id
stringlengths 1
5
| document_id
stringlengths 1
5
| passages
list | entities
list | events
list | coreferences
list | relations
list |
|---|---|---|---|---|---|---|
0 | 0 | [
{
"id": "1",
"type": "title",
"text": [
"A sequential procedure for monitoring clinical trials against historical controls."
],
"offsets": [
[
0,
82
]
]
},
{
"id": "2",
"type": "abstract",
"text": [
"In this paper, we develop a sequential procedure to monitor clinical trials against historical controls. When there is a strong ethical concern about randomizing patients to existing treatment because biological and medical evidence suggests that the new treatment is potentially superior to the existing one, or when the enrollment is too limited for randomization of subjects into experimental and control groups, one can monitor the trial sequentially against historical controls if the historical data with required quality and sample size are available to form a valid reference for the trial. This design of trial is sometimes the only alternative to a randomized phase III trial design that is intended but not feasible in situations such as above. Monitoring this type of clinical trial leads to a statistical problem of comparing two population means in a situation in which data from one population are sequentially collected and compared with all data from the other population at each interim look. The proposed sequential procedures is based on the sequential conditional probability ratio test (SCPRT) by which the conclusion of the sequential test would be virtually the same as that arrived at by a non-sequential test based on all data at the planned end of the trial. We develop the sequential procedure by proposing a Brownian motion that emulates the test statistic, and then proposing an SCPRT that is adapted to the special properties of the trial.CI - Copyright (c) 2006 John Wiley & Sons, Ltd."
],
"offsets": [
[
83,
1600
]
]
}
] | [] | [] | [] | [] |
4 | 4 | [
{
"id": "5",
"type": "title",
"text": [
"Prevention of early postoperative seizures in patients with primary brain tumors: preliminary experience with oxcarbazepine."
],
"offsets": [
[
0,
124
]
]
},
{
"id": "6",
"type": "abstract",
"text": [
"Early postoperative seizures are defined as those that appear within the first week after surgery and are a well-known and feared complication in patients with supratentorial brain tumors. Few studies have investigated the value of pharmacological prophylaxis in the prevention of postoperative seizures in these patients and their outcome has not been consistent. Furthermore, the efficacy of the new generation of antiepileptic agents in the prophylaxis of perioperative seizures has not been assessed so far. We analyzed the data related to 150 patients harboring supratentorial brain gliomas with the aim to assess the efficacy of oxcarbazepine in preventing the occurrence or the recurrence of early postoperative seizures and its tolerability when it is rapidly titrated. Only four patients (2.7%) experienced seizures within the first week after surgery. Patients did not report disturbances during the titration phase. Regarding adverse events in the first week, six patients (4%) showed minor skin rash. Persistent symptomatic hyponatremia never occurred. Our data showed that oxcarbazepine can be a good alternative to traditional antiepileptic agents in the prevention of perioperative seizures being efficacy, ease of use (rapid titration in 3 days, not requiring close plasma concentration monitoring) and good tolerability (no major side effects during titration and during the first postoperative week) the key factors. Moreover, oxcarbazepine can be a valid choice when long-term therapy is required because of the low interaction with other drugs and the low hematological side effects."
],
"offsets": [
[
125,
1728
]
]
}
] | [
{
"id": "7",
"type": "Diseases & Disorders",
"text": [
"early postoperative seizures"
],
"offsets": [
[
14,
42
]
],
"normalized": []
},
{
"id": "8",
"type": "Diseases & Disorders",
"text": [
"primary brain tumors"
],
"offsets": [
[
60,
80
]
],
"normalized": []
},
{
"id": "9",
"type": "Chemicals & Drugs",
"text": [
"oxcarbazepine"
],
"offsets": [
[
110,
123
]
],
"normalized": []
},
{
"id": "10",
"type": "Diseases & Disorders",
"text": [
"Early postoperative seizures"
],
"offsets": [
[
125,
153
]
],
"normalized": []
},
{
"id": "11",
"type": "Diseases & Disorders",
"text": [
"complication"
],
"offsets": [
[
255,
267
]
],
"normalized": []
},
{
"id": "12",
"type": "Diseases & Disorders",
"text": [
"supratentorial brain tumors"
],
"offsets": [
[
285,
312
]
],
"normalized": []
},
{
"id": "13",
"type": "Diseases & Disorders",
"text": [
"postoperative seizures"
],
"offsets": [
[
406,
428
]
],
"normalized": []
},
{
"id": "14",
"type": "Chemicals & Drugs",
"text": [
"antiepileptic agents"
],
"offsets": [
[
541,
561
]
],
"normalized": []
},
{
"id": "15",
"type": "Diseases & Disorders",
"text": [
"perioperative seizures"
],
"offsets": [
[
584,
606
]
],
"normalized": []
},
{
"id": "16",
"type": "Diseases & Disorders",
"text": [
"supratentorial brain gliomas"
],
"offsets": [
[
692,
720
]
],
"normalized": []
},
{
"id": "17",
"type": "Chemicals & Drugs",
"text": [
"oxcarbazepine"
],
"offsets": [
[
760,
773
]
],
"normalized": []
},
{
"id": "18",
"type": "Diseases & Disorders",
"text": [
"early postoperative seizures"
],
"offsets": [
[
824,
852
]
],
"normalized": []
},
{
"id": "19",
"type": "Diseases & Disorders",
"text": [
"seizures"
],
"offsets": [
[
941,
949
]
],
"normalized": []
},
{
"id": "20",
"type": "Diseases & Disorders",
"text": [
"minor skin rash"
],
"offsets": [
[
1121,
1136
]
],
"normalized": []
},
{
"id": "21",
"type": "Diseases & Disorders",
"text": [
"hyponatremia"
],
"offsets": [
[
1161,
1173
]
],
"normalized": []
},
{
"id": "22",
"type": "Chemicals & Drugs",
"text": [
"oxcarbazepine"
],
"offsets": [
[
1211,
1224
]
],
"normalized": []
},
{
"id": "23",
"type": "Chemicals & Drugs",
"text": [
"antiepileptic agents"
],
"offsets": [
[
1266,
1286
]
],
"normalized": []
},
{
"id": "24",
"type": "Diseases & Disorders",
"text": [
"perioperative seizures"
],
"offsets": [
[
1308,
1330
]
],
"normalized": []
},
{
"id": "25",
"type": "Diseases & Disorders",
"text": [
"major side effects"
],
"offsets": [
[
1466,
1484
]
],
"normalized": []
},
{
"id": "26",
"type": "Chemicals & Drugs",
"text": [
"oxcarbazepine"
],
"offsets": [
[
1570,
1583
]
],
"normalized": []
},
{
"id": "27",
"type": "Diseases & Disorders",
"text": [
"hematological side effects"
],
"offsets": [
[
1701,
1727
]
],
"normalized": []
},
{
"id": "28",
"type": "",
"text": [
"antiepileptic agents"
],
"offsets": [
[
541,
561
]
],
"normalized": []
},
{
"id": "29",
"type": "",
"text": [
"perioperative seizures"
],
"offsets": [
[
584,
606
]
],
"normalized": []
},
{
"id": "31",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
1211,
1224
]
],
"normalized": []
},
{
"id": "32",
"type": "",
"text": [
"perioperative seizures"
],
"offsets": [
[
1308,
1330
]
],
"normalized": []
},
{
"id": "34",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
1211,
1224
]
],
"normalized": []
},
{
"id": "35",
"type": "",
"text": [
"major side effects"
],
"offsets": [
[
1466,
1484
]
],
"normalized": []
},
{
"id": "37",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
1570,
1583
]
],
"normalized": []
},
{
"id": "38",
"type": "",
"text": [
"hematological side effects"
],
"offsets": [
[
1701,
1727
]
],
"normalized": []
},
{
"id": "40",
"type": "",
"text": [
"antiepileptic agents"
],
"offsets": [
[
1266,
1286
]
],
"normalized": []
},
{
"id": "41",
"type": "",
"text": [
"perioperative seizures"
],
"offsets": [
[
1308,
1330
]
],
"normalized": []
},
{
"id": "43",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
110,
123
]
],
"normalized": []
},
{
"id": "44",
"type": "",
"text": [
"early postoperative seizures"
],
"offsets": [
[
14,
42
]
],
"normalized": []
},
{
"id": "46",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
110,
123
]
],
"normalized": []
},
{
"id": "47",
"type": "",
"text": [
"primary brain tumors"
],
"offsets": [
[
60,
80
]
],
"normalized": []
},
{
"id": "49",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
760,
773
]
],
"normalized": []
},
{
"id": "50",
"type": "",
"text": [
"early postoperative seizures"
],
"offsets": [
[
824,
852
]
],
"normalized": []
},
{
"id": "52",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
760,
773
]
],
"normalized": []
},
{
"id": "53",
"type": "",
"text": [
"supratentorial brain gliomas"
],
"offsets": [
[
692,
720
]
],
"normalized": []
},
{
"id": "55",
"type": "",
"text": [
"oxcarbazepine"
],
"offsets": [
[
1211,
1224
]
],
"normalized": []
},
{
"id": "56",
"type": "",
"text": [
"major side effects"
],
"offsets": [
[
1466,
1484
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "30",
"type": "SA",
"arg1_id": "28",
"arg2_id": "29",
"normalized": []
},
{
"id": "33",
"type": "PA",
"arg1_id": "31",
"arg2_id": "32",
"normalized": []
},
{
"id": "36",
"type": "NA",
"arg1_id": "34",
"arg2_id": "35",
"normalized": []
},
{
"id": "39",
"type": "PA",
"arg1_id": "37",
"arg2_id": "38",
"normalized": []
},
{
"id": "42",
"type": "PA",
"arg1_id": "40",
"arg2_id": "41",
"normalized": []
},
{
"id": "45",
"type": "PA",
"arg1_id": "43",
"arg2_id": "44",
"normalized": []
},
{
"id": "48",
"type": "PA",
"arg1_id": "46",
"arg2_id": "47",
"normalized": []
},
{
"id": "51",
"type": "PA",
"arg1_id": "49",
"arg2_id": "50",
"normalized": []
},
{
"id": "54",
"type": "PA",
"arg1_id": "52",
"arg2_id": "53",
"normalized": []
},
{
"id": "57",
"type": "PA",
"arg1_id": "55",
"arg2_id": "56",
"normalized": []
}
] |
59 | 59 | [
{
"id": "60",
"type": "title",
"text": [
"Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjögren's syndrome."
],
"offsets": [
[
0,
146
]
]
},
{
"id": "61",
"type": "abstract",
"text": [
"OBJECTIVE: To investigate the safety and efficacy of rituximab (RTX) for systemic symptoms in patients with primary Sjögren's syndrome (pSS), and changes in B cell biomarkers. PATIENTS AND METHODS: The records of 16 patients with pSS according to the American European consensus group criteria were reviewed retrospectively. RESULTS: Patients, all women, had a median age of 58.5 (range 41-71) years and a disease duration of 9.5 (range 0-25) years. RTX was prescribed for lymphoma (n = 5), refractory pulmonary disease with polysynovitis (n = 2), severe polysynovitis (n = 2), mixed cryoglobulinaemia (n = 5), thrombocytopenia (n = 1) and mononeuritis multiplex (n = 1). The median follow-up duration was 14.5 (range 2-48) months. Three patients experienced adverse events, including one mild serum sickness-like reaction with the presence of human antichimeric antibodies. Efficacy of treatment was observed in 4 of 5 patients with lymphomas and in 9 of 11 patients with systemic involvement. Dryness was improved in only a minority of patients. Corticosteroid dose was reduced in 11 patients. RTX induced decreased rheumatoid factor, gamma-globulin and beta2-microglobulin levels, and the level of B cell activating factor of the tumour necrosis factor family (BAFF) increased concomitantly with B cell depletion. Five patients were re-treated, with good efficacy and tolerance, except for one with probable serum sickness-like reaction. CONCLUSION: This study shows good efficacy and fair tolerance of RTX for systemic features. In addition, RTX allows for a marked reduction in corticosteroid use. Except for BAFF, the level of which increases, serum B cell biomarker levels decrease after taking RTX. Controlled trials should be performed to confirm the efficacy of RTX in pSS."
],
"offsets": [
[
147,
1931
]
]
}
] | [
{
"id": "62",
"type": "Diseases & Disorders",
"text": [
"Tolerance"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "63",
"type": "Chemicals & Drugs",
"text": [
"rituximab"
],
"offsets": [
[
26,
35
]
],
"normalized": []
},
{
"id": "64",
"type": "Diseases & Disorders",
"text": [
"complications"
],
"offsets": [
[
101,
114
]
],
"normalized": []
},
{
"id": "65",
"type": "Diseases & Disorders",
"text": [
"primary Sjögren's syndrome"
],
"offsets": [
[
118,
145
]
],
"normalized": []
},
{
"id": "66",
"type": "Chemicals & Drugs",
"text": [
"rituximab"
],
"offsets": [
[
200,
209
]
],
"normalized": []
},
{
"id": "67",
"type": "Chemicals & Drugs",
"text": [
"RTX"
],
"offsets": [
[
211,
214
]
],
"normalized": []
},
{
"id": "68",
"type": "Diseases & Disorders",
"text": [
"systemic symptoms"
],
"offsets": [
[
220,
237
]
],
"normalized": []
},
{
"id": "69",
"type": "Diseases & Disorders",
"text": [
"primary Sjögren's syndrome"
],
"offsets": [
[
255,
282
]
],
"normalized": []
},
{
"id": "70",
"type": "Diseases & Disorders",
"text": [
"pSS"
],
"offsets": [
[
284,
287
]
],
"normalized": []
},
{
"id": "71",
"type": "Diseases & Disorders",
"text": [
"pSS"
],
"offsets": [
[
378,
381
]
],
"normalized": []
},
{
"id": "72",
"type": "Diseases & Disorders",
"text": [
"disease"
],
"offsets": [
[
554,
561
]
],
"normalized": []
},
{
"id": "73",
"type": "Chemicals & Drugs",
"text": [
"RTX"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "74",
"type": "Diseases & Disorders",
"text": [
"lymphoma"
],
"offsets": [
[
621,
629
]
],
"normalized": []
},
{
"id": "75",
"type": "Diseases & Disorders",
"text": [
"refractory pulmonary disease with polysynovitis"
],
"offsets": [
[
639,
686
]
],
"normalized": []
},
{
"id": "76",
"type": "Diseases & Disorders",
"text": [
"pulmonary disease"
],
"offsets": [
[
650,
667
]
],
"normalized": []
},
{
"id": "77",
"type": "Diseases & Disorders",
"text": [
"severe polysynovitis"
],
"offsets": [
[
696,
716
]
],
"normalized": []
},
{
"id": "78",
"type": "Diseases & Disorders",
"text": [
"mixed cryoglobulinaemia"
],
"offsets": [
[
726,
749
]
],
"normalized": []
},
{
"id": "79",
"type": "Diseases & Disorders",
"text": [
"thrombocytopenia"
],
"offsets": [
[
759,
775
]
],
"normalized": []
},
{
"id": "80",
"type": "Diseases & Disorders",
"text": [
"mononeuritis multiplex"
],
"offsets": [
[
788,
810
]
],
"normalized": []
},
{
"id": "81",
"type": "Diseases & Disorders",
"text": [
"serum sickness-like reaction"
],
"offsets": [
[
942,
970
]
],
"normalized": []
},
{
"id": "82",
"type": "Diseases & Disorders",
"text": [
"lymphomas"
],
"offsets": [
[
1082,
1091
]
],
"normalized": []
},
{
"id": "83",
"type": "Diseases & Disorders",
"text": [
"Dryness"
],
"offsets": [
[
1143,
1150
]
],
"normalized": []
},
{
"id": "84",
"type": "Chemicals & Drugs",
"text": [
"Corticosteroid"
],
"offsets": [
[
1196,
1210
]
],
"normalized": []
},
{
"id": "85",
"type": "Chemicals & Drugs",
"text": [
"RTX"
],
"offsets": [
[
1244,
1247
]
],
"normalized": []
},
{
"id": "86",
"type": "Diseases & Disorders",
"text": [
"tumour necrosis"
],
"offsets": [
[
1381,
1396
]
],
"normalized": []
},
{
"id": "87",
"type": "Diseases & Disorders",
"text": [
"tolerance"
],
"offsets": [
[
1519,
1528
]
],
"normalized": []
},
{
"id": "88",
"type": "Diseases & Disorders",
"text": [
"serum sickness-like reaction"
],
"offsets": [
[
1559,
1587
]
],
"normalized": []
},
{
"id": "89",
"type": "Diseases & Disorders",
"text": [
"tolerance"
],
"offsets": [
[
1641,
1650
]
],
"normalized": []
},
{
"id": "90",
"type": "Chemicals & Drugs",
"text": [
"RTX"
],
"offsets": [
[
1654,
1657
]
],
"normalized": []
},
{
"id": "91",
"type": "Chemicals & Drugs",
"text": [
"RTX"
],
"offsets": [
[
1694,
1697
]
],
"normalized": []
},
{
"id": "92",
"type": "Chemicals & Drugs",
"text": [
"corticosteroid"
],
"offsets": [
[
1731,
1745
]
],
"normalized": []
},
{
"id": "93",
"type": "Chemicals & Drugs",
"text": [
"RTX"
],
"offsets": [
[
1850,
1853
]
],
"normalized": []
},
{
"id": "94",
"type": "Chemicals & Drugs",
"text": [
"RTX"
],
"offsets": [
[
1920,
1923
]
],
"normalized": []
},
{
"id": "95",
"type": "Diseases & Disorders",
"text": [
"pSS"
],
"offsets": [
[
1927,
1930
]
],
"normalized": []
},
{
"id": "96",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "97",
"type": "",
"text": [
"lymphoma"
],
"offsets": [
[
621,
629
]
],
"normalized": []
},
{
"id": "99",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "100",
"type": "",
"text": [
"mixed cryoglobulinaemia"
],
"offsets": [
[
726,
749
]
],
"normalized": []
},
{
"id": "102",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "103",
"type": "",
"text": [
"thrombocytopenia"
],
"offsets": [
[
759,
775
]
],
"normalized": []
},
{
"id": "105",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "106",
"type": "",
"text": [
"mononeuritis multiplex"
],
"offsets": [
[
788,
810
]
],
"normalized": []
},
{
"id": "108",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "109",
"type": "",
"text": [
"refractory pulmonary disease with polysynovitis"
],
"offsets": [
[
639,
686
]
],
"normalized": []
},
{
"id": "111",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
598,
601
]
],
"normalized": []
},
{
"id": "112",
"type": "",
"text": [
"severe polysynovitis"
],
"offsets": [
[
696,
716
]
],
"normalized": []
},
{
"id": "114",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
1920,
1923
]
],
"normalized": []
},
{
"id": "115",
"type": "",
"text": [
"pSS"
],
"offsets": [
[
1927,
1930
]
],
"normalized": []
},
{
"id": "117",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
1244,
1247
]
],
"normalized": []
},
{
"id": "118",
"type": "",
"text": [
"tumour necrosis"
],
"offsets": [
[
1381,
1396
]
],
"normalized": []
},
{
"id": "120",
"type": "",
"text": [
"rituximab"
],
"offsets": [
[
26,
35
]
],
"normalized": []
},
{
"id": "121",
"type": "",
"text": [
"complications"
],
"offsets": [
[
101,
114
]
],
"normalized": []
},
{
"id": "123",
"type": "",
"text": [
"rituximab"
],
"offsets": [
[
26,
35
]
],
"normalized": []
},
{
"id": "124",
"type": "",
"text": [
"primary Sjögren's syndrome"
],
"offsets": [
[
118,
145
]
],
"normalized": []
},
{
"id": "126",
"type": "",
"text": [
"rituximab"
],
"offsets": [
[
200,
209
]
],
"normalized": []
},
{
"id": "127",
"type": "",
"text": [
"primary Sjögren's syndrome"
],
"offsets": [
[
255,
282
]
],
"normalized": []
},
{
"id": "129",
"type": "",
"text": [
"rituximab"
],
"offsets": [
[
200,
209
]
],
"normalized": []
},
{
"id": "130",
"type": "",
"text": [
"systemic symptoms"
],
"offsets": [
[
220,
237
]
],
"normalized": []
},
{
"id": "132",
"type": "",
"text": [
"rituximab"
],
"offsets": [
[
200,
209
]
],
"normalized": []
},
{
"id": "133",
"type": "",
"text": [
"pSS"
],
"offsets": [
[
284,
287
]
],
"normalized": []
},
{
"id": "135",
"type": "",
"text": [
"RTX"
],
"offsets": [
[
211,
214
]
],
"normalized": []
},
{
"id": "136",
"type": "",
"text": [
"pSS"
],
"offsets": [
[
284,
287
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "98",
"type": "PA",
"arg1_id": "96",
"arg2_id": "97",
"normalized": []
},
{
"id": "101",
"type": "PA",
"arg1_id": "99",
"arg2_id": "100",
"normalized": []
},
{
"id": "104",
"type": "PA",
"arg1_id": "102",
"arg2_id": "103",
"normalized": []
},
{
"id": "107",
"type": "PA",
"arg1_id": "105",
"arg2_id": "106",
"normalized": []
},
{
"id": "110",
"type": "PA",
"arg1_id": "108",
"arg2_id": "109",
"normalized": []
},
{
"id": "113",
"type": "PA",
"arg1_id": "111",
"arg2_id": "112",
"normalized": []
},
{
"id": "116",
"type": "SA",
"arg1_id": "114",
"arg2_id": "115",
"normalized": []
},
{
"id": "119",
"type": "PA",
"arg1_id": "117",
"arg2_id": "118",
"normalized": []
},
{
"id": "122",
"type": "PA",
"arg1_id": "120",
"arg2_id": "121",
"normalized": []
},
{
"id": "125",
"type": "PA",
"arg1_id": "123",
"arg2_id": "124",
"normalized": []
},
{
"id": "128",
"type": "PA",
"arg1_id": "126",
"arg2_id": "127",
"normalized": []
},
{
"id": "131",
"type": "PA",
"arg1_id": "129",
"arg2_id": "130",
"normalized": []
},
{
"id": "134",
"type": "PA",
"arg1_id": "132",
"arg2_id": "133",
"normalized": []
},
{
"id": "137",
"type": "PA",
"arg1_id": "135",
"arg2_id": "136",
"normalized": []
}
] |
139 | 139 | [
{
"id": "140",
"type": "title",
"text": [
"Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas."
],
"offsets": [
[
0,
114
]
]
},
{
"id": "141",
"type": "abstract",
"text": [
"Perturbations to the Wnt signaling pathway have been implicated in a large proportion of human hepatocellular carcinomas (HCCs). Activating beta-catenin mutations and loss of function mutations in Axin1 are thought to be functionally equivalent. We examined the Wnt pathway in HCC by comparing the expression of beta-catenin target genes and the level of beta-catenin-dependent transcriptional activation, in 45 HCC tumors and four cell lines. Among these samples, beta-catenin and AXIN1 were mutated in 20 and seven cases, respectively. We found a significant correlation between activated beta-catenin mutations and overexpression of mRNA for the target genes glutamine synthetase (GS), G-protein-coupled receptor (GPR)49 and glutamate transporter (GLT)-1 (P=0.0001), but not for the genes ornithine aminotransferase, LECT2, c-myc and cyclin D1. We also showed that GS is a good immunohistochemical marker of beta-catenin activation in HCC. However, we observed no induction of GS, GPR49 or GLT-1 in the five inactivated Axin1 tumors. Beta-catenin-dependent transcriptional activation in two Axin1-mutated HCC cell lines was much weaker than in beta-catenin-mutated cell lines. Our results strongly suggest that in HCC, contrary to expectation, the loss of function of Axin1 is not equivalent to the gain of function of beta-catenin. Our results also suggest that the tumor suppressor function of Axin1 in HCC may be related to another, non-Wnt pathway."
],
"offsets": [
[
115,
1570
]
]
}
] | [
{
"id": "142",
"type": "SNP & Sequence variations",
"text": [
"inactivated Axin1"
],
"offsets": [
[
24,
41
]
],
"normalized": []
},
{
"id": "143",
"type": "Genes & Molecular Sequences",
"text": [
"inactivated Axin1"
],
"offsets": [
[
24,
41
]
],
"normalized": []
},
{
"id": "144",
"type": "SNP & Sequence variations",
"text": [
"activated beta-catenin mutations"
],
"offsets": [
[
46,
78
]
],
"normalized": []
},
{
"id": "145",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
56,
68
]
],
"normalized": []
},
{
"id": "146",
"type": "Genes & Molecular Sequences",
"text": [
"Wnt"
],
"offsets": [
[
136,
139
]
],
"normalized": []
},
{
"id": "147",
"type": "SNP & Sequence variations",
"text": [
"Activating beta-catenin mutations"
],
"offsets": [
[
244,
277
]
],
"normalized": []
},
{
"id": "148",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
255,
267
]
],
"normalized": []
},
{
"id": "149",
"type": "SNP & Sequence variations",
"text": [
"loss of function mutations in Axin1"
],
"offsets": [
[
282,
317
]
],
"normalized": []
},
{
"id": "150",
"type": "Genes & Molecular Sequences",
"text": [
"loss of function mutations in Axin1"
],
"offsets": [
[
282,
317
]
],
"normalized": []
},
{
"id": "151",
"type": "Genes & Molecular Sequences",
"text": [
"Wnt"
],
"offsets": [
[
377,
380
]
],
"normalized": []
},
{
"id": "152",
"type": "Genes & Molecular Sequences",
"text": [
"HCC"
],
"offsets": [
[
392,
395
]
],
"normalized": []
},
{
"id": "153",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
427,
439
]
],
"normalized": []
},
{
"id": "154",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
470,
482
]
],
"normalized": []
},
{
"id": "155",
"type": "Genes & Molecular Sequences",
"text": [
"HCC"
],
"offsets": [
[
527,
530
]
],
"normalized": []
},
{
"id": "156",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
580,
592
]
],
"normalized": []
},
{
"id": "157",
"type": "Genes & Molecular Sequences",
"text": [
"AXIN1"
],
"offsets": [
[
597,
602
]
],
"normalized": []
},
{
"id": "158",
"type": "SNP & Sequence variations",
"text": [
"activated beta-catenin mutations"
],
"offsets": [
[
696,
728
]
],
"normalized": []
},
{
"id": "159",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
706,
718
]
],
"normalized": []
},
{
"id": "160",
"type": "Genes & Molecular Sequences",
"text": [
"glutamine synthetase"
],
"offsets": [
[
777,
797
]
],
"normalized": []
},
{
"id": "161",
"type": "Genes & Molecular Sequences",
"text": [
"GS"
],
"offsets": [
[
799,
801
]
],
"normalized": []
},
{
"id": "162",
"type": "Genes & Molecular Sequences",
"text": [
"G-protein-coupled receptor"
],
"offsets": [
[
804,
830
]
],
"normalized": []
},
{
"id": "163",
"type": "Genes & Molecular Sequences",
"text": [
"GPR)49"
],
"offsets": [
[
832,
838
]
],
"normalized": []
},
{
"id": "164",
"type": "Genes & Molecular Sequences",
"text": [
"glutamate transporter"
],
"offsets": [
[
843,
864
]
],
"normalized": []
},
{
"id": "165",
"type": "Genes & Molecular Sequences",
"text": [
"GLT)-1"
],
"offsets": [
[
866,
872
]
],
"normalized": []
},
{
"id": "166",
"type": "Genes & Molecular Sequences",
"text": [
"ornithine aminotransferase"
],
"offsets": [
[
907,
933
]
],
"normalized": []
},
{
"id": "167",
"type": "Genes & Molecular Sequences",
"text": [
"LECT2"
],
"offsets": [
[
935,
940
]
],
"normalized": []
},
{
"id": "168",
"type": "Genes & Molecular Sequences",
"text": [
"c-myc"
],
"offsets": [
[
942,
947
]
],
"normalized": []
},
{
"id": "169",
"type": "Genes & Molecular Sequences",
"text": [
"cyclin D1"
],
"offsets": [
[
952,
961
]
],
"normalized": []
},
{
"id": "170",
"type": "Genes & Molecular Sequences",
"text": [
"GS"
],
"offsets": [
[
983,
985
]
],
"normalized": []
},
{
"id": "171",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
1026,
1038
]
],
"normalized": []
},
{
"id": "172",
"type": "Genes & Molecular Sequences",
"text": [
"HCC"
],
"offsets": [
[
1053,
1056
]
],
"normalized": []
},
{
"id": "173",
"type": "Genes & Molecular Sequences",
"text": [
"GS"
],
"offsets": [
[
1095,
1097
]
],
"normalized": []
},
{
"id": "174",
"type": "Genes & Molecular Sequences",
"text": [
"GPR49"
],
"offsets": [
[
1099,
1104
]
],
"normalized": []
},
{
"id": "175",
"type": "Genes & Molecular Sequences",
"text": [
"GLT-1"
],
"offsets": [
[
1108,
1113
]
],
"normalized": []
},
{
"id": "176",
"type": "SNP & Sequence variations",
"text": [
"inactivated Axin1"
],
"offsets": [
[
1126,
1143
]
],
"normalized": []
},
{
"id": "177",
"type": "Genes & Molecular Sequences",
"text": [
"inactivated Axin1"
],
"offsets": [
[
1126,
1143
]
],
"normalized": []
},
{
"id": "178",
"type": "Genes & Molecular Sequences",
"text": [
"Beta-catenin"
],
"offsets": [
[
1152,
1164
]
],
"normalized": []
},
{
"id": "179",
"type": "Genes & Molecular Sequences",
"text": [
"Axin1"
],
"offsets": [
[
1209,
1214
]
],
"normalized": []
},
{
"id": "180",
"type": "Genes & Molecular Sequences",
"text": [
"HCC"
],
"offsets": [
[
1223,
1226
]
],
"normalized": []
},
{
"id": "181",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
1262,
1274
]
],
"normalized": []
},
{
"id": "182",
"type": "Genes & Molecular Sequences",
"text": [
"HCC"
],
"offsets": [
[
1332,
1335
]
],
"normalized": []
},
{
"id": "183",
"type": "Genes & Molecular Sequences",
"text": [
"Axin1"
],
"offsets": [
[
1386,
1391
]
],
"normalized": []
},
{
"id": "184",
"type": "Genes & Molecular Sequences",
"text": [
"beta-catenin"
],
"offsets": [
[
1437,
1449
]
],
"normalized": []
},
{
"id": "185",
"type": "Genes & Molecular Sequences",
"text": [
"Axin1"
],
"offsets": [
[
1514,
1519
]
],
"normalized": []
},
{
"id": "186",
"type": "Genes & Molecular Sequences",
"text": [
"HCC"
],
"offsets": [
[
1523,
1526
]
],
"normalized": []
},
{
"id": "187",
"type": "Genes & Molecular Sequences",
"text": [
"Wnt"
],
"offsets": [
[
1558,
1561
]
],
"normalized": []
}
] | [] | [] | [] |
189 | 189 | [
{
"id": "190",
"type": "title",
"text": [
"ATM regulates ionizing radiation-induced disruption of HDAC1:PP1:Rb complexes."
