Disorders", "text": [ "still" ], "offsets": [ [ 101, 106 ] ], "normalized": [] }, { "id": "10162", "type": "Diseases & Disorders", "text": [ "drinking" ], "offsets": [ [ 169, 177 ] ], "normalized": [] }, { "id": "10163", "type": "Diseases & Disorders", "text": [ "diarrhoeal diseases" ], "offsets": [ [ 329, 348 ] ], "normalized": [] }, { "id": "10164", "type": "Genes & Molecular Sequences", "text": [ "Cryptosporidium sp" ], "offsets": [ [ 387, 405 ] ], "normalized": [] }, { "id": "10165", "type": "Genes & Molecular Sequences", "text": [ "Giardia duodenalis" ], "offsets": [ [ 408, 426 ] ], "normalized": [] }, { "id": "10166", "type": "Genes & Molecular Sequences", "text": [ "Entamoeba histolytica" ], "offsets": [ [ 431, 452 ] ], "normalized": [] }, { "id": "10167", "type": "Diseases & Disorders", "text": [ "drinking" ], "offsets": [ [ 476, 484 ] ], "normalized": [] }, { "id": "10168", "type": "", "text": [ "Cryptosporidium sp" ], "offsets": [ [ 387, 405 ] ], "normalized": [] }, { "id": "10169", "type": "", "text": [ "diarrhoeal diseases" ], "offsets": [ [ 329, 348 ] ], "normalized": [] }, { "id": "10171", "type": "", "text": [ "Giardia duodenalis" ], "offsets": [ [ 408, 426 ] ], "normalized": [] }, { "id": "10172", "type": "", "text": [ "diarrhoeal diseases" ], "offsets": [ [ 329, 348 ] ], "normalized": [] }, { "id": "10174", "type": "", "text": [ "Entamoeba histolytica" ], "offsets": [ [ 431, 452 ] ], "normalized": [] }, { "id": "10175", "type": "", "text": [ "diarrhoeal diseases" ], "offsets": [ [ 329, 348 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10170", "type": "PA", "arg1_id": "10168", "arg2_id": "10169", "normalized": [] }, { "id": "10173", "type": "PA", "arg1_id": "10171", "arg2_id": "10172", "normalized": [] }, { "id": "10176", "type": "PA", "arg1_id": "10174", "arg2_id": "10175", "normalized": [] } ]

[ { "id": "10179", "type": "title", "text": [ "Targeting of sonic hedgehog-GLI signaling: a potential strategy to improve therapy for mantle cell lymphoma." ], "offsets": [ [ 0, 108 ] ] }, { "id": "10180", "type": "abstract", "text": [ "Mantle cell lymphoma (MCL) has one of the worst clinical outcomes among the B-cell lymphomas, with a median survival of only 3 to 4 years. Therefore, a better understanding of the underlying mechanisms that regulate MCL proliferation/survival is needed to develop an effective therapy. Because sonic hedgehog (Shh)-GLI signaling has been shown to be important in the proliferation and survival of several cancers, and no such information is available for MCL, this study was undertaken. Our results show that the molecules associated with Shh-GLI signaling, such as PTCH and SMO receptors, and GLI1 and GLI2 target transcription factors were expressed in the human MCL cell lines and primary MCL cells from patients. Perturbation of this signaling in the presence of exogenous Shh/cyclopamine significantly (P < 0.001) influenced the proliferation of JVM2 MCL cells. Furthermore, down-regulation of GLI transcription factors using antisense oligonucleotides not only resulted in significantly (P < 0.001) decreased proliferation of the MCL cells but also significantly (P < 0.05) increased their susceptibility to chemotherapeutic drug, doxorubicin. Also, down-regulation of GLI decreased cyclin D1 and BCL2 transcript levels, which suggests that these key molecules might be regulated by GLI in MCL. Thus, our results indicate a significant role for Shh-GLI signaling in the proliferation of MCL, and molecular targeting of GLI is a potential therapeutic approach to improve the treatment for MCL." ], "offsets": [ [ 109, 1607 ] ] } ]

[ { "id": "10181", "type": "Genes & Molecular Sequences", "text": [ "sonic hedgehog-GLI" ], "offsets": [ [ 13, 31 ] ], "normalized": [] }, { "id": "10182", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 131, 134 ] ], "normalized": [] }, { "id": "10183", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 325, 328 ] ], "normalized": [] }, { "id": "10184", "type": "Genes & Molecular Sequences", "text": [ "sonic hedgehog" ], "offsets": [ [ 403, 417 ] ], "normalized": [] }, { "id": "10185", "type": "Genes & Molecular Sequences", "text": [ "Shh)-GLI" ], "offsets": [ [ 419, 427 ] ], "normalized": [] }, { "id": "10186", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "10187", "type": "Genes & Molecular Sequences", "text": [ "Shh-GLI" ], "offsets": [ [ 648, 655 ] ], "normalized": [] }, { "id": "10188", "type": "Genes & Molecular Sequences", "text": [ "PTCH" ], "offsets": [ [ 675, 679 ] ], "normalized": [] }, { "id": "10189", "type": "Genes & Molecular Sequences", "text": [ "SMO" ], "offsets": [ [ 684, 687 ] ], "normalized": [] }, { "id": "10190", "type": "Genes & Molecular Sequences", "text": [ "GLI1" ], "offsets": [ [ 703, 707 ] ], "normalized": [] }, { "id": "10191", "type": "Genes & Molecular Sequences", "text": [ "GLI2" ], "offsets": [ [ 712, 716 ] ], "normalized": [] }, { "id": "10192", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 774, 777 ] ], "normalized": [] }, { "id": "10193", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "10194", "type": "Chemicals & Drugs", "text": [ "Shh/cyclopamine" ], "offsets": [ [ 886, 901 ] ], "normalized": [] }, { "id": "10195", "type": "Genes & Molecular Sequences", "text": [ "Shh/cyclopamine" ], "offsets": [ [ 886, 901 ] ], "normalized": [] }, { "id": "10196", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 965, 968 ] ], "normalized": [] }, { "id": "10197", "type": "Genes & Molecular Sequences", "text": [ "GLI" ], "offsets": [ [ 1008, 1011 ] ], "normalized": [] }, { "id": "10198", "type": "Genes & Molecular Sequences", "text": [ "antisense oligonucleotides" ], "offsets": [ [ 1040, 1066 ] ], "normalized": [] }, { "id": "10199", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 1145, 1148 ] ], "normalized": [] }, { "id": "10200", "type": "Chemicals & Drugs", "text": [ "doxorubicin" ], "offsets": [ [ 1246, 1257 ] ], "normalized": [] }, { "id": "10201", "type": "Genes & Molecular Sequences", "text": [ "GLI" ], "offsets": [ [ 1284, 1287 ] ], "normalized": [] }, { "id": "10202", "type": "Genes & Molecular Sequences", "text": [ "cyclin D1" ], "offsets": [ [ 1298, 1307 ] ], "normalized": [] }, { "id": "10203", "type": "Genes & Molecular Sequences", "text": [ "BCL2" ], "offsets": [ [ 1312, 1316 ] ], "normalized": [] }, { "id": "10204", "type": "Genes & Molecular Sequences", "text": [ "GLI" ], "offsets": [ [ 1398, 1401 ] ], "normalized": [] }, { "id": "10205", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 1405, 1408 ] ], "normalized": [] }, { "id": "10206", "type": "Genes & Molecular Sequences", "text": [ "Shh-GLI" ], "offsets": [ [ 1460, 1467 ] ], "normalized": [] }, { "id": "10207", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 1502, 1505 ] ], "normalized": [] }, { "id": "10208", "type": "Genes & Molecular Sequences", "text": [ "GLI" ], "offsets": [ [ 1534, 1537 ] ], "normalized": [] }, { "id": "10209", "type": "Genes & Molecular Sequences", "text": [ "MCL" ], "offsets": [ [ 1603, 1606 ] ], "normalized": [] }, { "id": "10210", "type": "", "text": [ "doxorubicin" ], "offsets": [ [ 1246, 1257 ] ], "normalized": [] }, { "id": "10211", "type": "", "text": [ "GLI" ], "offsets": [ [ 1008, 1011 ] ], "normalized": [] }, { "id": "10213", "type": "", "text": [ "doxorubicin" ], "offsets": [ [ 1246, 1257 ] ], "normalized": [] }, { "id": "10214", "type": "", "text": [ "MCL" ], "offsets": [ [ 1145, 1148 ] ], "normalized": [] }, { "id": "10216", "type": "", "text": [ "sonic hedgehog-GLI" ], "offsets": [ [ 13, 31 ] ], "normalized": [] }, { "id": "10217", "type": "", "text": [ "mantle cell lymphoma" ], "offsets": [ [ 87, 107 ] ], "normalized": [] }, { "id": "10219", "type": "", "text": [ "Shh)-GLI" ], "offsets": [ [ 419, 427 ] ], "normalized": [] }, { "id": "10220", "type": "", "text": [ "cancers" ], "offsets": [ [ 514, 521 ] ], "normalized": [] }, { "id": "10222", "type": "", "text": [ "Shh)-GLI" ], "offsets": [ [ 419, 427 ] ], "normalized": [] }, { "id": "10223", "type": "", "text": [ "MCL" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "10225", "type": "", "text": [ "GLI1" ], "offsets": [ [ 703, 707 ] ], "normalized": [] }, { "id": "10226", "type": "", "text": [ "MCL" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "10228", "type": "", "text": [ "Shh-GLI" ], "offsets": [ [ 648, 655 ] ], "normalized": [] }, { "id": "10229", "type": "", "text": [ "MCL" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "10231", "type": "", "text": [ "PTCH" ], "offsets": [ [ 675, 679 ] ], "normalized": [] }, { "id": "10232", "type": "", "text": [ "MCL" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "10234", "type": "", "text": [ "SMO" ], "offsets": [ [ 684, 687 ] ], "normalized": [] }, { "id": "10235", "type": "", "text": [ "MCL" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "10237", "type": "", "text": [ "GLI2" ], "offsets": [ [ 712, 716 ] ], "normalized": [] }, { "id": "10238", "type": "", "text": [ "MCL" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "10240", "type": "", "text": [ "Shh/cyclopamine" ], "offsets": [ [ 886, 901 ] ], "normalized": [] }, { "id": "10241", "type": "", "text": [ "MCL" ], "offsets": [ [ 965, 968 ] ], "normalized": [] }, { "id": "10243", "type": "", "text": [ "GLI" ], "offsets": [ [ 1008, 1011 ] ], "normalized": [] }, { "id": "10244", "type": "", "text": [ "MCL" ], "offsets": [ [ 1145, 1148 ] ], "normalized": [] }, { "id": "10246", "type": "", "text": [ "GLI" ], "offsets": [ [ 1398, 1401 ] ], "normalized": [] }, { "id": "10247", "type": "", "text": [ "MCL" ], "offsets": [ [ 1405, 1408 ] ], "normalized": [] }, { "id": "10249", "type": "", "text": [ "cyclin D1" ], "offsets": [ [ 1298, 1307 ] ], "normalized": [] }, { "id": "10250", "type": "", "text": [ "MCL" ], "offsets": [ [ 1405, 1408 ] ], "normalized": [] }, { "id": "10252", "type": "", "text": [ "BCL2" ], "offsets": [ [ 1312, 1316 ] ], "normalized": [] }, { "id": "10253", "type": "", "text": [ "MCL" ], "offsets": [ [ 1405, 1408 ] ], "normalized": [] }, { "id": "10255", "type": "", "text": [ "GLI" ], "offsets": [ [ 1534, 1537 ] ], "normalized": [] }, { "id": "10256", "type": "", "text": [ "MCL" ], "offsets": [ [ 1603, 1606 ] ], "normalized": [] }, { "id": "10258", "type": "", "text": [ "Shh-GLI" ], "offsets": [ [ 1460, 1467 ] ], "normalized": [] }, { "id": "10259", "type": "", "text": [ "MCL" ], "offsets": [ [ 1603, 1606 ] ], "normalized": [] }, { "id": "10261", "type": "", "text": [ "doxorubicin" ], "offsets": [ [ 1246, 1257 ] ], "normalized": [] }, { "id": "10262", "type": "", "text": [ "antisense oligonucleotides" ], "offsets": [ [ 1040, 1066 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10212", "type": "PA", "arg1_id": "10210", "arg2_id": "10211", "normalized": [] }, { "id": "10215", "type": "PA", "arg1_id": "10213", "arg2_id": "10214", "normalized": [] }, { "id": "10218", "type": "PA", "arg1_id": "10216", "arg2_id": "10217", "normalized": [] }, { "id": "10221", "type": "PA", "arg1_id": "10219", "arg2_id": "10220", "normalized": [] }, { "id": "10224", "type": "PA", "arg1_id": "10222", "arg2_id": "10223", "normalized": [] }, { "id": "10227", "type": "PA", "arg1_id": "10225", "arg2_id": "10226", "normalized": [] }, { "id": "10230", "type": "PA", "arg1_id": "10228", "arg2_id": "10229", "normalized": [] }, { "id": "10233", "type": "PA", "arg1_id": "10231", "arg2_id": "10232", "normalized": [] }, { "id": "10236", "type": "PA", "arg1_id": "10234", "arg2_id": "10235", "normalized": [] }, { "id": "10239", "type": "PA", "arg1_id": "10237", "arg2_id": "10238", "normalized": [] }, { "id": "10242", "type": "PA", "arg1_id": "10240", "arg2_id": "10241", "normalized": [] }, { "id": "10245", "type": "PA", "arg1_id": "10243", "arg2_id": "10244", "normalized": [] }, { "id": "10248", "type": "PA", "arg1_id": "10246", "arg2_id": "10247", "normalized": [] }, { "id": "10251", "type": "PA", "arg1_id": "10249", "arg2_id": "10250", "normalized": [] }, { "id": "10254", "type": "PA", "arg1_id": "10252", "arg2_id": "10253", "normalized": [] }, { "id": "10257", "type": "PA", "arg1_id": "10255", "arg2_id": "10256", "normalized": [] }, { "id": "10260", "type": "PA", "arg1_id": "10258", "arg2_id": "10259", "normalized": [] }, { "id": "10263", "type": "PA", "arg1_id": "10261", "arg2_id": "10262", "normalized": [] } ]