],
"offsets": [
[
0,
78
]
]
},
{
"id": "191",
"type": "abstract",
"text": [
"Ionizing radiation elicits signaling events that coordinate DNA repair and interruption of cell cycle progression. We previously demonstrated that ionizing radiation (IR) of cells activates nuclear protein phosphatase-1 (PP1) by promoting dephosphorylation of Thr320, an inhibitory site in the enzyme and that the ATM kinase is required for this response. We sought to identify potential targets of IR-activated PP1. Untreated and IR-treated Jurkat cells were labeled with (32)P orthophosphate, and nuclear extracts were subjected to microcystin affinity chromatography to recover phosphatase complexes that were analyzed by 2D-PAGE and mass spectrometry. Several proteins associated with protein phosphatases demonstrated a significant decrease in (32)P intensity following IR, and one of these was identified as HDAC1. Co-immunoprecipitation revealed complexes containing PP1 with HDAC1 and Rb in cell extracts. In response to IR, there was an ATM-dependent activation of PP1, dephosphorylation of HDAC1, dissociation of HDAC1-PP1-Rb complexes and increased HDAC1 activity. These results suggest that IR regulates HDAC1 phosphorylation and activity through ATM-dependent activation of PP1."
],
"offsets": [
[
79,
1270
]
]
}
] | [
{
"id": "192",
"type": "Genes & Molecular Sequences",
"text": [
"ATM"
],
"offsets": [
[
0,
3
]
],
"normalized": []
},
{
"id": "193",
"type": "Genes & Molecular Sequences",
"text": [
"HDAC1:PP1:Rb"
],
"offsets": [
[
55,
67
]
],
"normalized": []
},
{
"id": "194",
"type": "Genes & Molecular Sequences",
"text": [
"PP1"
],
"offsets": [
[
61,
64
]
],
"normalized": []
},
{
"id": "195",
"type": "Genes & Molecular Sequences",
"text": [
"phosphatase"
],
"offsets": [
[
285,
296
]
],
"normalized": []
},
{
"id": "196",
"type": "Genes & Molecular Sequences",
"text": [
"PP1"
],
"offsets": [
[
300,
303
]
],
"normalized": []
},
{
"id": "197",
"type": "Genes & Molecular Sequences",
"text": [
"ATM kinase"
],
"offsets": [
[
393,
403
]
],
"normalized": []
},
{
"id": "198",
"type": "Genes & Molecular Sequences",
"text": [
"PP1"
],
"offsets": [
[
491,
494
]
],
"normalized": []
},
{
"id": "199",
"type": "Chemicals & Drugs",
"text": [
"(32)P orthophosphate"
],
"offsets": [
[
552,
572
]
],
"normalized": []
},
{
"id": "200",
"type": "Genes & Molecular Sequences",
"text": [
"phosphatase"
],
"offsets": [
[
660,
671
]
],
"normalized": []
},
{
"id": "201",
"type": "Genes & Molecular Sequences",
"text": [
"phosphatases"
],
"offsets": [
[
776,
788
]
],
"normalized": []
},
{
"id": "202",
"type": "Chemicals & Drugs",
"text": [
"(32)P"
],
"offsets": [
[
828,
833
]
],
"normalized": []
},
{
"id": "203",
"type": "Genes & Molecular Sequences",
"text": [
"HDAC1"
],
"offsets": [
[
893,
898
]
],
"normalized": []
},
{
"id": "204",
"type": "Genes & Molecular Sequences",
"text": [
"PP1"
],
"offsets": [
[
953,
956
]
],
"normalized": []
},
{
"id": "205",
"type": "Genes & Molecular Sequences",
"text": [
"HDAC1"
],
"offsets": [
[
962,
967
]
],
"normalized": []
},
{
"id": "206",
"type": "Genes & Molecular Sequences",
"text": [
"Rb"
],
"offsets": [
[
972,
974
]
],
"normalized": []
},
{
"id": "207",
"type": "Genes & Molecular Sequences",
"text": [
"ATM"
],
"offsets": [
[
1025,
1028
]
],
"normalized": []
},
{
"id": "208",
"type": "Genes & Molecular Sequences",
"text": [
"PP1"
],
"offsets": [
[
1053,
1056
]
],
"normalized": []
},
{
"id": "209",
"type": "Genes & Molecular Sequences",
"text": [
"HDAC1"
],
"offsets": [
[
1079,
1084
]
],
"normalized": []
},
{
"id": "210",
"type": "Genes & Molecular Sequences",
"text": [
"HDAC1-PP1-Rb"
],
"offsets": [
[
1102,
1114
]
],
"normalized": []
},
{
"id": "211",
"type": "Genes & Molecular Sequences",
"text": [
"HDAC1"
],
"offsets": [
[
1139,
1144
]
],
"normalized": []
},
{
"id": "212",
"type": "Genes & Molecular Sequences",
"text": [
"HDAC1"
],
"offsets": [
[
1195,
1200
]
],
"normalized": []
},
{
"id": "213",
"type": "Genes & Molecular Sequences",
"text": [
"ATM"
],
"offsets": [
[
1238,
1241
]
],
"normalized": []
},
{
"id": "214",
"type": "Genes & Molecular Sequences",
"text": [
"PP1"
],
"offsets": [
[
1266,
1269
]
],
"normalized": []
}
] | [] | [] | [] |
216 | 216 | [
{
"id": "217",
"type": "title",
"text": [
"Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma."
],
"offsets": [
[
0,
108
]
]
},
{
"id": "218",
"type": "abstract",
"text": [
"Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non-Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer-related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population-based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51-0.85, p = 0.001), especially B-cell lymphoma (OR = 0.61, 95% CI: 0.47-0.80, p <or= 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation.CI - (c) 2006 Wiley-Liss, Inc."
],
"offsets": [
[
109,
1281
]
]
}
] | [
{
"id": "219",
"type": "SNP & Sequence variations",
"text": [
"Ala394Thr"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "220",
"type": "Genes & Molecular Sequences",
"text": [
"clock"
],
"offsets": [
[
30,
35
]
],
"normalized": []
},
{
"id": "221",
"type": "Genes & Molecular Sequences",
"text": [
"NPAS2"
],
"offsets": [
[
41,
46
]
],
"normalized": []
},
{
"id": "222",
"type": "Diseases & Disorders",
"text": [
"non-Hodgkin's lymphoma"
],
"offsets": [
[
85,
107
]
],
"normalized": []
},
{
"id": "223",
"type": "Diseases & Disorders",
"text": [
"non-Hodgkin's lymphoma"
],
"offsets": [
[
220,
242
]
],
"normalized": []
},
{
"id": "224",
"type": "Diseases & Disorders",
"text": [
"NHL"
],
"offsets": [
[
244,
247
]
],
"normalized": []
},
{
"id": "225",
"type": "Genes & Molecular Sequences",
"text": [
"NHL"
],
"offsets": [
[
244,
247
]
],
"normalized": []
},
{
"id": "226",
"type": "Diseases & Disorders",
"text": [
"cancer"
],
"offsets": [
[
310,
316
]
],
"normalized": []
},
{
"id": "227",
"type": "Diseases & Disorders",
"text": [
"tumor"
],
"offsets": [
[
358,
363
]
],
"normalized": []
},
{
"id": "228",
"type": "Genes & Molecular Sequences",
"text": [
"circadian genes"
],
"offsets": [
[
441,
456
]
],
"normalized": []
},
{
"id": "229",
"type": "Diseases & Disorders",
"text": [
"NHL"
],
"offsets": [
[
461,
464
]
],
"normalized": []
},
{
"id": "230",
"type": "Genes & Molecular Sequences",
"text": [
"NHL"
],
"offsets": [
[
461,
464
]
],
"normalized": []
},
{
"id": "231",
"type": "SNP & Sequence variations",
"text": [
"Ala394Thr"
],
"offsets": [
[
606,
615
]
],
"normalized": []
},
{
"id": "232",
"type": "SNP & Sequence variations",
"text": [
"rs2305160"
],
"offsets": [
[
617,
626
]
],
"normalized": []
},
{
"id": "233",
"type": "Genes & Molecular Sequences",
"text": [
"circadian gene"
],
"offsets": [
[
643,
657
]
],
"normalized": []
},
{
"id": "234",
"type": "Genes & Molecular Sequences",
"text": [
"neuronal PAS domain protein 2"
],
"offsets": [
[
659,
688
]
],
"normalized": []
},
{
"id": "235",
"type": "Genes & Molecular Sequences",
"text": [
"NPAS2"
],
"offsets": [
[
690,
695
]
],
"normalized": []
},
{
"id": "236",
"type": "Diseases & Disorders",
"text": [
"NHL"
],
"offsets": [
[
732,
735
]
],
"normalized": []
},
{
"id": "237",
"type": "Genes & Molecular Sequences",
"text": [
"NHL"
],
"offsets": [
[
732,
735
]
],
"normalized": []
},
{
"id": "238",
"type": "SNP & Sequence variations",
"text": [
"Thr genotypes"
],
"offsets": [
[
802,
815
]
],
"normalized": []
},
{
"id": "239",
"type": "SNP & Sequence variations",
"text": [
"Ala/Thr"
],
"offsets": [
[
817,
824
]
],
"normalized": []
},
{
"id": "240",
"type": "SNP & Sequence variations",
"text": [
"Thr/Thr"
],
"offsets": [
[
829,
836
]
],
"normalized": []
},
{
"id": "241",
"type": "Diseases & Disorders",
"text": [
"NHL"
],
"offsets": [
[
859,
862
]
],
"normalized": []
},
{
"id": "242",
"type": "Genes & Molecular Sequences",
"text": [
"NHL"
],
"offsets": [
[
859,
862
]
],
"normalized": []
},
{
"id": "243",
"type": "Diseases & Disorders",
"text": [
"B-cell lymphoma"
],
"offsets": [
[
917,
932
]
],
"normalized": []
},
{
"id": "244",
"type": "Genes & Molecular Sequences",
"text": [
"circadian genes"
],
"offsets": [
[
1067,
1082
]
],
"normalized": []
},
{
"id": "245",
"type": "Diseases & Disorders",
"text": [
"lymphomagenesis"
],
"offsets": [
[
1086,
1101
]
],
"normalized": []
},
{
"id": "246",
"type": "Genes & Molecular Sequences",
"text": [
"circadian genes"
],
"offsets": [
[
1145,
1160
]
],
"normalized": []
},
{
"id": "247",
"type": "Diseases & Disorders",
"text": [
"NHL"
],
"offsets": [
[
1212,
1215
]
],
"normalized": []
},
{
"id": "248",
"type": "Genes & Molecular Sequences",
"text": [
"NHL"
],
"offsets": [
[
1212,
1215
]
],
"normalized": []
},
{
"id": "249",
"type": "",
"text": [
"Thr genotypes"
],
"offsets": [
[
802,
815
]
],
"normalized": []
},
{
"id": "250",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
859,
862
]
],
"normalized": []
},
{
"id": "252",
"type": "",
"text": [
"Thr genotypes"
],
"offsets": [
[
802,
815
]
],
"normalized": []
},
{
"id": "253",
"type": "",
"text": [
"B-cell lymphoma"
],
"offsets": [
[
917,
932
]
],
"normalized": []
},
{
"id": "255",
"type": "",
"text": [
"Ala/Thr"
],
"offsets": [
[
817,
824
]
],
"normalized": []
},
{
"id": "256",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
859,
862
]
],
"normalized": []
},
{
"id": "258",
"type": "",
"text": [
"Ala/Thr"
],
"offsets": [
[
817,
824
]
],
"normalized": []
},
{
"id": "259",
"type": "",
"text": [
"B-cell lymphoma"
],
"offsets": [
[
917,
932
]
],
"normalized": []
},
{
"id": "261",
"type": "",
"text": [
"Thr/Thr"
],
"offsets": [
[
829,
836
]
],
"normalized": []
},
{
"id": "262",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
859,
862
]
],
"normalized": []
},
{
"id": "264",
"type": "",
"text": [
"Thr/Thr"
],
"offsets": [
[
829,
836
]
],
"normalized": []
},
{
"id": "265",
"type": "",
"text": [
"B-cell lymphoma"
],
"offsets": [
[
917,
932
]
],
"normalized": []
},
{
"id": "267",
"type": "",
"text": [
"circadian genes"
],
"offsets": [
[
1145,
1160
]
],
"normalized": []
},
{
"id": "268",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
1212,
1215
]
],
"normalized": []
},
{
"id": "270",
"type": "",
"text": [
"circadian genes"
],
"offsets": [
[
1145,
1160
]
],
"normalized": []
},
{
"id": "271",
"type": "",
"text": [
"lymphomagenesis"
],
"offsets": [
[
1086,
1101
]
],
"normalized": []
},
{
"id": "273",
"type": "",
"text": [
"clock"
],
"offsets": [
[
30,
35
]
],
"normalized": []
},
{
"id": "274",
"type": "",
"text": [
"non-Hodgkin's lymphoma"
],
"offsets": [
[
85,
107
]
],
"normalized": []
},
{
"id": "276",
"type": "",
"text": [
"NPAS2"
],
"offsets": [
[
41,
46
]
],
"normalized": []
},
{
"id": "277",
"type": "",
"text": [
"non-Hodgkin's lymphoma"
],
"offsets": [
[
85,
107
]
],
"normalized": []
},
{
"id": "279",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
244,
247
]
],
"normalized": []
},
{
"id": "280",
"type": "",
"text": [
"non-Hodgkin's lymphoma"
],
"offsets": [
[
220,
242
]
],
"normalized": []
},
{
"id": "282",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
859,
862
]
],
"normalized": []
},
{
"id": "283",
"type": "",
"text": [
"B-cell lymphoma"
],
"offsets": [
[
917,
932
]
],
"normalized": []
},
{
"id": "285",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
1212,
1215
]
],
"normalized": []
},
{
"id": "286",
"type": "",
"text": [
"lymphomagenesis"
],
"offsets": [
[
1086,
1101
]
],
"normalized": []
},
{
"id": "288",
"type": "",
"text": [
"Ala394Thr"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "289",
"type": "",
"text": [
"non-Hodgkin's lymphoma"
],
"offsets": [
[
85,
107
]
],
"normalized": []
},
{
"id": "291",
"type": "",
"text": [
"NPAS2"
],
"offsets": [
[
690,
695
]
],
"normalized": []
},
{
"id": "292",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
732,
735
]
],
"normalized": []
},
{
"id": "294",
"type": "",
"text": [
"Ala394Thr"
],
"offsets": [
[
606,
615
]
],
"normalized": []
},
{
"id": "295",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
732,
735
]
],
"normalized": []
},
{
"id": "297",
"type": "",
"text": [
"rs2305160"
],
"offsets": [
[
617,
626
]
],
"normalized": []
},
{
"id": "298",
"type": "",
"text": [
"NHL"
],
"offsets": [
[
732,
735
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "251",
"type": "PA",
"arg1_id": "249",
"arg2_id": "250",
"normalized": []
},
{
"id": "254",
"type": "PA",
"arg1_id": "252",
"arg2_id": "253",
"normalized": []
},
{
"id": "257",
"type": "PA",
"arg1_id": "255",
"arg2_id": "256",
"normalized": []
},
{
"id": "260",
"type": "PA",
"arg1_id": "258",
"arg2_id": "259",
"normalized": []
},
{
"id": "263",
"type": "PA",
"arg1_id": "261",
"arg2_id": "262",
"normalized": []
},
{
"id": "266",
"type": "PA",
"arg1_id": "264",
"arg2_id": "265",
"normalized": []
},
{
"id": "269",
"type": "SA",
"arg1_id": "267",
"arg2_id": "268",
"normalized": []
},
{
"id": "272",
"type": "PA",
"arg1_id": "270",
"arg2_id": "271",
"normalized": []
},
{
"id": "275",
"type": "PA",
"arg1_id": "273",
"arg2_id": "274",
"normalized": []
},
{
"id": "278",
"type": "PA",
"arg1_id": "276",
"arg2_id": "277",
"normalized": []
},
{
"id": "281",
"type": "PA",
"arg1_id": "279",
"arg2_id": "280",
"normalized": []
},
{
"id": "284",
"type": "PA",
"arg1_id": "282",
"arg2_id": "283",
"normalized": []
},
{
"id": "287",
"type": "PA",
"arg1_id": "285",
"arg2_id": "286",
"normalized": []
},
{
"id": "290",
"type": "PA",
"arg1_id": "288",
"arg2_id": "289",
"normalized": []
},
{
"id": "293",
"type": "SA",
"arg1_id": "291",
"arg2_id": "292",
"normalized": []
},
{
"id": "296",
"type": "SA",
"arg1_id": "294",
"arg2_id": "295",
"normalized": []
},
{
"id": "299",
"type": "SA",
"arg1_id": "297",
"arg2_id": "298",
"normalized": []
}
] |
301 | 301 | [
{
"id": "302",
"type": "title",
"text": [
"Association study of putative promoter polymorphisms in the neuroplastin gene and schizophrenia."
],
"offsets": [
[
0,
96
]
]
},
{
"id": "303",
"type": "abstract",
"text": [
"A previous study revealed a number of methamphetamine (METH) and phencyclidine (PCP)-reactive tags in a rat brain through serial analysis of gene expression. The present study extends this previous study by investigating whether two genes, which deduced from METH/PCP-reactive tags, were identified as those encoding human transmembrane proteins of the immunoglobulin (Ig) superfamily, neuroplastin (NPTN) and basigin (BSG), confer genetic susceptibility to schizophrenia by analyzing single nucleotide polymorphisms (SNPs). There were nominally significant differences between the two groups in their allelic frequencies (T Ins/Del, chi2=4.910, d.f.=1, P=0.040) and genotypic distributions (T/T or T/Del, chi2=5.116, d.f.=1, P=0.036) of rs3840846 in the 5'-upstream of NPTN. The two groups differed significantly also in their allelic frequencies (G/T, chi2=4.229, d.f.=1, P=0.044), but not genotypic distributions of rs3743500 in the 5'-upstream of NPTN. The haplotypes constructed from the three SNPs (rs3840846, rs3826047 and rs3743500, in order) in the 5'-upstream of NPTN showed a significant association with schizophrenia (permutation P=0.036), in that T-G-T (permutation P=0.028) and del-G-G (permutation P=0.040) were under-represented and over-represented, respectively, in schizophrenia. A reporter construct driven by the 5'-upstream region containing any haplotype consisting of the three SNPs had substantial transcriptional activity. Notably, a reporter construct containing a haplotype T-G-T had significantly lower transcriptional activity as compared with one having a haplotype T-G-G or T-A-G. There was no significant difference between the two groups regarding allelic frequencies, genotypic distribution or the adopted SNP-combinatory haplotype for BSG. These results suggest that NPTN may be involved in genetic susceptibility to schizophrenia."
],
"offsets": [
[
97,
1965
]
]
}
] | [
{
"id": "304",
"type": "SNP & Sequence variations",
"text": [
"promoter polymorphisms in the neuroplastin"
],
"offsets": [
[
30,
72
]
],
"normalized": []
},
{
"id": "305",
"type": "Genes & Molecular Sequences",
"text": [
"promoter polymorphisms in the neuroplastin"
],
"offsets": [
[
30,
72
]
],
"normalized": []
},
{
"id": "306",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
82,
95
]
],
"normalized": []
},
{
"id": "307",
"type": "Genes & Molecular Sequences",
"text": [
"methamphetamine"
],
"offsets": [
[
135,
150
]
],
"normalized": []
},
{
"id": "308",
"type": "Genes & Molecular Sequences",
"text": [
"METH"
],
"offsets": [
[
152,
156
]
],
"normalized": []
},
{
"id": "309",
"type": "Genes & Molecular Sequences",
"text": [
"phencyclidine"
],
"offsets": [
[
162,
175
]
],
"normalized": []
},
{
"id": "310",
"type": "Genes & Molecular Sequences",
"text": [
"PCP)-reactive tags"
],
"offsets": [
[
177,
195
]
],
"normalized": []
},
{
"id": "311",
"type": "Diseases & Disorders",
"text": [
"PCP)-reactive tags"
],
"offsets": [
[
177,
195
]
],
"normalized": []
},
{
"id": "312",
"type": "Genes & Molecular Sequences",
"text": [
"METH/PCP-reactive tags"
],
"offsets": [
[
356,
378
]
],
"normalized": []
},
{
"id": "313",
"type": "Diseases & Disorders",
"text": [
"METH/PCP-reactive tags"
],
"offsets": [
[
356,
378
]
],
"normalized": []
},
{
"id": "314",
"type": "Genes & Molecular Sequences",
"text": [
"PCP"
],
"offsets": [
[
361,
364
]
],
"normalized": []
},
{
"id": "315",
"type": "Diseases & Disorders",
"text": [
"PCP"
],
"offsets": [
[
361,
364
]
],
"normalized": []
},
{
"id": "316",
"type": "Genes & Molecular Sequences",
"text": [
"immunoglobulin"
],
"offsets": [
[
450,
464
]
],
"normalized": []
},
{
"id": "317",
"type": "Genes & Molecular Sequences",
"text": [
"neuroplastin"
],
"offsets": [
[
483,
495
]
],
"normalized": []
},
{
"id": "318",
"type": "Genes & Molecular Sequences",
"text": [
"NPTN"
],
"offsets": [
[
497,
501
]
],
"normalized": []
},
{
"id": "319",
"type": "Genes & Molecular Sequences",
"text": [
"basigin"
],
"offsets": [
[
507,
514
]
],
"normalized": []
},
{
"id": "320",
"type": "Genes & Molecular Sequences",
"text": [
"BSG"
],
"offsets": [
[
516,
519
]
],
"normalized": []
},
{
"id": "321",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
555,
568
]
],
"normalized": []
},
{
"id": "322",
"type": "SNP & Sequence variations",
"text": [
"T Ins/Del"
],
"offsets": [
[
720,
729
]
],
"normalized": []
},
{
"id": "323",
"type": "SNP & Sequence variations",
"text": [
"T/T"
],
"offsets": [
[
789,
792
]
],
"normalized": []
},
{
"id": "324",
"type": "SNP & Sequence variations",
"text": [
"T/Del"
],
"offsets": [
[
796,
801
]
],
"normalized": []
},
{
"id": "325",
"type": "SNP & Sequence variations",
"text": [
"rs3840846 in the 5'-upstream of NPTN"
],
"offsets": [
[
835,
871
]
],
"normalized": []
},
{
"id": "326",
"type": "Genes & Molecular Sequences",
"text": [
"rs3840846 in the 5'-upstream of NPTN"
],
"offsets": [
[
835,
871
]
],
"normalized": []
},
{
"id": "327",
"type": "SNP & Sequence variations",
"text": [
"G/T"
],
"offsets": [
[
946,
949
]
],
"normalized": []
},
{
"id": "328",
"type": "SNP & Sequence variations",
"text": [
"rs3743500"
],
"offsets": [
[
1016,
1025
]
],
"normalized": []
},
{
"id": "329",
"type": "Genes & Molecular Sequences",
"text": [
"NPTN"
],
"offsets": [
[
1048,
1052
]
],
"normalized": []
},
{
"id": "330",
"type": "SNP & Sequence variations",
"text": [
"rs3840846"
],
"offsets": [
[
1102,
1111
]
],
"normalized": []
},
{
"id": "331",
"type": "SNP & Sequence variations",
"text": [
"rs3826047"
],
"offsets": [
[
1113,
1122
]
],
"normalized": []
},
{
"id": "332",
"type": "SNP & Sequence variations",
"text": [
"rs3743500"
],
"offsets": [
[
1127,
1136
]
],
"normalized": []
},
{
"id": "333",
"type": "Genes & Molecular Sequences",
"text": [
"NPTN"
],
"offsets": [
[
1170,
1174
]
],
"normalized": []
},
{
"id": "334",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
1213,
1226
]
],
"normalized": []
},
{
"id": "335",
"type": "SNP & Sequence variations",
"text": [
"T-G-T"
],
"offsets": [
[
1258,
1263
]
],
"normalized": []
},
{
"id": "336",
"type": "SNP & Sequence variations",
"text": [
"del-G-G"
],
"offsets": [
[
1290,
1297
]
],
"normalized": []
},
{
"id": "337",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
1382,
1395
]
],
"normalized": []
},
{
"id": "338",
"type": "SNP & Sequence variations",
"text": [
"T-G-T"
],
"offsets": [
[
1600,
1605
]
],
"normalized": []
},
{
"id": "339",
"type": "SNP & Sequence variations",
"text": [
"T-G-G"
],
"offsets": [
[
1695,
1700
]
],
"normalized": []
},
{
"id": "340",
"type": "SNP & Sequence variations",
"text": [
"T-A-G"
],
"offsets": [
[
1704,
1709
]
],
"normalized": []
},
{
"id": "341",
"type": "Genes & Molecular Sequences",
"text": [
"BSG"
],
"offsets": [
[
1869,
1872
]
],
"normalized": []
},
{
"id": "342",
"type": "Genes & Molecular Sequences",
"text": [
"NPTN"
],
"offsets": [
[
1901,
1905
]
],
"normalized": []
},
{
"id": "343",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
1951,
1964
]
],
"normalized": []
},
{
"id": "344",
"type": "",
"text": [
"rs3840846"
],
"offsets": [
[
1102,
1111
]
],
"normalized": []
},
{
"id": "345",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1382,
1395
]
],
"normalized": []
},
{
"id": "347",
"type": "",
"text": [
"rs3826047"
],
"offsets": [
[
1113,
1122
]
],
"normalized": []
},
{
"id": "348",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1382,
1395
]
],
"normalized": []
},
{
"id": "350",
"type": "",
"text": [
"rs3743500"
],
"offsets": [
[
1127,
1136
]
],
"normalized": []
},
{
"id": "351",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1382,
1395
]
],
"normalized": []
},
{
"id": "353",
"type": "",
"text": [
"T-G-T"
],
"offsets": [
[
1258,
1263
]
],
"normalized": []
},
{
"id": "354",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1382,
1395
]
],
"normalized": []
},
{
"id": "356",
"type": "",
"text": [
"del-G-G"
],
"offsets": [
[
1290,
1297
]
],
"normalized": []
},
{
"id": "357",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1382,
1395
]
],
"normalized": []
},
{
"id": "359",
"type": "",
"text": [
"NPTN"
],
"offsets": [
[
1901,
1905
]
],
"normalized": []
},
{
"id": "360",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1951,
1964
]
],
"normalized": []
},
{
"id": "362",
"type": "",
"text": [
"promoter polymorphisms in the neuroplastin"
],
"offsets": [
[
30,
72
]
],
"normalized": []
},
{
"id": "363",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
82,
95
]
],
"normalized": []
},
{
"id": "365",
"type": "",
"text": [
"NPTN"
],
"offsets": [
[
497,
501
]
],
"normalized": []
},
{
"id": "366",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
555,
568
]
],
"normalized": []
},
{
"id": "368",
"type": "",
"text": [
"NPTN"
],
"offsets": [
[
497,
501
]
],
"normalized": []
},
{
"id": "369",
"type": "",
"text": [
"METH/PCP-reactive tags"
],
"offsets": [
[
356,
378
]
],
"normalized": []
},
{
"id": "371",
"type": "",
"text": [
"PCP"
],
"offsets": [
[
361,
364
]
],
"normalized": []
},
{
"id": "372",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
555,
568
]
],
"normalized": []
},
{
"id": "374",
"type": "",
"text": [
"PCP"
],
"offsets": [
[
361,
364
]
],
"normalized": []
},
{
"id": "375",
"type": "",
"text": [
"METH/PCP-reactive tags"
],
"offsets": [
[
356,
378
]
],
"normalized": []
},
{
"id": "377",
"type": "",
"text": [
"BSG"
],
"offsets": [
[
516,
519
]
],
"normalized": []
},
{
"id": "378",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
555,
568
]
],
"normalized": []
},
{
"id": "380",
"type": "",
"text": [
"BSG"
],
"offsets": [
[
516,
519
]
],
"normalized": []
},
{
"id": "381",
"type": "",
"text": [
"METH/PCP-reactive tags"
],
"offsets": [
[
356,
378
]
],
"normalized": []
},
{
"id": "383",
"type": "",
"text": [
"NPTN"
],
"offsets": [
[
1170,
1174
]
],
"normalized": []
},
{
"id": "384",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1382,
1395
]
],
"normalized": []
},
{
"id": "386",
"type": "",
"text": [
"immunoglobulin"
],
"offsets": [
[
450,
464
]
],
"normalized": []
},
{
"id": "387",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
555,
568
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "346",
"type": "PA",
"arg1_id": "344",
"arg2_id": "345",
"normalized": []
},
{
"id": "349",
"type": "PA",
"arg1_id": "347",
"arg2_id": "348",
"normalized": []
},
{
"id": "352",
"type": "PA",
"arg1_id": "350",
"arg2_id": "351",
"normalized": []
},
{
"id": "355",
"type": "PA",
"arg1_id": "353",
"arg2_id": "354",
"normalized": []
},
{
"id": "358",
"type": "PA",
"arg1_id": "356",
"arg2_id": "357",
"normalized": []
},
{
"id": "361",
"type": "SA",
"arg1_id": "359",
"arg2_id": "360",
"normalized": []
},
{
"id": "364",
"type": "PA",
"arg1_id": "362",
"arg2_id": "363",
"normalized": []
},
{
"id": "367",
"type": "PA",
"arg1_id": "365",
"arg2_id": "366",
"normalized": []
},
{
"id": "370",
"type": "PA",
"arg1_id": "368",
"arg2_id": "369",
"normalized": []
},
{
"id": "373",
"type": "PA",
"arg1_id": "371",
"arg2_id": "372",
"normalized": []
},
{
"id": "376",
"type": "PA",
"arg1_id": "374",
"arg2_id": "375",
"normalized": []
},
{
"id": "379",
"type": "PA",
"arg1_id": "377",
"arg2_id": "378",
"normalized": []
},
{
"id": "382",
"type": "PA",
"arg1_id": "380",
"arg2_id": "381",
"normalized": []
},
{
"id": "385",
"type": "PA",
"arg1_id": "383",
"arg2_id": "384",
"normalized": []
},
{
"id": "388",
"type": "SA",
"arg1_id": "386",
"arg2_id": "387",
"normalized": []
}
] |
390 | 390 | [
{
"id": "391",
"type": "title",
"text": [
"Caspase-3 regulates catalytic activity and scaffolding functions of the protein tyrosine phosphatase PEST, a novel modulator of the apoptotic response."