[ { "id": "10266", "type": "title", "text": [ "Multiple relapses of hyperthyroidism after thyroid surgeries in a patient with long term follow-up of sporadic non-autoimmune hyperthyroidism." ], "offsets": [ [ 0, 142 ] ] }, { "id": "10267", "type": "abstract", "text": [ "Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. Patients with relapsing hyperthyroidism were previously treated with surgery and radioiodine. We report on a 22-year-old male patient who was treated for his multiple relapses of hyperthyroidism by repeated subtotal thyroidectomies (STE). During the 22 years of follow-up, the patient developed several relapses of hyperthyroidism, four of them after thyroid surgeries. Sequencing of the TSHR gene revealed a gain-of-function mutation with an amino acid exchange of aspartate to tyrosine in codon 633 which is located in the sixth transmembrane domain of the TSH receptor. The absence of the mutation in all other family members identifies the patient's TSHR mutation as a sporadic germline mutation. In this patient, thyroid tissue growth and hyperthyroidism could repeatedly be controlled only for limited periods by near total thyroidectomy. Therefore, this case confirms that early combined treatment with near-total thyroidectomy plus radioiodine therapy seems to be the treatment of choice for patients with sporadic non-autoimmune hyperthyroidism." ], "offsets": [ [ 143, 1343 ] ] } ]

[ { "id": "10268", "type": "Diseases & Disorders", "text": [ "relapses" ], "offsets": [ [ 9, 17 ] ], "normalized": [] }, { "id": "10269", "type": "Diseases & Disorders", "text": [ "hyperthyroidism" ], "offsets": [ [ 21, 36 ] ], "normalized": [] }, { "id": "10270", "type": "Diseases & Disorders", "text": [ "sporadic non-autoimmune hyperthyroidism" ], "offsets": [ [ 102, 141 ] ], "normalized": [] }, { "id": "10271", "type": "Genes & Molecular Sequences", "text": [ "thyrotropin receptor" ], "offsets": [ [ 169, 189 ] ], "normalized": [] }, { "id": "10272", "type": "SNP & Sequence variations", "text": [ "thyrotropin receptor" ], "offsets": [ [ 169, 189 ] ], "normalized": [] }, { "id": "10273", "type": "SNP & Sequence variations", "text": [ "TSHR) germline mutations" ], "offsets": [ [ 191, 215 ] ], "normalized": [] }, { "id": "10274", "type": "Genes & Molecular Sequences", "text": [ "TSHR) germline mutations" ], "offsets": [ [ 191, 215 ] ], "normalized": [] }, { "id": "10275", "type": "Diseases & Disorders", "text": [ "TSHR) germline mutations" ], "offsets": [ [ 191, 215 ] ], "normalized": [] }, { "id": "10276", "type": "Diseases & Disorders", "text": [ "congenital hyperthyroidism" ], "offsets": [ [ 261, 287 ] ], "normalized": [] }, { "id": "10277", "type": "Diseases & Disorders", "text": [ "relapsing" ], "offsets": [ [ 303, 312 ] ], "normalized": [] }, { "id": "10278", "type": "Diseases & Disorders", "text": [ "hyperthyroidism" ], "offsets": [ [ 313, 328 ] ], "normalized": [] }, { "id": "10279", "type": "Diseases & Disorders", "text": [ "relapses" ], "offsets": [ [ 456, 464 ] ], "normalized": [] }, { "id": "10280", "type": "Diseases & Disorders", "text": [ "hyperthyroidism" ], "offsets": [ [ 468, 483 ] ], "normalized": [] }, { "id": "10281", "type": "Genes & Molecular Sequences", "text": [ "STE" ], "offsets": [ [ 522, 525 ] ], "normalized": [] }, { "id": "10282", "type": "Diseases & Disorders", "text": [ "relapses" ], "offsets": [ [ 592, 600 ] ], "normalized": [] }, { "id": "10283", "type": "Diseases & Disorders", "text": [ "hyperthyroidism" ], "offsets": [ [ 604, 619 ] ], "normalized": [] }, { "id": "10284", "type": "Genes & Molecular Sequences", "text": [ "TSHR" ], "offsets": [ [ 677, 681 ] ], "normalized": [] }, { "id": "10285", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 715, 723 ] ], "normalized": [] }, { "id": "10286", "type": "SNP & Sequence variations", "text": [ "exchange of aspartate to tyrosine in codon 633" ], "offsets": [ [ 743, 789 ] ], "normalized": [] }, { "id": "10287", "type": "Genes & Molecular Sequences", "text": [ "TSH" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "10288", "type": "Diseases & Disorders", "text": [ "absence" ], "offsets": [ [ 866, 873 ] ], "normalized": [] }, { "id": "10289", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 881, 889 ] ], "normalized": [] }, { "id": "10290", "type": "Genes & Molecular Sequences", "text": [ "TSHR" ], "offsets": [ [ 943, 947 ] ], "normalized": [] }, { "id": "10291", "type": "SNP & Sequence variations", "text": [ "TSHR" ], "offsets": [ [ 943, 947 ] ], "normalized": [] }, { "id": "10292", "type": "Diseases & Disorders", "text": [ "mutation" ], "offsets": [ [ 948, 956 ] ], "normalized": [] }, { "id": "10293", "type": "SNP & Sequence variations", "text": [ "germline mutation" ], "offsets": [ [ 971, 988 ] ], "normalized": [] }, { "id": "10294", "type": "Diseases & Disorders", "text": [ "germline mutation" ], "offsets": [ [ 971, 988 ] ], "normalized": [] }, { "id": "10295", "type": "Diseases & Disorders", "text": [ "hyperthyroidism" ], "offsets": [ [ 1033, 1048 ] ], "normalized": [] }, { "id": "10296", "type": "Diseases & Disorders", "text": [ "sporadic non-autoimmune hyperthyroidism" ], "offsets": [ [ 1303, 1342 ] ], "normalized": [] }, { "id": "10297", "type": "", "text": [ "TSHR) germline mutations" ], "offsets": [ [ 191, 215 ] ], "normalized": [] }, { "id": "10298", "type": "", "text": [ "congenital hyperthyroidism" ], "offsets": [ [ 261, 287 ] ], "normalized": [] }, { "id": "10300", "type": "", "text": [ "TSHR) germline mutations" ], "offsets": [ [ 191, 215 ] ], "normalized": [] }, { "id": "10301", "type": "", "text": [ "TSHR) germline mutations" ], "offsets": [ [ 191, 215 ] ], "normalized": [] }, { "id": "10303", "type": "", "text": [ "STE" ], "offsets": [ [ 522, 525 ] ], "normalized": [] }, { "id": "10304", "type": "", "text": [ "relapses" ], "offsets": [ [ 456, 464 ] ], "normalized": [] }, { "id": "10306", "type": "", "text": [ "STE" ], "offsets": [ [ 522, 525 ] ], "normalized": [] }, { "id": "10307", "type": "", "text": [ "hyperthyroidism" ], "offsets": [ [ 468, 483 ] ], "normalized": [] }, { "id": "10309", "type": "", "text": [ "TSHR" ], "offsets": [ [ 677, 681 ] ], "normalized": [] }, { "id": "10310", "type": "", "text": [ "mutation" ], "offsets": [ [ 715, 723 ] ], "normalized": [] }, { "id": "10312", "type": "", "text": [ "TSHR" ], "offsets": [ [ 943, 947 ] ], "normalized": [] }, { "id": "10313", "type": "", "text": [ "germline mutation" ], "offsets": [ [ 971, 988 ] ], "normalized": [] }, { "id": "10315", "type": "", "text": [ "TSHR" ], "offsets": [ [ 943, 947 ] ], "normalized": [] }, { "id": "10316", "type": "", "text": [ "mutation" ], "offsets": [ [ 948, 956 ] ], "normalized": [] }, { "id": "10318", "type": "", "text": [ "thyrotropin receptor" ], "offsets": [ [ 169, 189 ] ], "normalized": [] }, { "id": "10319", "type": "", "text": [ "congenital hyperthyroidism" ], "offsets": [ [ 261, 287 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10299", "type": "PA", "arg1_id": "10297", "arg2_id": "10298", "normalized": [] }, { "id": "10302", "type": "PA", "arg1_id": "10300", "arg2_id": "10301", "normalized": [] }, { "id": "10305", "type": "PA", "arg1_id": "10303", "arg2_id": "10304", "normalized": [] }, { "id": "10308", "type": "PA", "arg1_id": "10306", "arg2_id": "10307", "normalized": [] }, { "id": "10311", "type": "PA", "arg1_id": "10309", "arg2_id": "10310", "normalized": [] }, { "id": "10314", "type": "PA", "arg1_id": "10312", "arg2_id": "10313", "normalized": [] }, { "id": "10317", "type": "PA", "arg1_id": "10315", "arg2_id": "10316", "normalized": [] }, { "id": "10320", "type": "PA", "arg1_id": "10318", "arg2_id": "10319", "normalized": [] } ]

[ { "id": "10323", "type": "title", "text": [ "Epoetin beta once weekly: review of its efficacy and safety in patients with chemotherapy-induced anemia." ], "offsets": [ [ 0, 105 ] ] }, { "id": "10324", "type": "abstract", "text": [ "Epoetin beta effectively increases hemoglobin levels, reduces the need for transfusions and improves the quality of life in patients with symptomatic chemotherapy-induced anemia with a range of solid tumors and lymphoid malignancies. Recent evidence-based guidelines recommend the once weekly administration of epoetin beta. This once-weekly regimen is generally well tolerated, and studies to date have reported that epoetin beta has a neutral effect on survival of patients with cancer. The once-weekly administration regimen is convenient for the physician and patient alike. Methods to further optimize this treatment are discussed." ], "offsets": [ [ 106, 742 ] ] } ]

[ { "id": "10325", "type": "Chemicals & Drugs", "text": [ "Epoetin beta" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "10326", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 77, 89 ] ], "normalized": [] }, { "id": "10327", "type": "Diseases & Disorders", "text": [ "anemia" ], "offsets": [ [ 98, 104 ] ], "normalized": [] }, { "id": "10328", "type": "Chemicals & Drugs", "text": [ "Epoetin beta" ], "offsets": [ [ 106, 118 ] ], "normalized": [] }, { "id": "10329", "type": "Chemicals & Drugs", "text": [ "chemotherapy" ], "offsets": [ [ 256, 268 ] ], "normalized": [] }, { "id": "10330", "type": "Diseases & Disorders", "text": [ "anemia" ], "offsets": [ [ 277, 283 ] ], "normalized": [] }, { "id": "10331", "type": "Diseases & Disorders", "text": [ "solid tumors" ], "offsets": [ [ 300, 312 ] ], "normalized": [] }, { "id": "10332", "type": "Diseases & Disorders", "text": [ "lymphoid malignancies" ], "offsets": [ [ 317, 338 ] ], "normalized": [] }, { "id": "10333", "type": "Chemicals & Drugs", "text": [ "epoetin beta" ], "offsets": [ [ 417, 429 ] ], "normalized": [] }, { "id": "10334", "type": "Chemicals & Drugs", "text": [ "epoetin beta" ], "offsets": [ [ 524, 536 ] ], "normalized": [] }, { "id": "10335", "type": "Diseases & Disorders", "text": [ "cancer" ], "offsets": [ [ 587, 593 ] ], "normalized": [] }, { "id": "10336", "type": "", "text": [ "Epoetin beta" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "10337", "type": "", "text": [ "anemia" ], "offsets": [ [ 98, 104 ] ], "normalized": [] }, { "id": "10339", "type": "", "text": [ "Epoetin beta" ], "offsets": [ [ 106, 118 ] ], "normalized": [] }, { "id": "10340", "type": "", "text": [ "anemia" ], "offsets": [ [ 277, 283 ] ], "normalized": [] }, { "id": "10342", "type": "", "text": [ "epoetin beta" ], "offsets": [ [ 524, 536 ] ], "normalized": [] }, { "id": "10343", "type": "", "text": [ "cancer" ], "offsets": [ [ 587, 593 ] ], "normalized": [] }, { "id": "10345", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 77, 89 ] ], "normalized": [] }, { "id": "10346", "type": "", "text": [ "anemia" ], "offsets": [ [ 98, 104 ] ], "normalized": [] }, { "id": "10348", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 256, 268 ] ], "normalized": [] }, { "id": "10349", "type": "", "text": [ "anemia" ], "offsets": [ [ 277, 283 ] ], "normalized": [] }, { "id": "10351", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 256, 268 ] ], "normalized": [] }, { "id": "10352", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 300, 312 ] ], "normalized": [] }, { "id": "10354", "type": "", "text": [ "chemotherapy" ], "offsets": [ [ 256, 268 ] ], "normalized": [] }, { "id": "10355", "type": "", "text": [ "lymphoid malignancies" ], "offsets": [ [ 317, 338 ] ], "normalized": [] }, { "id": "10357", "type": "", "text": [ "Epoetin beta" ], "offsets": [ [ 106, 118 ] ], "normalized": [] }, { "id": "10358", "type": "", "text": [ "solid tumors" ], "offsets": [ [ 300, 312 ] ], "normalized": [] }, { "id": "10360", "type": "", "text": [ "Epoetin beta" ], "offsets": [ [ 106, 118 ] ], "normalized": [] }, { "id": "10361", "type": "", "text": [ "lymphoid malignancies" ], "offsets": [ [ 317, 338 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10338", "type": "PA", "arg1_id": "10336", "arg2_id": "10337", "normalized": [] }, { "id": "10341", "type": "PA", "arg1_id": "10339", "arg2_id": "10340", "normalized": [] }, { "id": "10344", "type": "PA", "arg1_id": "10342", "arg2_id": "10343", "normalized": [] }, { "id": "10347", "type": "PA", "arg1_id": "10345", "arg2_id": "10346", "normalized": [] }, { "id": "10350", "type": "PA", "arg1_id": "10348", "arg2_id": "10349", "normalized": [] }, { "id": "10353", "type": "PA", "arg1_id": "10351", "arg2_id": "10352", "normalized": [] }, { "id": "10356", "type": "PA", "arg1_id": "10354", "arg2_id": "10355", "normalized": [] }, { "id": "10359", "type": "PA", "arg1_id": "10357", "arg2_id": "10358", "normalized": [] }, { "id": "10362", "type": "PA", "arg1_id": "10360", "arg2_id": "10361", "normalized": [] } ]