],
"offsets": [
[
0,
151
]
]
},
{
"id": "392",
"type": "abstract",
"text": [
"The protein tyrosine phosphatase PEST (PTP-PEST) is involved in the regulation of the actin cytoskeleton. Despite the emerging functions attributed to both PTPs and the actin cytoskeleton in apoptosis, the involvement of PTP-PEST in apoptotic cell death remains to be established. Using several cell-based assays, we showed that PTP-PEST participates in the regulation of apoptosis. As apoptosis progressed, a pool of PTP-PEST localized to the edge of retracting lamellipodia. Expression of PTP-PEST also sensitized cells to receptor-mediated apoptosis. Concertedly, specific degradation of PTP-PEST was observed during apoptosis. Pharmacological inhibitors, immunodepletion experiments, and in vitro cleavage assays identified caspase-3 as the primary regulator of PTP-PEST processing during apoptosis. Caspase-3 specifically cleaved PTP-PEST at the (549)DSPD motif and generated fragments, some of which displayed increased catalytic activity. Moreover, caspase-3 regulated PTP-PEST interactions with paxillin, leupaxin, Shc, and PSTPIP. PTP-PEST acted as a scaffolding molecule connecting PSTPIP to additional partners: paxillin, Shc, Csk, and activation of caspase-3 correlated with the modulation of the PTP-PEST adaptor function. In addition, cleavage of PTP-PEST facilitated cellular detachment during apoptosis. Together, our data demonstrate that PTP-PEST actively contributes to the cellular apoptotic response and reveal the importance of caspases as regulators of PTPs in apoptosis."
],
"offsets": [
[
152,
1646
]
]
}
] | [
{
"id": "393",
"type": "Genes & Molecular Sequences",
"text": [
"Caspase-3"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "394",
"type": "Genes & Molecular Sequences",
"text": [
"protein tyrosine phosphatase PEST"
],
"offsets": [
[
72,
105
]
],
"normalized": []
},
{
"id": "395",
"type": "Genes & Molecular Sequences",
"text": [
"tyrosine phosphatase"
],
"offsets": [
[
80,
100
]
],
"normalized": []
},
{
"id": "396",
"type": "Genes & Molecular Sequences",
"text": [
"protein tyrosine phosphatase PEST"
],
"offsets": [
[
156,
189
]
],
"normalized": []
},
{
"id": "397",
"type": "Genes & Molecular Sequences",
"text": [
"tyrosine phosphatase"
],
"offsets": [
[
164,
184
]
],
"normalized": []
},
{
"id": "398",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
191,
199
]
],
"normalized": []
},
{
"id": "399",
"type": "Genes & Molecular Sequences",
"text": [
"actin"
],
"offsets": [
[
238,
243
]
],
"normalized": []
},
{
"id": "400",
"type": "Genes & Molecular Sequences",
"text": [
"PTPs"
],
"offsets": [
[
308,
312
]
],
"normalized": []
},
{
"id": "401",
"type": "Genes & Molecular Sequences",
"text": [
"actin"
],
"offsets": [
[
321,
326
]
],
"normalized": []
},
{
"id": "402",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
373,
381
]
],
"normalized": []
},
{
"id": "403",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
481,
489
]
],
"normalized": []
},
{
"id": "404",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
570,
578
]
],
"normalized": []
},
{
"id": "405",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
643,
651
]
],
"normalized": []
},
{
"id": "406",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
743,
751
]
],
"normalized": []
},
{
"id": "407",
"type": "Genes & Molecular Sequences",
"text": [
"caspase-3"
],
"offsets": [
[
880,
889
]
],
"normalized": []
},
{
"id": "408",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
918,
926
]
],
"normalized": []
},
{
"id": "409",
"type": "Genes & Molecular Sequences",
"text": [
"Caspase-3"
],
"offsets": [
[
956,
965
]
],
"normalized": []
},
{
"id": "410",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
987,
995
]
],
"normalized": []
},
{
"id": "411",
"type": "Genes & Molecular Sequences",
"text": [
"(549)DSPD"
],
"offsets": [
[
1003,
1012
]
],
"normalized": []
},
{
"id": "412",
"type": "Genes & Molecular Sequences",
"text": [
"caspase-3"
],
"offsets": [
[
1108,
1117
]
],
"normalized": []
},
{
"id": "413",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
1128,
1136
]
],
"normalized": []
},
{
"id": "414",
"type": "Genes & Molecular Sequences",
"text": [
"paxillin"
],
"offsets": [
[
1155,
1163
]
],
"normalized": []
},
{
"id": "415",
"type": "Genes & Molecular Sequences",
"text": [
"leupaxin"
],
"offsets": [
[
1165,
1173
]
],
"normalized": []
},
{
"id": "416",
"type": "Genes & Molecular Sequences",
"text": [
"Shc"
],
"offsets": [
[
1175,
1178
]
],
"normalized": []
},
{
"id": "417",
"type": "Genes & Molecular Sequences",
"text": [
"PSTPIP"
],
"offsets": [
[
1184,
1190
]
],
"normalized": []
},
{
"id": "418",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
1192,
1200
]
],
"normalized": []
},
{
"id": "419",
"type": "Genes & Molecular Sequences",
"text": [
"PSTPIP"
],
"offsets": [
[
1244,
1250
]
],
"normalized": []
},
{
"id": "420",
"type": "Genes & Molecular Sequences",
"text": [
"paxillin"
],
"offsets": [
[
1275,
1283
]
],
"normalized": []
},
{
"id": "421",
"type": "Genes & Molecular Sequences",
"text": [
"Shc"
],
"offsets": [
[
1285,
1288
]
],
"normalized": []
},
{
"id": "422",
"type": "Genes & Molecular Sequences",
"text": [
"Csk"
],
"offsets": [
[
1290,
1293
]
],
"normalized": []
},
{
"id": "423",
"type": "Genes & Molecular Sequences",
"text": [
"caspase-3"
],
"offsets": [
[
1313,
1322
]
],
"normalized": []
},
{
"id": "424",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
1361,
1369
]
],
"normalized": []
},
{
"id": "425",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
1413,
1421
]
],
"normalized": []
},
{
"id": "426",
"type": "Genes & Molecular Sequences",
"text": [
"PTP-PEST"
],
"offsets": [
[
1508,
1516
]
],
"normalized": []
},
{
"id": "427",
"type": "Genes & Molecular Sequences",
"text": [
"caspases"
],
"offsets": [
[
1602,
1610
]
],
"normalized": []
},
{
"id": "428",
"type": "Genes & Molecular Sequences",
"text": [
"PTPs"
],
"offsets": [
[
1628,
1632
]
],
"normalized": []
}
] | [] | [] | [] |
430 | 430 | [
{
"id": "431",
"type": "title",
"text": [
"The 2nd ADAO Asbestos Conference."
],
"offsets": [
[
0,
33
]
]
},
{
"id": "432",
"type": "abstract",
"text": [
"On National Asbestos Awareness Day 2006, a conference was held at Mount Sinai, the home ground of Dr. Irving J. Selikoff, who, more than any other single individual, started the debate about occupational hazards in the U.S. Four decades after the pioneering conference on the Biological Effects of Asbestos was organized by Drs. Selikoff and Churg, asbestos victims and their relatives, public health campaigners, medical professionals, journalists and community representatives convened in New York City to assess the progress that had been made in raising public, professional and political awareness of asbestos-related diseases. The report which follows conveys the substance of their presentations and highlights key issues which were discussed.CI - (c) 2006 Wiley-Liss, Inc."
],
"offsets": [
[
34,
814
]
]
}
] | [
{
"id": "433",
"type": "Chemicals & Drugs",
"text": [
"Asbestos"
],
"offsets": [
[
13,
21
]
],
"normalized": []
},
{
"id": "434",
"type": "Chemicals & Drugs",
"text": [
"Asbestos"
],
"offsets": [
[
46,
54
]
],
"normalized": []
},
{
"id": "435",
"type": "Chemicals & Drugs",
"text": [
"Asbestos"
],
"offsets": [
[
332,
340
]
],
"normalized": []
},
{
"id": "436",
"type": "Chemicals & Drugs",
"text": [
"asbestos"
],
"offsets": [
[
383,
391
]
],
"normalized": []
},
{
"id": "437",
"type": "Diseases & Disorders",
"text": [
"asbestos-related diseases"
],
"offsets": [
[
640,
665
]
],
"normalized": []
},
{
"id": "438",
"type": "Chemicals & Drugs",
"text": [
"asbestos-related diseases"
],
"offsets": [
[
640,
665
]
],
"normalized": []
},
{
"id": "439",
"type": "",
"text": [
"asbestos"
],
"offsets": [
[
383,
391
]
],
"normalized": []
},
{
"id": "440",
"type": "",
"text": [
"asbestos-related diseases"
],
"offsets": [
[
640,
665
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "441",
"type": "PA",
"arg1_id": "439",
"arg2_id": "440",
"normalized": []
}
] |
443 | 443 | [
{
"id": "444",
"type": "title",
"text": [
"Novel CCR5 monoclonal antibodies with potent and broad-spectrum anti-HIV activities."
],
"offsets": [
[
0,
84
]
]
},
{
"id": "445",
"type": "abstract",
"text": [
"To identify monoclonal antibodies (mAbs) with high potency and novel recognition sites, more than 25,000 of mouse hybridomas were screened and 4 novel anti-human CCR5 mAbs ROAb12, ROAb13, ROAb14, and ROAb18 showing potent activity in cell-cell fusion (CCF) assay were identified. These mAbs demonstrated potent antiviral activities in both single-cycle HIV infection (IC(50) range: 0.16-4.3 microg/ml) and PBMC viral replication (IC(50) range: 0.02-0.04 microg/ml) assays. These potent antiviral effects were donor-independent. All 4 mAbs were also highly potent in the PhenoSense assay against 29 HIV isolates covering clade A through G. In all antiviral assays, these mAbs showed potency superior to the previously reported mAb 2D7 in side-by-side comparison studies. All 4 mAbs were also fully active against viruses resistant to HIV fusion inhibitor enfuvirtide and CCR5 antagonist maraviroc. Although ROAb12, ROAb14, and ROAb18 inhibited RANTES, MIP1alpha and MIP1beta binding and cell activation, the other novel mAb ROAb13 was inactive in inhibiting cell activation by these three ligands. Furthermore, highly synergistic antiviral effects were found between mAb ROAb13 and 2D7 or ROAb12. In addition, none of these mAbs showed agonist activity or caused internalization of the CCR5 receptor."
],
"offsets": [
[
85,
1384
]
]
}
] | [
{
"id": "446",
"type": "Genes & Molecular Sequences",
"text": [
"CCR5"
],
"offsets": [
[
6,
10
]
],
"normalized": []
},
{
"id": "447",
"type": "Chemicals & Drugs",
"text": [
"monoclonal antibodies"
],
"offsets": [
[
11,
32
]
],
"normalized": []
},
{
"id": "448",
"type": "Genes & Molecular Sequences",
"text": [
"monoclonal antibodies"
],
"offsets": [
[
11,
32
]
],
"normalized": []
},
{
"id": "449",
"type": "Chemicals & Drugs",
"text": [
"monoclonal antibodies"
],
"offsets": [
[
97,
118
]
],
"normalized": []
},
{
"id": "450",
"type": "Chemicals & Drugs",
"text": [
"mAbs"
],
"offsets": [
[
120,
124
]
],
"normalized": []
},
{
"id": "451",
"type": "Genes & Molecular Sequences",
"text": [
"CCR5"
],
"offsets": [
[
247,
251
]
],
"normalized": []
},
{
"id": "452",
"type": "Chemicals & Drugs",
"text": [
"mAbs"
],
"offsets": [
[
252,
256
]
],
"normalized": []
},
{
"id": "453",
"type": "Genes & Molecular Sequences",
"text": [
"mAbs"
],
"offsets": [
[
252,
256
]
],
"normalized": []
},
{
"id": "454",
"type": "Chemicals & Drugs",
"text": [
"ROAb12"
],
"offsets": [
[
257,
263
]
],
"normalized": []
},
{
"id": "455",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb12"
],
"offsets": [
[
257,
263
]
],
"normalized": []
},
{
"id": "456",
"type": "Chemicals & Drugs",
"text": [
"ROAb13"
],
"offsets": [
[
265,
271
]
],
"normalized": []
},
{
"id": "457",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb13"
],
"offsets": [
[
265,
271
]
],
"normalized": []
},
{
"id": "458",
"type": "Chemicals & Drugs",
"text": [
"ROAb14"
],
"offsets": [
[
273,
279
]
],
"normalized": []
},
{
"id": "459",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb14"
],
"offsets": [
[
273,
279
]
],
"normalized": []
},
{
"id": "460",
"type": "Chemicals & Drugs",
"text": [
"ROAb18"
],
"offsets": [
[
285,
291
]
],
"normalized": []
},
{
"id": "461",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb18"
],
"offsets": [
[
285,
291
]
],
"normalized": []
},
{
"id": "462",
"type": "Chemicals & Drugs",
"text": [
"mAbs"
],
"offsets": [
[
371,
375
]
],
"normalized": []
},
{
"id": "463",
"type": "Chemicals & Drugs",
"text": [
"mAbs"
],
"offsets": [
[
619,
623
]
],
"normalized": []
},
{
"id": "464",
"type": "Chemicals & Drugs",
"text": [
"mAbs"
],
"offsets": [
[
755,
759
]
],
"normalized": []
},
{
"id": "465",
"type": "Chemicals & Drugs",
"text": [
"mAb"
],
"offsets": [
[
811,
814
]
],
"normalized": []
},
{
"id": "466",
"type": "Chemicals & Drugs",
"text": [
"2D7"
],
"offsets": [
[
815,
818
]
],
"normalized": []
},
{
"id": "467",
"type": "Genes & Molecular Sequences",
"text": [
"2D7"
],
"offsets": [
[
815,
818
]
],
"normalized": []
},
{
"id": "468",
"type": "Chemicals & Drugs",
"text": [
"mAbs"
],
"offsets": [
[
861,
865
]
],
"normalized": []
},
{
"id": "469",
"type": "Chemicals & Drugs",
"text": [
"HIV fusion inhibitor"
],
"offsets": [
[
918,
938
]
],
"normalized": []
},
{
"id": "470",
"type": "Chemicals & Drugs",
"text": [
"enfuvirtide"
],
"offsets": [
[
939,
950
]
],
"normalized": []
},
{
"id": "471",
"type": "Chemicals & Drugs",
"text": [
"CCR5 antagonist"
],
"offsets": [
[
955,
970
]
],
"normalized": []
},
{
"id": "472",
"type": "Genes & Molecular Sequences",
"text": [
"CCR5 antagonist"
],
"offsets": [
[
955,
970
]
],
"normalized": []
},
{
"id": "473",
"type": "Chemicals & Drugs",
"text": [
"maraviroc"
],
"offsets": [
[
971,
980
]
],
"normalized": []
},
{
"id": "474",
"type": "Chemicals & Drugs",
"text": [
"ROAb12"
],
"offsets": [
[
991,
997
]
],
"normalized": []
},
{
"id": "475",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb12"
],
"offsets": [
[
991,
997
]
],
"normalized": []
},
{
"id": "476",
"type": "Chemicals & Drugs",
"text": [
"ROAb14"
],
"offsets": [
[
999,
1005
]
],
"normalized": []
},
{
"id": "477",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb14"
],
"offsets": [
[
999,
1005
]
],
"normalized": []
},
{
"id": "478",
"type": "Chemicals & Drugs",
"text": [
"ROAb18"
],
"offsets": [
[
1011,
1017
]
],
"normalized": []
},
{
"id": "479",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb18"
],
"offsets": [
[
1011,
1017
]
],
"normalized": []
},
{
"id": "480",
"type": "Genes & Molecular Sequences",
"text": [
"RANTES"
],
"offsets": [
[
1028,
1034
]
],
"normalized": []
},
{
"id": "481",
"type": "Genes & Molecular Sequences",
"text": [
"MIP1alpha"
],
"offsets": [
[
1036,
1045
]
],
"normalized": []
},
{
"id": "482",
"type": "Genes & Molecular Sequences",
"text": [
"MIP1beta"
],
"offsets": [
[
1050,
1058
]
],
"normalized": []
},
{
"id": "483",
"type": "Chemicals & Drugs",
"text": [
"mAb"
],
"offsets": [
[
1104,
1107
]
],
"normalized": []
},
{
"id": "484",
"type": "Chemicals & Drugs",
"text": [
"ROAb13"
],
"offsets": [
[
1108,
1114
]
],
"normalized": []
},
{
"id": "485",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb13"
],
"offsets": [
[
1108,
1114
]
],
"normalized": []
},
{
"id": "486",
"type": "Chemicals & Drugs",
"text": [
"mAb"
],
"offsets": [
[
1251,
1254
]
],
"normalized": []
},
{
"id": "487",
"type": "Chemicals & Drugs",
"text": [
"ROAb13"
],
"offsets": [
[
1255,
1261
]
],
"normalized": []
},
{
"id": "488",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb13"
],
"offsets": [
[
1255,
1261
]
],
"normalized": []
},
{
"id": "489",
"type": "Chemicals & Drugs",
"text": [
"2D7"
],
"offsets": [
[
1266,
1269
]
],
"normalized": []
},
{
"id": "490",
"type": "Genes & Molecular Sequences",
"text": [
"2D7"
],
"offsets": [
[
1266,
1269
]
],
"normalized": []
},
{
"id": "491",
"type": "Chemicals & Drugs",
"text": [
"ROAb12"
],
"offsets": [
[
1273,
1279
]
],
"normalized": []
},
{
"id": "492",
"type": "Genes & Molecular Sequences",
"text": [
"ROAb12"
],
"offsets": [
[
1273,
1279
]
],
"normalized": []
},
{
"id": "493",
"type": "Chemicals & Drugs",
"text": [
"mAbs"
],
"offsets": [
[
1308,
1312
]
],
"normalized": []
},
{
"id": "494",
"type": "Genes & Molecular Sequences",
"text": [
"CCR5"
],
"offsets": [
[
1370,
1374
]
],
"normalized": []
},
{
"id": "495",
"type": "",
"text": [
"ROAb12"
],
"offsets": [
[
991,
997
]
],
"normalized": []
},
{
"id": "496",
"type": "",
"text": [
"RANTES"
],
"offsets": [
[
1028,
1034
]
],
"normalized": []
},
{
"id": "498",
"type": "",
"text": [
"ROAb12"
],
"offsets": [
[
991,
997
]
],
"normalized": []
},
{
"id": "499",
"type": "",
"text": [
"MIP1alpha"
],
"offsets": [
[
1036,
1045
]
],
"normalized": []
},
{
"id": "501",
"type": "",
"text": [
"ROAb12"
],
"offsets": [
[
991,
997
]
],
"normalized": []
},
{
"id": "502",
"type": "",
"text": [
"MIP1beta"
],
"offsets": [
[
1050,
1058
]
],
"normalized": []
},
{
"id": "504",
"type": "",
"text": [
"ROAb13"
],
"offsets": [
[
1108,
1114
]
],
"normalized": []
},
{
"id": "505",
"type": "",
"text": [
"RANTES"
],
"offsets": [
[
1028,
1034
]
],
"normalized": []
},
{
"id": "507",
"type": "",
"text": [
"ROAb13"
],
"offsets": [
[
1108,
1114
]
],
"normalized": []
},
{
"id": "508",
"type": "",
"text": [
"MIP1alpha"
],
"offsets": [
[
1036,
1045
]
],
"normalized": []
},
{
"id": "510",
"type": "",
"text": [
"ROAb13"
],
"offsets": [
[
1108,
1114
]
],
"normalized": []
},
{
"id": "511",
"type": "",
"text": [
"MIP1beta"
],
"offsets": [
[
1050,
1058
]
],
"normalized": []
},
{
"id": "513",
"type": "",
"text": [
"ROAb14"
],
"offsets": [
[
999,
1005
]
],
"normalized": []
},
{
"id": "514",
"type": "",
"text": [
"RANTES"
],
"offsets": [
[
1028,
1034
]
],
"normalized": []
},
{
"id": "516",
"type": "",
"text": [
"ROAb14"
],
"offsets": [
[
999,
1005
]
],
"normalized": []
},
{
"id": "517",
"type": "",
"text": [
"MIP1alpha"
],
"offsets": [
[
1036,
1045
]
],
"normalized": []
},
{
"id": "519",
"type": "",
"text": [
"ROAb14"
],
"offsets": [
[
999,
1005
]
],
"normalized": []
},
{
"id": "520",
"type": "",
"text": [
"MIP1beta"
],
"offsets": [
[
1050,
1058
]
],
"normalized": []
},
{
"id": "522",
"type": "",
"text": [
"ROAb18"
],
"offsets": [
[
1011,
1017
]
],
"normalized": []
},
{
"id": "523",
"type": "",
"text": [
"RANTES"
],
"offsets": [
[
1028,
1034
]
],
"normalized": []
},
{
"id": "525",
"type": "",
"text": [
"ROAb18"
],
"offsets": [
[
1011,
1017
]
],
"normalized": []
},
{
"id": "526",
"type": "",
"text": [
"MIP1alpha"
],
"offsets": [
[
1036,
1045
]
],
"normalized": []
},
{
"id": "528",
"type": "",
"text": [
"ROAb18"
],
"offsets": [
[
1011,
1017
]
],
"normalized": []
},
{
"id": "529",
"type": "",
"text": [
"MIP1beta"
],
"offsets": [
[
1050,
1058
]
],
"normalized": []
},
{
"id": "531",
"type": "",
"text": [
"mAbs"
],
"offsets": [
[
1308,
1312
]
],
"normalized": []
},
{
"id": "532",
"type": "",
"text": [
"CCR5"
],
"offsets": [
[
1370,
1374
]
],
"normalized": []
},
{
"id": "534",
"type": "",
"text": [
"enfuvirtide"
],
"offsets": [
[
939,
950
]
],
"normalized": []
},
{
"id": "535",
"type": "",
"text": [
"CCR5 antagonist"
],
"offsets": [
[
955,
970
]
],
"normalized": []
},
{
"id": "537",
"type": "",
"text": [
"maraviroc"
],
"offsets": [
[
971,
980
]
],
"normalized": []
},
{
"id": "538",
"type": "",
"text": [
"CCR5 antagonist"
],
"offsets": [
[
955,
970
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "497",
"type": "PA",
"arg1_id": "495",
"arg2_id": "496",
"normalized": []
},
{
"id": "500",
"type": "PA",
"arg1_id": "498",
"arg2_id": "499",
"normalized": []
},
{
"id": "503",
"type": "PA",
"arg1_id": "501",
"arg2_id": "502",
"normalized": []
},
{
"id": "506",
"type": "NA",
"arg1_id": "504",
"arg2_id": "505",
"normalized": []
},
{
"id": "509",
"type": "NA",
"arg1_id": "507",
"arg2_id": "508",
"normalized": []
},
{
"id": "512",
"type": "NA",
"arg1_id": "510",
"arg2_id": "511",
"normalized": []
},
{
"id": "515",
"type": "PA",
"arg1_id": "513",
"arg2_id": "514",
"normalized": []
},
{
"id": "518",
"type": "PA",
"arg1_id": "516",
"arg2_id": "517",
"normalized": []
},
{
"id": "521",
"type": "PA",
"arg1_id": "519",
"arg2_id": "520",
"normalized": []
},
{
"id": "524",
"type": "PA",
"arg1_id": "522",
"arg2_id": "523",
"normalized": []
},
{
"id": "527",
"type": "PA",
"arg1_id": "525",
"arg2_id": "526",
"normalized": []
},
{
"id": "530",
"type": "PA",
"arg1_id": "528",
"arg2_id": "529",
"normalized": []
},
{
"id": "533",
"type": "NA",
"arg1_id": "531",
"arg2_id": "532",
"normalized": []
},
{
"id": "536",
"type": "PA",
"arg1_id": "534",
"arg2_id": "535",
"normalized": []
},
{
"id": "539",
"type": "PA",
"arg1_id": "537",
"arg2_id": "538",
"normalized": []
}
] |
541 | 541 | [
{
"id": "542",
"type": "title",
"text": [
"Neuroprotective efficacy of the peroxisome proliferator-activated receptor delta-selective agonists in vitro and in vivo."
],
"offsets": [
[
0,
121
]
]
},
{
"id": "543",
"type": "abstract",
"text": [
"Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and function as ligand-modulated transcription factors that regulate gene expression in many important biological processes. The PPARdelta subtype has the highest expression in the brain and is postulated to play a major role in neuronal cell function; however, the precise physiological roles of this receptor remain to be elucidated. Herein, we show that the high-affinity PPARdelta agonists L-165041 [4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid] and GW501516 [2-methyl4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-triazol-5-yl)-methylsulfanyl)phenoxy acetic acid] protect against cytotoxin-induced SH-SY5Y cell injury in vitro and both ischemic brain injury and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in vivo. In the SH-SY5Y studies, treatment with L-165041 or GW501516 significantly and concentration-dependently attenuated cell death following thapsigargin, 1-methyl-4-phenylpyridinium, or staurosporine exposure, with the extent of damage correlated with the level of caspase-3 inhibition. In the transient (90 min) middle cerebral artery occlusion model of ischemic brain injury in rats, i.c.v. infusion of L-165041 or GW501516 significantly attenuated the ischemic brain damage measured 24 h after reperfusion. Moreover, the PPARdelta agonists also significantly attenuated MPTP-induced depletion of striatal dopamine and related metabolite contents in mouse brain. These results demonstrate that subtype-selective PPARdelta agonists possess antiapoptotic properties in vitro, which may underlie their potential neuroprotective potential in in vivo experimental models of cerebral ischemia and Parkinson's disease (PD). These findings suggest that PPARdelta agonists could be useful tools for understanding the role of PPARdelta in other neurodegenerative disorders, as well as attractive therapeutic candidates for stroke and neurodegenerative diseases such as PD."
],
"offsets": [
[
122,
2149
]
]
}
] | [
{
"id": "544",
"type": "Chemicals & Drugs",
"text": [
"peroxisome proliferator-activated receptor delta-selective agonists"
],
"offsets": [
[
32,
99
]
],
"normalized": []
},
{
"id": "545",
"type": "Genes & Molecular Sequences",
"text": [
"peroxisome proliferator-activated receptor delta-selective agonists"
],
"offsets": [
[
32,
99
]
],
"normalized": []
},
{
"id": "546",
"type": "Genes & Molecular Sequences",
"text": [
"Peroxisome proliferator-activated receptors"
],
"offsets": [
[
122,
165
]
],
"normalized": []
},
{
"id": "547",
"type": "Genes & Molecular Sequences",
"text": [
"PPARs"
],
"offsets": [
[
167,
172
]
],
"normalized": []
},
{
"id": "548",
"type": "Genes & Molecular Sequences",
"text": [
"PPARdelta"
],
"offsets": [
[
351,
360
]
],
"normalized": []
},
{
"id": "549",
"type": "Chemicals & Drugs",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "550",
"type": "Genes & Molecular Sequences",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "551",
"type": "Chemicals & Drugs",
"text": [
"L-165041"
],
"offsets": [
[
616,
624
]
],
"normalized": []
},
{
"id": "552",
"type": "Chemicals & Drugs",
"text": [
"4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid"
],
"offsets": [
[
626,
697
]
],
"normalized": []
},
{
"id": "553",
"type": "Chemicals & Drugs",
"text": [
"GW501516"
],
"offsets": [
[
703,
711
]
],
"normalized": []
},
{
"id": "554",
"type": "Chemicals & Drugs",
"text": [
"2-methyl4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-triazol-5-yl)-methylsulfanyl)phenoxy acetic acid"
],
"offsets": [
[
713,
814
]
],
"normalized": []
},
{
"id": "555",
"type": "Chemicals & Drugs",
"text": [
"1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine"
],
"offsets": [
[
914,
958
]
],
"normalized": []
},
{
"id": "556",
"type": "Chemicals & Drugs",
"text": [
"MPTP"
],
"offsets": [
[
960,
964
]
],
"normalized": []
},
{
"id": "557",
"type": "Chemicals & Drugs",
"text": [
"L-165041"
],
"offsets": [
[
1028,
1036
]
],
"normalized": []
},
{
"id": "558",
"type": "Chemicals & Drugs",
"text": [
"GW501516"
],
"offsets": [
[
1040,
1048
]
],
"normalized": []
},
{
"id": "559",
"type": "Chemicals & Drugs",
"text": [
"thapsigargin"
],
"offsets": [
[
1125,
1137
]
],
"normalized": []
},
{
"id": "560",
"type": "Chemicals & Drugs",
"text": [
"1-methyl-4-phenylpyridinium"
],
"offsets": [
[
1139,
1166
]
],
"normalized": []
},
{
"id": "561",
"type": "Chemicals & Drugs",
"text": [
"staurosporine"
],
"offsets": [
[
1171,
1184
]
],
"normalized": []
},
{
"id": "562",
"type": "Genes & Molecular Sequences",
"text": [
"caspase-3"
],
"offsets": [
[
1250,
1259
]
],
"normalized": []
},
{
"id": "563",
"type": "Chemicals & Drugs",
"text": [
"L-165041"
],
"offsets": [
[
1390,
1398
]
],
"normalized": []
},
{
"id": "564",
"type": "Chemicals & Drugs",
"text": [
"GW501516"
],
"offsets": [
[
1402,
1410
]
],
"normalized": []
},
{
"id": "565",
"type": "Chemicals & Drugs",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1509,
1527
]
],
"normalized": []
},
{
"id": "566",
"type": "Genes & Molecular Sequences",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1509,
1527
]
],
"normalized": []
},
{
"id": "567",
"type": "Chemicals & Drugs",
"text": [
"MPTP"
],
"offsets": [
[
1558,
1562
]
],
"normalized": []
},
{
"id": "568",
"type": "Genes & Molecular Sequences",
"text": [
"dopamine"
],
"offsets": [
[
1593,
1601
]
],
"normalized": []
},
{
"id": "569",
"type": "Chemicals & Drugs",
"text": [
"dopamine"
],
"offsets": [
[
1593,
1601
]
],
"normalized": []
},
{
"id": "570",
"type": "Chemicals & Drugs",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1699,
1717
]
],
"normalized": []
},
{
"id": "571",
"type": "Genes & Molecular Sequences",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1699,
1717
]
],
"normalized": []
},
{
"id": "572",
"type": "Chemicals & Drugs",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1932,
1950
]
],
"normalized": []
},
{
"id": "573",
"type": "Genes & Molecular Sequences",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1932,
1950
]
],
"normalized": []
},
{
"id": "574",
"type": "Genes & Molecular Sequences",
"text": [
"PPARdelta"
],
"offsets": [
[
2003,
2012
]
],
"normalized": []
},
{
"id": "575",
"type": "",
"text": [
"L-165041"
],
"offsets": [
[
1028,
1036
]
],
"normalized": []
},
{
"id": "576",
"type": "",
"text": [
"caspase-3"
],
"offsets": [
[
1250,
1259
]
],
"normalized": []
},
{
"id": "578",
"type": "",
"text": [
"GW501516"
],
"offsets": [
[
1040,
1048
]
],
"normalized": []
},
{
"id": "579",
"type": "",
"text": [
"caspase-3"
],
"offsets": [
[
1250,
1259
]
],
"normalized": []
},
{
"id": "581",
"type": "",
"text": [
"MPTP"
],
"offsets": [
[
1558,
1562
]
],
"normalized": []
},
{
"id": "582",
"type": "",
"text": [
"dopamine"
],
"offsets": [
[
1593,
1601
]
],
"normalized": []
},
{
"id": "584",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1932,
1950
]
],
"normalized": []
},
{
"id": "585",
"type": "",
"text": [
"PPARdelta"
],
"offsets": [
[
2003,
2012
]
],
"normalized": []
},
{
"id": "587",
"type": "",
"text": [
"L-165041"
],
"offsets": [
[
616,
624
]
],
"normalized": []
},
{
"id": "588",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "590",
"type": "",
"text": [
"4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid"
],
"offsets": [
[
626,
697
]
],
"normalized": []
},
{
"id": "591",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "593",
"type": "",
"text": [
"GW501516"
],
"offsets": [
[
703,
711
]
],
"normalized": []
},
{
"id": "594",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "596",
"type": "",
"text": [
"2-methyl4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-triazol-5-yl)-methylsulfanyl)phenoxy acetic acid"
],
"offsets": [
[
713,
814
]
],
"normalized": []
},
{
"id": "597",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "599",
"type": "",
"text": [
"1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine"
],
"offsets": [
[
914,
958
]
],
"normalized": []
},
{
"id": "600",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "602",
"type": "",
"text": [
"MPTP"
],
"offsets": [
[
960,
964
]
],
"normalized": []
},
{
"id": "603",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
597,
615
]
],
"normalized": []
},
{
"id": "605",
"type": "",
"text": [
"dopamine"
],
"offsets": [
[
1593,
1601
]
],
"normalized": []
},
{
"id": "606",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1509,
1527
]
],
"normalized": []
},
{
"id": "608",
"type": "",
"text": [
"MPTP"
],
"offsets": [
[
1558,
1562
]
],
"normalized": []
},
{
"id": "609",
"type": "",
"text": [
"PPARdelta agonists"
],
"offsets": [
[
1509,
1527
]
],
"normalized": []
},
{
"id": "611",
"type": "",
"text": [
"thapsigargin"
],
"offsets": [
[
1125,
1137
]
],
"normalized": []
},
{
"id": "612",
"type": "",
"text": [
"caspase-3"
],
"offsets": [
[
1250,
1259
]
],
"normalized": []
},
{
"id": "614",
"type": "",
"text": [
"1-methyl-4-phenylpyridinium"
],
"offsets": [
[
1139,
1166
]
],
"normalized": []
},
{
"id": "615",
"type": "",
"text": [
"caspase-3"
],
"offsets": [
[
1250,
1259
]
],
"normalized": []
},
{
"id": "617",
"type": "",
"text": [
"staurosporine"
],
"offsets": [
[
1171,
1184
]
],
"normalized": []
},
{
"id": "618",
"type": "",
"text": [
"caspase-3"
],
"offsets": [
[
1250,
1259
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "577",
"type": "PA",
"arg1_id": "575",
"arg2_id": "576",
"normalized": []
},
{
"id": "580",
"type": "PA",
"arg1_id": "578",
"arg2_id": "579",
"normalized": []
},
{
"id": "583",
"type": "PA",
"arg1_id": "581",
"arg2_id": "582",
"normalized": []
},
{
"id": "586",
"type": "SA",
"arg1_id": "584",
"arg2_id": "585",
"normalized": []
},
{
"id": "589",
"type": "PA",
"arg1_id": "587",
"arg2_id": "588",
"normalized": []
},
{
"id": "592",
"type": "PA",
"arg1_id": "590",
"arg2_id": "591",
"normalized": []
},
{
"id": "595",
"type": "PA",
"arg1_id": "593",
"arg2_id": "594",
"normalized": []
},
{
"id": "598",
"type": "PA",
"arg1_id": "596",
"arg2_id": "597",
"normalized": []
},
{
"id": "601",
"type": "PA",
"arg1_id": "599",
"arg2_id": "600",
"normalized": []
},
{
"id": "604",
"type": "PA",
"arg1_id": "602",
"arg2_id": "603",
"normalized": []
},
{
"id": "607",
"type": "SA",
"arg1_id": "605",
"arg2_id": "606",
"normalized": []
},
{
"id": "610",
"type": "SA",
"arg1_id": "608",
"arg2_id": "609",
"normalized": []
},
{
"id": "613",
"type": "PA",
"arg1_id": "611",
"arg2_id": "612",
"normalized": []
},
{
"id": "616",
"type": "PA",
"arg1_id": "614",
"arg2_id": "615",
"normalized": []
},
{
"id": "619",
"type": "PA",
"arg1_id": "617",
"arg2_id": "618",
"normalized": []
}
] |
621 | 621 | [
{
"id": "622",
"type": "title",
"text": [
"Spinal cord infarction secondary to cocaine use."
],
"offsets": [
[
0,
48
]
]
},
{
"id": "623",
"type": "abstract",
"text": [
"A 27-yr-old woman recreationally inhaled cocaine. Several hours later, she noted chest tightness, back and neck pain, and later bilateral upper-extremity weakness. Physical examination revealed flaccid paresis of the upper extremities. Spasticity at 2 mos after injury, but no detectable weakness, developed in the lower extremities. Cocaine was detected in her urine. Magnetic resonance imaging showed hyperintensity in the anterior cervicothoracic spinal cord. Electrodiagnostic studies of the upper extremities were consistent with anterior horn cell death. Cocaine abuse is associated with cerebrovascular events; spinal cord effects are rarely reported. The patient seems to have an infarct in the anterior spinal artery distribution, with clinical, imaging, and electrodiagnostic findings of upper-extremity lower-motor neuron injury, accompanied by spasticity of the lower extremities. Gray matter has increased susceptibility to ischemia compared with white matter, producing flaccid weakness in the cervical region with isolated arm weakness. Although uncommon, cocaine abuse can cause spinal cord infarction."
],
"offsets": [
[
49,
1167
]
]
}
] | [
{
"id": "624",
"type": "Diseases & Disorders",
"text": [
"Spinal cord infarction"
],
"offsets": [
[
0,
22
]
],
"normalized": []
},
{
"id": "625",
"type": "Diseases & Disorders",
"text": [
"secondary"
],
"offsets": [
[
23,
32
]
],
"normalized": []
},
{
"id": "626",
"type": "Chemicals & Drugs",
"text": [
"cocaine"
],
"offsets": [
[
36,
43
]
],
"normalized": []
},
{
"id": "627",
"type": "Chemicals & Drugs",
"text": [
"cocaine"
],
"offsets": [
[
90,
97
]
],
"normalized": []
},
{
"id": "628",
"type": "Diseases & Disorders",
"text": [
"chest tightness"
],
"offsets": [
[
130,
145
]
],
"normalized": []
},
{
"id": "629",
"type": "Diseases & Disorders",
"text": [
"neck pain"
],
"offsets": [
[
156,
165
]
],
"normalized": []
},
{
"id": "630",
"type": "Diseases & Disorders",
"text": [
"weakness"
],
"offsets": [
[
203,
211
]
],
"normalized": []
},
{
"id": "631",
"type": "Diseases & Disorders",
"text": [
"flaccid paresis"
],
"offsets": [
[
243,
258
]
],
"normalized": []
},
{
"id": "632",
"type": "Diseases & Disorders",
"text": [
"Spasticity"
],
"offsets": [
[
285,
295
]
],
"normalized": []
},
{
"id": "633",
"type": "Diseases & Disorders",
"text": [
"mos"
],
"offsets": [
[
301,
304
]
],
"normalized": []
},
{
"id": "634",
"type": "Diseases & Disorders",
"text": [
"weakness"
],
"offsets": [
[
337,
345
]
],
"normalized": []
},
{
"id": "635",
"type": "Chemicals & Drugs",
"text": [
"Cocaine"
],
"offsets": [
[
383,
390
]
],
"normalized": []
},
{
"id": "636",
"type": "Chemicals & Drugs",
"text": [
"her"
],
"offsets": [
[
407,
410
]
],
"normalized": []
},
{
"id": "637",
"type": "Diseases & Disorders",
"text": [
"anterior"
],
"offsets": [
[
474,
482
]
],
"normalized": []
},
{
"id": "638",
"type": "Diseases & Disorders",
"text": [
"anterior"
],
"offsets": [
[
584,
592
]
],
"normalized": []
},
{
"id": "639",
"type": "Chemicals & Drugs",
"text": [
"Cocaine"
],
"offsets": [
[
610,
617
]
],
"normalized": []
},
{
"id": "640",
"type": "Diseases & Disorders",
"text": [
"Cocaine"
],
"offsets": [
[
610,
617
]
],
"normalized": []
},
{
"id": "641",
"type": "Diseases & Disorders",
"text": [
"cerebrovascular events"
],
"offsets": [
[
643,
665
]
],
"normalized": []
},
{
"id": "642",
"type": "Diseases & Disorders",
"text": [
"spinal cord effects"
],
"offsets": [
[
667,
686
]
],
"normalized": []
},
{
"id": "643",
"type": "Diseases & Disorders",
"text": [
"infarct"
],
"offsets": [
[
737,
744
]
],
"normalized": []
},
{
"id": "644",
"type": "Diseases & Disorders",
"text": [
"anterior"
],
"offsets": [
[
752,
760
]
],
"normalized": []
},
{
"id": "645",
"type": "Diseases & Disorders",
"text": [
"artery"
],
"offsets": [
[
768,
774
]
],
"normalized": []
},
{
"id": "646",
"type": "Diseases & Disorders",
"text": [
"spasticity"
],
"offsets": [
[
905,
915
]
],
"normalized": []
},
{
"id": "647",
"type": "Diseases & Disorders",
"text": [
"ischemia"
],
"offsets": [
[
986,
994
]
],
"normalized": []
},
{
"id": "648",
"type": "Diseases & Disorders",
"text": [
"weakness"
],
"offsets": [
[
1041,
1049
]
],
"normalized": []
},
{
"id": "649",
"type": "Diseases & Disorders",
"text": [
"arm weakness"
],
"offsets": [
[
1087,
1099
]
],
"normalized": []
},
{
"id": "650",
"type": "Chemicals & Drugs",
"text": [
"cocaine"
],
"offsets": [
[
1120,
1127
]
],
"normalized": []
},
{
"id": "651",
"type": "Diseases & Disorders",
"text": [
"cocaine"
],
"offsets": [
[
1120,
1127
]
],
"normalized": []
},
{
"id": "652",
"type": "Diseases & Disorders",
"text": [
"spinal cord infarction"
],
"offsets": [
[
1144,
1166
]
],
"normalized": []
},
{
"id": "653",
"type": "",
"text": [
"cocaine"
],
"offsets": [
[
36,
43
]
],
"normalized": []
},
{
"id": "654",
"type": "",
"text": [
"Spinal cord infarction"
],
"offsets": [
[
0,
22
]
],
"normalized": []
},
{
"id": "656",
"type": "",
"text": [
"Cocaine"
],
"offsets": [
[
610,
617
]
],
"normalized": []
},
{
"id": "657",
"type": "",
"text": [
"cerebrovascular events"
],
"offsets": [
[
643,
665
]
],
"normalized": []
},
{
"id": "659",
"type": "",
"text": [
"Cocaine"
],
"offsets": [
[
610,
617
]
],
"normalized": []
},
{
"id": "660",
"type": "",
"text": [
"spinal cord effects"
],
"offsets": [
[
667,
686
]
],
"normalized": []
},
{
"id": "662",
"type": "",
"text": [
"cocaine"
],
"offsets": [
[
1120,
1127
]
],
"normalized": []
},
{
"id": "663",
"type": "",
"text": [
"spinal cord infarction"
],
"offsets": [
[
1144,
1166
]
],
"normalized": []
},
{
"id": "665",
"type": "",
"text": [
"cocaine"
],
"offsets": [
[
36,
43
]
],
"normalized": []
},
{
"id": "666",
"type": "",
"text": [
"secondary"
],
"offsets": [
[
23,
32
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "655",
"type": "PA",
"arg1_id": "653",
"arg2_id": "654",
"normalized": []
},
{
"id": "658",
"type": "PA",
"arg1_id": "656",
"arg2_id": "657",
"normalized": []
},
{
"id": "661",
"type": "PA",
"arg1_id": "659",
"arg2_id": "660",
"normalized": []
},
{
"id": "664",
"type": "PA",
"arg1_id": "662",
"arg2_id": "663",
"normalized": []
},
{
"id": "667",
"type": "PA",
"arg1_id": "665",
"arg2_id": "666",
"normalized": []
}
] |
669 | 669 | [
{
"id": "670",
"type": "title",
"text": [
"The variation in Fas localization and the changes in Fas expression level upon stimulation with growth factors."
],
"offsets": [
[
0,
111
]
]
},
{
"id": "671",
"type": "abstract",
"text": [
"Although Fas (APO-1/CD95) is well known as a death receptor, its stimulation occasionally fails to induce apoptosis in malignant cells. On the contrary, Fas is reported to advance the cell cycle in cancer cells. Therefore, we investigated roles of Fas in cell growth and apoptosis using human lung cancer cell lines. Fas was localized in the cytoplasm in exponentially growing cells, whereas only confluent cells expressed Fas on the cell membrane. A stimulation of confluent cells by either of EGF, IGF-I or VEGF induced once a decrease in Fas expression level and its sequential recovery. Fas expression levels in confluent cells were negatively correlated with cell doubling times (r=0.757, p=0.0088). Fas remained on the cell membrane of IgM-treated cells even after the growth factor stimulation, leading to apoptosis with abnormal mitosis, whereas the same stimulation induced Fas internalization in IgG(1)-treated cells. From these results, we suggest that Fas remaining on the cell membrane amplifies to induce apoptosis. Conversely, Fas internalization may enable cancer cells to escape from apoptosis. Our results suggest that growth factor may contribute to the resistance of cancer cells to Fas-mediated apoptosis in an autocrine or paracrine fashion."
],
"offsets": [
[
112,
1375
]
]
}
] | [
{
"id": "672",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
17,
20
]
],
"normalized": []
},
{
"id": "673",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
53,
56
]
],
"normalized": []
},
{
"id": "674",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
121,
124
]
],
"normalized": []
},
{
"id": "675",
"type": "Genes & Molecular Sequences",
"text": [
"APO-1/CD95"
],
"offsets": [
[
126,
136
]
],
"normalized": []
},
{
"id": "676",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
265,
268
]
],
"normalized": []
},
{
"id": "677",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
360,
363
]
],
"normalized": []
},
{
"id": "678",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
429,
432
]
],
"normalized": []
},
{
"id": "679",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
535,
538
]
],
"normalized": []
},
{
"id": "680",
"type": "Genes & Molecular Sequences",
"text": [
"EGF"
],
"offsets": [
[
607,
610
]
],
"normalized": []
},
{
"id": "681",
"type": "Chemicals & Drugs",
"text": [
"EGF"
],
"offsets": [
[
607,
610
]
],
"normalized": []
},
{
"id": "682",
"type": "Genes & Molecular Sequences",
"text": [
"IGF-I"
],
"offsets": [
[
612,
617
]
],
"normalized": []
},
{
"id": "683",
"type": "Chemicals & Drugs",
"text": [
"IGF-I"
],
"offsets": [
[
612,
617
]
],
"normalized": []
},
{
"id": "684",
"type": "Genes & Molecular Sequences",
"text": [
"VEGF"
],
"offsets": [
[
621,
625
]
],
"normalized": []
},
{
"id": "685",
"type": "Chemicals & Drugs",
"text": [
"VEGF"
],
"offsets": [
[
621,
625
]
],
"normalized": []
},
{
"id": "686",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
653,
656
]
],
"normalized": []
},
{
"id": "687",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
703,
706
]
],
"normalized": []
},
{
"id": "688",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
817,
820
]
],
"normalized": []
},
{
"id": "689",
"type": "Genes & Molecular Sequences",
"text": [
"IgM"
],
"offsets": [
[
854,
857
]
],
"normalized": []
},
{
"id": "690",
"type": "Genes & Molecular Sequences",
"text": [
"growth factor"
],
"offsets": [
[
887,
900
]
],
"normalized": []
},
{
"id": "691",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
995,
998
]
],
"normalized": []
},
{
"id": "692",
"type": "Genes & Molecular Sequences",
"text": [
"IgG(1)"
],
"offsets": [
[
1018,
1024
]
],
"normalized": []
},
{
"id": "693",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
1076,
1079
]
],
"normalized": []
},
{
"id": "694",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
1154,
1157
]
],
"normalized": []
},
{
"id": "695",
"type": "Genes & Molecular Sequences",
"text": [
"growth factor"
],
"offsets": [
[
1249,
1262
]
],
"normalized": []
},
{
"id": "696",
"type": "Genes & Molecular Sequences",
"text": [
"Fas"
],
"offsets": [
[
1315,
1318
]
],
"normalized": []
},
{
"id": "697",
"type": "",
"text": [
"EGF"
],
"offsets": [
[
607,
610
]
],
"normalized": []
},
{
"id": "698",
"type": "",
"text": [
"Fas"
],
"offsets": [
[
653,
656
]
],
"normalized": []
},
{
"id": "700",
"type": "",
"text": [
"IGF-I"
],
"offsets": [
[
612,
617
]
],
"normalized": []
},
{
"id": "701",
"type": "",
"text": [
"Fas"
],
"offsets": [
[
653,
656
]
],
"normalized": []
},
{
"id": "703",
"type": "",
"text": [
"VEGF"
],
"offsets": [
[
621,
625
]
],
"normalized": []
},
{
"id": "704",
"type": "",
"text": [
"Fas"
],
"offsets": [
[
653,
656
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "699",
"type": "PA",
"arg1_id": "697",
"arg2_id": "698",
"normalized": []
},
{
"id": "702",
"type": "PA",
"arg1_id": "700",
"arg2_id": "701",
"normalized": []
},
{
"id": "705",
"type": "PA",
"arg1_id": "703",
"arg2_id": "704",
"normalized": []
}
] |
707 | 707 | [
{
"id": "708",
"type": "title",
"text": [
"Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells."
],
"offsets": [
[
0,
146
]
]
},
{
"id": "709",
"type": "abstract",
"text": [
"Exposure of adult humans to manganese (Mn) has long been known to cause neurotoxicity. Recent evidence also suggests that exposure of children to Mn is associated with developmental neurotoxicity. Astrocytes are critical for the proper functioning of the nervous system, and they play active roles in neurogenesis, synaptogenesis and synaptic neurotransmission. In this report, to help elucidate the molecular events underlying Mn neurotoxicity, we systematically identified the molecular targets of Mn in primary human astrocytes at a genome-wide level, by using microarray gene expression profiling and computational data analysis algorithms. We found that Mn altered the expression of diverse genes ranging from those encoding cytokines and transporters to signal transducers and transcriptional regulators. Particularly, 28 genes encoding proinflammatory chemokines, cytokines and related functions were up-regulated, whereas 15 genes encoding functions involved in DNA replication and repair and cell cycle checkpoint control were down-regulated. Consistent with the increased expression of proinflammatory factors, analysis of common regulators revealed that 16 targets known to be positively affected by the interferon-gamma signaling pathway were up-regulated by Mn(2+). In addition, 68 genes were found to be similarly up- or down-regulated by both Mn(2+) and hypoxia. These results from genomic analysis are further supported by data from real-time RT-PCR, Western blotting, flow cytometric and toxicological analyses. Together, these analyses show that Mn(2+) selectively affects cell cycle progression, the expression of hypoxia-responsive genes, and the expression of proinflammatory factors in primary human astrocytes. These results provide important insights into the molecular mechanisms underlying Mn neurotoxicity."
],
"offsets": [
[
147,
1980
]
]
}
] | [
{
"id": "710",
"type": "Chemicals & Drugs",
"text": [
"manganese"
],
"offsets": [
[
65,
74
]
],
"normalized": []
},
{
"id": "711",
"type": "Chemicals & Drugs",
"text": [
"manganese"
],
"offsets": [
[
175,
184
]
],
"normalized": []
},
{
"id": "712",
"type": "Chemicals & Drugs",
"text": [
"Mn"
],
"offsets": [
[
186,
188
]
],
"normalized": []
},
{
"id": "713",
"type": "Chemicals & Drugs",
"text": [
"Mn"
],
"offsets": [
[
293,
295
]
],
"normalized": []
},
{
"id": "714",
"type": "Chemicals & Drugs",
"text": [
"Mn"
],
"offsets": [
[
575,
577
]
],
"normalized": []
},
{
"id": "715",
"type": "Chemicals & Drugs",
"text": [
"Mn"
],
"offsets": [
[
647,
649
]
],
"normalized": []
},
{
"id": "716",
"type": "Chemicals & Drugs",
"text": [
"Mn"
],
"offsets": [
[
806,
808
]
],
"normalized": []
},
{
"id": "717",
"type": "Genes & Molecular Sequences",
"text": [
"cytokines"
],
"offsets": [
[
877,
886
]
],
"normalized": []
},
{
"id": "718",
"type": "Genes & Molecular Sequences",
"text": [
"transporters"
],
"offsets": [
[
891,
903
]
],
"normalized": []
},
{
"id": "719",
"type": "Genes & Molecular Sequences",
"text": [
"signal transducers"
],
"offsets": [
[
907,
925
]
],
"normalized": []
},
{
"id": "720",
"type": "Genes & Molecular Sequences",
"text": [
"transcriptional regulators"
],
"offsets": [
[
930,
956
]
],
"normalized": []
},
{
"id": "721",
"type": "Genes & Molecular Sequences",
"text": [
"proinflammatory chemokines"
],
"offsets": [
[
990,
1016
]
],
"normalized": []
},
{
"id": "722",
"type": "Genes & Molecular Sequences",
"text": [
"cytokines"
],
"offsets": [
[
1018,
1027
]
],
"normalized": []
},
{
"id": "723",
"type": "Chemicals & Drugs",
"text": [
"Mn(2+)"
],
"offsets": [
[
1418,
1424
]
],
"normalized": []
},
{
"id": "724",
"type": "Chemicals & Drugs",
"text": [
"Mn(2+)"
],
"offsets": [
[
1505,
1511
]
],
"normalized": []
},
{
"id": "725",
"type": "Chemicals & Drugs",
"text": [
"Mn(2+)"
],
"offsets": [
[
1711,
1717
]
],
"normalized": []
},
{
"id": "726",
"type": "Chemicals & Drugs",
"text": [
"Mn"
],
"offsets": [
[
1963,
1965
]
],
"normalized": []
},
{
"id": "727",
"type": "",
"text": [
"Mn"
],
"offsets": [
[
806,
808
]
],
"normalized": []
},
{
"id": "728",
"type": "",
"text": [
"cytokines"
],
"offsets": [
[
877,
886
]
],
"normalized": []
},
{
"id": "730",
"type": "",
"text": [
"Mn"
],
"offsets": [
[
806,
808
]
],
"normalized": []
},
{
"id": "731",
"type": "",
"text": [
"transporters"
],
"offsets": [
[
891,
903
]
],
"normalized": []
},
{
"id": "733",
"type": "",
"text": [
"Mn"
],
"offsets": [
[
806,
808
]
],
"normalized": []
},
{
"id": "734",
"type": "",
"text": [
"signal transducers"
],
"offsets": [
[
907,
925
]
],
"normalized": []
},
{
"id": "736",
"type": "",
"text": [
"Mn"
],
"offsets": [
[
806,
808
]
],
"normalized": []
},
{
"id": "737",
"type": "",
"text": [
"transcriptional regulators"
],
"offsets": [
[
930,
956
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "729",
"type": "PA",
"arg1_id": "727",
"arg2_id": "728",
"normalized": []
},
{
"id": "732",
"type": "PA",
"arg1_id": "730",
"arg2_id": "731",
"normalized": []
},
{
"id": "735",
"type": "PA",
"arg1_id": "733",
"arg2_id": "734",
"normalized": []
},
{
"id": "738",
"type": "PA",
"arg1_id": "736",
"arg2_id": "737",
"normalized": []
}
] |
740 | 740 | [
{
"id": "741",
"type": "title",
"text": [
"The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells."
],
"offsets": [
[
0,
178
]
]
},
{
"id": "742",
"type": "abstract",
"text": [
"Gene therapy of cancer using adenovirus as a single treatment modality has met limited success and efforts to enhance therapeutic outcomes have included combination of gene therapy with chemotherapy. The goal of this study was to investigate which chemotherapeutic agents may be suitable for combination with gene therapy of prostate cancer. Using an adenovirus expressing green fluorescent protein (GFP), we determined the effect of cisplatin, gemcitabine, doxorubicin, depsipeptide and MS-275 on adenoviral infectivity and transgene expression in LNCaP cells. We found that the two histone deacetylase inhibitors (HDACi), depsipeptide and MS-275, and to a lesser extent doxorubicin, increased infectivity and transgene expression. However, only the HDACi selectively increased infectivity in LNCaP cells while doxorubicin increased infectivity to a greater extent in normal prostate epithelial cells (PrEC). The increase in infectivity but not transgene expression correlated to increased surface expression of coxsackie and adenovirus receptor (CAR). Increased transgene expression following infection with an adenovirus expressing tumor necrosis factor-related apoptosis inducing ligand (TRAIL) was observed only in LNCaP cells treated with depsipeptide or MS-275. Combination of TRAIL gene therapy with HDACi but not doxorubicin resulted in increased induction of apoptosis in LNCaP cells. In contrast, apoptosis was not enhanced by HDACi in normal PrEC. These results suggest that combination of HDACi with adenoviral TRAIL gene therapy may be a new therapeutic approach for the treatment of prostate cancer that warrants further investigation."