[ { "id": "10365", "type": "title", "text": [ "Update on novel therapeutic agents for cervical cancer." ], "offsets": [ [ 0, 55 ] ] }, { "id": "10366", "type": "abstract", "text": [ "Effective cytotoxic treatment options for advanced cervical cancer are exceedingly limited. Cisplatin-based combination chemotherapy, the most commonly used cytotoxic therapy, has produced response rates ranging from 20% to 30% and overall survival of less than 10 months. Because of the minimal degree of success with cytotoxic therapies and the poor prognosis of patients with this disease, interest has increased in targeted therapeutics for the treatment of cervical cancer. In recent years, significant improvements in our understanding of the altered molecular events in tumor cells have led to the discovery of new targets and agents for clinical testing. Two of these promising targets are epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) signaling pathway, which play critical roles in tumor growth and angiogenesis. Two monoclonal antibodies, cetuximab, which targets EGFR, and bevacizumab, which target the VEGF signaling pathway, are being evaluated as monotherapy and in combination with other agents and/or radiotherapy for the treatment of cervical cancer. In addition, VEGF receptor tyrosine kinase inhibitors, such as sorafenib and pazopanib, are being studied in phase I/II clinical trials. In this review, we discuss potential molecular targets and novel therapeutic strategies that are being investigated for the treatment of cervical cancer." ], "offsets": [ [ 56, 1459 ] ] } ]

[ { "id": "10367", "type": "Chemicals & Drugs", "text": [ "cytotoxic" ], "offsets": [ [ 66, 75 ] ], "normalized": [] }, { "id": "10368", "type": "Chemicals & Drugs", "text": [ "Cisplatin" ], "offsets": [ [ 148, 157 ] ], "normalized": [] }, { "id": "10369", "type": "Chemicals & Drugs", "text": [ "cytotoxic" ], "offsets": [ [ 213, 222 ] ], "normalized": [] }, { "id": "10370", "type": "Chemicals & Drugs", "text": [ "cytotoxic" ], "offsets": [ [ 375, 384 ] ], "normalized": [] }, { "id": "10371", "type": "Genes & Molecular Sequences", "text": [ "epidermal growth factor receptor" ], "offsets": [ [ 754, 786 ] ], "normalized": [] }, { "id": "10372", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 788, 792 ] ], "normalized": [] }, { "id": "10373", "type": "Genes & Molecular Sequences", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 802, 836 ] ], "normalized": [] }, { "id": "10374", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 838, 842 ] ], "normalized": [] }, { "id": "10375", "type": "Chemicals & Drugs", "text": [ "cetuximab" ], "offsets": [ [ 950, 959 ] ], "normalized": [] }, { "id": "10376", "type": "Genes & Molecular Sequences", "text": [ "EGFR" ], "offsets": [ [ 975, 979 ] ], "normalized": [] }, { "id": "10377", "type": "Chemicals & Drugs", "text": [ "bevacizumab" ], "offsets": [ [ 985, 996 ] ], "normalized": [] }, { "id": "10378", "type": "Genes & Molecular Sequences", "text": [ "VEGF" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "10379", "type": "Chemicals & Drugs", "text": [ "VEGF receptor tyrosine kinase inhibitors" ], "offsets": [ [ 1182, 1222 ] ], "normalized": [] }, { "id": "10380", "type": "Genes & Molecular Sequences", "text": [ "VEGF receptor tyrosine kinase inhibitors" ], "offsets": [ [ 1182, 1222 ] ], "normalized": [] }, { "id": "10381", "type": "Chemicals & Drugs", "text": [ "sorafenib" ], "offsets": [ [ 1232, 1241 ] ], "normalized": [] }, { "id": "10382", "type": "Chemicals & Drugs", "text": [ "pazopanib" ], "offsets": [ [ 1246, 1255 ] ], "normalized": [] }, { "id": "10383", "type": "", "text": [ "cetuximab" ], "offsets": [ [ 950, 959 ] ], "normalized": [] }, { "id": "10384", "type": "", "text": [ "EGFR" ], "offsets": [ [ 975, 979 ] ], "normalized": [] }, { "id": "10386", "type": "", "text": [ "bevacizumab" ], "offsets": [ [ 985, 996 ] ], "normalized": [] }, { "id": "10387", "type": "", "text": [ "VEGF" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "10389", "type": "", "text": [ "cetuximab" ], "offsets": [ [ 950, 959 ] ], "normalized": [] }, { "id": "10390", "type": "", "text": [ "VEGF" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "10392", "type": "", "text": [ "bevacizumab" ], "offsets": [ [ 985, 996 ] ], "normalized": [] }, { "id": "10393", "type": "", "text": [ "EGFR" ], "offsets": [ [ 975, 979 ] ], "normalized": [] }, { "id": "10395", "type": "", "text": [ "sorafenib" ], "offsets": [ [ 1232, 1241 ] ], "normalized": [] }, { "id": "10396", "type": "", "text": [ "VEGF receptor tyrosine kinase inhibitors" ], "offsets": [ [ 1182, 1222 ] ], "normalized": [] }, { "id": "10398", "type": "", "text": [ "EGFR" ], "offsets": [ [ 788, 792 ] ], "normalized": [] }, { "id": "10399", "type": "", "text": [ "tumor growth" ], "offsets": [ [ 892, 904 ] ], "normalized": [] }, { "id": "10401", "type": "", "text": [ "VEGF" ], "offsets": [ [ 838, 842 ] ], "normalized": [] }, { "id": "10402", "type": "", "text": [ "tumor growth" ], "offsets": [ [ 892, 904 ] ], "normalized": [] }, { "id": "10404", "type": "", "text": [ "EGFR" ], "offsets": [ [ 975, 979 ] ], "normalized": [] }, { "id": "10405", "type": "", "text": [ "cervical cancer" ], "offsets": [ [ 1152, 1167 ] ], "normalized": [] }, { "id": "10407", "type": "", "text": [ "VEGF" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "10408", "type": "", "text": [ "cervical cancer" ], "offsets": [ [ 1152, 1167 ] ], "normalized": [] }, { "id": "10410", "type": "", "text": [ "cetuximab" ], "offsets": [ [ 950, 959 ] ], "normalized": [] }, { "id": "10411", "type": "", "text": [ "cervical cancer" ], "offsets": [ [ 1152, 1167 ] ], "normalized": [] }, { "id": "10413", "type": "", "text": [ "bevacizumab" ], "offsets": [ [ 985, 996 ] ], "normalized": [] }, { "id": "10414", "type": "", "text": [ "cervical cancer" ], "offsets": [ [ 1152, 1167 ] ], "normalized": [] }, { "id": "10416", "type": "", "text": [ "pazopanib" ], "offsets": [ [ 1246, 1255 ] ], "normalized": [] }, { "id": "10417", "type": "", "text": [ "VEGF receptor tyrosine kinase inhibitors" ], "offsets": [ [ 1182, 1222 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10385", "type": "PA", "arg1_id": "10383", "arg2_id": "10384", "normalized": [] }, { "id": "10388", "type": "PA", "arg1_id": "10386", "arg2_id": "10387", "normalized": [] }, { "id": "10391", "type": "PA", "arg1_id": "10389", "arg2_id": "10390", "normalized": [] }, { "id": "10394", "type": "PA", "arg1_id": "10392", "arg2_id": "10393", "normalized": [] }, { "id": "10397", "type": "PA", "arg1_id": "10395", "arg2_id": "10396", "normalized": [] }, { "id": "10400", "type": "PA", "arg1_id": "10398", "arg2_id": "10399", "normalized": [] }, { "id": "10403", "type": "PA", "arg1_id": "10401", "arg2_id": "10402", "normalized": [] }, { "id": "10406", "type": "PA", "arg1_id": "10404", "arg2_id": "10405", "normalized": [] }, { "id": "10409", "type": "PA", "arg1_id": "10407", "arg2_id": "10408", "normalized": [] }, { "id": "10412", "type": "PA", "arg1_id": "10410", "arg2_id": "10411", "normalized": [] }, { "id": "10415", "type": "PA", "arg1_id": "10413", "arg2_id": "10414", "normalized": [] }, { "id": "10418", "type": "PA", "arg1_id": "10416", "arg2_id": "10417", "normalized": [] } ]

[ { "id": "10421", "type": "title", "text": [ "Improvement of meta-tetra(hydroxyphenyl)chlorin-like photosensitizer selectivity with folate-based targeted delivery. synthesis and in vivo delivery studies." ], "offsets": [ [ 0, 157 ] ] }, { "id": "10422", "type": "abstract", "text": [ "The cell membrane folate receptor (FR) is a molecular target for tumor-selective drug delivery, including delivery of photosensitizers for anticancer photodynamic therapy (PDT). Tumor selectivity of meta-tetra(hydroxyphenyl)chlorin ( m-THPC), a photosensitizer used in PDT clinical trials, demonstrates a low tumor-to-normal epithelial uptake ratio. We report on the synthesis and on the photophysical properties of a m-THPC-like photosensitizer 1 conjugated to folic acid (compound 8). A comparative study of the accumulation of photosensitizers 1 and 8 is described. Nude mice were xenografted with FR-alpha-positive KB or HT-29 cells lacking FR-alpha as a negative control. Using optical fiber fluorimetry, we demonstrated that conjugate 8 exhibited enhanced accumulation in KB tumors compared to 1 4 h after injection. No significant difference between KB and HT-29 tumors was observed in case of compound 1. Tumor-to-normal tissue ratio exhibited a very interesting selectivity for conjugate 8 (5:1) in KB tumors 4 h postinjection." ], "offsets": [ [ 158, 1194 ] ] } ]

[ { "id": "10423", "type": "Chemicals & Drugs", "text": [ "meta-tetra(hydroxyphenyl)chlorin" ], "offsets": [ [ 15, 47 ] ], "normalized": [] }, { "id": "10424", "type": "Chemicals & Drugs", "text": [ "tetra" ], "offsets": [ [ 20, 25 ] ], "normalized": [] }, { "id": "10425", "type": "Chemicals & Drugs", "text": [ "photosensitizer" ], "offsets": [ [ 53, 68 ] ], "normalized": [] }, { "id": "10426", "type": "Chemicals & Drugs", "text": [ "folate" ], "offsets": [ [ 86, 92 ] ], "normalized": [] }, { "id": "10427", "type": "Genes & Molecular Sequences", "text": [ "folate receptor" ], "offsets": [ [ 176, 191 ] ], "normalized": [] }, { "id": "10428", "type": "Chemicals & Drugs", "text": [ "folate receptor" ], "offsets": [ [ 176, 191 ] ], "normalized": [] }, { "id": "10429", "type": "Genes & Molecular Sequences", "text": [ "FR" ], "offsets": [ [ 193, 195 ] ], "normalized": [] }, { "id": "10430", "type": "Chemicals & Drugs", "text": [ "photosensitizers" ], "offsets": [ [ 276, 292 ] ], "normalized": [] }, { "id": "10431", "type": "Chemicals & Drugs", "text": [ "anticancer photodynamic therapy" ], "offsets": [ [ 297, 328 ] ], "normalized": [] }, { "id": "10432", "type": "Chemicals & Drugs", "text": [ "PDT" ], "offsets": [ [ 330, 333 ] ], "normalized": [] }, { "id": "10433", "type": "Chemicals & Drugs", "text": [ "meta-tetra(hydroxyphenyl)chlorin" ], "offsets": [ [ 357, 389 ] ], "normalized": [] }, { "id": "10434", "type": "Chemicals & Drugs", "text": [ "tetra" ], "offsets": [ [ 362, 367 ] ], "normalized": [] }, { "id": "10435", "type": "Chemicals & Drugs", "text": [ "m-THPC" ], "offsets": [ [ 392, 398 ] ], "normalized": [] }, { "id": "10436", "type": "Chemicals & Drugs", "text": [ "photosensitizer" ], "offsets": [ [ 403, 418 ] ], "normalized": [] }, { "id": "10437", "type": "Chemicals & Drugs", "text": [ "PDT" ], "offsets": [ [ 427, 430 ] ], "normalized": [] }, { "id": "10438", "type": "Chemicals & Drugs", "text": [ "m-THPC" ], "offsets": [ [ 576, 582 ] ], "normalized": [] }, { "id": "10439", "type": "Chemicals & Drugs", "text": [ "1" ], "offsets": [ [ 604, 605 ] ], "normalized": [] }, { "id": "10440", "type": "Chemicals & Drugs", "text": [ "folic acid" ], "offsets": [ [ 620, 630 ] ], "normalized": [] }, { "id": "10441", "type": "Chemicals & Drugs", "text": [ "8" ], "offsets": [ [ 641, 642 ] ], "normalized": [] }, { "id": "10442", "type": "Chemicals & Drugs", "text": [ "photosensitizers" ], "offsets": [ [ 688, 704 ] ], "normalized": [] }, { "id": "10443", "type": "Chemicals & Drugs", "text": [ "1" ], "offsets": [ [ 705, 706 ] ], "normalized": [] }, { "id": "10444", "type": "Chemicals & Drugs", "text": [ "8" ], "offsets": [ [ 711, 712 ] ], "normalized": [] }, { "id": "10445", "type": "Genes & Molecular Sequences", "text": [ "FR-alpha" ], "offsets": [ [ 759, 767 ] ], "normalized": [] }, { "id": "10446", "type": "Genes & Molecular Sequences", "text": [ "HT-29" ], "offsets": [ [ 783, 788 ] ], "normalized": [] }, { "id": "10447", "type": "Genes & Molecular Sequences", "text": [ "FR-alpha" ], "offsets": [ [ 803, 811 ] ], "normalized": [] }, { "id": "10448", "type": "Chemicals & Drugs", "text": [ "8" ], "offsets": [ [ 899, 900 ] ], "normalized": [] }, { "id": "10449", "type": "Genes & Molecular Sequences", "text": [ "KB" ], "offsets": [ [ 936, 938 ] ], "normalized": [] }, { "id": "10450", "type": "Chemicals & Drugs", "text": [ "1" ], "offsets": [ [ 958, 959 ] ], "normalized": [] }, { "id": "10451", "type": "Genes & Molecular Sequences", "text": [ "KB" ], "offsets": [ [ 1015, 1017 ] ], "normalized": [] }, { "id": "10452", "type": "Genes & Molecular Sequences", "text": [ "HT-29" ], "offsets": [ [ 1022, 1027 ] ], "normalized": [] }, { "id": "10453", "type": "Chemicals & Drugs", "text": [ "1" ], "offsets": [ [ 1068, 1069 ] ], "normalized": [] }, { "id": "10454", "type": "Chemicals & Drugs", "text": [ "8" ], "offsets": [ [ 1155, 1156 ] ], "normalized": [] }, { "id": "10455", "type": "Chemicals & Drugs", "text": [ "1" ], "offsets": [ [ 1160, 1161 ] ], "normalized": [] }, { "id": "10456", "type": "Genes & Molecular Sequences", "text": [ "KB" ], "offsets": [ [ 1166, 1168 ] ], "normalized": [] }, { "id": "10457", "type": "", "text": [ "photosensitizers" ], "offsets": [ [ 276, 292 ] ], "normalized": [] }, { "id": "10458", "type": "", "text": [ "folate receptor" ], "offsets": [ [ 176, 191 ] ], "normalized": [] }, { "id": "10460", "type": "", "text": [ "photosensitizers" ], "offsets": [ [ 276, 292 ] ], "normalized": [] }, { "id": "10461", "type": "", "text": [ "FR" ], "offsets": [ [ 193, 195 ] ], "normalized": [] }, { "id": "10463", "type": "", "text": [ "folate receptor" ], "offsets": [ [ 176, 191 ] ], "normalized": [] }, { "id": "10464", "type": "", "text": [ "tumor" ], "offsets": [ [ 223, 228 ] ], "normalized": [] }, { "id": "10466", "type": "", "text": [ "FR" ], "offsets": [ [ 193, 195 ] ], "normalized": [] }, { "id": "10467", "type": "", "text": [ "tumor" ], "offsets": [ [ 223, 228 ] ], "normalized": [] }, { "id": "10469", "type": "", "text": [ "m-THPC" ], "offsets": [ [ 392, 398 ] ], "normalized": [] }, { "id": "10470", "type": "", "text": [ "tumor" ], "offsets": [ [ 467, 472 ] ], "normalized": [] }, { "id": "10472", "type": "", "text": [ "PDT" ], "offsets": [ [ 330, 333 ] ], "normalized": [] }, { "id": "10473", "type": "", "text": [ "folate receptor" ], "offsets": [ [ 176, 191 ] ], "normalized": [] }, { "id": "10475", "type": "", "text": [ "PDT" ], "offsets": [ [ 330, 333 ] ], "normalized": [] }, { "id": "10476", "type": "", "text": [ "FR" ], "offsets": [ [ 193, 195 ] ], "normalized": [] }, { "id": "10478", "type": "", "text": [ "anticancer photodynamic therapy" ], "offsets": [ [ 297, 328 ] ], "normalized": [] }, { "id": "10479", "type": "", "text": [ "folate receptor" ], "offsets": [ [ 176, 191 ] ], "normalized": [] }, { "id": "10481", "type": "", "text": [ "anticancer photodynamic therapy" ], "offsets": [ [ 297, 328 ] ], "normalized": [] }, { "id": "10482", "type": "", "text": [ "FR" ], "offsets": [ [ 193, 195 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10459", "type": "PA", "arg1_id": "10457", "arg2_id": "10458", "normalized": [] }, { "id": "10462", "type": "PA", "arg1_id": "10460", "arg2_id": "10461", "normalized": [] }, { "id": "10465", "type": "PA", "arg1_id": "10463", "arg2_id": "10464", "normalized": [] }, { "id": "10468", "type": "PA", "arg1_id": "10466", "arg2_id": "10467", "normalized": [] }, { "id": "10471", "type": "PA", "arg1_id": "10469", "arg2_id": "10470", "normalized": [] }, { "id": "10474", "type": "PA", "arg1_id": "10472", "arg2_id": "10473", "normalized": [] }, { "id": "10477", "type": "PA", "arg1_id": "10475", "arg2_id": "10476", "normalized": [] }, { "id": "10480", "type": "PA", "arg1_id": "10478", "arg2_id": "10479", "normalized": [] }, { "id": "10483", "type": "PA", "arg1_id": "10481", "arg2_id": "10482", "normalized": [] } ]

[ { "id": "10486", "type": "title", "text": [ "Celiac crisis in an adult on immunosuppressive therapy." ], "offsets": [ [ 0, 55 ] ] }, { "id": "10487", "type": "abstract", "text": [ "'Celiac crisis' is a rare presentation of celiac disease with manifestations that include severe diarrhea, and severe metabolic and electrolyte abnormalities. It is most frequently seen in children younger than two years of age and has been rarely described in adults. A case of a 50-year-old woman who presented with diarrhea, severe dehydration, hypokalemia and metabolic acidosis is described. Based on positive serology and small bowel biopsy, she was diagnosed with celiac disease. She also had histological evidence of lymphocytic colitis. Microscopic colitis has not previously been described in association with celiac crisis, but it may have contributed to the presentation of celiac crisis in the current case. The patient was on corticosteroids and azathioprine for autoimmune hepatitis at the time of her presentation. The current case demonstrates that modest immunosuppression does not prevent a celiac crisis, although previous reports have shown that patients may respond rapidly to high-dose corticosteroids." ], "offsets": [ [ 56, 1081 ] ] } ]

[ { "id": "10488", "type": "Diseases & Disorders", "text": [ "Celiac crisis" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "10489", "type": "Chemicals & Drugs", "text": [ "immunosuppressive therapy" ], "offsets": [ [ 29, 54 ] ], "normalized": [] }, { "id": "10490", "type": "Diseases & Disorders", "text": [ "Celiac crisis" ], "offsets": [ [ 57, 70 ] ], "normalized": [] }, { "id": "10491", "type": "Diseases & Disorders", "text": [ "celiac disease" ], "offsets": [ [ 98, 112 ] ], "normalized": [] }, { "id": "10492", "type": "Diseases & Disorders", "text": [ "severe diarrhea" ], "offsets": [ [ 146, 161 ] ], "normalized": [] }, { "id": "10493", "type": "Diseases & Disorders", "text": [ "severe metabolic and electrolyte abnormalities" ], "offsets": [ [ 167, 213 ] ], "normalized": [] }, { "id": "10494", "type": "Diseases & Disorders", "text": [ "diarrhea" ], "offsets": [ [ 374, 382 ] ], "normalized": [] }, { "id": "10495", "type": "Diseases & Disorders", "text": [ "severe dehydration" ], "offsets": [ [ 384, 402 ] ], "normalized": [] }, { "id": "10496", "type": "Diseases & Disorders", "text": [ "hypokalemia" ], "offsets": [ [ 404, 415 ] ], "normalized": [] }, { "id": "10497", "type": "Diseases & Disorders", "text": [ "metabolic acidosis" ], "offsets": [ [ 420, 438 ] ], "normalized": [] }, { "id": "10498", "type": "Diseases & Disorders", "text": [ "celiac disease" ], "offsets": [ [ 527, 541 ] ], "normalized": [] }, { "id": "10499", "type": "Diseases & Disorders", "text": [ "lymphocytic colitis" ], "offsets": [ [ 581, 600 ] ], "normalized": [] }, { "id": "10500", "type": "Diseases & Disorders", "text": [ "Microscopic colitis" ], "offsets": [ [ 602, 621 ] ], "normalized": [] }, { "id": "10501", "type": "Diseases & Disorders", "text": [ "celiac crisis" ], "offsets": [ [ 676, 689 ] ], "normalized": [] }, { "id": "10502", "type": "Diseases & Disorders", "text": [ "celiac crisis" ], "offsets": [ [ 742, 755 ] ], "normalized": [] }, { "id": "10503", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 796, 811 ] ], "normalized": [] }, { "id": "10504", "type": "Chemicals & Drugs", "text": [ "azathioprine" ], "offsets": [ [ 816, 828 ] ], "normalized": [] }, { "id": "10505", "type": "Diseases & Disorders", "text": [ "autoimmune hepatitis" ], "offsets": [ [ 833, 853 ] ], "normalized": [] }, { "id": "10506", "type": "Chemicals & Drugs", "text": [ "her" ], "offsets": [ [ 869, 872 ] ], "normalized": [] }, { "id": "10507", "type": "Diseases & Disorders", "text": [ "immunosuppression" ], "offsets": [ [ 929, 946 ] ], "normalized": [] }, { "id": "10508", "type": "Diseases & Disorders", "text": [ "celiac crisis" ], "offsets": [ [ 966, 979 ] ], "normalized": [] }, { "id": "10509", "type": "Chemicals & Drugs", "text": [ "corticosteroids" ], "offsets": [ [ 1065, 1080 ] ], "normalized": [] }, { "id": "10510", "type": "", "text": [ "azathioprine" ], "offsets": [ [ 816, 828 ] ], "normalized": [] }, { "id": "10511", "type": "", "text": [ "autoimmune hepatitis" ], "offsets": [ [ 833, 853 ] ], "normalized": [] }, { "id": "10513", "type": "", "text": [ "corticosteroids" ], "offsets": [ [ 796, 811 ] ], "normalized": [] }, { "id": "10514", "type": "", "text": [ "autoimmune hepatitis" ], "offsets": [ [ 833, 853 ] ], "normalized": [] }, { "id": "10516", "type": "", "text": [ "corticosteroids" ], "offsets": [ [ 1065, 1080 ] ], "normalized": [] }, { "id": "10517", "type": "", "text": [ "celiac crisis" ], "offsets": [ [ 966, 979 ] ], "normalized": [] }, { "id": "10519", "type": "", "text": [ "azathioprine" ], "offsets": [ [ 816, 828 ] ], "normalized": [] }, { "id": "10520", "type": "", "text": [ "autoimmune hepatitis" ], "offsets": [ [ 833, 853 ] ], "normalized": [] }, { "id": "10522", "type": "", "text": [ "her" ], "offsets": [ [ 869, 872 ] ], "normalized": [] }, { "id": "10523", "type": "", "text": [ "autoimmune hepatitis" ], "offsets": [ [ 833, 853 ] ], "normalized": [] }, { "id": "10525", "type": "", "text": [ "immunosuppressive therapy" ], "offsets": [ [ 29, 54 ] ], "normalized": [] }, { "id": "10526", "type": "", "text": [ "Celiac crisis" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "10528", "type": "", "text": [ "corticosteroids" ], "offsets": [ [ 1065, 1080 ] ], "normalized": [] }, { "id": "10529", "type": "", "text": [ "celiac crisis" ], "offsets": [ [ 966, 979 ] ], "normalized": [] }, { "id": "10531", "type": "", "text": [ "corticosteroids" ], "offsets": [ [ 1065, 1080 ] ], "normalized": [] }, { "id": "10532", "type": "", "text": [ "immunosuppression" ], "offsets": [ [ 929, 946 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10512", "type": "PA", "arg1_id": "10510", "arg2_id": "10511", "normalized": [] }, { "id": "10515", "type": "PA", "arg1_id": "10513", "arg2_id": "10514", "normalized": [] }, { "id": "10518", "type": "SA", "arg1_id": "10516", "arg2_id": "10517", "normalized": [] }, { "id": "10521", "type": "NA", "arg1_id": "10519", "arg2_id": "10520", "normalized": [] }, { "id": "10524", "type": "PA", "arg1_id": "10522", "arg2_id": "10523", "normalized": [] }, { "id": "10527", "type": "PA", "arg1_id": "10525", "arg2_id": "10526", "normalized": [] }, { "id": "10530", "type": "NA", "arg1_id": "10528", "arg2_id": "10529", "normalized": [] }, { "id": "10533", "type": "PA", "arg1_id": "10531", "arg2_id": "10532", "normalized": [] } ]

[ { "id": "10536", "type": "title", "text": [ "Preoperative periumbilical ultrasound-guided saline infusion (PUGSI) as a tool in predicting obliterating subumbilical adhesions in laparoscopy." ], "offsets": [ [ 0, 144 ] ] }, { "id": "10537", "type": "abstract", "text": [ "OBJECTIVE: To report the novel technique of periumbilical ultrasound-guided saline infusion (PUGSI). DESIGN: Prospective study of two noninvasive diagnostic tests to detect obliterating subumbilical adhesions. SETTING: Tertiary care center. PATIENT(S): One hundred fifty patients were included in the study. Patients without risk factors for adhesions were used as a control group (n = 38), whereas the study group had risk factors for intra-abdominal adhesions (n = 112). INTERVENTION(S): Preoperative examination with the visceral slide and the PUGSI. MAIN OUTCOME MEASURE(S): The presence of obliterating subumbilical adhesions in the high-risk patient and the ability of the PUGSI to detect them preoperatively. RESULT(S): There were no obliterating umbilical adhesions in the control group. The prevalence of obliterating umbilical adhesions in the risk group was 3.6%. The visceral slide test had an accuracy of 96.4%, a sensitivity of 50%, and a specificity of 98.1%, with a negative predictive value of 98.1% and a positive predictive value of 50%. The PUGSI test was able to detect all cases of obliterating subumbilical adhesions, demonstrating sensitivity and specificity of 100%. CONCLUSION(S): The PUGSI test has excellent negative and positive predictive values and is useful in determining patients who have obliterating subumbilical adhesions. Use of both tests preoperatively appears to be helpful in identifying patients at risk for visceral injury during laparoscopic surgery." ], "offsets": [ [ 145, 1640 ] ] } ]