],
"offsets": [
[
179,
1829
]
]
}
] | [
{
"id": "743",
"type": "Genes & Molecular Sequences",
"text": [
"TRAIL"
],
"offsets": [
[
68,
73
]
],
"normalized": []
},
{
"id": "744",
"type": "Diseases & Disorders",
"text": [
"prostate cancer"
],
"offsets": [
[
96,
111
]
],
"normalized": []
},
{
"id": "745",
"type": "Diseases & Disorders",
"text": [
"adverse effects"
],
"offsets": [
[
126,
141
]
],
"normalized": []
},
{
"id": "746",
"type": "Diseases & Disorders",
"text": [
"cancer"
],
"offsets": [
[
195,
201
]
],
"normalized": []
},
{
"id": "747",
"type": "Diseases & Disorders",
"text": [
"adenovirus"
],
"offsets": [
[
208,
218
]
],
"normalized": []
},
{
"id": "748",
"type": "Diseases & Disorders",
"text": [
"met"
],
"offsets": [
[
254,
257
]
],
"normalized": []
},
{
"id": "749",
"type": "Diseases & Disorders",
"text": [
"prostate cancer"
],
"offsets": [
[
504,
519
]
],
"normalized": []
},
{
"id": "750",
"type": "Diseases & Disorders",
"text": [
"adenovirus"
],
"offsets": [
[
530,
540
]
],
"normalized": []
},
{
"id": "751",
"type": "Genes & Molecular Sequences",
"text": [
"green fluorescent protein"
],
"offsets": [
[
552,
577
]
],
"normalized": []
},
{
"id": "752",
"type": "Genes & Molecular Sequences",
"text": [
"GFP"
],
"offsets": [
[
579,
582
]
],
"normalized": []
},
{
"id": "753",
"type": "Genes & Molecular Sequences",
"text": [
"coxsackie and adenovirus receptor"
],
"offsets": [
[
1192,
1225
]
],
"normalized": []
},
{
"id": "754",
"type": "Diseases & Disorders",
"text": [
"adenovirus"
],
"offsets": [
[
1206,
1216
]
],
"normalized": []
},
{
"id": "755",
"type": "Genes & Molecular Sequences",
"text": [
"CAR"
],
"offsets": [
[
1227,
1230
]
],
"normalized": []
},
{
"id": "756",
"type": "Diseases & Disorders",
"text": [
"CAR"
],
"offsets": [
[
1227,
1230
]
],
"normalized": []
},
{
"id": "757",
"type": "Diseases & Disorders",
"text": [
"infection with an adenovirus"
],
"offsets": [
[
1274,
1302
]
],
"normalized": []
},
{
"id": "758",
"type": "Genes & Molecular Sequences",
"text": [
"tumor necrosis factor-related apoptosis inducing ligand "
],
"offsets": [
[
1314,
1370
]
],
"normalized": []
},
{
"id": "759",
"type": "Genes & Molecular Sequences",
"text": [
"TRAIL"
],
"offsets": [
[
1371,
1376
]
],
"normalized": []
},
{
"id": "760",
"type": "Genes & Molecular Sequences",
"text": [
"TRAIL"
],
"offsets": [
[
1463,
1468
]
],
"normalized": []
},
{
"id": "761",
"type": "Genes & Molecular Sequences",
"text": [
"TRAIL"
],
"offsets": [
[
1703,
1708
]
],
"normalized": []
},
{
"id": "762",
"type": "Diseases & Disorders",
"text": [
"prostate cancer"
],
"offsets": [
[
1777,
1792
]
],
"normalized": []
},
{
"id": "763",
"type": "",
"text": [
"tumor necrosis factor-related apoptosis inducing ligand "
],
"offsets": [
[
1314,
1370
]
],
"normalized": []
},
{
"id": "764",
"type": "",
"text": [
"infection with an adenovirus"
],
"offsets": [
[
1274,
1302
]
],
"normalized": []
},
{
"id": "766",
"type": "",
"text": [
"TRAIL"
],
"offsets": [
[
68,
73
]
],
"normalized": []
},
{
"id": "767",
"type": "",
"text": [
"prostate cancer"
],
"offsets": [
[
96,
111
]
],
"normalized": []
},
{
"id": "769",
"type": "",
"text": [
"CAR"
],
"offsets": [
[
1227,
1230
]
],
"normalized": []
},
{
"id": "770",
"type": "",
"text": [
"adenovirus"
],
"offsets": [
[
1206,
1216
]
],
"normalized": []
},
{
"id": "772",
"type": "",
"text": [
"TRAIL"
],
"offsets": [
[
1371,
1376
]
],
"normalized": []
},
{
"id": "773",
"type": "",
"text": [
"infection with an adenovirus"
],
"offsets": [
[
1274,
1302
]
],
"normalized": []
},
{
"id": "775",
"type": "",
"text": [
"TRAIL"
],
"offsets": [
[
1703,
1708
]
],
"normalized": []
},
{
"id": "776",
"type": "",
"text": [
"prostate cancer"
],
"offsets": [
[
1777,
1792
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "765",
"type": "PA",
"arg1_id": "763",
"arg2_id": "764",
"normalized": []
},
{
"id": "768",
"type": "PA",
"arg1_id": "766",
"arg2_id": "767",
"normalized": []
},
{
"id": "771",
"type": "PA",
"arg1_id": "769",
"arg2_id": "770",
"normalized": []
},
{
"id": "774",
"type": "PA",
"arg1_id": "772",
"arg2_id": "773",
"normalized": []
},
{
"id": "777",
"type": "PA",
"arg1_id": "775",
"arg2_id": "776",
"normalized": []
}
] |
779 | 779 | [
{
"id": "780",
"type": "title",
"text": [
"The Connectivity Map: a new tool for biomedical research."
],
"offsets": [
[
0,
57
]
]
},
{
"id": "781",
"type": "abstract",
"text": [
"The ultimate objective of biomedical research is to connect human diseases with the genes that underlie them and drugs that treat them. But this remains a daunting task, and even the most inspired researchers still have to resort to laborious screens of genetic or chemical libraries. What if at least some parts of this screening process could be systematized and centralized? And hits found and hypotheses generated with something resembling an internet search engine? These are the questions the Connectivity Map project set out to answer."
],
"offsets": [
[
58,
600
]
]
}
] | [
{
"id": "782",
"type": "Diseases & Disorders",
"text": [
"diseases"
],
"offsets": [
[
124,
132
]
],
"normalized": []
},
{
"id": "783",
"type": "Diseases & Disorders",
"text": [
"still"
],
"offsets": [
[
267,
272
]
],
"normalized": []
}
] | [] | [] | [] |
785 | 785 | [
{
"id": "786",
"type": "title",
"text": [
"Urtica ferox neuropathy."
],
"offsets": [
[
0,
24
]
]
},
{
"id": "787",
"type": "abstract",
"text": [
"A 21-year-old student developed an acute, symmetrical, predominantly motor polyneuropathy within 48 h of walking through a patch of nettles (Urtica ferox). Two companions had similar but less severe symptoms. Nerve conduction studies demonstrated markedly reduced compound muscle action potentials and prolonged distal motor latencies. Recovery occurred over a period of a few weeks. This case demonstrates that cutaneous exposure to Urtica ferox can cause an acute polyneuropathy and that its stinging hairs contain an unidentified neurotoxin."
],
"offsets": [
[
25,
569
]
]
}
] | [
{
"id": "788",
"type": "Diseases & Disorders",
"text": [
"Urtica ferox neuropathy"
],
"offsets": [
[
0,
23
]
],
"normalized": []
},
{
"id": "789",
"type": "Chemicals & Drugs",
"text": [
"Urtica ferox neuropathy"
],
"offsets": [
[
0,
23
]
],
"normalized": []
},
{
"id": "790",
"type": "Diseases & Disorders",
"text": [
"motor polyneuropathy"
],
"offsets": [
[
94,
114
]
],
"normalized": []
},
{
"id": "791",
"type": "Diseases & Disorders",
"text": [
"patch"
],
"offsets": [
[
148,
153
]
],
"normalized": []
},
{
"id": "792",
"type": "Chemicals & Drugs",
"text": [
"Urtica ferox"
],
"offsets": [
[
166,
178
]
],
"normalized": []
},
{
"id": "793",
"type": "Diseases & Disorders",
"text": [
"symptoms"
],
"offsets": [
[
224,
232
]
],
"normalized": []
},
{
"id": "794",
"type": "Chemicals & Drugs",
"text": [
"Urtica ferox"
],
"offsets": [
[
459,
471
]
],
"normalized": []
},
{
"id": "795",
"type": "Diseases & Disorders",
"text": [
"acute polyneuropathy"
],
"offsets": [
[
485,
505
]
],
"normalized": []
},
{
"id": "796",
"type": "Diseases & Disorders",
"text": [
"stinging"
],
"offsets": [
[
519,
527
]
],
"normalized": []
},
{
"id": "797",
"type": "Chemicals & Drugs",
"text": [
"unidentified neurotoxin"
],
"offsets": [
[
545,
568
]
],
"normalized": []
},
{
"id": "798",
"type": "",
"text": [
"unidentified neurotoxin"
],
"offsets": [
[
545,
568
]
],
"normalized": []
},
{
"id": "799",
"type": "",
"text": [
"acute polyneuropathy"
],
"offsets": [
[
485,
505
]
],
"normalized": []
},
{
"id": "801",
"type": "",
"text": [
"Urtica ferox"
],
"offsets": [
[
166,
178
]
],
"normalized": []
},
{
"id": "802",
"type": "",
"text": [
"motor polyneuropathy"
],
"offsets": [
[
94,
114
]
],
"normalized": []
},
{
"id": "804",
"type": "",
"text": [
"Urtica ferox"
],
"offsets": [
[
459,
471
]
],
"normalized": []
},
{
"id": "805",
"type": "",
"text": [
"acute polyneuropathy"
],
"offsets": [
[
485,
505
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "800",
"type": "PA",
"arg1_id": "798",
"arg2_id": "799",
"normalized": []
},
{
"id": "803",
"type": "PA",
"arg1_id": "801",
"arg2_id": "802",
"normalized": []
},
{
"id": "806",
"type": "PA",
"arg1_id": "804",
"arg2_id": "805",
"normalized": []
}
] |
808 | 808 | [
{
"id": "809",
"type": "title",
"text": [
"Effect of botulinum toxin type a on tear production after treatment of lateral canthal rhytids."
],
"offsets": [
[
0,
95
]
]
},
{
"id": "810",
"type": "abstract",
"text": [
"PURPOSE: To evaluate the incidence of temporary dry eye and the effects on lacrimal gland tear production after treatment of lateral canthal rhytids with botulinum toxin type A injections. METHODS: Twenty-six crow's feet areas were injected with botulinum toxin type A in 13 women with an age range of 31 to 58 years. A total of 10 units of botulinum toxin was injected per side, with two separate injections. Schirmer 1 testing was performed before and at 1 week, 1 month, and 4 months after the injections in all patients. The test was repeated at 6 months and 9 months for the patients whose Schirmer test results were not back to baseline at the 4-month follow-up. Statistical significance was evaluated with paired t test analysis. RESULTS: Overall, no statistical difference was found in Schirmer test results from baseline at 1 week (p = 0.23), 1 month (p = 0.32), or 4 months (p = 0.30) after injection. Five eyes of three patients had a significant decrease in Schirmer test results from baseline at 1 week and 1 month after injection. Three eyes of 2 patients had a significant decrease in Schirmer test results at 4 months after injection. Only one patient reported dry-eye symptoms at the 4-month follow-up. Schirmer test results of two eyes of one patient remained significantly lower than baseline at 6 months follow-up, which returned to the normal range at 9 months. CONCLUSIONS: Botulinum toxin for lateral canthal rhytids usually does not suppress tear production. However, decreased tear production after botulinum toxin injection for crow's feet is a possible complication and patients should be advised of the small but definite risk of a temporary dry eye."
],
"offsets": [
[
96,
1774
]
]
}
] | [
{
"id": "811",
"type": "Chemicals & Drugs",
"text": [
"botulinum toxin type a"
],
"offsets": [
[
10,
32
]
],
"normalized": []
},
{
"id": "812",
"type": "Diseases & Disorders",
"text": [
"tear"
],
"offsets": [
[
36,
40
]
],
"normalized": []
},
{
"id": "813",
"type": "Diseases & Disorders",
"text": [
"lateral canthal rhytids"
],
"offsets": [
[
71,
94
]
],
"normalized": []
},
{
"id": "814",
"type": "Diseases & Disorders",
"text": [
"dry eye"
],
"offsets": [
[
144,
151
]
],
"normalized": []
},
{
"id": "815",
"type": "Diseases & Disorders",
"text": [
"tear"
],
"offsets": [
[
186,
190
]
],
"normalized": []
},
{
"id": "816",
"type": "Diseases & Disorders",
"text": [
"lateral canthal rhytids"
],
"offsets": [
[
221,
244
]
],
"normalized": []
},
{
"id": "817",
"type": "Chemicals & Drugs",
"text": [
"botulinum toxin type A injections"
],
"offsets": [
[
250,
283
]
],
"normalized": []
},
{
"id": "818",
"type": "Chemicals & Drugs",
"text": [
"botulinum toxin type A"
],
"offsets": [
[
342,
364
]
],
"normalized": []
},
{
"id": "819",
"type": "Chemicals & Drugs",
"text": [
"botulinum toxin"
],
"offsets": [
[
437,
452
]
],
"normalized": []
},
{
"id": "820",
"type": "Diseases & Disorders",
"text": [
"dry-eye"
],
"offsets": [
[
1273,
1280
]
],
"normalized": []
},
{
"id": "821",
"type": "Diseases & Disorders",
"text": [
"symptoms"
],
"offsets": [
[
1281,
1289
]
],
"normalized": []
},
{
"id": "822",
"type": "Chemicals & Drugs",
"text": [
"Botulinum toxin"
],
"offsets": [
[
1492,
1507
]
],
"normalized": []
},
{
"id": "823",
"type": "Diseases & Disorders",
"text": [
"lateral canthal rhytids"
],
"offsets": [
[
1512,
1535
]
],
"normalized": []
},
{
"id": "824",
"type": "Diseases & Disorders",
"text": [
"tear"
],
"offsets": [
[
1562,
1566
]
],
"normalized": []
},
{
"id": "825",
"type": "Diseases & Disorders",
"text": [
"tear production"
],
"offsets": [
[
1598,
1613
]
],
"normalized": []
},
{
"id": "826",
"type": "Chemicals & Drugs",
"text": [
"botulinum toxin"
],
"offsets": [
[
1620,
1635
]
],
"normalized": []
},
{
"id": "827",
"type": "Diseases & Disorders",
"text": [
"complication"
],
"offsets": [
[
1676,
1688
]
],
"normalized": []
},
{
"id": "828",
"type": "Diseases & Disorders",
"text": [
"dry eye"
],
"offsets": [
[
1766,
1773
]
],
"normalized": []
},
{
"id": "829",
"type": "",
"text": [
"botulinum toxin type A injections"
],
"offsets": [
[
250,
283
]
],
"normalized": []
},
{
"id": "830",
"type": "",
"text": [
"lateral canthal rhytids"
],
"offsets": [
[
221,
244
]
],
"normalized": []
},
{
"id": "832",
"type": "",
"text": [
"Botulinum toxin"
],
"offsets": [
[
1492,
1507
]
],
"normalized": []
},
{
"id": "833",
"type": "",
"text": [
"lateral canthal rhytids"
],
"offsets": [
[
1512,
1535
]
],
"normalized": []
},
{
"id": "835",
"type": "",
"text": [
"botulinum toxin"
],
"offsets": [
[
1620,
1635
]
],
"normalized": []
},
{
"id": "836",
"type": "",
"text": [
"dry eye"
],
"offsets": [
[
1766,
1773
]
],
"normalized": []
},
{
"id": "838",
"type": "",
"text": [
"botulinum toxin type a"
],
"offsets": [
[
10,
32
]
],
"normalized": []
},
{
"id": "839",
"type": "",
"text": [
"tear"
],
"offsets": [
[
36,
40
]
],
"normalized": []
},
{
"id": "841",
"type": "",
"text": [
"botulinum toxin type A injections"
],
"offsets": [
[
250,
283
]
],
"normalized": []
},
{
"id": "842",
"type": "",
"text": [
"tear"
],
"offsets": [
[
186,
190
]
],
"normalized": []
},
{
"id": "844",
"type": "",
"text": [
"botulinum toxin type A injections"
],
"offsets": [
[
250,
283
]
],
"normalized": []
},
{
"id": "845",
"type": "",
"text": [
"dry eye"
],
"offsets": [
[
144,
151
]
],
"normalized": []
},
{
"id": "847",
"type": "",
"text": [
"Botulinum toxin"
],
"offsets": [
[
1492,
1507
]
],
"normalized": []
},
{
"id": "848",
"type": "",
"text": [
"tear"
],
"offsets": [
[
1562,
1566
]
],
"normalized": []
},
{
"id": "850",
"type": "",
"text": [
"botulinum toxin"
],
"offsets": [
[
1620,
1635
]
],
"normalized": []
},
{
"id": "851",
"type": "",
"text": [
"complication"
],
"offsets": [
[
1676,
1688
]
],
"normalized": []
},
{
"id": "853",
"type": "",
"text": [
"botulinum toxin"
],
"offsets": [
[
1620,
1635
]
],
"normalized": []
},
{
"id": "854",
"type": "",
"text": [
"tear production"
],
"offsets": [
[
1598,
1613
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "831",
"type": "PA",
"arg1_id": "829",
"arg2_id": "830",
"normalized": []
},
{
"id": "834",
"type": "PA",
"arg1_id": "832",
"arg2_id": "833",
"normalized": []
},
{
"id": "837",
"type": "PA",
"arg1_id": "835",
"arg2_id": "836",
"normalized": []
},
{
"id": "840",
"type": "PA",
"arg1_id": "838",
"arg2_id": "839",
"normalized": []
},
{
"id": "843",
"type": "PA",
"arg1_id": "841",
"arg2_id": "842",
"normalized": []
},
{
"id": "846",
"type": "PA",
"arg1_id": "844",
"arg2_id": "845",
"normalized": []
},
{
"id": "849",
"type": "PA",
"arg1_id": "847",
"arg2_id": "848",
"normalized": []
},
{
"id": "852",
"type": "PA",
"arg1_id": "850",
"arg2_id": "851",
"normalized": []
},
{
"id": "855",
"type": "PA",
"arg1_id": "853",
"arg2_id": "854",
"normalized": []
}
] |
857 | 857 | [
{
"id": "858",
"type": "title",
"text": [
"Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites."
],
"offsets": [
[
0,
134
]
]
},
{
"id": "859",
"type": "abstract",
"text": [
"In this study, the associations of novel LRP5 variants with BMD variation were detected and some replicated in the two ethnic groups of Chinese and white origins, respectively. These data support the concept that LRP5 variation can contribute to minor and major variation in bone structure. INTRODUCTION: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been shown to cause both high and low bone mass. However, it is still controversial whether LRP5 is associated with normal BMD variation. This study explored the association of LRP5 with BMD phenotypes at three clinically important skeletal sites-the spine, hip, and ultradistal radius (UD)-in two independent populations of Chinese and white ethnicities, respectively. MATERIALS AND METHODS: The Chinese sample consisted of 733 unrelated subjects. The white sample was made up of 1873 subjects from 405 nuclear families. High-density single nucleotide polymorphisms (SNPs) across the whole LRP5 gene were genotyped and analyzed in both samples. RESULTS: Linkage disequilibrium (LD) analyses showed that the haplotype structures of LRP5 between Chinese and whites were in good agreement. Association tests showed that polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5 significantly associated with spine BMD variation in both samples. Particularly, the significant association of SNP rs491347 in intron 7 with spine BMD in the Chinese sample (p=0.002) was replicated in whites, even after adjusting for multiple testing (p=0.005). Its strongly associated SNP rs1784235 could cause the loss of an estrogen receptor alpha (ERalpha) binding site in LRP5, which could partially explain the above replicated association. However, we did not observe any significant replication with BMD variation at the hip and UD. After accounting for multiple testing, associations with BMD variation at these two sites were mainly found in Chinese. Sex-stratified analyses further revealed that the LRP5 associations with BMD in Chinese and whites were driven by male and female subjects, respectively. CONCLUSIONS: Our work supported LRP5 genetic variants as possible susceptibility factors for osteoporosis and fractures in humans. Especially, the SNP rs491347 and its strongly associated SNPs (e.g., rs1784235) could be important to human osteoporosis phenotypes."
],
"offsets": [
[
135,
2486
]
]
}
] | [
{
"id": "860",
"type": "Genes & Molecular Sequences",
"text": [
"Low-density lipoprotein receptor-related protein 5"
],
"offsets": [
[
0,
50
]
],
"normalized": []
},
{
"id": "861",
"type": "SNP & Sequence variations",
"text": [
"(LRP5) gene polymorphisms"
],
"offsets": [
[
51,
76
]
],
"normalized": []
},
{
"id": "862",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
52,
56
]
],
"normalized": []
},
{
"id": "863",
"type": "Diseases & Disorders",
"text": [
"bone mass"
],
"offsets": [
[
97,
106
]
],
"normalized": []
},
{
"id": "864",
"type": "SNP & Sequence variations",
"text": [
"LRP5 variants"
],
"offsets": [
[
176,
189
]
],
"normalized": []
},
{
"id": "865",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5 variants"
],
"offsets": [
[
176,
189
]
],
"normalized": []
},
{
"id": "866",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
195,
198
]
],
"normalized": []
},
{
"id": "867",
"type": "SNP & Sequence variations",
"text": [
"LRP5 variation"
],
"offsets": [
[
348,
362
]
],
"normalized": []
},
{
"id": "868",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5 variation"
],
"offsets": [
[
348,
362
]
],
"normalized": []
},
{
"id": "869",
"type": "Diseases & Disorders",
"text": [
"minor"
],
"offsets": [
[
381,
386
]
],
"normalized": []
},
{
"id": "870",
"type": "Diseases & Disorders",
"text": [
"bone structure"
],
"offsets": [
[
410,
424
]
],
"normalized": []
},
{
"id": "871",
"type": "SNP & Sequence variations",
"text": [
"Mutations in the low-density lipoprotein receptor-related protein 5"
],
"offsets": [
[
440,
507
]
],
"normalized": []
},
{
"id": "872",
"type": "Diseases & Disorders",
"text": [
"Mutations in the low-density lipoprotein receptor-related protein 5"
],
"offsets": [
[
440,
507
]
],
"normalized": []
},
{
"id": "873",
"type": "Genes & Molecular Sequences",
"text": [
"Mutations in the low-density lipoprotein receptor-related protein 5"
],
"offsets": [
[
440,
507
]
],
"normalized": []
},
{
"id": "874",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
509,
513
]
],
"normalized": []
},
{
"id": "875",
"type": "Diseases & Disorders",
"text": [
"high"
],
"offsets": [
[
550,
554
]
],
"normalized": []
},
{
"id": "876",
"type": "Diseases & Disorders",
"text": [
"low bone mass"
],
"offsets": [
[
559,
572
]
],
"normalized": []
},
{
"id": "877",
"type": "Diseases & Disorders",
"text": [
"still"
],
"offsets": [
[
589,
594
]
],
"normalized": []
},
{
"id": "878",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
617,
621
]
],
"normalized": []
},
{
"id": "879",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
648,
651
]
],
"normalized": []
},
{
"id": "880",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
702,
706
]
],
"normalized": []
},
{
"id": "881",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
712,
715
]
],
"normalized": []
},
{
"id": "882",
"type": "Diseases & Disorders",
"text": [
"High"
],
"offsets": [
[
1047,
1051
]
],
"normalized": []
},
{
"id": "883",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
1116,
1120
]
],
"normalized": []
},
{
"id": "884",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
1257,
1261
]
],
"normalized": []
},
{
"id": "885",
"type": "SNP & Sequence variations",
"text": [
"polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5"
],
"offsets": [
[
1343,
1406
]
],
"normalized": []
},
{
"id": "886",
"type": "Genes & Molecular Sequences",
"text": [
"polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5"
],
"offsets": [
[
1343,
1406
]
],
"normalized": []
},
{
"id": "887",
"type": "Diseases & Disorders",
"text": [
"block"
],
"offsets": [
[
1360,
1365
]
],
"normalized": []
},
{
"id": "888",
"type": "SNP & Sequence variations",
"text": [
"block"
],
"offsets": [
[
1360,
1365
]
],
"normalized": []
},
{
"id": "889",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
1443,
1446
]
],
"normalized": []
},
{
"id": "890",
"type": "SNP & Sequence variations",
"text": [
"rs491347 in intron 7"
],
"offsets": [
[
1523,
1543
]
],
"normalized": []
},
{
"id": "891",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
1555,
1558
]
],
"normalized": []
},
{
"id": "892",
"type": "SNP & Sequence variations",
"text": [
"rs1784235"
],
"offsets": [
[
1698,
1707
]
],
"normalized": []
},
{
"id": "893",
"type": "Genes & Molecular Sequences",
"text": [
"estrogen receptor alpha"
],
"offsets": [
[
1735,
1758
]
],
"normalized": []
},
{
"id": "894",
"type": "Genes & Molecular Sequences",
"text": [
"ERalpha) binding site"
],
"offsets": [
[
1760,
1781
]
],
"normalized": []
},
{
"id": "895",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
1785,
1789
]
],
"normalized": []
},
{
"id": "896",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
1916,
1919
]
],
"normalized": []
},
{
"id": "897",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
2006,
2009
]
],
"normalized": []
},
{
"id": "898",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
2119,
2123
]
],
"normalized": []
},
{
"id": "899",
"type": "Diseases & Disorders",
"text": [
"BMD"
],
"offsets": [
[
2142,
2145
]
],
"normalized": []
},
{
"id": "900",
"type": "Genes & Molecular Sequences",
"text": [
"LRP5"
],
"offsets": [
[
2255,
2259
]
],
"normalized": []
},
{
"id": "901",
"type": "Diseases & Disorders",
"text": [
"osteoporosis"
],
"offsets": [
[
2316,
2328
]
],
"normalized": []
},
{
"id": "902",
"type": "Diseases & Disorders",
"text": [
"fractures"
],
"offsets": [
[
2333,
2342
]
],
"normalized": []
},
{
"id": "903",
"type": "SNP & Sequence variations",
"text": [
"rs491347"
],
"offsets": [
[
2374,
2382
]
],
"normalized": []
},
{
"id": "904",
"type": "SNP & Sequence variations",
"text": [
"rs1784235"
],
"offsets": [
[
2423,
2432
]
],
"normalized": []
},
{
"id": "905",
"type": "Diseases & Disorders",
"text": [
"osteoporosis"
],
"offsets": [
[
2462,
2474
]
],
"normalized": []
},
{
"id": "906",
"type": "",
"text": [
"Mutations in the low-density lipoprotein receptor-related protein 5"
],
"offsets": [
[
440,
507
]
],
"normalized": []
},
{
"id": "907",
"type": "",
"text": [
"low bone mass"
],
"offsets": [
[
559,
572
]
],
"normalized": []
},
{
"id": "909",
"type": "",
"text": [
"Mutations in the low-density lipoprotein receptor-related protein 5"
],
"offsets": [
[
440,
507
]
],
"normalized": []
},
{
"id": "910",
"type": "",
"text": [
"high"
],
"offsets": [
[
550,
554
]
],
"normalized": []
},
{
"id": "912",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
2255,
2259
]
],
"normalized": []
},
{
"id": "913",
"type": "",
"text": [
"osteoporosis"
],
"offsets": [
[
2316,
2328
]
],
"normalized": []
},
{
"id": "915",
"type": "",
"text": [
"rs1784235"
],
"offsets": [
[
2423,
2432
]
],
"normalized": []
},
{
"id": "916",
"type": "",
"text": [
"osteoporosis"
],
"offsets": [
[
2462,
2474
]
],
"normalized": []
},
{
"id": "918",
"type": "",
"text": [
"rs491347"
],
"offsets": [
[
2374,
2382
]
],
"normalized": []
},
{
"id": "919",
"type": "",
"text": [
"osteoporosis"
],
"offsets": [
[
2462,
2474
]
],
"normalized": []
},
{
"id": "921",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
52,
56
]
],
"normalized": []
},
{
"id": "922",
"type": "",
"text": [
"bone mass"
],
"offsets": [
[
97,
106
]
],
"normalized": []
},
{
"id": "924",
"type": "",
"text": [
"LRP5 variants"
],
"offsets": [
[
176,
189
]
],
"normalized": []
},
{
"id": "925",
"type": "",
"text": [
"BMD"
],
"offsets": [
[
195,
198
]
],
"normalized": []
},
{
"id": "927",
"type": "",
"text": [
"LRP5 variation"
],
"offsets": [
[
348,
362
]
],
"normalized": []
},
{
"id": "928",
"type": "",
"text": [
"minor"
],
"offsets": [
[
381,
386
]
],
"normalized": []
},
{
"id": "930",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
509,
513
]
],
"normalized": []
},
{
"id": "931",
"type": "",
"text": [
"Mutations in the low-density lipoprotein receptor-related protein 5"
],
"offsets": [
[
440,
507
]
],
"normalized": []
},
{
"id": "933",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
617,
621
]
],
"normalized": []
},
{
"id": "934",
"type": "",
"text": [
"BMD"
],
"offsets": [
[
648,
651
]
],
"normalized": []
},
{
"id": "936",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
617,
621
]
],
"normalized": []
},
{
"id": "937",
"type": "",
"text": [
"still"
],
"offsets": [
[
589,
594
]
],
"normalized": []
},
{
"id": "939",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
702,
706
]
],
"normalized": []
},
{
"id": "940",
"type": "",
"text": [
"BMD"
],
"offsets": [
[
712,
715
]
],
"normalized": []
},
{
"id": "942",
"type": "",
"text": [
"polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5"
],
"offsets": [
[
1343,
1406
]
],
"normalized": []
},
{
"id": "943",
"type": "",
"text": [
"BMD"
],
"offsets": [
[
1443,
1446
]
],
"normalized": []
},
{
"id": "945",
"type": "",
"text": [
"polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5"
],
"offsets": [
[
1343,
1406
]
],
"normalized": []
},
{
"id": "946",
"type": "",
"text": [
"block"
],
"offsets": [
[
1360,
1365
]
],
"normalized": []
},
{
"id": "948",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
2119,
2123
]
],
"normalized": []
},
{
"id": "949",
"type": "",
"text": [
"BMD"
],
"offsets": [
[
2142,
2145
]
],
"normalized": []
},
{
"id": "951",
"type": "",
"text": [
"LRP5 variation"
],
"offsets": [
[
348,
362
]
],
"normalized": []
},
{
"id": "952",
"type": "",
"text": [
"bone structure"
],
"offsets": [
[
410,
424
]
],
"normalized": []
},
{
"id": "954",
"type": "",
"text": [
"block"
],
"offsets": [
[
1360,
1365
]
],
"normalized": []
},
{
"id": "955",
"type": "",
"text": [
"BMD"
],
"offsets": [
[
1443,
1446
]
],
"normalized": []
},
{
"id": "957",
"type": "",
"text": [
"rs491347 in intron 7"
],
"offsets": [
[
1523,
1543
]
],
"normalized": []
},
{
"id": "958",
"type": "",
"text": [
"BMD"
],
"offsets": [
[
1555,
1558
]
],
"normalized": []
},
{
"id": "960",
"type": "",
"text": [
"LRP5"
],
"offsets": [
[
2255,
2259
]
],
"normalized": []
},
{
"id": "961",
"type": "",
"text": [
"fractures"
],
"offsets": [
[
2333,
2342
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "908",
"type": "PA",
"arg1_id": "906",
"arg2_id": "907",
"normalized": []
},
{
"id": "911",
"type": "PA",
"arg1_id": "909",
"arg2_id": "910",
"normalized": []
},
{
"id": "914",
"type": "SA",
"arg1_id": "912",
"arg2_id": "913",
"normalized": []
},
{
"id": "917",
"type": "SA",
"arg1_id": "915",
"arg2_id": "916",
"normalized": []
},
{
"id": "920",
"type": "SA",
"arg1_id": "918",
"arg2_id": "919",
"normalized": []
},
{
"id": "923",
"type": "PA",
"arg1_id": "921",
"arg2_id": "922",
"normalized": []
},
{
"id": "926",
"type": "PA",
"arg1_id": "924",
"arg2_id": "925",
"normalized": []
},
{
"id": "929",
"type": "PA",
"arg1_id": "927",
"arg2_id": "928",
"normalized": []
},
{
"id": "932",
"type": "PA",
"arg1_id": "930",
"arg2_id": "931",
"normalized": []
},
{
"id": "935",
"type": "PA",
"arg1_id": "933",
"arg2_id": "934",
"normalized": []
},
{
"id": "938",
"type": "PA",
"arg1_id": "936",
"arg2_id": "937",
"normalized": []
},
{
"id": "941",
"type": "PA",
"arg1_id": "939",
"arg2_id": "940",
"normalized": []
},
{
"id": "944",
"type": "PA",
"arg1_id": "942",
"arg2_id": "943",
"normalized": []
},
{
"id": "947",
"type": "PA",
"arg1_id": "945",
"arg2_id": "946",
"normalized": []
},
{
"id": "950",
"type": "PA",
"arg1_id": "948",
"arg2_id": "949",
"normalized": []
},
{
"id": "953",
"type": "PA",
"arg1_id": "951",
"arg2_id": "952",
"normalized": []
},
{
"id": "956",
"type": "PA",
"arg1_id": "954",
"arg2_id": "955",
"normalized": []
},
{
"id": "959",
"type": "PA",
"arg1_id": "957",
"arg2_id": "958",
"normalized": []
},
{
"id": "962",
"type": "PA",
"arg1_id": "960",
"arg2_id": "961",
"normalized": []
}
] |
964 | 964 | [
{
"id": "965",
"type": "title",
"text": [
"A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease."