[ { "id": "10538", "type": "Chemicals & Drugs", "text": [ "ultrasound-guided saline infusion" ], "offsets": [ [ 27, 60 ] ], "normalized": [] }, { "id": "10539", "type": "Chemicals & Drugs", "text": [ "PUGSI" ], "offsets": [ [ 62, 67 ] ], "normalized": [] }, { "id": "10540", "type": "Diseases & Disorders", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 93, 128 ] ], "normalized": [] }, { "id": "10541", "type": "Chemicals & Drugs", "text": [ "ultrasound-guided saline infusion" ], "offsets": [ [ 203, 236 ] ], "normalized": [] }, { "id": "10542", "type": "Chemicals & Drugs", "text": [ "PUGSI" ], "offsets": [ [ 238, 243 ] ], "normalized": [] }, { "id": "10543", "type": "Diseases & Disorders", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 318, 353 ] ], "normalized": [] }, { "id": "10544", "type": "Diseases & Disorders", "text": [ "adhesions" ], "offsets": [ [ 487, 496 ] ], "normalized": [] }, { "id": "10545", "type": "Diseases & Disorders", "text": [ "intra-abdominal adhesions" ], "offsets": [ [ 581, 606 ] ], "normalized": [] }, { "id": "10546", "type": "Chemicals & Drugs", "text": [ "PUGSI" ], "offsets": [ [ 692, 697 ] ], "normalized": [] }, { "id": "10547", "type": "Diseases & Disorders", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 740, 775 ] ], "normalized": [] }, { "id": "10548", "type": "Chemicals & Drugs", "text": [ "PUGSI" ], "offsets": [ [ 824, 829 ] ], "normalized": [] }, { "id": "10549", "type": "Diseases & Disorders", "text": [ "obliterating umbilical adhesions" ], "offsets": [ [ 886, 918 ] ], "normalized": [] }, { "id": "10550", "type": "Diseases & Disorders", "text": [ "obliterating umbilical adhesions" ], "offsets": [ [ 959, 991 ] ], "normalized": [] }, { "id": "10551", "type": "Chemicals & Drugs", "text": [ "PUGSI" ], "offsets": [ [ 1206, 1211 ] ], "normalized": [] }, { "id": "10552", "type": "Diseases & Disorders", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 1249, 1284 ] ], "normalized": [] }, { "id": "10553", "type": "Chemicals & Drugs", "text": [ "PUGSI" ], "offsets": [ [ 1356, 1361 ] ], "normalized": [] }, { "id": "10554", "type": "Diseases & Disorders", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 1468, 1503 ] ], "normalized": [] }, { "id": "10555", "type": "Diseases & Disorders", "text": [ "visceral injury" ], "offsets": [ [ 1596, 1611 ] ], "normalized": [] }, { "id": "10556", "type": "", "text": [ "PUGSI" ], "offsets": [ [ 1206, 1211 ] ], "normalized": [] }, { "id": "10557", "type": "", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 1249, 1284 ] ], "normalized": [] }, { "id": "10559", "type": "", "text": [ "PUGSI" ], "offsets": [ [ 1356, 1361 ] ], "normalized": [] }, { "id": "10560", "type": "", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 1468, 1503 ] ], "normalized": [] }, { "id": "10562", "type": "", "text": [ "PUGSI" ], "offsets": [ [ 62, 67 ] ], "normalized": [] }, { "id": "10563", "type": "", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 93, 128 ] ], "normalized": [] }, { "id": "10565", "type": "", "text": [ "PUGSI" ], "offsets": [ [ 824, 829 ] ], "normalized": [] }, { "id": "10566", "type": "", "text": [ "obliterating subumbilical adhesions" ], "offsets": [ [ 740, 775 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10558", "type": "PA", "arg1_id": "10556", "arg2_id": "10557", "normalized": [] }, { "id": "10561", "type": "PA", "arg1_id": "10559", "arg2_id": "10560", "normalized": [] }, { "id": "10564", "type": "PA", "arg1_id": "10562", "arg2_id": "10563", "normalized": [] }, { "id": "10567", "type": "PA", "arg1_id": "10565", "arg2_id": "10566", "normalized": [] } ]

[ { "id": "10570", "type": "title", "text": [ "Secreted frizzled-related protein 4 regulates two Wnt7a signaling pathways and inhibits proliferation in endometrial cancer cells." ], "offsets": [ [ 0, 130 ] ] }, { "id": "10571", "type": "abstract", "text": [ "In the endometrium, hormonal effects on epithelial cells are often elicited through stromal hormone receptors via unknown paracrine mechanisms. Several lines of evidence support the hypothesis that Wnts participate in stromal-epithelial cell communication. Wnt7a is expressed in the luminal epithelium, whereas the extracellular modulator of Wnt signaling, secreted frizzled-related protein 4 (SFRP4), is localized to the stroma. Studies have reported that SFRP4 expression is significantly decreased in endometrial carcinoma and that both SFRP4 and Wnt7a genes are differentially regulated in response to estrogenic stimuli. Aberrant Wnt7a signaling irrevocably causes organ defects and infertility and contributes to the onset of disease. However, specific frizzled receptors (Fzd) that bind Wnt7a and the particular signal transduction pathway each Wnt7a-Fzd pair activates have not been identified. Additionally, the function of SFRP4 in the endometrium has not been addressed. We show here that Wnt7a coimmunoprecipitates with Fzd5, Fzd10, and SFRP4 in Ishikawa cells. Wnt7a binding to Fzd5 was shown to activate beta-catenin/canonical Wnt signaling and increase cellular proliferation. Conversely, Wnt7a signaling mediated by Fzd10 induced a noncanonical c-Jun NH2-terminal kinase-responsive pathway. SFRP4 suppresses activation of Wnt7a signaling in both an autocrine and paracrine manner. Stable overexpression of SFRP4 and treatment with recombinant SFRP4 protein inhibited endometrial cancer cell growth in vitro. These findings support a mechanism by which the nature of the Wnt7a signal in the endometrium is dependent on the Fzd repertoire of the cell and can be regulated by SFRP4." ], "offsets": [ [ 131, 1826 ] ] } ]

[ { "id": "10572", "type": "Genes & Molecular Sequences", "text": [ "Secreted frizzled-related protein 4" ], "offsets": [ [ 0, 35 ] ], "normalized": [] }, { "id": "10573", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 50, 55 ] ], "normalized": [] }, { "id": "10574", "type": "Genes & Molecular Sequences", "text": [ "Wnts" ], "offsets": [ [ 329, 333 ] ], "normalized": [] }, { "id": "10575", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 388, 393 ] ], "normalized": [] }, { "id": "10576", "type": "Chemicals & Drugs", "text": [ "luminal" ], "offsets": [ [ 414, 421 ] ], "normalized": [] }, { "id": "10577", "type": "Genes & Molecular Sequences", "text": [ "Wnt" ], "offsets": [ [ 473, 476 ] ], "normalized": [] }, { "id": "10578", "type": "Genes & Molecular Sequences", "text": [ "secreted frizzled-related protein 4" ], "offsets": [ [ 488, 523 ] ], "normalized": [] }, { "id": "10579", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 525, 530 ] ], "normalized": [] }, { "id": "10580", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 588, 593 ] ], "normalized": [] }, { "id": "10581", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "10582", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 681, 686 ] ], "normalized": [] }, { "id": "10583", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 766, 771 ] ], "normalized": [] }, { "id": "10584", "type": "Genes & Molecular Sequences", "text": [ "specific frizzled receptors" ], "offsets": [ [ 881, 908 ] ], "normalized": [] }, { "id": "10585", "type": "Genes & Molecular Sequences", "text": [ "Fzd" ], "offsets": [ [ 910, 913 ] ], "normalized": [] }, { "id": "10586", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 925, 930 ] ], "normalized": [] }, { "id": "10587", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a-Fzd" ], "offsets": [ [ 983, 992 ] ], "normalized": [] }, { "id": "10588", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 1064, 1069 ] ], "normalized": [] }, { "id": "10589", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 1131, 1136 ] ], "normalized": [] }, { "id": "10590", "type": "Genes & Molecular Sequences", "text": [ "Fzd5" ], "offsets": [ [ 1163, 1167 ] ], "normalized": [] }, { "id": "10591", "type": "Genes & Molecular Sequences", "text": [ "Fzd10" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "10592", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 1180, 1185 ] ], "normalized": [] }, { "id": "10593", "type": "Genes & Molecular Sequences", "text": [ "Ishikawa cells" ], "offsets": [ [ 1189, 1203 ] ], "normalized": [] }, { "id": "10594", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 1205, 1210 ] ], "normalized": [] }, { "id": "10595", "type": "Genes & Molecular Sequences", "text": [ "Fzd5" ], "offsets": [ [ 1222, 1226 ] ], "normalized": [] }, { "id": "10596", "type": "Genes & Molecular Sequences", "text": [ "beta-catenin" ], "offsets": [ [ 1249, 1261 ] ], "normalized": [] }, { "id": "10597", "type": "Genes & Molecular Sequences", "text": [ "Wnt" ], "offsets": [ [ 1272, 1275 ] ], "normalized": [] }, { "id": "10598", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 1335, 1340 ] ], "normalized": [] }, { "id": "10599", "type": "Genes & Molecular Sequences", "text": [ "Fzd10" ], "offsets": [ [ 1363, 1368 ] ], "normalized": [] }, { "id": "10600", "type": "Genes & Molecular Sequences", "text": [ "c-Jun" ], "offsets": [ [ 1392, 1397 ] ], "normalized": [] }, { "id": "10601", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 1438, 1443 ] ], "normalized": [] }, { "id": "10602", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 1469, 1474 ] ], "normalized": [] }, { "id": "10603", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 1553, 1558 ] ], "normalized": [] }, { "id": "10604", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 1590, 1595 ] ], "normalized": [] }, { "id": "10605", "type": "Genes & Molecular Sequences", "text": [ "Wnt7a" ], "offsets": [ [ 1717, 1722 ] ], "normalized": [] }, { "id": "10606", "type": "Genes & Molecular Sequences", "text": [ "Fzd" ], "offsets": [ [ 1769, 1772 ] ], "normalized": [] }, { "id": "10607", "type": "Genes & Molecular Sequences", "text": [ "SFRP4" ], "offsets": [ [ 1820, 1825 ] ], "normalized": [] }, { "id": "10608", "type": "", "text": [ "luminal" ], "offsets": [ [ 414, 421 ] ], "normalized": [] }, { "id": "10609", "type": "", "text": [ "SFRP4" ], "offsets": [ [ 525, 530 ] ], "normalized": [] }, { "id": "10611", "type": "", "text": [ "luminal" ], "offsets": [ [ 414, 421 ] ], "normalized": [] }, { "id": "10612", "type": "", "text": [ "Wnt7a" ], "offsets": [ [ 388, 393 ] ], "normalized": [] }, { "id": "10614", "type": "", "text": [ "Secreted frizzled-related protein 4" ], "offsets": [ [ 0, 35 ] ], "normalized": [] }, { "id": "10615", "type": "", "text": [ "endometrial cancer" ], "offsets": [ [ 105, 123 ] ], "normalized": [] }, { "id": "10617", "type": "", "text": [ "Wnt7a" ], "offsets": [ [ 50, 55 ] ], "normalized": [] }, { "id": "10618", "type": "", "text": [ "endometrial cancer" ], "offsets": [ [ 105, 123 ] ], "normalized": [] }, { "id": "10620", "type": "", "text": [ "SFRP4" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "10621", "type": "", "text": [ "endometrial carcinoma" ], "offsets": [ [ 635, 656 ] ], "normalized": [] }, { "id": "10623", "type": "", "text": [ "Wnt7a" ], "offsets": [ [ 681, 686 ] ], "normalized": [] }, { "id": "10624", "type": "", "text": [ "endometrial carcinoma" ], "offsets": [ [ 635, 656 ] ], "normalized": [] }, { "id": "10626", "type": "", "text": [ "Wnt7a" ], "offsets": [ [ 766, 771 ] ], "normalized": [] }, { "id": "10627", "type": "", "text": [ "infertility" ], "offsets": [ [ 819, 830 ] ], "normalized": [] }, { "id": "10629", "type": "", "text": [ "Wnt7a" ], "offsets": [ [ 766, 771 ] ], "normalized": [] }, { "id": "10630", "type": "", "text": [ "organ defects" ], "offsets": [ [ 801, 814 ] ], "normalized": [] }, { "id": "10632", "type": "", "text": [ "Wnt7a" ], "offsets": [ [ 1205, 1210 ] ], "normalized": [] }, { "id": "10633", "type": "", "text": [ "cellular proliferation" ], "offsets": [ [ 1299, 1321 ] ], "normalized": [] }, { "id": "10635", "type": "", "text": [ "Fzd5" ], "offsets": [ [ 1222, 1226 ] ], "normalized": [] }, { "id": "10636", "type": "", "text": [ "cellular proliferation" ], "offsets": [ [ 1299, 1321 ] ], "normalized": [] }, { "id": "10638", "type": "", "text": [ "beta-catenin" ], "offsets": [ [ 1249, 1261 ] ], "normalized": [] }, { "id": "10639", "type": "", "text": [ "cellular proliferation" ], "offsets": [ [ 1299, 1321 ] ], "normalized": [] }, { "id": "10641", "type": "", "text": [ "SFRP4" ], "offsets": [ [ 1590, 1595 ] ], "normalized": [] }, { "id": "10642", "type": "", "text": [ "cancer cell growth" ], "offsets": [ [ 1626, 1644 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10610", "type": "PA", "arg1_id": "10608", "arg2_id": "10609", "normalized": [] }, { "id": "10613", "type": "PA", "arg1_id": "10611", "arg2_id": "10612", "normalized": [] }, { "id": "10616", "type": "PA", "arg1_id": "10614", "arg2_id": "10615", "normalized": [] }, { "id": "10619", "type": "PA", "arg1_id": "10617", "arg2_id": "10618", "normalized": [] }, { "id": "10622", "type": "PA", "arg1_id": "10620", "arg2_id": "10621", "normalized": [] }, { "id": "10625", "type": "PA", "arg1_id": "10623", "arg2_id": "10624", "normalized": [] }, { "id": "10628", "type": "PA", "arg1_id": "10626", "arg2_id": "10627", "normalized": [] }, { "id": "10631", "type": "PA", "arg1_id": "10629", "arg2_id": "10630", "normalized": [] }, { "id": "10634", "type": "PA", "arg1_id": "10632", "arg2_id": "10633", "normalized": [] }, { "id": "10637", "type": "PA", "arg1_id": "10635", "arg2_id": "10636", "normalized": [] }, { "id": "10640", "type": "PA", "arg1_id": "10638", "arg2_id": "10639", "normalized": [] }, { "id": "10643", "type": "PA", "arg1_id": "10641", "arg2_id": "10642", "normalized": [] } ]

[ { "id": "10646", "type": "title", "text": [ "Novel iminobenzoxathiolone compound inhibits nuclear factor-kappaB activation targeting inhibitory kappaB kinase beta and down-regulating interleukin-1beta expression in lipopolysaccharide-activated macrophages." ], "offsets": [ [ 0, 211 ] ] }, { "id": "10647", "type": "abstract", "text": [ "Benzoxathiolone derivatives have been reported to show pharmacological potentials in the psoriasis and acne. However, molecular basis for these pharmacological properties is little known. We postulated that the derivatives could mediate some of their pharmacological actions by modulating nuclear factor (NF)-kappaB activation, which is closely linked to the inflammatory and immune disorders. In this study, a novel iminobenzoxathiolone LYR-71 of 6-methyl-2-propylimino-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one has been demonstrated to inhibit in vitro catalytic activity of inhibitory kappaB (IkappaB) kinase beta (IKKbeta), a key enzyme required for NF-kappaB activation, with an IC(50) value of 7 microM. LYR-71 inhibited IKKbeta-mediated phosphorylation of cytoplasmic IkappaBalpha in lipopolysaccharide (LPS)-activated macrophages, and sequentially preventing IkappaBalpha degradation as well as transcriptional activation of NF-kappaB. Furthermore, LYR-71 down-regulated LPS-induced transcription of interleukin (IL)-1beta or other cytokines in the cells, and inhibited expression vector IKKbeta-elicited IL-1beta promoter activity. Taken together, LYR-71 was an efficient inhibitor of IKKbeta, preventing NF-kappaB activation in macrophages, and this mechanism of action could contribute its down-regulatory effect on LPS-induced expression of inflammatory cytokines at the transcription level." ], "offsets": [ [ 212, 1613 ] ] } ]

[ { "id": "10648", "type": "Chemicals & Drugs", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 6, 26 ] ], "normalized": [] }, { "id": "10649", "type": "Genes & Molecular Sequences", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 45, 66 ] ], "normalized": [] }, { "id": "10650", "type": "Genes & Molecular Sequences", "text": [ "inhibitory kappaB" ], "offsets": [ [ 88, 105 ] ], "normalized": [] }, { "id": "10651", "type": "Genes & Molecular Sequences", "text": [ "interleukin-1beta" ], "offsets": [ [ 138, 155 ] ], "normalized": [] }, { "id": "10652", "type": "Chemicals & Drugs", "text": [ "lipopolysaccharide" ], "offsets": [ [ 170, 188 ] ], "normalized": [] }, { "id": "10653", "type": "Genes & Molecular Sequences", "text": [ "lipopolysaccharide" ], "offsets": [ [ 170, 188 ] ], "normalized": [] }, { "id": "10654", "type": "Chemicals & Drugs", "text": [ "Benzoxathiolone derivatives" ], "offsets": [ [ 212, 239 ] ], "normalized": [] }, { "id": "10655", "type": "Genes & Molecular Sequences", "text": [ "nuclear factor" ], "offsets": [ [ 501, 515 ] ], "normalized": [] }, { "id": "10656", "type": "Genes & Molecular Sequences", "text": [ "NF)-kappaB" ], "offsets": [ [ 517, 527 ] ], "normalized": [] }, { "id": "10657", "type": "Chemicals & Drugs", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 629, 649 ] ], "normalized": [] }, { "id": "10658", "type": "Chemicals & Drugs", "text": [ "LYR-71" ], "offsets": [ [ 650, 656 ] ], "normalized": [] }, { "id": "10659", "type": "Chemicals & Drugs", "text": [ "6-methyl-2-propylimino-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one" ], "offsets": [ [ 660, 722 ] ], "normalized": [] }, { "id": "10660", "type": "Genes & Molecular Sequences", "text": [ "inhibitory kappaB" ], "offsets": [ [ 787, 804 ] ], "normalized": [] }, { "id": "10661", "type": "Genes & Molecular Sequences", "text": [ "IkappaB) kinase beta" ], "offsets": [ [ 806, 826 ] ], "normalized": [] }, { "id": "10662", "type": "Genes & Molecular Sequences", "text": [ "IKKbeta" ], "offsets": [ [ 828, 835 ] ], "normalized": [] }, { "id": "10663", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 864, 873 ] ], "normalized": [] }, { "id": "10664", "type": "Chemicals & Drugs", "text": [ "LYR-71" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "10665", "type": "Genes & Molecular Sequences", "text": [ "IKKbeta" ], "offsets": [ [ 937, 944 ] ], "normalized": [] }, { "id": "10666", "type": "Genes & Molecular Sequences", "text": [ "IkappaBalpha" ], "offsets": [ [ 985, 997 ] ], "normalized": [] }, { "id": "10667", "type": "Chemicals & Drugs", "text": [ "lipopolysaccharide" ], "offsets": [ [ 1001, 1019 ] ], "normalized": [] }, { "id": "10668", "type": "Chemicals & Drugs", "text": [ "LPS" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "10669", "type": "Genes & Molecular Sequences", "text": [ "LPS" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "10670", "type": "Genes & Molecular Sequences", "text": [ "IkappaBalpha" ], "offsets": [ [ 1077, 1089 ] ], "normalized": [] }, { "id": "10671", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 1143, 1152 ] ], "normalized": [] }, { "id": "10672", "type": "Chemicals & Drugs", "text": [ "LYR-71" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "10673", "type": "Genes & Molecular Sequences", "text": [ "LPS" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [] }, { "id": "10674", "type": "Chemicals & Drugs", "text": [ "LPS" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [] }, { "id": "10675", "type": "Genes & Molecular Sequences", "text": [ "interleukin" ], "offsets": [ [ 1218, 1229 ] ], "normalized": [] }, { "id": "10676", "type": "Genes & Molecular Sequences", "text": [ "IL)-1beta" ], "offsets": [ [ 1231, 1240 ] ], "normalized": [] }, { "id": "10677", "type": "Genes & Molecular Sequences", "text": [ "cytokines" ], "offsets": [ [ 1250, 1259 ] ], "normalized": [] }, { "id": "10678", "type": "Genes & Molecular Sequences", "text": [ "IKKbeta" ], "offsets": [ [ 1306, 1313 ] ], "normalized": [] }, { "id": "10679", "type": "Genes & Molecular Sequences", "text": [ "IL-1beta" ], "offsets": [ [ 1323, 1331 ] ], "normalized": [] }, { "id": "10680", "type": "Chemicals & Drugs", "text": [ "LYR-71" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "10681", "type": "Genes & Molecular Sequences", "text": [ "IKKbeta" ], "offsets": [ [ 1404, 1411 ] ], "normalized": [] }, { "id": "10682", "type": "Genes & Molecular Sequences", "text": [ "NF-kappaB" ], "offsets": [ [ 1424, 1433 ] ], "normalized": [] }, { "id": "10683", "type": "Genes & Molecular Sequences", "text": [ "LPS" ], "offsets": [ [ 1537, 1540 ] ], "normalized": [] }, { "id": "10684", "type": "Chemicals & Drugs", "text": [ "LPS" ], "offsets": [ [ 1537, 1540 ] ], "normalized": [] }, { "id": "10685", "type": "Genes & Molecular Sequences", "text": [ "inflammatory cytokines" ], "offsets": [ [ 1563, 1585 ] ], "normalized": [] }, { "id": "10686", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 6, 26 ] ], "normalized": [] }, { "id": "10687", "type": "", "text": [ "inhibitory kappaB" ], "offsets": [ [ 88, 105 ] ], "normalized": [] }, { "id": "10689", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 650, 656 ] ], "normalized": [] }, { "id": "10690", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 864, 873 ] ], "normalized": [] }, { "id": "10692", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 650, 656 ] ], "normalized": [] }, { "id": "10693", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 828, 835 ] ], "normalized": [] }, { "id": "10695", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 650, 656 ] ], "normalized": [] }, { "id": "10696", "type": "", "text": [ "inhibitory kappaB" ], "offsets": [ [ 787, 804 ] ], "normalized": [] }, { "id": "10698", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 650, 656 ] ], "normalized": [] }, { "id": "10699", "type": "", "text": [ "IkappaB) kinase beta" ], "offsets": [ [ 806, 826 ] ], "normalized": [] }, { "id": "10701", "type": "", "text": [ "6-methyl-2-propylimino-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one" ], "offsets": [ [ 660, 722 ] ], "normalized": [] }, { "id": "10702", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 864, 873 ] ], "normalized": [] }, { "id": "10704", "type": "", "text": [ "6-methyl-2-propylimino-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one" ], "offsets": [ [ 660, 722 ] ], "normalized": [] }, { "id": "10705", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 828, 835 ] ], "normalized": [] }, { "id": "10707", "type": "", "text": [ "6-methyl-2-propylimino-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one" ], "offsets": [ [ 660, 722 ] ], "normalized": [] }, { "id": "10708", "type": "", "text": [ "inhibitory kappaB" ], "offsets": [ [ 787, 804 ] ], "normalized": [] }, { "id": "10710", "type": "", "text": [ "6-methyl-2-propylimino-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one" ], "offsets": [ [ 660, 722 ] ], "normalized": [] }, { "id": "10711", "type": "", "text": [ "IkappaB) kinase beta" ], "offsets": [ [ 806, 826 ] ], "normalized": [] }, { "id": "10713", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "10714", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 1143, 1152 ] ], "normalized": [] }, { "id": "10716", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "10717", "type": "", "text": [ "IkappaBalpha" ], "offsets": [ [ 1077, 1089 ] ], "normalized": [] }, { "id": "10719", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "10720", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 937, 944 ] ], "normalized": [] }, { "id": "10722", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "10723", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 1323, 1331 ] ], "normalized": [] }, { "id": "10725", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "10726", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 1306, 1313 ] ], "normalized": [] }, { "id": "10728", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "10729", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 1424, 1433 ] ], "normalized": [] }, { "id": "10731", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "10732", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 1404, 1411 ] ], "normalized": [] }, { "id": "10734", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "10735", "type": "", "text": [ "inflammatory cytokines" ], "offsets": [ [ 1563, 1585 ] ], "normalized": [] }, { "id": "10737", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 6, 26 ] ], "normalized": [] }, { "id": "10738", "type": "", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 45, 66 ] ], "normalized": [] }, { "id": "10740", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 6, 26 ] ], "normalized": [] }, { "id": "10741", "type": "", "text": [ "interleukin-1beta" ], "offsets": [ [ 138, 155 ] ], "normalized": [] }, { "id": "10743", "type": "", "text": [ "lipopolysaccharide" ], "offsets": [ [ 170, 188 ] ], "normalized": [] }, { "id": "10744", "type": "", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 45, 66 ] ], "normalized": [] }, { "id": "10746", "type": "", "text": [ "lipopolysaccharide" ], "offsets": [ [ 170, 188 ] ], "normalized": [] }, { "id": "10747", "type": "", "text": [ "inhibitory kappaB" ], "offsets": [ [ 88, 105 ] ], "normalized": [] }, { "id": "10749", "type": "", "text": [ "lipopolysaccharide" ], "offsets": [ [ 170, 188 ] ], "normalized": [] }, { "id": "10750", "type": "", "text": [ "interleukin-1beta" ], "offsets": [ [ 138, 155 ] ], "normalized": [] }, { "id": "10752", "type": "", "text": [ "Benzoxathiolone derivatives" ], "offsets": [ [ 212, 239 ] ], "normalized": [] }, { "id": "10753", "type": "", "text": [ "psoriasis" ], "offsets": [ [ 301, 310 ] ], "normalized": [] }, { "id": "10755", "type": "", "text": [ "Benzoxathiolone derivatives" ], "offsets": [ [ 212, 239 ] ], "normalized": [] }, { "id": "10756", "type": "", "text": [ "acne" ], "offsets": [ [ 315, 319 ] ], "normalized": [] }, { "id": "10758", "type": "", "text": [ "NF)-kappaB" ], "offsets": [ [ 517, 527 ] ], "normalized": [] }, { "id": "10759", "type": "", "text": [ "immune disorders" ], "offsets": [ [ 588, 604 ] ], "normalized": [] }, { "id": "10761", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 629, 649 ] ], "normalized": [] }, { "id": "10762", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 864, 873 ] ], "normalized": [] }, { "id": "10764", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 629, 649 ] ], "normalized": [] }, { "id": "10765", "type": "", "text": [ "IkappaB) kinase beta" ], "offsets": [ [ 806, 826 ] ], "normalized": [] }, { "id": "10767", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 629, 649 ] ], "normalized": [] }, { "id": "10768", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 828, 835 ] ], "normalized": [] }, { "id": "10770", "type": "", "text": [ "lipopolysaccharide" ], "offsets": [ [ 1001, 1019 ] ], "normalized": [] }, { "id": "10771", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 1143, 1152 ] ], "normalized": [] }, { "id": "10773", "type": "", "text": [ "lipopolysaccharide" ], "offsets": [ [ 1001, 1019 ] ], "normalized": [] }, { "id": "10774", "type": "", "text": [ "IkappaBalpha" ], "offsets": [ [ 1077, 1089 ] ], "normalized": [] }, { "id": "10776", "type": "", "text": [ "lipopolysaccharide" ], "offsets": [ [ 1001, 1019 ] ], "normalized": [] }, { "id": "10777", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 937, 944 ] ], "normalized": [] }, { "id": "10779", "type": "", "text": [ "LPS" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "10780", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 1143, 1152 ] ], "normalized": [] }, { "id": "10782", "type": "", "text": [ "LPS" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "10783", "type": "", "text": [ "IkappaBalpha" ], "offsets": [ [ 1077, 1089 ] ], "normalized": [] }, { "id": "10785", "type": "", "text": [ "LPS" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "10786", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 937, 944 ] ], "normalized": [] }, { "id": "10788", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "10789", "type": "", "text": [ "cytokines" ], "offsets": [ [ 1250, 1259 ] ], "normalized": [] }, { "id": "10791", "type": "", "text": [ "LPS" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [] }, { "id": "10792", "type": "", "text": [ "IL-1beta" ], "offsets": [ [ 1323, 1331 ] ], "normalized": [] }, { "id": "10794", "type": "", "text": [ "LPS" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [] }, { "id": "10795", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 1306, 1313 ] ], "normalized": [] }, { "id": "10797", "type": "", "text": [ "LPS" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [] }, { "id": "10798", "type": "", "text": [ "cytokines" ], "offsets": [ [ 1250, 1259 ] ], "normalized": [] }, { "id": "10800", "type": "", "text": [ "LPS" ], "offsets": [ [ 1537, 1540 ] ], "normalized": [] }, { "id": "10801", "type": "", "text": [ "NF-kappaB" ], "offsets": [ [ 1424, 1433 ] ], "normalized": [] }, { "id": "10803", "type": "", "text": [ "LPS" ], "offsets": [ [ 1537, 1540 ] ], "normalized": [] }, { "id": "10804", "type": "", "text": [ "IKKbeta" ], "offsets": [ [ 1404, 1411 ] ], "normalized": [] }, { "id": "10806", "type": "", "text": [ "LPS" ], "offsets": [ [ 1537, 1540 ] ], "normalized": [] }, { "id": "10807", "type": "", "text": [ "inflammatory cytokines" ], "offsets": [ [ 1563, 1585 ] ], "normalized": [] }, { "id": "10809", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 6, 26 ] ], "normalized": [] }, { "id": "10810", "type": "", "text": [ "lipopolysaccharide" ], "offsets": [ [ 170, 188 ] ], "normalized": [] }, { "id": "10812", "type": "", "text": [ "iminobenzoxathiolone" ], "offsets": [ [ 629, 649 ] ], "normalized": [] }, { "id": "10813", "type": "", "text": [ "inhibitory kappaB" ], "offsets": [ [ 787, 804 ] ], "normalized": [] }, { "id": "10815", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "10816", "type": "", "text": [ "LPS" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] }, { "id": "10818", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "10819", "type": "", "text": [ "IL)-1beta" ], "offsets": [ [ 1231, 1240 ] ], "normalized": [] }, { "id": "10821", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "10822", "type": "", "text": [ "LPS" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [] }, { "id": "10824", "type": "", "text": [ "LYR-71" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "10825", "type": "", "text": [ "LPS" ], "offsets": [ [ 1537, 1540 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "10829", "type": "title", "text": [ "A comparative intervention trial on fish sauce fortified with NaFe-EDTA and FeSO4+citrate in iron deficiency anemic school children in Kampot, Cambodia." ], "offsets": [ [ 0, 152 ] ] }, { "id": "10830", "type": "abstract", "text": [ "BACKGROUND: Inhabitants of agrarian villages of rural Cambodia suffer from high prevalences of iron deficiency and anemia in the context of a monotonous diet. OBJECTIVE: To compare the efficacy and safety of placebo Khmer fish sauce to that of 10 mL of fish sauce containing 10 mg of iron, added to daily school meals either as NaFe-EDTA or as FeSO4+ citrate. METHODS: 140 students aged 6-21 years were enrolled in a double-blinded, placebo-controlled intervention trial. They were randomly allocated to one of three treatment groups, and followed for 21 weeks during which 114 school meals seasoned with 10 mL of fish sauce were consumed by each participant. Changes in the concentrations of hemoglobin (hb), serum ferritin (SF), and C-reactive protein (CRP) and in body weight and standing height were determined. Prevalences of vomiting, diarrhea, and acute respiratory infections were monitored weekly. RESULTS: Both iron-fortified fish sauces increased hb and SF concentrations significantly as compared to placebo. No significant differences were observed between FeSO4+citrate and NaFe-EDTA fortification, regarding mitigation of iron-deficiency anemia (IDA) or regarding CRP, growth, infections, or side-effects. CONCLUSIONS: Iron-fortified Khmer fish sauce added to Khmer food is a suitable vehicle for iron fortification in children and adolescents. FeSO4+citrate and NaFe-EDTA show equivalent efficacy and safety." ], "offsets": [ [ 153, 1577 ] ] } ]