],
"offsets": [
[
0,
154
]
]
},
{
"id": "966",
"type": "abstract",
"text": [
"We tested the hypothesis that oral beclomethasone dipropionate (BDP) would control gastrointestinal graft-versus-host disease (GVHD) in patients with anorexia, vomiting, and diarrhea. Patients were randomized to prednisone for 10 days and either oral BDP 8 mg/d (n = 62) or placebo (n = 67) tablets for 50 days. At study day 10, prednisone was rapidly tapered while continuing study drug. On an intent-to-treat basis, the risk of GVHD-treatment failure was reduced for the BDP group at study day 50 (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.35-1.13) and at 30 days follow-up (HR 0.55, 95% CI 0.32-0.93). Among patients eligible for prednisone taper at study day 10, the risk of GVHD-treatment failure was significantly reduced at both study days 50 and 80 (HR 0.39 and 0.38, respectively). By day 200 after transplantation, 5 patients randomized to BDP had died compared with 16 deaths on placebo, a 67% reduction in the hazard of mortality (HR 0.33, P = .03). In 47 recipients of unrelated and HLA-mismatched stem cells, mortality at transplantation day 200 was reduced by 91% in the BDP group compared with placebo (HR 0.09, P = .02). The survival benefit was durable to 1 year after randomization. Oral BDP prevents relapses of gastrointestinal GVHD following tapering of prednisone; survival is statistically significantly better among patients receiving BDP."
],
"offsets": [
[
155,
1532
]
]
}
] | [
{
"id": "967",
"type": "Chemicals & Drugs",
"text": [
"oral beclomethasone dipropionate"
],
"offsets": [
[
42,
74
]
],
"normalized": []
},
{
"id": "968",
"type": "Chemicals & Drugs",
"text": [
"prednisone"
],
"offsets": [
[
80,
90
]
],
"normalized": []
},
{
"id": "969",
"type": "Diseases & Disorders",
"text": [
"gastrointestinal graft-versus-host disease"
],
"offsets": [
[
111,
153
]
],
"normalized": []
},
{
"id": "970",
"type": "Chemicals & Drugs",
"text": [
"oral beclomethasone dipropionate"
],
"offsets": [
[
185,
217
]
],
"normalized": []
},
{
"id": "971",
"type": "Chemicals & Drugs",
"text": [
"BDP"
],
"offsets": [
[
219,
222
]
],
"normalized": []
},
{
"id": "972",
"type": "Diseases & Disorders",
"text": [
"gastrointestinal graft-versus-host disease"
],
"offsets": [
[
238,
280
]
],
"normalized": []
},
{
"id": "973",
"type": "Diseases & Disorders",
"text": [
"GVHD"
],
"offsets": [
[
282,
286
]
],
"normalized": []
},
{
"id": "974",
"type": "Diseases & Disorders",
"text": [
"anorexia"
],
"offsets": [
[
305,
313
]
],
"normalized": []
},
{
"id": "975",
"type": "Diseases & Disorders",
"text": [
"vomiting"
],
"offsets": [
[
315,
323
]
],
"normalized": []
},
{
"id": "976",
"type": "Diseases & Disorders",
"text": [
"diarrhea"
],
"offsets": [
[
329,
337
]
],
"normalized": []
},
{
"id": "977",
"type": "Chemicals & Drugs",
"text": [
"prednisone"
],
"offsets": [
[
367,
377
]
],
"normalized": []
},
{
"id": "978",
"type": "Chemicals & Drugs",
"text": [
"BDP"
],
"offsets": [
[
406,
409
]
],
"normalized": []
},
{
"id": "979",
"type": "Chemicals & Drugs",
"text": [
"prednisone"
],
"offsets": [
[
484,
494
]
],
"normalized": []
},
{
"id": "980",
"type": "Diseases & Disorders",
"text": [
"GVHD"
],
"offsets": [
[
585,
589
]
],
"normalized": []
},
{
"id": "981",
"type": "Chemicals & Drugs",
"text": [
"BDP"
],
"offsets": [
[
628,
631
]
],
"normalized": []
},
{
"id": "982",
"type": "Chemicals & Drugs",
"text": [
"prednisone"
],
"offsets": [
[
801,
811
]
],
"normalized": []
},
{
"id": "983",
"type": "Diseases & Disorders",
"text": [
"GVHD"
],
"offsets": [
[
847,
851
]
],
"normalized": []
},
{
"id": "984",
"type": "Chemicals & Drugs",
"text": [
"BDP"
],
"offsets": [
[
1018,
1021
]
],
"normalized": []
},
{
"id": "985",
"type": "Diseases & Disorders",
"text": [
"mortality"
],
"offsets": [
[
1100,
1109
]
],
"normalized": []
},
{
"id": "986",
"type": "Diseases & Disorders",
"text": [
"mortality"
],
"offsets": [
[
1191,
1200
]
],
"normalized": []
},
{
"id": "987",
"type": "Chemicals & Drugs",
"text": [
"BDP"
],
"offsets": [
[
1254,
1257
]
],
"normalized": []
},
{
"id": "988",
"type": "Chemicals & Drugs",
"text": [
"BDP"
],
"offsets": [
[
1375,
1378
]
],
"normalized": []
},
{
"id": "989",
"type": "Diseases & Disorders",
"text": [
"relapses of gastrointestinal GVHD"
],
"offsets": [
[
1388,
1421
]
],
"normalized": []
},
{
"id": "990",
"type": "Chemicals & Drugs",
"text": [
"prednisone"
],
"offsets": [
[
1444,
1454
]
],
"normalized": []
},
{
"id": "991",
"type": "Chemicals & Drugs",
"text": [
"BDP"
],
"offsets": [
[
1528,
1531
]
],
"normalized": []
},
{
"id": "992",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
219,
222
]
],
"normalized": []
},
{
"id": "993",
"type": "",
"text": [
"GVHD"
],
"offsets": [
[
282,
286
]
],
"normalized": []
},
{
"id": "995",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
219,
222
]
],
"normalized": []
},
{
"id": "996",
"type": "",
"text": [
"gastrointestinal graft-versus-host disease"
],
"offsets": [
[
238,
280
]
],
"normalized": []
},
{
"id": "998",
"type": "",
"text": [
"oral beclomethasone dipropionate"
],
"offsets": [
[
185,
217
]
],
"normalized": []
},
{
"id": "999",
"type": "",
"text": [
"GVHD"
],
"offsets": [
[
282,
286
]
],
"normalized": []
},
{
"id": "1001",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
1528,
1531
]
],
"normalized": []
},
{
"id": "1002",
"type": "",
"text": [
"relapses of gastrointestinal GVHD"
],
"offsets": [
[
1388,
1421
]
],
"normalized": []
},
{
"id": "1004",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
628,
631
]
],
"normalized": []
},
{
"id": "1005",
"type": "",
"text": [
"GVHD"
],
"offsets": [
[
585,
589
]
],
"normalized": []
},
{
"id": "1007",
"type": "",
"text": [
"prednisone"
],
"offsets": [
[
801,
811
]
],
"normalized": []
},
{
"id": "1008",
"type": "",
"text": [
"GVHD"
],
"offsets": [
[
847,
851
]
],
"normalized": []
},
{
"id": "1010",
"type": "",
"text": [
"prednisone"
],
"offsets": [
[
1444,
1454
]
],
"normalized": []
},
{
"id": "1011",
"type": "",
"text": [
"relapses of gastrointestinal GVHD"
],
"offsets": [
[
1388,
1421
]
],
"normalized": []
},
{
"id": "1013",
"type": "",
"text": [
"oral beclomethasone dipropionate"
],
"offsets": [
[
42,
74
]
],
"normalized": []
},
{
"id": "1014",
"type": "",
"text": [
"gastrointestinal graft-versus-host disease"
],
"offsets": [
[
111,
153
]
],
"normalized": []
},
{
"id": "1016",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
219,
222
]
],
"normalized": []
},
{
"id": "1017",
"type": "",
"text": [
"anorexia"
],
"offsets": [
[
305,
313
]
],
"normalized": []
},
{
"id": "1019",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
219,
222
]
],
"normalized": []
},
{
"id": "1020",
"type": "",
"text": [
"vomiting"
],
"offsets": [
[
315,
323
]
],
"normalized": []
},
{
"id": "1022",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
219,
222
]
],
"normalized": []
},
{
"id": "1023",
"type": "",
"text": [
"diarrhea"
],
"offsets": [
[
329,
337
]
],
"normalized": []
},
{
"id": "1025",
"type": "",
"text": [
"prednisone"
],
"offsets": [
[
80,
90
]
],
"normalized": []
},
{
"id": "1026",
"type": "",
"text": [
"gastrointestinal graft-versus-host disease"
],
"offsets": [
[
111,
153
]
],
"normalized": []
},
{
"id": "1028",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
1018,
1021
]
],
"normalized": []
},
{
"id": "1029",
"type": "",
"text": [
"mortality"
],
"offsets": [
[
1100,
1109
]
],
"normalized": []
},
{
"id": "1031",
"type": "",
"text": [
"BDP"
],
"offsets": [
[
1254,
1257
]
],
"normalized": []
},
{
"id": "1032",
"type": "",
"text": [
"mortality"
],
"offsets": [
[
1191,
1200
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "994",
"type": "PA",
"arg1_id": "992",
"arg2_id": "993",
"normalized": []
},
{
"id": "997",
"type": "SA",
"arg1_id": "995",
"arg2_id": "996",
"normalized": []
},
{
"id": "1000",
"type": "SA",
"arg1_id": "998",
"arg2_id": "999",
"normalized": []
},
{
"id": "1003",
"type": "PA",
"arg1_id": "1001",
"arg2_id": "1002",
"normalized": []
},
{
"id": "1006",
"type": "PA",
"arg1_id": "1004",
"arg2_id": "1005",
"normalized": []
},
{
"id": "1009",
"type": "PA",
"arg1_id": "1007",
"arg2_id": "1008",
"normalized": []
},
{
"id": "1012",
"type": "PA",
"arg1_id": "1010",
"arg2_id": "1011",
"normalized": []
},
{
"id": "1015",
"type": "PA",
"arg1_id": "1013",
"arg2_id": "1014",
"normalized": []
},
{
"id": "1018",
"type": "PA",
"arg1_id": "1016",
"arg2_id": "1017",
"normalized": []
},
{
"id": "1021",
"type": "PA",
"arg1_id": "1019",
"arg2_id": "1020",
"normalized": []
},
{
"id": "1024",
"type": "PA",
"arg1_id": "1022",
"arg2_id": "1023",
"normalized": []
},
{
"id": "1027",
"type": "PA",
"arg1_id": "1025",
"arg2_id": "1026",
"normalized": []
},
{
"id": "1030",
"type": "PA",
"arg1_id": "1028",
"arg2_id": "1029",
"normalized": []
},
{
"id": "1033",
"type": "PA",
"arg1_id": "1031",
"arg2_id": "1032",
"normalized": []
}
] |
1035 | 1035 | [
{
"id": "1036",
"type": "title",
"text": [
"Malic enzyme 2 and susceptibility to psychosis and mania."
],
"offsets": [
[
0,
57
]
]
},
{
"id": "1037",
"type": "abstract",
"text": [
"Previous studies have identified a putative gene locus for both schizophrenia and bipolar disorder in the chromosome 18q21 region. To identify candidate genes associated with these disorders we completed fine mapping analyses (using microsatellite markers) in 152 families from the Central Valley of Costa Rica (CVCR) (376 total subjects, 151 with a history of psychosis, 97 with a history of mania). Microsatellite analyses showed evidence of association at two contiguous markers, both located at the same genetic distance and spanning approximately 11 known genes. In a corollary gene expression study, one of these genes, malic enzyme 2 (ME2), showed levels of gene expression 5.6-fold lower in anterior cingulate tissue from post-mortem bipolar brains. Subsequent analysis of individual SNPs in strong linkage disequilibrium with the ME2 gene revealed one SNP and one haplotype associated with the phenotype of psychosis in the CVCR sample. ME2 interacts directly with the malate shuttle system, which has been shown to be altered in schizophrenia and bipolar disorder, and has roles in neuronal synthesis of glutamate and gamma-amino butyric acid. The present study suggests that genetic variation in or near the ME2 gene is associated with both psychotic and manic disorders, including schizophrenia and bipolar disorder."
],
"offsets": [
[
58,
1386
]
]
}
] | [
{
"id": "1038",
"type": "Genes & Molecular Sequences",
"text": [
"Malic enzyme 2"
],
"offsets": [
[
0,
14
]
],
"normalized": []
},
{
"id": "1039",
"type": "Diseases & Disorders",
"text": [
"psychosis"
],
"offsets": [
[
37,
46
]
],
"normalized": []
},
{
"id": "1040",
"type": "Diseases & Disorders",
"text": [
"mania"
],
"offsets": [
[
51,
56
]
],
"normalized": []
},
{
"id": "1041",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
122,
135
]
],
"normalized": []
},
{
"id": "1042",
"type": "Diseases & Disorders",
"text": [
"bipolar disorder"
],
"offsets": [
[
140,
156
]
],
"normalized": []
},
{
"id": "1043",
"type": "Genes & Molecular Sequences",
"text": [
"18q21"
],
"offsets": [
[
175,
180
]
],
"normalized": []
},
{
"id": "1044",
"type": "SNP & Sequence variations",
"text": [
"18q21"
],
"offsets": [
[
175,
180
]
],
"normalized": []
},
{
"id": "1045",
"type": "Diseases & Disorders",
"text": [
"disorders"
],
"offsets": [
[
239,
248
]
],
"normalized": []
},
{
"id": "1046",
"type": "Diseases & Disorders",
"text": [
"psychosis"
],
"offsets": [
[
419,
428
]
],
"normalized": []
},
{
"id": "1047",
"type": "Diseases & Disorders",
"text": [
"mania"
],
"offsets": [
[
451,
456
]
],
"normalized": []
},
{
"id": "1048",
"type": "Genes & Molecular Sequences",
"text": [
"malic enzyme 2"
],
"offsets": [
[
684,
698
]
],
"normalized": []
},
{
"id": "1049",
"type": "Genes & Molecular Sequences",
"text": [
"ME2"
],
"offsets": [
[
700,
703
]
],
"normalized": []
},
{
"id": "1050",
"type": "Diseases & Disorders",
"text": [
"anterior"
],
"offsets": [
[
757,
765
]
],
"normalized": []
},
{
"id": "1051",
"type": "Diseases & Disorders",
"text": [
"bipolar brains"
],
"offsets": [
[
800,
814
]
],
"normalized": []
},
{
"id": "1052",
"type": "Genes & Molecular Sequences",
"text": [
"ME2"
],
"offsets": [
[
897,
900
]
],
"normalized": []
},
{
"id": "1053",
"type": "Diseases & Disorders",
"text": [
"psychosis"
],
"offsets": [
[
974,
983
]
],
"normalized": []
},
{
"id": "1054",
"type": "Genes & Molecular Sequences",
"text": [
"ME2"
],
"offsets": [
[
1004,
1007
]
],
"normalized": []
},
{
"id": "1055",
"type": "Genes & Molecular Sequences",
"text": [
"malate"
],
"offsets": [
[
1036,
1042
]
],
"normalized": []
},
{
"id": "1056",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
1097,
1110
]
],
"normalized": []
},
{
"id": "1057",
"type": "Diseases & Disorders",
"text": [
"bipolar disorder"
],
"offsets": [
[
1115,
1131
]
],
"normalized": []
},
{
"id": "1058",
"type": "Genes & Molecular Sequences",
"text": [
"glutamate"
],
"offsets": [
[
1172,
1181
]
],
"normalized": []
},
{
"id": "1059",
"type": "Genes & Molecular Sequences",
"text": [
"gamma-amino butyric acid"
],
"offsets": [
[
1186,
1210
]
],
"normalized": []
},
{
"id": "1060",
"type": "Genes & Molecular Sequences",
"text": [
"ME2"
],
"offsets": [
[
1277,
1280
]
],
"normalized": []
},
{
"id": "1061",
"type": "Diseases & Disorders",
"text": [
"psychotic"
],
"offsets": [
[
1310,
1319
]
],
"normalized": []
},
{
"id": "1062",
"type": "Diseases & Disorders",
"text": [
"manic disorders"
],
"offsets": [
[
1324,
1339
]
],
"normalized": []
},
{
"id": "1063",
"type": "Diseases & Disorders",
"text": [
"schizophrenia"
],
"offsets": [
[
1351,
1364
]
],
"normalized": []
},
{
"id": "1064",
"type": "Diseases & Disorders",
"text": [
"bipolar disorder"
],
"offsets": [
[
1369,
1385
]
],
"normalized": []
},
{
"id": "1065",
"type": "",
"text": [
"18q21"
],
"offsets": [
[
175,
180
]
],
"normalized": []
},
{
"id": "1066",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
122,
135
]
],
"normalized": []
},
{
"id": "1068",
"type": "",
"text": [
"18q21"
],
"offsets": [
[
175,
180
]
],
"normalized": []
},
{
"id": "1069",
"type": "",
"text": [
"bipolar disorder"
],
"offsets": [
[
140,
156
]
],
"normalized": []
},
{
"id": "1071",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
700,
703
]
],
"normalized": []
},
{
"id": "1072",
"type": "",
"text": [
"bipolar brains"
],
"offsets": [
[
800,
814
]
],
"normalized": []
},
{
"id": "1074",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
897,
900
]
],
"normalized": []
},
{
"id": "1075",
"type": "",
"text": [
"psychosis"
],
"offsets": [
[
974,
983
]
],
"normalized": []
},
{
"id": "1077",
"type": "",
"text": [
"malate"
],
"offsets": [
[
1036,
1042
]
],
"normalized": []
},
{
"id": "1078",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1097,
1110
]
],
"normalized": []
},
{
"id": "1080",
"type": "",
"text": [
"malate"
],
"offsets": [
[
1036,
1042
]
],
"normalized": []
},
{
"id": "1081",
"type": "",
"text": [
"bipolar disorder"
],
"offsets": [
[
1115,
1131
]
],
"normalized": []
},
{
"id": "1083",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
1277,
1280
]
],
"normalized": []
},
{
"id": "1084",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1351,
1364
]
],
"normalized": []
},
{
"id": "1086",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
1277,
1280
]
],
"normalized": []
},
{
"id": "1087",
"type": "",
"text": [
"bipolar disorder"
],
"offsets": [
[
1369,
1385
]
],
"normalized": []
},
{
"id": "1089",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
1277,
1280
]
],
"normalized": []
},
{
"id": "1090",
"type": "",
"text": [
"psychotic"
],
"offsets": [
[
1310,
1319
]
],
"normalized": []
},
{
"id": "1092",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
1277,
1280
]
],
"normalized": []
},
{
"id": "1093",
"type": "",
"text": [
"manic disorders"
],
"offsets": [
[
1324,
1339
]
],
"normalized": []
},
{
"id": "1095",
"type": "",
"text": [
"Malic enzyme 2"
],
"offsets": [
[
0,
14
]
],
"normalized": []
},
{
"id": "1096",
"type": "",
"text": [
"psychosis"
],
"offsets": [
[
37,
46
]
],
"normalized": []
},
{
"id": "1098",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
700,
703
]
],
"normalized": []
},
{
"id": "1099",
"type": "",
"text": [
"anterior"
],
"offsets": [
[
757,
765
]
],
"normalized": []
},
{
"id": "1101",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
1004,
1007
]
],
"normalized": []
},
{
"id": "1102",
"type": "",
"text": [
"schizophrenia"
],
"offsets": [
[
1097,
1110
]
],
"normalized": []
},
{
"id": "1104",
"type": "",
"text": [
"ME2"
],
"offsets": [
[
1004,
1007
]
],
"normalized": []
},
{
"id": "1105",
"type": "",
"text": [
"bipolar disorder"
],
"offsets": [
[
1115,
1131
]
],
"normalized": []
},
{
"id": "1107",
"type": "",
"text": [
"Malic enzyme 2"
],
"offsets": [
[
0,
14
]
],
"normalized": []
},
{
"id": "1108",
"type": "",
"text": [
"mania"
],
"offsets": [
[
51,
56
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1067",
"type": "PA",
"arg1_id": "1065",
"arg2_id": "1066",
"normalized": []
},
{
"id": "1070",
"type": "PA",
"arg1_id": "1068",
"arg2_id": "1069",
"normalized": []
},
{
"id": "1073",
"type": "PA",
"arg1_id": "1071",
"arg2_id": "1072",
"normalized": []
},
{
"id": "1076",
"type": "PA",
"arg1_id": "1074",
"arg2_id": "1075",
"normalized": []
},
{
"id": "1079",
"type": "PA",
"arg1_id": "1077",
"arg2_id": "1078",
"normalized": []
},
{
"id": "1082",
"type": "PA",
"arg1_id": "1080",
"arg2_id": "1081",
"normalized": []
},
{
"id": "1085",
"type": "PA",
"arg1_id": "1083",
"arg2_id": "1084",
"normalized": []
},
{
"id": "1088",
"type": "PA",
"arg1_id": "1086",
"arg2_id": "1087",
"normalized": []
},
{
"id": "1091",
"type": "PA",
"arg1_id": "1089",
"arg2_id": "1090",
"normalized": []
},
{
"id": "1094",
"type": "PA",
"arg1_id": "1092",
"arg2_id": "1093",
"normalized": []
},
{
"id": "1097",
"type": "PA",
"arg1_id": "1095",
"arg2_id": "1096",
"normalized": []
},
{
"id": "1100",
"type": "PA",
"arg1_id": "1098",
"arg2_id": "1099",
"normalized": []
},
{
"id": "1103",
"type": "PA",
"arg1_id": "1101",
"arg2_id": "1102",
"normalized": []
},
{
"id": "1106",
"type": "PA",
"arg1_id": "1104",
"arg2_id": "1105",
"normalized": []
},
{
"id": "1109",
"type": "SA",
"arg1_id": "1107",
"arg2_id": "1108",
"normalized": []
}
] |
1111 | 1111 | [
{
"id": "1112",
"type": "title",
"text": [
"p53 and the pathogenesis of skin cancer."
],
"offsets": [
[
0,
40
]
]
},
{
"id": "1113",
"type": "abstract",
"text": [
"The p53 tumor suppressor gene and gene product are among the most diverse and complex molecules involved in cellular functions. Genetic alterations within the p53 gene have been shown to have a direct correlation with cancer development and have been shown to occur in nearly 50% of all cancers. p53 mutations are particularly common in skin cancers and UV irradiation has been shown to be a primary cause of specific 'signature' mutations that can result in oncogenic transformation. There are certain 'hot-spots' in the p53 gene where mutations are commonly found that result in a mutated dipyrimidine site. This review discusses the role of p53 from normal function and its dysfunction in pre-cancerous lesions and non-melanoma skin cancers. Additionally, special situations are explored, such as Li-Fraumeni syndrome in which there is an inherited p53 mutation, and the consequences of immune suppression on p53 mutations and the resulting increase in non-melanoma skin cancer in these patients."