[ { "id": "10831", "type": "Chemicals & Drugs", "text": [ "fish sauce" ], "offsets": [ [ 36, 46 ] ], "normalized": [] }, { "id": "10832", "type": "Chemicals & Drugs", "text": [ "NaFe-EDTA" ], "offsets": [ [ 62, 71 ] ], "normalized": [] }, { "id": "10833", "type": "Chemicals & Drugs", "text": [ "FeSO4" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "10834", "type": "Chemicals & Drugs", "text": [ "citrate" ], "offsets": [ [ 82, 89 ] ], "normalized": [] }, { "id": "10835", "type": "Diseases & Disorders", "text": [ "iron deficiency" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "10836", "type": "Diseases & Disorders", "text": [ "anemic" ], "offsets": [ [ 109, 115 ] ], "normalized": [] }, { "id": "10837", "type": "Diseases & Disorders", "text": [ "suffer" ], "offsets": [ [ 216, 222 ] ], "normalized": [] }, { "id": "10838", "type": "Diseases & Disorders", "text": [ "iron deficiency" ], "offsets": [ [ 248, 263 ] ], "normalized": [] }, { "id": "10839", "type": "Diseases & Disorders", "text": [ "anemia" ], "offsets": [ [ 268, 274 ] ], "normalized": [] }, { "id": "10840", "type": "Chemicals & Drugs", "text": [ "fish sauce" ], "offsets": [ [ 375, 385 ] ], "normalized": [] }, { "id": "10841", "type": "Chemicals & Drugs", "text": [ "fish sauce" ], "offsets": [ [ 406, 416 ] ], "normalized": [] }, { "id": "10842", "type": "Chemicals & Drugs", "text": [ "NaFe-EDTA" ], "offsets": [ [ 481, 490 ] ], "normalized": [] }, { "id": "10843", "type": "Chemicals & Drugs", "text": [ "FeSO4" ], "offsets": [ [ 497, 502 ] ], "normalized": [] }, { "id": "10844", "type": "Chemicals & Drugs", "text": [ "citrate" ], "offsets": [ [ 504, 511 ] ], "normalized": [] }, { "id": "10845", "type": "Chemicals & Drugs", "text": [ "fish sauce" ], "offsets": [ [ 767, 777 ] ], "normalized": [] }, { "id": "10846", "type": "Diseases & Disorders", "text": [ "weight" ], "offsets": [ [ 925, 931 ] ], "normalized": [] }, { "id": "10847", "type": "Diseases & Disorders", "text": [ "vomiting" ], "offsets": [ [ 984, 992 ] ], "normalized": [] }, { "id": "10848", "type": "Diseases & Disorders", "text": [ "diarrhea" ], "offsets": [ [ 994, 1002 ] ], "normalized": [] }, { "id": "10849", "type": "Diseases & Disorders", "text": [ "acute respiratory infections" ], "offsets": [ [ 1008, 1036 ] ], "normalized": [] }, { "id": "10850", "type": "Chemicals & Drugs", "text": [ "iron-fortified fish sauces" ], "offsets": [ [ 1074, 1100 ] ], "normalized": [] }, { "id": "10851", "type": "Chemicals & Drugs", "text": [ "FeSO4" ], "offsets": [ [ 1223, 1228 ] ], "normalized": [] }, { "id": "10852", "type": "Chemicals & Drugs", "text": [ "citrate" ], "offsets": [ [ 1229, 1236 ] ], "normalized": [] }, { "id": "10853", "type": "Chemicals & Drugs", "text": [ "NaFe-EDTA" ], "offsets": [ [ 1241, 1250 ] ], "normalized": [] }, { "id": "10854", "type": "Diseases & Disorders", "text": [ "iron-deficiency anemia" ], "offsets": [ [ 1290, 1312 ] ], "normalized": [] }, { "id": "10855", "type": "Diseases & Disorders", "text": [ "IDA" ], "offsets": [ [ 1314, 1317 ] ], "normalized": [] }, { "id": "10856", "type": "Chemicals & Drugs", "text": [ "IDA" ], "offsets": [ [ 1314, 1317 ] ], "normalized": [] }, { "id": "10857", "type": "Diseases & Disorders", "text": [ "infections" ], "offsets": [ [ 1345, 1355 ] ], "normalized": [] }, { "id": "10858", "type": "Diseases & Disorders", "text": [ "side-effects" ], "offsets": [ [ 1360, 1372 ] ], "normalized": [] }, { "id": "10859", "type": "Chemicals & Drugs", "text": [ "fish sauce" ], "offsets": [ [ 1408, 1418 ] ], "normalized": [] }, { "id": "10860", "type": "Chemicals & Drugs", "text": [ "FeSO4" ], "offsets": [ [ 1513, 1518 ] ], "normalized": [] }, { "id": "10861", "type": "Chemicals & Drugs", "text": [ "citrate" ], "offsets": [ [ 1519, 1526 ] ], "normalized": [] }, { "id": "10862", "type": "Chemicals & Drugs", "text": [ "NaFe-EDTA" ], "offsets": [ [ 1531, 1540 ] ], "normalized": [] }, { "id": "10863", "type": "", "text": [ "FeSO4" ], "offsets": [ [ 1223, 1228 ] ], "normalized": [] }, { "id": "10864", "type": "", "text": [ "infections" ], "offsets": [ [ 1345, 1355 ] ], "normalized": [] }, { "id": "10866", "type": "", "text": [ "FeSO4" ], "offsets": [ [ 1223, 1228 ] ], "normalized": [] }, { "id": "10867", "type": "", "text": [ "iron-deficiency anemia" ], "offsets": [ [ 1290, 1312 ] ], "normalized": [] }, { "id": "10869", "type": "", "text": [ "NaFe-EDTA" ], "offsets": [ [ 1241, 1250 ] ], "normalized": [] }, { "id": "10870", "type": "", "text": [ "infections" ], "offsets": [ [ 1345, 1355 ] ], "normalized": [] }, { "id": "10872", "type": "", "text": [ "NaFe-EDTA" ], "offsets": [ [ 1241, 1250 ] ], "normalized": [] }, { "id": "10873", "type": "", "text": [ "iron-deficiency anemia" ], "offsets": [ [ 1290, 1312 ] ], "normalized": [] }, { "id": "10875", "type": "", "text": [ "citrate" ], "offsets": [ [ 1229, 1236 ] ], "normalized": [] }, { "id": "10876", "type": "", "text": [ "infections" ], "offsets": [ [ 1345, 1355 ] ], "normalized": [] }, { "id": "10878", "type": "", "text": [ "citrate" ], "offsets": [ [ 1229, 1236 ] ], "normalized": [] }, { "id": "10879", "type": "", "text": [ "iron-deficiency anemia" ], "offsets": [ [ 1290, 1312 ] ], "normalized": [] }, { "id": "10881", "type": "", "text": [ "fish sauce" ], "offsets": [ [ 36, 46 ] ], "normalized": [] }, { "id": "10882", "type": "", "text": [ "iron deficiency" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "10884", "type": "", "text": [ "NaFe-EDTA" ], "offsets": [ [ 62, 71 ] ], "normalized": [] }, { "id": "10885", "type": "", "text": [ "anemic" ], "offsets": [ [ 109, 115 ] ], "normalized": [] }, { "id": "10887", "type": "", "text": [ "NaFe-EDTA" ], "offsets": [ [ 62, 71 ] ], "normalized": [] }, { "id": "10888", "type": "", "text": [ "iron deficiency" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "10890", "type": "", "text": [ "FeSO4" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "10891", "type": "", "text": [ "anemic" ], "offsets": [ [ 109, 115 ] ], "normalized": [] }, { "id": "10893", "type": "", "text": [ "FeSO4" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "10894", "type": "", "text": [ "iron deficiency" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "10896", "type": "", "text": [ "NaFe-EDTA" ], "offsets": [ [ 1241, 1250 ] ], "normalized": [] }, { "id": "10897", "type": "", "text": [ "IDA" ], "offsets": [ [ 1314, 1317 ] ], "normalized": [] }, { "id": "10899", "type": "", "text": [ "FeSO4" ], "offsets": [ [ 1223, 1228 ] ], "normalized": [] }, { "id": "10900", "type": "", "text": [ "IDA" ], "offsets": [ [ 1314, 1317 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10865", "type": "NA", "arg1_id": "10863", "arg2_id": "10864", "normalized": [] }, { "id": "10868", "type": "NA", "arg1_id": "10866", "arg2_id": "10867", "normalized": [] }, { "id": "10871", "type": "NA", "arg1_id": "10869", "arg2_id": "10870", "normalized": [] }, { "id": "10874", "type": "NA", "arg1_id": "10872", "arg2_id": "10873", "normalized": [] }, { "id": "10877", "type": "NA", "arg1_id": "10875", "arg2_id": "10876", "normalized": [] }, { "id": "10880", "type": "NA", "arg1_id": "10878", "arg2_id": "10879", "normalized": [] }, { "id": "10883", "type": "PA", "arg1_id": "10881", "arg2_id": "10882", "normalized": [] }, { "id": "10886", "type": "PA", "arg1_id": "10884", "arg2_id": "10885", "normalized": [] }, { "id": "10889", "type": "PA", "arg1_id": "10887", "arg2_id": "10888", "normalized": [] }, { "id": "10892", "type": "PA", "arg1_id": "10890", "arg2_id": "10891", "normalized": [] }, { "id": "10895", "type": "PA", "arg1_id": "10893", "arg2_id": "10894", "normalized": [] }, { "id": "10898", "type": "NA", "arg1_id": "10896", "arg2_id": "10897", "normalized": [] }, { "id": "10901", "type": "NA", "arg1_id": "10899", "arg2_id": "10900", "normalized": [] } ]