],
"offsets": [
[
41,
1040
]
]
}
] | [
{
"id": "1114",
"type": "Genes & Molecular Sequences",
"text": [
"p53"
],
"offsets": [
[
0,
3
]
],
"normalized": []
},
{
"id": "1115",
"type": "Diseases & Disorders",
"text": [
"pathogenesis"
],
"offsets": [
[
12,
24
]
],
"normalized": []
},
{
"id": "1116",
"type": "Diseases & Disorders",
"text": [
"skin cancer"
],
"offsets": [
[
28,
39
]
],
"normalized": []
},
{
"id": "1117",
"type": "Genes & Molecular Sequences",
"text": [
"p53 tumor suppressor"
],
"offsets": [
[
45,
65
]
],
"normalized": []
},
{
"id": "1118",
"type": "Diseases & Disorders",
"text": [
"Genetic alterations"
],
"offsets": [
[
169,
188
]
],
"normalized": []
},
{
"id": "1119",
"type": "Genes & Molecular Sequences",
"text": [
"p53"
],
"offsets": [
[
200,
203
]
],
"normalized": []
},
{
"id": "1120",
"type": "Diseases & Disorders",
"text": [
"cancer"
],
"offsets": [
[
259,
265
]
],
"normalized": []
},
{
"id": "1121",
"type": "Diseases & Disorders",
"text": [
"cancers"
],
"offsets": [
[
328,
335
]
],
"normalized": []
},
{
"id": "1122",
"type": "SNP & Sequence variations",
"text": [
"p53 mutations"
],
"offsets": [
[
337,
350
]
],
"normalized": []
},
{
"id": "1123",
"type": "Genes & Molecular Sequences",
"text": [
"p53 mutations"
],
"offsets": [
[
337,
350
]
],
"normalized": []
},
{
"id": "1124",
"type": "Diseases & Disorders",
"text": [
"p53 mutations"
],
"offsets": [
[
337,
350
]
],
"normalized": []
},
{
"id": "1125",
"type": "Diseases & Disorders",
"text": [
"skin cancers"
],
"offsets": [
[
378,
390
]
],
"normalized": []
},
{
"id": "1126",
"type": "Diseases & Disorders",
"text": [
"mutations"
],
"offsets": [
[
471,
480
]
],
"normalized": []
},
{
"id": "1127",
"type": "Diseases & Disorders",
"text": [
"transformation"
],
"offsets": [
[
510,
524
]
],
"normalized": []
},
{
"id": "1128",
"type": "Genes & Molecular Sequences",
"text": [
"p53"
],
"offsets": [
[
563,
566
]
],
"normalized": []
},
{
"id": "1129",
"type": "Diseases & Disorders",
"text": [
"mutations"
],
"offsets": [
[
578,
587
]
],
"normalized": []
},
{
"id": "1130",
"type": "Genes & Molecular Sequences",
"text": [
"dipyrimidine"
],
"offsets": [
[
632,
644
]
],
"normalized": []
},
{
"id": "1131",
"type": "Genes & Molecular Sequences",
"text": [
"p53"
],
"offsets": [
[
685,
688
]
],
"normalized": []
},
{
"id": "1132",
"type": "Diseases & Disorders",
"text": [
"dysfunction"
],
"offsets": [
[
718,
729
]
],
"normalized": []
},
{
"id": "1133",
"type": "Diseases & Disorders",
"text": [
"pre-cancerous lesions"
],
"offsets": [
[
733,
754
]
],
"normalized": []
},
{
"id": "1134",
"type": "Diseases & Disorders",
"text": [
"non-melanoma skin cancers"
],
"offsets": [
[
759,
784
]
],
"normalized": []
},
{
"id": "1135",
"type": "Diseases & Disorders",
"text": [
"Li-Fraumeni syndrome"
],
"offsets": [
[
841,
861
]
],
"normalized": []
},
{
"id": "1136",
"type": "SNP & Sequence variations",
"text": [
"p53 mutation"
],
"offsets": [
[
893,
905
]
],
"normalized": []
},
{
"id": "1137",
"type": "Genes & Molecular Sequences",
"text": [
"p53 mutation"
],
"offsets": [
[
893,
905
]
],
"normalized": []
},
{
"id": "1138",
"type": "Diseases & Disorders",
"text": [
"p53 mutation"
],
"offsets": [
[
893,
905
]
],
"normalized": []
},
{
"id": "1139",
"type": "Diseases & Disorders",
"text": [
"immune suppression"
],
"offsets": [
[
931,
949
]
],
"normalized": []
},
{
"id": "1140",
"type": "SNP & Sequence variations",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1141",
"type": "Genes & Molecular Sequences",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1142",
"type": "Diseases & Disorders",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1143",
"type": "Diseases & Disorders",
"text": [
"non-melanoma skin cancer"
],
"offsets": [
[
997,
1021
]
],
"normalized": []
},
{
"id": "1144",
"type": "",
"text": [
"p53"
],
"offsets": [
[
200,
203
]
],
"normalized": []
},
{
"id": "1145",
"type": "",
"text": [
"cancers"
],
"offsets": [
[
328,
335
]
],
"normalized": []
},
{
"id": "1147",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
337,
350
]
],
"normalized": []
},
{
"id": "1148",
"type": "",
"text": [
"skin cancers"
],
"offsets": [
[
378,
390
]
],
"normalized": []
},
{
"id": "1150",
"type": "",
"text": [
"p53"
],
"offsets": [
[
0,
3
]
],
"normalized": []
},
{
"id": "1151",
"type": "",
"text": [
"pathogenesis"
],
"offsets": [
[
12,
24
]
],
"normalized": []
},
{
"id": "1153",
"type": "",
"text": [
"p53"
],
"offsets": [
[
0,
3
]
],
"normalized": []
},
{
"id": "1154",
"type": "",
"text": [
"skin cancer"
],
"offsets": [
[
28,
39
]
],
"normalized": []
},
{
"id": "1156",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
337,
350
]
],
"normalized": []
},
{
"id": "1157",
"type": "",
"text": [
"Genetic alterations"
],
"offsets": [
[
169,
188
]
],
"normalized": []
},
{
"id": "1159",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
337,
350
]
],
"normalized": []
},
{
"id": "1160",
"type": "",
"text": [
"mutations"
],
"offsets": [
[
471,
480
]
],
"normalized": []
},
{
"id": "1162",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
337,
350
]
],
"normalized": []
},
{
"id": "1163",
"type": "",
"text": [
"transformation"
],
"offsets": [
[
510,
524
]
],
"normalized": []
},
{
"id": "1165",
"type": "",
"text": [
"p53"
],
"offsets": [
[
563,
566
]
],
"normalized": []
},
{
"id": "1166",
"type": "",
"text": [
"mutations"
],
"offsets": [
[
578,
587
]
],
"normalized": []
},
{
"id": "1168",
"type": "",
"text": [
"p53"
],
"offsets": [
[
685,
688
]
],
"normalized": []
},
{
"id": "1169",
"type": "",
"text": [
"dysfunction"
],
"offsets": [
[
718,
729
]
],
"normalized": []
},
{
"id": "1171",
"type": "",
"text": [
"p53"
],
"offsets": [
[
685,
688
]
],
"normalized": []
},
{
"id": "1172",
"type": "",
"text": [
"non-melanoma skin cancers"
],
"offsets": [
[
759,
784
]
],
"normalized": []
},
{
"id": "1174",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1175",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1177",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1178",
"type": "",
"text": [
"non-melanoma skin cancer"
],
"offsets": [
[
997,
1021
]
],
"normalized": []
},
{
"id": "1180",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1181",
"type": "",
"text": [
"Li-Fraumeni syndrome"
],
"offsets": [
[
841,
861
]
],
"normalized": []
},
{
"id": "1183",
"type": "",
"text": [
"p53 mutations"
],
"offsets": [
[
953,
966
]
],
"normalized": []
},
{
"id": "1184",
"type": "",
"text": [
"immune suppression"
],
"offsets": [
[
931,
949
]
],
"normalized": []
},
{
"id": "1186",
"type": "",
"text": [
"p53"
],
"offsets": [
[
685,
688
]
],
"normalized": []
},
{
"id": "1187",
"type": "",
"text": [
"pre-cancerous lesions"
],
"offsets": [
[
733,
754
]
],
"normalized": []
},
{
"id": "1189",
"type": "",
"text": [
"p53 mutation"
],
"offsets": [
[
893,
905
]
],
"normalized": []
},
{
"id": "1190",
"type": "",
"text": [
"non-melanoma skin cancer"
],
"offsets": [
[
997,
1021
]
],
"normalized": []
},
{
"id": "1192",
"type": "",
"text": [
"p53 mutation"
],
"offsets": [
[
893,
905
]
],
"normalized": []
},
{
"id": "1193",
"type": "",
"text": [
"Li-Fraumeni syndrome"
],
"offsets": [
[
841,
861
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1146",
"type": "PA",
"arg1_id": "1144",
"arg2_id": "1145",
"normalized": []
},
{
"id": "1149",
"type": "PA",
"arg1_id": "1147",
"arg2_id": "1148",
"normalized": []
},
{
"id": "1152",
"type": "PA",
"arg1_id": "1150",
"arg2_id": "1151",
"normalized": []
},
{
"id": "1155",
"type": "PA",
"arg1_id": "1153",
"arg2_id": "1154",
"normalized": []
},
{
"id": "1158",
"type": "PA",
"arg1_id": "1156",
"arg2_id": "1157",
"normalized": []
},
{
"id": "1161",
"type": "PA",
"arg1_id": "1159",
"arg2_id": "1160",
"normalized": []
},
{
"id": "1164",
"type": "PA",
"arg1_id": "1162",
"arg2_id": "1163",
"normalized": []
},
{
"id": "1167",
"type": "PA",
"arg1_id": "1165",
"arg2_id": "1166",
"normalized": []
},
{
"id": "1170",
"type": "PA",
"arg1_id": "1168",
"arg2_id": "1169",
"normalized": []
},
{
"id": "1173",
"type": "PA",
"arg1_id": "1171",
"arg2_id": "1172",
"normalized": []
},
{
"id": "1176",
"type": "PA",
"arg1_id": "1174",
"arg2_id": "1175",
"normalized": []
},
{
"id": "1179",
"type": "PA",
"arg1_id": "1177",
"arg2_id": "1178",
"normalized": []
},
{
"id": "1182",
"type": "PA",
"arg1_id": "1180",
"arg2_id": "1181",
"normalized": []
},
{
"id": "1185",
"type": "PA",
"arg1_id": "1183",
"arg2_id": "1184",
"normalized": []
},
{
"id": "1188",
"type": "PA",
"arg1_id": "1186",
"arg2_id": "1187",
"normalized": []
},
{
"id": "1191",
"type": "PA",
"arg1_id": "1189",
"arg2_id": "1190",
"normalized": []
},
{
"id": "1194",
"type": "PA",
"arg1_id": "1192",
"arg2_id": "1193",
"normalized": []
}
] |
1196 | 1196 | [
{
"id": "1197",
"type": "title",
"text": [
"Endothelin-1 and its receptors ET(A) and ET(B) in drug-induced gingival overgrowth."
],
"offsets": [
[
0,
83
]
]
},
{
"id": "1198",
"type": "abstract",
"text": [
"BACKGROUND: The purpose of this study was to study the expression of endothelin-1 (ET-1) and its receptors ETA and ETB in normal human gingiva and cyclosporin-induced gingival fibroblasts. METHODS: Gingival samples were collected from eight normal healthy individuals, eight patients with periodontitis, and eight patients with cyclosporin A (CsA)-induced gingival overgrowth. Total RNA was extracted from tissue samples, and reverse transcriptase-polymerase chain reaction was performed for ET-1, ETA, and ETB. ET-1 protein was estimated from the tissues by enzyme-linked immunosorbent assay. The expression of ET-1 and its receptors was also examined in gingival fibroblast cells treated with CsA. RESULTS: ET-1 mRNA expression was significantly higher in patients with CsA-induced gingival overgrowth (P <0.001) than in patients with periodontitis and the controls. ETA mRNA was expressed more than the ETB in all examined samples. In human gingival fibroblasts, ET-1 expression was increased with CsA incorporation compared to controls (P <0.001). CONCLUSION: These results suggest that CsA can modulate the expression of ET-1 in gingival fibroblasts and CsA-induced gingival overgrowth."
],
"offsets": [
[
84,
1275
]
]
}
] | [
{
"id": "1199",
"type": "Chemicals & Drugs",
"text": [
"Endothelin-1"
],
"offsets": [
[
0,
12
]
],
"normalized": []
},
{
"id": "1200",
"type": "Diseases & Disorders",
"text": [
"drug-induced gingival overgrowth"
],
"offsets": [
[
50,
82
]
],
"normalized": []
},
{
"id": "1201",
"type": "Chemicals & Drugs",
"text": [
"endothelin-1"
],
"offsets": [
[
153,
165
]
],
"normalized": []
},
{
"id": "1202",
"type": "Chemicals & Drugs",
"text": [
"ETA"
],
"offsets": [
[
191,
194
]
],
"normalized": []
},
{
"id": "1203",
"type": "Chemicals & Drugs",
"text": [
"cyclosporin"
],
"offsets": [
[
231,
242
]
],
"normalized": []
},
{
"id": "1204",
"type": "Diseases & Disorders",
"text": [
"periodontitis"
],
"offsets": [
[
373,
386
]
],
"normalized": []
},
{
"id": "1205",
"type": "Chemicals & Drugs",
"text": [
"cyclosporin A"
],
"offsets": [
[
412,
425
]
],
"normalized": []
},
{
"id": "1206",
"type": "Chemicals & Drugs",
"text": [
"CsA"
],
"offsets": [
[
427,
430
]
],
"normalized": []
},
{
"id": "1207",
"type": "Diseases & Disorders",
"text": [
"gingival overgrowth"
],
"offsets": [
[
440,
459
]
],
"normalized": []
},
{
"id": "1208",
"type": "Chemicals & Drugs",
"text": [
"ETA"
],
"offsets": [
[
582,
585
]
],
"normalized": []
},
{
"id": "1209",
"type": "Chemicals & Drugs",
"text": [
"CsA"
],
"offsets": [
[
779,
782
]
],
"normalized": []
},
{
"id": "1210",
"type": "Chemicals & Drugs",
"text": [
"CsA"
],
"offsets": [
[
856,
859
]
],
"normalized": []
},
{
"id": "1211",
"type": "Diseases & Disorders",
"text": [
"gingival overgrowth"
],
"offsets": [
[
868,
887
]
],
"normalized": []
},
{
"id": "1212",
"type": "Diseases & Disorders",
"text": [
"periodontitis"
],
"offsets": [
[
921,
934
]
],
"normalized": []
},
{
"id": "1213",
"type": "Chemicals & Drugs",
"text": [
"ETA"
],
"offsets": [
[
953,
956
]
],
"normalized": []
},
{
"id": "1214",
"type": "Chemicals & Drugs",
"text": [
"CsA"
],
"offsets": [
[
1085,
1088
]
],
"normalized": []
},
{
"id": "1215",
"type": "Chemicals & Drugs",
"text": [
"CsA"
],
"offsets": [
[
1175,
1178
]
],
"normalized": []
},
{
"id": "1216",
"type": "Chemicals & Drugs",
"text": [
"CsA"
],
"offsets": [
[
1243,
1246
]
],
"normalized": []
},
{
"id": "1217",
"type": "Diseases & Disorders",
"text": [
"gingival overgrowth"
],
"offsets": [
[
1255,
1274
]
],
"normalized": []
},
{
"id": "1218",
"type": "",
"text": [
"cyclosporin A"
],
"offsets": [
[
412,
425
]
],
"normalized": []
},
{
"id": "1219",
"type": "",
"text": [
"gingival overgrowth"
],
"offsets": [
[
440,
459
]
],
"normalized": []
},
{
"id": "1221",
"type": "",
"text": [
"CsA"
],
"offsets": [
[
427,
430
]
],
"normalized": []
},
{
"id": "1222",
"type": "",
"text": [
"gingival overgrowth"
],
"offsets": [
[
440,
459
]
],
"normalized": []
},
{
"id": "1224",
"type": "",
"text": [
"CsA"
],
"offsets": [
[
427,
430
]
],
"normalized": []
},
{
"id": "1225",
"type": "",
"text": [
"periodontitis"
],
"offsets": [
[
373,
386
]
],
"normalized": []
},
{
"id": "1227",
"type": "",
"text": [
"CsA"
],
"offsets": [
[
856,
859
]
],
"normalized": []
},
{
"id": "1228",
"type": "",
"text": [
"gingival overgrowth"
],
"offsets": [
[
868,
887
]
],
"normalized": []
},
{
"id": "1230",
"type": "",
"text": [
"CsA"
],
"offsets": [
[
1243,
1246
]
],
"normalized": []
},
{
"id": "1231",
"type": "",
"text": [
"gingival overgrowth"
],
"offsets": [
[
1255,
1274
]
],
"normalized": []
},
{
"id": "1233",
"type": "",
"text": [
"CsA"
],
"offsets": [
[
856,
859
]
],
"normalized": []
},
{
"id": "1234",
"type": "",
"text": [
"periodontitis"
],
"offsets": [
[
921,
934
]
],
"normalized": []
},
{
"id": "1236",
"type": "",
"text": [
"cyclosporin A"
],
"offsets": [
[
412,
425
]
],
"normalized": []
},
{
"id": "1237",
"type": "",
"text": [
"periodontitis"
],
"offsets": [
[
373,
386
]
],
"normalized": []
},
{
"id": "1239",
"type": "",
"text": [
"Endothelin-1"
],
"offsets": [
[
0,
12
]
],
"normalized": []
},
{
"id": "1240",
"type": "",
"text": [
"drug-induced gingival overgrowth"
],
"offsets": [
[
50,
82
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1220",
"type": "PA",
"arg1_id": "1218",
"arg2_id": "1219",
"normalized": []
},
{
"id": "1223",
"type": "PA",
"arg1_id": "1221",
"arg2_id": "1222",
"normalized": []
},
{
"id": "1226",
"type": "PA",
"arg1_id": "1224",
"arg2_id": "1225",
"normalized": []
},
{
"id": "1229",
"type": "PA",
"arg1_id": "1227",
"arg2_id": "1228",
"normalized": []
},
{
"id": "1232",
"type": "PA",
"arg1_id": "1230",
"arg2_id": "1231",
"normalized": []
},
{
"id": "1235",
"type": "PA",
"arg1_id": "1233",
"arg2_id": "1234",
"normalized": []
},
{
"id": "1238",
"type": "PA",
"arg1_id": "1236",
"arg2_id": "1237",
"normalized": []
},
{
"id": "1241",
"type": "PA",
"arg1_id": "1239",
"arg2_id": "1240",
"normalized": []
}
] |
1243 | 1243 | [
{
"id": "1244",
"type": "title",
"text": [
"Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-kappaB signaling pathways."
],
"offsets": [
[
0,
211
]
]
},
{
"id": "1245",
"type": "abstract",
"text": [
"Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of the traditionally used Chinese herb Paeonia lactiflora Pallas, has anti-inflammatory, antioxidant and cardiovascular protective activities. We studied how the levels of intercellular adhesion molecule-1 (ICAM-1), one of the key molecules in the development of atherosclerosis, might be affected by paeonol in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF-alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha-induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis."
],
"offsets": [
[
212,
1603
]
]
}
] | [
{
"id": "1246",
"type": "Chemicals & Drugs",
"text": [
"Paeonol"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "1247",
"type": "Genes & Molecular Sequences",
"text": [
"intercellular adhesion molecule-1"
],
"offsets": [
[
19,
52
]
],
"normalized": []
},
{
"id": "1248",
"type": "Genes & Molecular Sequences",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
67,
94
]
],
"normalized": []
},
{
"id": "1249",
"type": "Genes & Molecular Sequences",
"text": [
"p38"
],
"offsets": [
[
157,
160
]
],
"normalized": []
},
{
"id": "1250",
"type": "Genes & Molecular Sequences",
"text": [
"ERK"
],
"offsets": [
[
162,
165
]
],
"normalized": []
},
{
"id": "1251",
"type": "Genes & Molecular Sequences",
"text": [
"nuclear factor-kappaB"
],
"offsets": [
[
170,
191
]
],
"normalized": []
},
{
"id": "1252",
"type": "Chemicals & Drugs",
"text": [
"Paeonol"
],
"offsets": [
[
212,
219
]
],
"normalized": []
},
{
"id": "1253",
"type": "Chemicals & Drugs",
"text": [
"2'-hydroxy-4'-methoxyacetophenone"
],
"offsets": [
[
221,
254
]
],
"normalized": []
},
{
"id": "1254",
"type": "Chemicals & Drugs",
"text": [
"Paeonia lactiflora Pallas"
],
"offsets": [
[
321,
346
]
],
"normalized": []
},
{
"id": "1255",
"type": "Genes & Molecular Sequences",
"text": [
"intercellular adhesion molecule-1"
],
"offsets": [
[
454,
487
]
],
"normalized": []
},
{
"id": "1256",
"type": "Genes & Molecular Sequences",
"text": [
"ICAM-1"
],
"offsets": [
[
489,
495
]
],
"normalized": []
},
{
"id": "1257",
"type": "Chemicals & Drugs",
"text": [
"paeonol"
],
"offsets": [
[
583,
590
]
],
"normalized": []
},
{
"id": "1258",
"type": "Genes & Molecular Sequences",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
594,
621
]
],
"normalized": []
},
{
"id": "1259",
"type": "Genes & Molecular Sequences",
"text": [
"TNF-alpha"
],
"offsets": [
[
623,
632
]
],
"normalized": []
},
{
"id": "1260",
"type": "Chemicals & Drugs",
"text": [
"Paeonol"
],
"offsets": [
[
693,
700
]
],
"normalized": []
},
{
"id": "1261",
"type": "Genes & Molecular Sequences",
"text": [
"ICAM-1"
],
"offsets": [
[
755,
761
]
],
"normalized": []
},
{
"id": "1262",
"type": "Genes & Molecular Sequences",
"text": [
"nuclear factor-kappaB"
],
"offsets": [
[
776,
797
]
],
"normalized": []
},
{
"id": "1263",
"type": "Genes & Molecular Sequences",
"text": [
"NF-kappaB"
],
"offsets": [
[
799,
808
]
],
"normalized": []
},
{
"id": "1264",
"type": "Genes & Molecular Sequences",
"text": [
"p65"
],
"offsets": [
[
810,
813
]
],
"normalized": []
},
{
"id": "1265",
"type": "Genes & Molecular Sequences",
"text": [
"inhibitory factor kappaBalpha"
],
"offsets": [
[
872,
901
]
],
"normalized": []
},
{
"id": "1266",
"type": "Genes & Molecular Sequences",
"text": [
"IkappaBalpha"
],
"offsets": [
[
903,
915
]
],
"normalized": []
},
{
"id": "1267",
"type": "Genes & Molecular Sequences",
"text": [
"TNF-alpha"
],
"offsets": [
[
938,
947
]
],
"normalized": []
},
{
"id": "1268",
"type": "Genes & Molecular Sequences",
"text": [
"p38"
],
"offsets": [
[
975,
978
]
],
"normalized": []
},
{
"id": "1269",
"type": "Genes & Molecular Sequences",
"text": [
"extracellular signal-regulated kinase"
],
"offsets": [
[
983,
1020
]
],
"normalized": []
},
{
"id": "1270",
"type": "Genes & Molecular Sequences",
"text": [
"ERK"
],
"offsets": [
[
1022,
1025
]
],
"normalized": []
},
{
"id": "1271",
"type": "Genes & Molecular Sequences",
"text": [
"ICAM-1"
],
"offsets": [
[
1061,
1067
]
],
"normalized": []
},
{
"id": "1272",
"type": "Genes & Molecular Sequences",
"text": [
"TNF-alpha"
],
"offsets": [
[
1082,
1091
]
],
"normalized": []
},
{
"id": "1273",
"type": "Chemicals & Drugs",
"text": [
"Paeonol"
],
"offsets": [
[
1093,
1100
]
],
"normalized": []
},
{
"id": "1274",
"type": "Genes & Molecular Sequences",
"text": [
"TNF-alpha"
],
"offsets": [
[
1158,
1167
]
],
"normalized": []
},
{
"id": "1275",
"type": "Genes & Molecular Sequences",
"text": [
"TNF-alpha"
],
"offsets": [
[
1303,
1312
]
],
"normalized": []
},
{
"id": "1276",
"type": "Chemicals & Drugs",
"text": [
"paeonol"
],
"offsets": [
[
1339,
1346
]
],
"normalized": []
},
{
"id": "1277",
"type": "Genes & Molecular Sequences",
"text": [
"ICAM-1"
],
"offsets": [
[
1350,
1356
]
],
"normalized": []
},
{
"id": "1278",
"type": "Genes & Molecular Sequences",
"text": [
"p38"
],
"offsets": [
[
1400,
1403
]
],
"normalized": []
},
{
"id": "1279",
"type": "Genes & Molecular Sequences",
"text": [
"ERK"
],
"offsets": [
[
1405,
1408
]
],
"normalized": []
},
{
"id": "1280",
"type": "Genes & Molecular Sequences",
"text": [
"NF-kappaB"
],
"offsets": [
[
1413,
1422
]
],
"normalized": []
},
{
"id": "1281",
"type": "Genes & Molecular Sequences",
"text": [
"TNF-alpha"
],
"offsets": [
[
1465,
1474
]
],
"normalized": []
},
{
"id": "1282",
"type": "Genes & Molecular Sequences",
"text": [
"ICAM-1"
],
"offsets": [
[
1483,
1489
]
],
"normalized": []
},
{
"id": "1283",
"type": "Chemicals & Drugs",
"text": [
"paeonol"
],
"offsets": [
[
1508,
1515
]
],
"normalized": []
},
{
"id": "1284",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "1285",
"type": "",
"text": [
"intercellular adhesion molecule-1"
],
"offsets": [
[
19,
52
]
],
"normalized": []
},
{
"id": "1287",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "1288",
"type": "",
"text": [
"p38"
],
"offsets": [
[
157,
160
]
],
"normalized": []
},
{
"id": "1290",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "1291",
"type": "",
"text": [
"ERK"
],
"offsets": [
[
162,
165
]
],
"normalized": []
},
{
"id": "1293",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "1294",
"type": "",
"text": [
"nuclear factor-kappaB"
],
"offsets": [
[
170,
191
]
],
"normalized": []
},
{
"id": "1296",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
583,
590
]
],
"normalized": []
},
{
"id": "1297",
"type": "",
"text": [
"ICAM-1"
],
"offsets": [
[
489,
495
]
],
"normalized": []
},
{
"id": "1299",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
693,
700
]
],
"normalized": []
},
{
"id": "1300",
"type": "",
"text": [
"ICAM-1"
],
"offsets": [
[
755,
761
]
],
"normalized": []
},
{
"id": "1302",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
693,
700
]
],
"normalized": []
},
{
"id": "1303",
"type": "",
"text": [
"NF-kappaB"
],
"offsets": [
[
799,
808
]
],
"normalized": []
},
{
"id": "1305",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
693,
700
]
],
"normalized": []
},
{
"id": "1306",
"type": "",
"text": [
"p65"
],
"offsets": [
[
810,
813
]
],
"normalized": []
},
{
"id": "1308",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
693,
700
]
],
"normalized": []
},
{
"id": "1309",
"type": "",
"text": [
"IkappaBalpha"
],
"offsets": [
[
903,
915
]
],
"normalized": []
},
{
"id": "1311",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
693,
700
]
],
"normalized": []
},
{
"id": "1312",
"type": "",
"text": [
"nuclear factor-kappaB"
],
"offsets": [
[
776,
797
]
],
"normalized": []
},
{
"id": "1314",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
693,
700
]
],
"normalized": []
},
{
"id": "1315",
"type": "",
"text": [
"inhibitory factor kappaBalpha"
],
"offsets": [
[
872,
901
]
],
"normalized": []
},
{
"id": "1317",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
1093,
1100
]
],
"normalized": []
},
{
"id": "1318",
"type": "",
"text": [
"TNF-alpha"
],
"offsets": [
[
1303,
1312
]
],
"normalized": []
},
{
"id": "1320",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
1339,
1346
]
],
"normalized": []
},
{
"id": "1321",
"type": "",
"text": [
"ICAM-1"
],
"offsets": [
[
1483,
1489
]
],
"normalized": []
},
{
"id": "1323",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
1339,
1346
]
],
"normalized": []
},
{
"id": "1324",
"type": "",
"text": [
"p38"
],
"offsets": [
[
1400,
1403
]
],
"normalized": []
},
{
"id": "1326",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
1339,
1346
]
],
"normalized": []
},
{
"id": "1327",
"type": "",
"text": [
"NF-kappaB"
],
"offsets": [
[
1413,
1422
]
],
"normalized": []
},
{
"id": "1329",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
1339,
1346
]
],
"normalized": []
},
{
"id": "1330",
"type": "",
"text": [
"ERK"
],
"offsets": [
[
1405,
1408
]
],
"normalized": []
},
{
"id": "1332",
"type": "",
"text": [
"Paeonol"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "1333",
"type": "",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
67,
94
]
],
"normalized": []
},
{
"id": "1335",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
583,
590
]
],
"normalized": []
},
{
"id": "1336",
"type": "",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
594,
621
]
],
"normalized": []
},
{
"id": "1338",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
583,
590
]
],
"normalized": []
},
{
"id": "1339",
"type": "",
"text": [
"TNF-alpha"
],
"offsets": [
[
623,
632
]
],
"normalized": []
},
{
"id": "1341",
"type": "",
"text": [
"paeonol"
],
"offsets": [
[
1339,
1346
]
],
"normalized": []
},
{
"id": "1342",
"type": "",
"text": [
"TNF-alpha"
],
"offsets": [
[
1465,
1474
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1286",
"type": "PA",
"arg1_id": "1284",
"arg2_id": "1285",
"normalized": []
},
{
"id": "1289",
"type": "PA",
"arg1_id": "1287",
"arg2_id": "1288",
"normalized": []
},
{
"id": "1292",
"type": "PA",
"arg1_id": "1290",
"arg2_id": "1291",
"normalized": []
},
{
"id": "1295",
"type": "PA",
"arg1_id": "1293",
"arg2_id": "1294",
"normalized": []
},
{
"id": "1298",
"type": "SA",
"arg1_id": "1296",
"arg2_id": "1297",
"normalized": []
},
{
"id": "1301",
"type": "PA",
"arg1_id": "1299",
"arg2_id": "1300",
"normalized": []
},
{
"id": "1304",
"type": "PA",
"arg1_id": "1302",
"arg2_id": "1303",
"normalized": []
},
{
"id": "1307",
"type": "PA",
"arg1_id": "1305",
"arg2_id": "1306",
"normalized": []
},
{
"id": "1310",
"type": "PA",
"arg1_id": "1308",
"arg2_id": "1309",
"normalized": []
},
{
"id": "1313",
"type": "PA",
"arg1_id": "1311",
"arg2_id": "1312",
"normalized": []
},
{
"id": "1316",
"type": "PA",
"arg1_id": "1314",
"arg2_id": "1315",
"normalized": []
},
{
"id": "1319",
"type": "PA",
"arg1_id": "1317",
"arg2_id": "1318",
"normalized": []
},
{
"id": "1322",
"type": "PA",
"arg1_id": "1320",
"arg2_id": "1321",
"normalized": []
},
{
"id": "1325",
"type": "SA",
"arg1_id": "1323",
"arg2_id": "1324",
"normalized": []
},
{
"id": "1328",
"type": "SA",
"arg1_id": "1326",
"arg2_id": "1327",
"normalized": []
},
{
"id": "1331",
"type": "SA",
"arg1_id": "1329",
"arg2_id": "1330",
"normalized": []
},
{
"id": "1334",
"type": "PA",
"arg1_id": "1332",
"arg2_id": "1333",
"normalized": []
},
{
"id": "1337",
"type": "SA",
"arg1_id": "1335",
"arg2_id": "1336",
"normalized": []
},
{
"id": "1340",
"type": "SA",
"arg1_id": "1338",
"arg2_id": "1339",
"normalized": []
},
{
"id": "1343",
"type": "PA",
"arg1_id": "1341",
"arg2_id": "1342",
"normalized": []
}
] |
1345 | 1345 | [
{
"id": "1346",
"type": "title",
"text": [
"Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus."
],
"offsets": [
[
0,
71
]
]
},
{
"id": "1347",
"type": "abstract",
"text": [
"The aim of our paper is to describe an unusual pulmonary toxicity of sirolimus (SRL) in a kidney transplant recipient. We present a 34-year-old woman with a second renal transplantation, complicated with steroid-resistant acute rejection and chronic allograft dysfunction. Two years after initiating SRL, she presented complaints of progressive dyspnoea, nonproductive cough, chest pain and low-grade fever of 1 month duration. She had chronic allograft nephropathy and slight elevation of lactic dehydrogenase levels. After exclusion of common reasons of this condition, a computed tomography (CT) of the thorax and bronchoscopy was performed, revealing ground-glass opacification with polygonal shapes on CT and an opaque appearance with numerous macrophages on bronchoalveolar lavage. The alveolar macrophages stained positive by Periodic acid-Schiff. Diagnosis of pulmonary alveolar proteinosis (PAP) was made and drug-induced toxicity was suspected. SRL was withdrawn with marked improvement in the patients' clinical and radiological status. PAP resolved within 3 months without further therapy. PAP is a very rare complication of SRL therapy with only a few cases described. Withdrawal of SRL with conversion to another immunosuppressant seems to be an appropriate procedure in this condition."