[ { "id": "10904", "type": "title", "text": [ "Inhibition of apoptosome formation by suppression of Hsp90beta phosphorylation in tyrosine kinase-induced leukemias." ], "offsets": [ [ 0, 116 ] ] }, { "id": "10905", "type": "abstract", "text": [ "Constitutively active tyrosine kinases promote leukemogenesis by increasing cell proliferation and inhibiting apoptosis. However, mechanisms underlying apoptotic inhibition have not been fully elucidated. In many settings, apoptosis occurs by mitochondrial cytochrome c release, which nucleates the Apaf-1/caspase-9 apoptosome. Here we report that the leukemogenic kinases, Bcr-Abl, FLT3/D835Y, and Tel-PDGFRbeta, all can inhibit apoptosome function. In cells expressing these kinases, the previously reported apoptosome inhibitor, Hsp90beta, bound strongly to Apaf-1, preventing cytochrome c-induced Apaf-1 oligomerization and caspase-9 recruitment. Hsp90beta interacted weakly with the apoptosome in untransformed cells. While Hsp90beta was phosphorylated at Ser 226/Ser 255 in untransformed cells, phosphorylation was absent in leukemic cells. Expression of mutant Hsp90beta (S226A/S255A), which mimics the hypophosphorylated form in leukemic cells, conferred resistance to cytochrome c-induced apoptosome activation in normal cells, reflecting enhanced binding of nonphosphorylatable Hsp90beta to Apaf-1. In Bcr-Abl-positive mouse bone marrow cells, nonphosphorylatable Hsp90beta expression conferred imatinib (Gleevec) resistance. These data provide an explanation for apoptosome inhibition by activated leukemogenic tyrosine kinases and suggest that alterations in Hsp90beta-apoptosome interactions may contribute to chemoresistance in leukemias." ], "offsets": [ [ 117, 1569 ] ] } ]

[ { "id": "10906", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta" ], "offsets": [ [ 53, 62 ] ], "normalized": [] }, { "id": "10907", "type": "Genes & Molecular Sequences", "text": [ "tyrosine kinases" ], "offsets": [ [ 139, 155 ] ], "normalized": [] }, { "id": "10908", "type": "Genes & Molecular Sequences", "text": [ "mitochondrial cytochrome c" ], "offsets": [ [ 360, 386 ] ], "normalized": [] }, { "id": "10909", "type": "Genes & Molecular Sequences", "text": [ "Apaf-1/caspase-9" ], "offsets": [ [ 416, 432 ] ], "normalized": [] }, { "id": "10910", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl" ], "offsets": [ [ 491, 498 ] ], "normalized": [] }, { "id": "10911", "type": "Genes & Molecular Sequences", "text": [ "FLT3/D835Y" ], "offsets": [ [ 500, 510 ] ], "normalized": [] }, { "id": "10912", "type": "SNP & Sequence variations", "text": [ "FLT3/D835Y" ], "offsets": [ [ 500, 510 ] ], "normalized": [] }, { "id": "10913", "type": "Genes & Molecular Sequences", "text": [ "Tel-PDGFRbeta" ], "offsets": [ [ 516, 529 ] ], "normalized": [] }, { "id": "10914", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta" ], "offsets": [ [ 649, 658 ] ], "normalized": [] }, { "id": "10915", "type": "Genes & Molecular Sequences", "text": [ "Apaf-1" ], "offsets": [ [ 678, 684 ] ], "normalized": [] }, { "id": "10916", "type": "Genes & Molecular Sequences", "text": [ "cytochrome c" ], "offsets": [ [ 697, 709 ] ], "normalized": [] }, { "id": "10917", "type": "Genes & Molecular Sequences", "text": [ "Apaf-1" ], "offsets": [ [ 718, 724 ] ], "normalized": [] }, { "id": "10918", "type": "Genes & Molecular Sequences", "text": [ "caspase-9" ], "offsets": [ [ 745, 754 ] ], "normalized": [] }, { "id": "10919", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta" ], "offsets": [ [ 768, 777 ] ], "normalized": [] }, { "id": "10920", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta" ], "offsets": [ [ 846, 855 ] ], "normalized": [] }, { "id": "10921", "type": "Genes & Molecular Sequences", "text": [ "Ser 226/Ser 255" ], "offsets": [ [ 878, 893 ] ], "normalized": [] }, { "id": "10922", "type": "Genes & Molecular Sequences", "text": [ "mutant" ], "offsets": [ [ 978, 984 ] ], "normalized": [] }, { "id": "10923", "type": "SNP & Sequence variations", "text": [ "Hsp90beta (S226A/S255A)" ], "offsets": [ [ 985, 1008 ] ], "normalized": [] }, { "id": "10924", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta (S226A/S255A)" ], "offsets": [ [ 985, 1008 ] ], "normalized": [] }, { "id": "10925", "type": "SNP & Sequence variations", "text": [ "S226A/S255A" ], "offsets": [ [ 996, 1007 ] ], "normalized": [] }, { "id": "10926", "type": "Genes & Molecular Sequences", "text": [ "S226A/S255A" ], "offsets": [ [ 996, 1007 ] ], "normalized": [] }, { "id": "10927", "type": "Genes & Molecular Sequences", "text": [ "cytochrome c" ], "offsets": [ [ 1094, 1106 ] ], "normalized": [] }, { "id": "10928", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta" ], "offsets": [ [ 1205, 1214 ] ], "normalized": [] }, { "id": "10929", "type": "Genes & Molecular Sequences", "text": [ "Apaf-1" ], "offsets": [ [ 1218, 1224 ] ], "normalized": [] }, { "id": "10930", "type": "Genes & Molecular Sequences", "text": [ "Bcr-Abl" ], "offsets": [ [ 1229, 1236 ] ], "normalized": [] }, { "id": "10931", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta" ], "offsets": [ [ 1291, 1300 ] ], "normalized": [] }, { "id": "10932", "type": "Chemicals & Drugs", "text": [ "imatinib" ], "offsets": [ [ 1322, 1330 ] ], "normalized": [] }, { "id": "10933", "type": "Chemicals & Drugs", "text": [ "Gleevec" ], "offsets": [ [ 1332, 1339 ] ], "normalized": [] }, { "id": "10934", "type": "Genes & Molecular Sequences", "text": [ "tyrosine kinases" ], "offsets": [ [ 1439, 1455 ] ], "normalized": [] }, { "id": "10935", "type": "Genes & Molecular Sequences", "text": [ "Hsp90beta" ], "offsets": [ [ 1488, 1497 ] ], "normalized": [] }, { "id": "10936", "type": "", "text": [ "Gleevec" ], "offsets": [ [ 1332, 1339 ] ], "normalized": [] }, { "id": "10937", "type": "", "text": [ "Bcr-Abl" ], "offsets": [ [ 1229, 1236 ] ], "normalized": [] }, { "id": "10939", "type": "", "text": [ "Gleevec" ], "offsets": [ [ 1332, 1339 ] ], "normalized": [] }, { "id": "10940", "type": "", "text": [ "Hsp90beta" ], "offsets": [ [ 1291, 1300 ] ], "normalized": [] }, { "id": "10942", "type": "", "text": [ "Hsp90beta" ], "offsets": [ [ 53, 62 ] ], "normalized": [] }, { "id": "10943", "type": "", "text": [ "leukemias" ], "offsets": [ [ 106, 115 ] ], "normalized": [] }, { "id": "10945", "type": "", "text": [ "Hsp90beta" ], "offsets": [ [ 1488, 1497 ] ], "normalized": [] }, { "id": "10946", "type": "", "text": [ "leukemias" ], "offsets": [ [ 1559, 1568 ] ], "normalized": [] }, { "id": "10948", "type": "", "text": [ "imatinib" ], "offsets": [ [ 1322, 1330 ] ], "normalized": [] }, { "id": "10949", "type": "", "text": [ "Hsp90beta" ], "offsets": [ [ 1291, 1300 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10938", "type": "PA", "arg1_id": "10936", "arg2_id": "10937", "normalized": [] }, { "id": "10941", "type": "PA", "arg1_id": "10939", "arg2_id": "10940", "normalized": [] }, { "id": "10944", "type": "PA", "arg1_id": "10942", "arg2_id": "10943", "normalized": [] }, { "id": "10947", "type": "PA", "arg1_id": "10945", "arg2_id": "10946", "normalized": [] }, { "id": "10950", "type": "PA", "arg1_id": "10948", "arg2_id": "10949", "normalized": [] } ]

[ { "id": "10953", "type": "title", "text": [ "Recurrent melanotic neuroectodermal tumor of infancy: a proposal for treatment protocol with surgery and adjuvant chemotherapy." ], "offsets": [ [ 0, 127 ] ] }, { "id": "10954", "type": "abstract", "text": [ "The case of a 4-month-old male infant treated with combined surgery and chemotherapy for an aggressive recurrent melanotic neuroectodermal tumor of infancy (MNTI) on the top of the alveolar process of the mandible with a long-term follow-up is presented. Initial treatment comprised conservative local excision and curettage of the mandible. After several local recurrences and because radical surgical excision would give gross functional and aesthetic mutilation, finally complete, long-lasting remission was achieved with adjuvant chemotherapy, according to a neuroblastoma protocol (10-year follow-up). The reason for this protocol was because molecular genetic studies of this tumor showed loss of heterozygosity of chromosome 1p and gain of chromosome 7q analogue to neuroblastomas. A combination of surgery and chemotherapy should be the preferred treatment in case of a recurrence MNTI because optimal functional and aesthetic outcome." ], "offsets": [ [ 128, 1071 ] ] } ]

[ { "id": "10955", "type": "Diseases & Disorders", "text": [ "Recurrent melanotic neuroectodermal tumor of infancy" ], "offsets": [ [ 0, 52 ] ], "normalized": [] }, { "id": "10956", "type": "Diseases & Disorders", "text": [ "aggressive" ], "offsets": [ [ 220, 230 ] ], "normalized": [] }, { "id": "10957", "type": "Diseases & Disorders", "text": [ "recurrent melanotic neuroectodermal tumor of infancy" ], "offsets": [ [ 231, 283 ] ], "normalized": [] }, { "id": "10958", "type": "Diseases & Disorders", "text": [ "MNTI" ], "offsets": [ [ 285, 289 ] ], "normalized": [] }, { "id": "10959", "type": "Diseases & Disorders", "text": [ "neuroblastoma" ], "offsets": [ [ 691, 704 ] ], "normalized": [] }, { "id": "10960", "type": "Diseases & Disorders", "text": [ "tumor" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "10961", "type": "SNP & Sequence variations", "text": [ "loss of heterozygosity of chromosome 1p" ], "offsets": [ [ 823, 862 ] ], "normalized": [] }, { "id": "10962", "type": "Genes & Molecular Sequences", "text": [ "loss of heterozygosity of chromosome 1p" ], "offsets": [ [ 823, 862 ] ], "normalized": [] }, { "id": "10963", "type": "SNP & Sequence variations", "text": [ "gain of chromosome 7q" ], "offsets": [ [ 867, 888 ] ], "normalized": [] }, { "id": "10964", "type": "Diseases & Disorders", "text": [ "gain of chromosome 7q" ], "offsets": [ [ 867, 888 ] ], "normalized": [] }, { "id": "10965", "type": "Genes & Molecular Sequences", "text": [ "gain of chromosome 7q" ], "offsets": [ [ 867, 888 ] ], "normalized": [] }, { "id": "10966", "type": "Diseases & Disorders", "text": [ "neuroblastomas" ], "offsets": [ [ 901, 915 ] ], "normalized": [] }, { "id": "10967", "type": "Diseases & Disorders", "text": [ "MNTI" ], "offsets": [ [ 1017, 1021 ] ], "normalized": [] }, { "id": "10968", "type": "", "text": [ "gain of chromosome 7q" ], "offsets": [ [ 867, 888 ] ], "normalized": [] }, { "id": "10969", "type": "", "text": [ "neuroblastomas" ], "offsets": [ [ 901, 915 ] ], "normalized": [] }, { "id": "10971", "type": "", "text": [ "gain of chromosome 7q" ], "offsets": [ [ 867, 888 ] ], "normalized": [] }, { "id": "10972", "type": "", "text": [ "tumor" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "10974", "type": "", "text": [ "loss of heterozygosity of chromosome 1p" ], "offsets": [ [ 823, 862 ] ], "normalized": [] }, { "id": "10975", "type": "", "text": [ "neuroblastomas" ], "offsets": [ [ 901, 915 ] ], "normalized": [] }, { "id": "10977", "type": "", "text": [ "loss of heterozygosity of chromosome 1p" ], "offsets": [ [ 823, 862 ] ], "normalized": [] }, { "id": "10978", "type": "", "text": [ "tumor" ], "offsets": [ [ 810, 815 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10970", "type": "PA", "arg1_id": "10968", "arg2_id": "10969", "normalized": [] }, { "id": "10973", "type": "PA", "arg1_id": "10971", "arg2_id": "10972", "normalized": [] }, { "id": "10976", "type": "PA", "arg1_id": "10974", "arg2_id": "10975", "normalized": [] }, { "id": "10979", "type": "PA", "arg1_id": "10977", "arg2_id": "10978", "normalized": [] } ]