],
"offsets": [
[
72,
1372
]
]
}
] | [
{
"id": "1348",
"type": "Diseases & Disorders",
"text": [
"Pulmonary alveolar proteinosis"
],
"offsets": [
[
0,
30
]
],
"normalized": []
},
{
"id": "1349",
"type": "Diseases & Disorders",
"text": [
"pulmonary toxicity"
],
"offsets": [
[
39,
57
]
],
"normalized": []
},
{
"id": "1350",
"type": "Chemicals & Drugs",
"text": [
"sirolimus"
],
"offsets": [
[
61,
70
]
],
"normalized": []
},
{
"id": "1351",
"type": "Diseases & Disorders",
"text": [
"pulmonary toxicity"
],
"offsets": [
[
119,
137
]
],
"normalized": []
},
{
"id": "1352",
"type": "Chemicals & Drugs",
"text": [
"sirolimus"
],
"offsets": [
[
141,
150
]
],
"normalized": []
},
{
"id": "1353",
"type": "Chemicals & Drugs",
"text": [
"SRL"
],
"offsets": [
[
152,
155
]
],
"normalized": []
},
{
"id": "1354",
"type": "Diseases & Disorders",
"text": [
"steroid-resistant acute rejection"
],
"offsets": [
[
276,
309
]
],
"normalized": []
},
{
"id": "1355",
"type": "Chemicals & Drugs",
"text": [
"steroid-resistant acute rejection"
],
"offsets": [
[
276,
309
]
],
"normalized": []
},
{
"id": "1356",
"type": "Diseases & Disorders",
"text": [
"chronic allograft dysfunction"
],
"offsets": [
[
314,
343
]
],
"normalized": []
},
{
"id": "1357",
"type": "Chemicals & Drugs",
"text": [
"SRL"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "1358",
"type": "Diseases & Disorders",
"text": [
"dyspnoea"
],
"offsets": [
[
417,
425
]
],
"normalized": []
},
{
"id": "1359",
"type": "Diseases & Disorders",
"text": [
"nonproductive cough"
],
"offsets": [
[
427,
446
]
],
"normalized": []
},
{
"id": "1360",
"type": "Diseases & Disorders",
"text": [
"chest pain"
],
"offsets": [
[
448,
458
]
],
"normalized": []
},
{
"id": "1361",
"type": "Diseases & Disorders",
"text": [
"low-grade fever"
],
"offsets": [
[
463,
478
]
],
"normalized": []
},
{
"id": "1362",
"type": "Diseases & Disorders",
"text": [
"chronic allograft nephropathy"
],
"offsets": [
[
508,
537
]
],
"normalized": []
},
{
"id": "1363",
"type": "Diseases & Disorders",
"text": [
"pulmonary alveolar proteinosis"
],
"offsets": [
[
940,
970
]
],
"normalized": []
},
{
"id": "1364",
"type": "Diseases & Disorders",
"text": [
"PAP"
],
"offsets": [
[
972,
975
]
],
"normalized": []
},
{
"id": "1365",
"type": "Chemicals & Drugs",
"text": [
"SRL"
],
"offsets": [
[
1027,
1030
]
],
"normalized": []
},
{
"id": "1366",
"type": "Diseases & Disorders",
"text": [
"PAP"
],
"offsets": [
[
1120,
1123
]
],
"normalized": []
},
{
"id": "1367",
"type": "Diseases & Disorders",
"text": [
"PAP"
],
"offsets": [
[
1174,
1177
]
],
"normalized": []
},
{
"id": "1368",
"type": "Diseases & Disorders",
"text": [
"complication"
],
"offsets": [
[
1193,
1205
]
],
"normalized": []
},
{
"id": "1369",
"type": "Chemicals & Drugs",
"text": [
"SRL"
],
"offsets": [
[
1209,
1212
]
],
"normalized": []
},
{
"id": "1370",
"type": "Chemicals & Drugs",
"text": [
"SRL"
],
"offsets": [
[
1268,
1271
]
],
"normalized": []
},
{
"id": "1371",
"type": "Chemicals & Drugs",
"text": [
"immunosuppressant"
],
"offsets": [
[
1299,
1316
]
],
"normalized": []
},
{
"id": "1372",
"type": "",
"text": [
"sirolimus"
],
"offsets": [
[
61,
70
]
],
"normalized": []
},
{
"id": "1373",
"type": "",
"text": [
"Pulmonary alveolar proteinosis"
],
"offsets": [
[
0,
30
]
],
"normalized": []
},
{
"id": "1375",
"type": "",
"text": [
"SRL"
],
"offsets": [
[
1209,
1212
]
],
"normalized": []
},
{
"id": "1376",
"type": "",
"text": [
"PAP"
],
"offsets": [
[
1174,
1177
]
],
"normalized": []
},
{
"id": "1378",
"type": "",
"text": [
"SRL"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "1379",
"type": "",
"text": [
"nonproductive cough"
],
"offsets": [
[
427,
446
]
],
"normalized": []
},
{
"id": "1381",
"type": "",
"text": [
"SRL"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "1382",
"type": "",
"text": [
"chest pain"
],
"offsets": [
[
448,
458
]
],
"normalized": []
},
{
"id": "1384",
"type": "",
"text": [
"SRL"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "1385",
"type": "",
"text": [
"low-grade fever"
],
"offsets": [
[
463,
478
]
],
"normalized": []
},
{
"id": "1387",
"type": "",
"text": [
"sirolimus"
],
"offsets": [
[
61,
70
]
],
"normalized": []
},
{
"id": "1388",
"type": "",
"text": [
"pulmonary toxicity"
],
"offsets": [
[
39,
57
]
],
"normalized": []
},
{
"id": "1390",
"type": "",
"text": [
"sirolimus"
],
"offsets": [
[
141,
150
]
],
"normalized": []
},
{
"id": "1391",
"type": "",
"text": [
"pulmonary toxicity"
],
"offsets": [
[
119,
137
]
],
"normalized": []
},
{
"id": "1393",
"type": "",
"text": [
"SRL"
],
"offsets": [
[
152,
155
]
],
"normalized": []
},
{
"id": "1394",
"type": "",
"text": [
"pulmonary toxicity"
],
"offsets": [
[
119,
137
]
],
"normalized": []
},
{
"id": "1396",
"type": "",
"text": [
"SRL"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "1397",
"type": "",
"text": [
"dyspnoea"
],
"offsets": [
[
417,
425
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1374",
"type": "PA",
"arg1_id": "1372",
"arg2_id": "1373",
"normalized": []
},
{
"id": "1377",
"type": "PA",
"arg1_id": "1375",
"arg2_id": "1376",
"normalized": []
},
{
"id": "1380",
"type": "SA",
"arg1_id": "1378",
"arg2_id": "1379",
"normalized": []
},
{
"id": "1383",
"type": "SA",
"arg1_id": "1381",
"arg2_id": "1382",
"normalized": []
},
{
"id": "1386",
"type": "SA",
"arg1_id": "1384",
"arg2_id": "1385",
"normalized": []
},
{
"id": "1389",
"type": "PA",
"arg1_id": "1387",
"arg2_id": "1388",
"normalized": []
},
{
"id": "1392",
"type": "PA",
"arg1_id": "1390",
"arg2_id": "1391",
"normalized": []
},
{
"id": "1395",
"type": "PA",
"arg1_id": "1393",
"arg2_id": "1394",
"normalized": []
},
{
"id": "1398",
"type": "PA",
"arg1_id": "1396",
"arg2_id": "1397",
"normalized": []
}
] |
1400 | 1400 | [
{
"id": "1401",
"type": "title",
"text": [
"Production of polyclonal antibodies against the human respiratory syncytial virus nucleoprotein and phosphoprotein expressed in Escherichia coli."
],
"offsets": [
[
0,
145
]
]
},
{
"id": "1402",
"type": "abstract",
"text": [
"The nucleoprotein (N) and the phosphoprotein (P) of the human respiratory syncytial virus (HRSV), A2 strain, were cloned into pMAL-c2e vector. The proteins were expressed fused with the maltose-binding protein (MBP) and were preferentially found in the soluble fraction of the bacterial lysate. After their purification using amylose resin, almost no other protein was detected in SDS-PAGE. The fused proteins were cleaved by digestion with enterokinase and then used as antigens for BALB/c mice immunization. The obtained polyclonal antibodies were tested against HRSV infected cells in immunofluorescence assays. The results indicate that the antibodies generated against the recombinant proteins were able to recognize the virus proteins. We now intend to purify the cleaved N and P proteins and use them in structural studies. The recombinant proteins will also be tested as potential inducers of a protective immunity against the HRSV."
],
"offsets": [
[
146,
1086
]
]
}
] | [
{
"id": "1403",
"type": "Diseases & Disorders",
"text": [
"virus"
],
"offsets": [
[
76,
81
]
],
"normalized": []
},
{
"id": "1404",
"type": "Genes & Molecular Sequences",
"text": [
"virus"
],
"offsets": [
[
76,
81
]
],
"normalized": []
},
{
"id": "1405",
"type": "Genes & Molecular Sequences",
"text": [
"nucleoprotein"
],
"offsets": [
[
82,
95
]
],
"normalized": []
},
{
"id": "1406",
"type": "Genes & Molecular Sequences",
"text": [
"phosphoprotein"
],
"offsets": [
[
100,
114
]
],
"normalized": []
},
{
"id": "1407",
"type": "Diseases & Disorders",
"text": [
"Escherichia"
],
"offsets": [
[
128,
139
]
],
"normalized": []
},
{
"id": "1408",
"type": "Genes & Molecular Sequences",
"text": [
"Escherichia"
],
"offsets": [
[
128,
139
]
],
"normalized": []
},
{
"id": "1409",
"type": "Genes & Molecular Sequences",
"text": [
"nucleoprotein"
],
"offsets": [
[
150,
163
]
],
"normalized": []
},
{
"id": "1410",
"type": "Genes & Molecular Sequences",
"text": [
"N"
],
"offsets": [
[
165,
166
]
],
"normalized": []
},
{
"id": "1411",
"type": "Genes & Molecular Sequences",
"text": [
"phosphoprotein"
],
"offsets": [
[
176,
190
]
],
"normalized": []
},
{
"id": "1412",
"type": "Genes & Molecular Sequences",
"text": [
"P"
],
"offsets": [
[
192,
193
]
],
"normalized": []
},
{
"id": "1413",
"type": "Diseases & Disorders",
"text": [
"virus"
],
"offsets": [
[
230,
235
]
],
"normalized": []
},
{
"id": "1414",
"type": "Genes & Molecular Sequences",
"text": [
"virus"
],
"offsets": [
[
230,
235
]
],
"normalized": []
},
{
"id": "1415",
"type": "Diseases & Disorders",
"text": [
"strain"
],
"offsets": [
[
247,
253
]
],
"normalized": []
},
{
"id": "1416",
"type": "Genes & Molecular Sequences",
"text": [
"strain"
],
"offsets": [
[
247,
253
]
],
"normalized": []
},
{
"id": "1417",
"type": "Genes & Molecular Sequences",
"text": [
"maltose-binding protein"
],
"offsets": [
[
332,
355
]
],
"normalized": []
},
{
"id": "1418",
"type": "Genes & Molecular Sequences",
"text": [
"MBP"
],
"offsets": [
[
357,
360
]
],
"normalized": []
},
{
"id": "1419",
"type": "Genes & Molecular Sequences",
"text": [
"enterokinase"
],
"offsets": [
[
587,
599
]
],
"normalized": []
},
{
"id": "1420",
"type": "Diseases & Disorders",
"text": [
"HRSV infected"
],
"offsets": [
[
711,
724
]
],
"normalized": []
},
{
"id": "1421",
"type": "Diseases & Disorders",
"text": [
"virus"
],
"offsets": [
[
872,
877
]
],
"normalized": []
},
{
"id": "1422",
"type": "Genes & Molecular Sequences",
"text": [
"N"
],
"offsets": [
[
924,
925
]
],
"normalized": []
},
{
"id": "1423",
"type": "Genes & Molecular Sequences",
"text": [
"P"
],
"offsets": [
[
930,
931
]
],
"normalized": []
},
{
"id": "1424",
"type": "Diseases & Disorders",
"text": [
"HRSV"
],
"offsets": [
[
1081,
1085
]
],
"normalized": []
}
] | [] | [] | [] |
1426 | 1426 | [
{
"id": "1427",
"type": "title",
"text": [
"Sequential metabolism is responsible for diltiazem-induced time-dependent loss of CYP3A."
],
"offsets": [
[
0,
88
]
]
},
{
"id": "1428",
"type": "abstract",
"text": [
"Kinetic parameters (k(inact) and K(I)) obtained in microsomes are often used to predict time-dependent inactivation. We previously reported that microsomal inactivation kinetic parameters of diltiazem underpredicted CYP3A inactivation in hepatocytes. In this study, we evaluated the contributions of inactivation and reversible inhibition of CYP3A by diltiazem and its N-desmethyl (MA) and N,N-didesmethyl (MD) metabolites. In human liver microsomes, MA was a more potent time-dependent inactivator of CYP3A than its parent drug, with apparent k(inact) approximately 4-fold higher than that of diltiazem at a microsomal protein concentration of 0.2 mg/ml. MD did not inactivate CYP3A. Inactivation of CYP3A by diltiazem was dependent on microsomal protein concentration (25, 36, and 41% decrease in CYP3A activity at 0.2, 0.4, and 0.8 mg/ml microsomal protein, respectively, incubated with 10 microM diltiazem over 20 min), whereas inactivation by MA did not seem to be protein concentration-dependent. MA and MD were reversible inhibitors of CYP3A with competitive Ki values of 2.7 and 0.2 microM, respectively. In cryopreserved hepatocytes incubated with diltiazem, time-dependent loss of CYP3A was accompanied by increased formation of MA and MD, with the MA level similar to its K(I) at higher diltiazem concentrations. In addition, the metabolites appeared to be accumulated inside the cells. In summary, time-dependent CYP3A inactivation by MA seems to be the major contributor responsible for the loss of CYP3A in human liver microsomes and human hepatocytes incubated with diltiazem. These findings suggest that prediction of CYP3A loss based solely on microsomal inactivation parameters of parent drug may be inadequate."
],
"offsets": [
[
89,
1818
]
]
}
] | [
{
"id": "1429",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
41,
50
]
],
"normalized": []
},
{
"id": "1430",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
82,
87
]
],
"normalized": []
},
{
"id": "1431",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
280,
289
]
],
"normalized": []
},
{
"id": "1432",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
305,
310
]
],
"normalized": []
},
{
"id": "1433",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
431,
436
]
],
"normalized": []
},
{
"id": "1434",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
440,
449
]
],
"normalized": []
},
{
"id": "1435",
"type": "Chemicals & Drugs",
"text": [
"N-desmethyl"
],
"offsets": [
[
458,
469
]
],
"normalized": []
},
{
"id": "1436",
"type": "Chemicals & Drugs",
"text": [
"MA"
],
"offsets": [
[
471,
473
]
],
"normalized": []
},
{
"id": "1437",
"type": "Chemicals & Drugs",
"text": [
"N,N-didesmethyl"
],
"offsets": [
[
479,
494
]
],
"normalized": []
},
{
"id": "1438",
"type": "Chemicals & Drugs",
"text": [
"MD"
],
"offsets": [
[
496,
498
]
],
"normalized": []
},
{
"id": "1439",
"type": "Chemicals & Drugs",
"text": [
"MA"
],
"offsets": [
[
540,
542
]
],
"normalized": []
},
{
"id": "1440",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
591,
596
]
],
"normalized": []
},
{
"id": "1441",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
683,
692
]
],
"normalized": []
},
{
"id": "1442",
"type": "Chemicals & Drugs",
"text": [
"MD"
],
"offsets": [
[
745,
747
]
],
"normalized": []
},
{
"id": "1443",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
767,
772
]
],
"normalized": []
},
{
"id": "1444",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
790,
795
]
],
"normalized": []
},
{
"id": "1445",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
799,
808
]
],
"normalized": []
},
{
"id": "1446",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
888,
893
]
],
"normalized": []
},
{
"id": "1447",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
989,
998
]
],
"normalized": []
},
{
"id": "1448",
"type": "Chemicals & Drugs",
"text": [
"MA"
],
"offsets": [
[
1037,
1039
]
],
"normalized": []
},
{
"id": "1449",
"type": "Chemicals & Drugs",
"text": [
"MA"
],
"offsets": [
[
1092,
1094
]
],
"normalized": []
},
{
"id": "1450",
"type": "Chemicals & Drugs",
"text": [
"MD"
],
"offsets": [
[
1099,
1101
]
],
"normalized": []
},
{
"id": "1451",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
1132,
1137
]
],
"normalized": []
},
{
"id": "1452",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
1246,
1255
]
],
"normalized": []
},
{
"id": "1453",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
1280,
1285
]
],
"normalized": []
},
{
"id": "1454",
"type": "Chemicals & Drugs",
"text": [
"MA"
],
"offsets": [
[
1328,
1330
]
],
"normalized": []
},
{
"id": "1455",
"type": "Chemicals & Drugs",
"text": [
"MD"
],
"offsets": [
[
1335,
1337
]
],
"normalized": []
},
{
"id": "1456",
"type": "Chemicals & Drugs",
"text": [
"MA"
],
"offsets": [
[
1348,
1350
]
],
"normalized": []
},
{
"id": "1457",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
1387,
1396
]
],
"normalized": []
},
{
"id": "1458",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
1514,
1519
]
],
"normalized": []
},
{
"id": "1459",
"type": "Chemicals & Drugs",
"text": [
"MA"
],
"offsets": [
[
1536,
1538
]
],
"normalized": []
},
{
"id": "1460",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
1601,
1606
]
],
"normalized": []
},
{
"id": "1461",
"type": "Chemicals & Drugs",
"text": [
"diltiazem"
],
"offsets": [
[
1670,
1679
]
],
"normalized": []
},
{
"id": "1462",
"type": "Genes & Molecular Sequences",
"text": [
"CYP3A"
],
"offsets": [
[
1723,
1728
]
],
"normalized": []
},
{
"id": "1463",
"type": "",
"text": [
"diltiazem"
],
"offsets": [
[
41,
50
]
],
"normalized": []
},
{
"id": "1464",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
82,
87
]
],
"normalized": []
},
{
"id": "1466",
"type": "",
"text": [
"diltiazem"
],
"offsets": [
[
683,
692
]
],
"normalized": []
},
{
"id": "1467",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
591,
596
]
],
"normalized": []
},
{
"id": "1469",
"type": "",
"text": [
"MA"
],
"offsets": [
[
540,
542
]
],
"normalized": []
},
{
"id": "1470",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
591,
596
]
],
"normalized": []
},
{
"id": "1472",
"type": "",
"text": [
"MD"
],
"offsets": [
[
745,
747
]
],
"normalized": []
},
{
"id": "1473",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
767,
772
]
],
"normalized": []
},
{
"id": "1475",
"type": "",
"text": [
"diltiazem"
],
"offsets": [
[
989,
998
]
],
"normalized": []
},
{
"id": "1476",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
888,
893
]
],
"normalized": []
},
{
"id": "1478",
"type": "",
"text": [
"MA"
],
"offsets": [
[
1037,
1039
]
],
"normalized": []
},
{
"id": "1479",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
888,
893
]
],
"normalized": []
},
{
"id": "1481",
"type": "",
"text": [
"MD"
],
"offsets": [
[
1099,
1101
]
],
"normalized": []
},
{
"id": "1482",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
1132,
1137
]
],
"normalized": []
},
{
"id": "1484",
"type": "",
"text": [
"MA"
],
"offsets": [
[
1092,
1094
]
],
"normalized": []
},
{
"id": "1485",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
1132,
1137
]
],
"normalized": []
},
{
"id": "1487",
"type": "",
"text": [
"diltiazem"
],
"offsets": [
[
1387,
1396
]
],
"normalized": []
},
{
"id": "1488",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
1280,
1285
]
],
"normalized": []
},
{
"id": "1490",
"type": "",
"text": [
"MA"
],
"offsets": [
[
1536,
1538
]
],
"normalized": []
},
{
"id": "1491",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
1601,
1606
]
],
"normalized": []
},
{
"id": "1493",
"type": "",
"text": [
"diltiazem"
],
"offsets": [
[
280,
289
]
],
"normalized": []
},
{
"id": "1494",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
305,
310
]
],
"normalized": []
},
{
"id": "1496",
"type": "",
"text": [
"diltiazem"
],
"offsets": [
[
440,
449
]
],
"normalized": []
},
{
"id": "1497",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
431,
436
]
],
"normalized": []
},
{
"id": "1499",
"type": "",
"text": [
"MD"
],
"offsets": [
[
496,
498
]
],
"normalized": []
},
{
"id": "1500",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
431,
436
]
],
"normalized": []
},
{
"id": "1502",
"type": "",
"text": [
"MD"
],
"offsets": [
[
1335,
1337
]
],
"normalized": []
},
{
"id": "1503",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
1280,
1285
]
],
"normalized": []
},
{
"id": "1505",
"type": "",
"text": [
"diltiazem"
],
"offsets": [
[
1670,
1679
]
],
"normalized": []
},
{
"id": "1506",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
1601,
1606
]
],
"normalized": []
},
{
"id": "1508",
"type": "",
"text": [
"MA"
],
"offsets": [
[
471,
473
]
],
"normalized": []
},
{
"id": "1509",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
431,
436
]
],
"normalized": []
},
{
"id": "1511",
"type": "",
"text": [
"MD"
],
"offsets": [
[
745,
747
]
],
"normalized": []
},
{
"id": "1512",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
767,
772
]
],
"normalized": []
},
{
"id": "1514",
"type": "",
"text": [
"MA"
],
"offsets": [
[
1348,
1350
]
],
"normalized": []
},
{
"id": "1515",
"type": "",
"text": [
"CYP3A"
],
"offsets": [
[
1280,
1285
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1465",
"type": "PA",
"arg1_id": "1463",
"arg2_id": "1464",
"normalized": []
},
{
"id": "1468",
"type": "PA",
"arg1_id": "1466",
"arg2_id": "1467",
"normalized": []
},
{
"id": "1471",
"type": "PA",
"arg1_id": "1469",
"arg2_id": "1470",
"normalized": []
},
{
"id": "1474",
"type": "PA",
"arg1_id": "1472",
"arg2_id": "1473",
"normalized": []
},
{
"id": "1477",
"type": "PA",
"arg1_id": "1475",
"arg2_id": "1476",
"normalized": []
},
{
"id": "1480",
"type": "PA",
"arg1_id": "1478",
"arg2_id": "1479",
"normalized": []
},
{
"id": "1483",
"type": "PA",
"arg1_id": "1481",
"arg2_id": "1482",
"normalized": []
},
{
"id": "1486",
"type": "PA",
"arg1_id": "1484",
"arg2_id": "1485",
"normalized": []
},
{
"id": "1489",
"type": "PA",
"arg1_id": "1487",
"arg2_id": "1488",
"normalized": []
},
{
"id": "1492",
"type": "PA",
"arg1_id": "1490",
"arg2_id": "1491",
"normalized": []
},
{
"id": "1495",
"type": "PA",
"arg1_id": "1493",
"arg2_id": "1494",
"normalized": []
},
{
"id": "1498",
"type": "PA",
"arg1_id": "1496",
"arg2_id": "1497",
"normalized": []
},
{
"id": "1501",
"type": "PA",
"arg1_id": "1499",
"arg2_id": "1500",
"normalized": []
},
{
"id": "1504",
"type": "PA",
"arg1_id": "1502",
"arg2_id": "1503",
"normalized": []
},
{
"id": "1507",
"type": "PA",
"arg1_id": "1505",
"arg2_id": "1506",
"normalized": []
},
{
"id": "1510",
"type": "SA",
"arg1_id": "1508",
"arg2_id": "1509",
"normalized": []
},
{
"id": "1513",
"type": "NA",
"arg1_id": "1511",
"arg2_id": "1512",
"normalized": []
},
{
"id": "1516",
"type": "PA",
"arg1_id": "1514",
"arg2_id": "1515",
"normalized": []
}
] |
1518 | 1518 | [
{
"id": "1519",
"type": "title",
"text": [
"Response to IL-1-receptor antagonist in a child with familial cold autoinflammatory syndrome."
],
"offsets": [
[
0,
93
]
]
},
{
"id": "1520",
"type": "abstract",
"text": [
"Familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurologic, cutaneous, articular syndrome are related disorders associated with mutations in the CIAS1 gene. They appear to represent a continuum of one disease characterized by IL-1-mediated inflammation. Until recently, these conditions have been difficult to treat; however, with the advent of IL-1-receptor antagonist therapy, many reports of successful treatment of patients with these autoinflammatory diseases have emerged in the past 2 years. We describe an 8-year-old girl, diagnosed with Familial cold auto-inflammatory syndrome, confirmed by presence of a novel CIAS1 mutation, who was refractory to symptomatic treatment. As frequent attacks of urticaria and associated arthralgia had a debilitating effect on the child's lifestyle, a trial of IL-1-receptor antagonist (anakinra) was instituted. Dramatic sustained clinical improvement was evident within days and serum amyloid and C-reactive protein levels normalized within a month. Although several authors have reported successful use of this agent in children with chronic infantile neurologic, cutaneous, articular syndrome, we believe ours is the first report of successful treatment with anakinra in a young child with familial cold auto-inflammatory syndrome."
],
"offsets": [
[
94,
1410
]
]
}
] | [
{
"id": "1521",
"type": "Chemicals & Drugs",
"text": [
"IL-1-receptor antagonist"
],
"offsets": [
[
12,
36
]
],
"normalized": []
},
{
"id": "1522",
"type": "Genes & Molecular Sequences",
"text": [
"familial cold autoinflammatory syndrome"
],
"offsets": [
[
53,
92
]
],
"normalized": []
},
{
"id": "1523",
"type": "Genes & Molecular Sequences",
"text": [
"Muckle-Wells syndrome"
],
"offsets": [
[
136,
157
]
],
"normalized": []
},
{
"id": "1524",
"type": "SNP & Sequence variations",
"text": [
"mutations in the CIAS1"
],
"offsets": [
[
260,
282
]
],
"normalized": []
},
{
"id": "1525",
"type": "Genes & Molecular Sequences",
"text": [
"mutations in the CIAS1"
],
"offsets": [
[
260,
282
]
],
"normalized": []
},
{
"id": "1526",
"type": "Genes & Molecular Sequences",
"text": [
"IL-1"
],
"offsets": [
[
358,
362
]
],
"normalized": []
},
{
"id": "1527",
"type": "Chemicals & Drugs",
"text": [
"IL-1-receptor antagonist"
],
"offsets": [
[
477,
501
]
],
"normalized": []
},
{
"id": "1528",
"type": "Chemicals & Drugs",
"text": [
"girl"
],
"offsets": [
[
657,
661
]
],
"normalized": []
},
{
"id": "1529",
"type": "SNP & Sequence variations",
"text": [
"CIAS1 mutation"
],
"offsets": [
[
753,
767
]
],
"normalized": []
},
{
"id": "1530",
"type": "Genes & Molecular Sequences",
"text": [
"CIAS1 mutation"
],
"offsets": [
[
753,
767
]
],
"normalized": []
},
{
"id": "1531",
"type": "Chemicals & Drugs",
"text": [
"IL-1-receptor antagonist"
],
"offsets": [
[
936,
960
]
],
"normalized": []
},
{
"id": "1532",
"type": "Chemicals & Drugs",
"text": [
"anakinra"
],
"offsets": [
[
962,
970
]
],
"normalized": []
},
{
"id": "1533",
"type": "Genes & Molecular Sequences",
"text": [
"amyloid"
],
"offsets": [
[
1062,
1069
]
],
"normalized": []
},
{
"id": "1534",
"type": "Genes & Molecular Sequences",
"text": [
"C-reactive protein"
],
"offsets": [
[
1074,
1092
]
],
"normalized": []
},
{
"id": "1535",
"type": "Chemicals & Drugs",
"text": [
"anakinra"
],
"offsets": [
[
1338,
1346
]
],
"normalized": []
},
{
"id": "1536",
"type": "",
"text": [
"girl"
],
"offsets": [
[
657,
661
]
],
"normalized": []
},
{
"id": "1537",
"type": "",
"text": [
"CIAS1 mutation"
],
"offsets": [
[
753,
767
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1538",
"type": "PA",
"arg1_id": "1536",
"arg2_id": "1537",
"normalized": []
}
] |
1540 | 1540 | [
{
"id": "1541",
"type": "title",
"text": [
"Effect of itraconazole on pharmacokinetics of paroxetine: the role of gut transporters."
],
"offsets": [
[
0,
87
]
]
},
{
"id": "1542",
"type": "abstract",
"text": [
"A recent in vitro study has shown that paroxetine is a substrate of P-glycoprotein. However, there was no in vivo information indicating the involvement of P-glycoprotein on the pharmacokinetics of paroxetine. The aim of this study was to examine the effects of itraconazole, a P-glycoprotein inhibitor, on the pharmacokinetics of paroxetine. Two 6 day courses of either 200 mg itraconazole daily or placebo with at least a 4 week washout period were conducted. Thirteen volunteers took a single oral 20 mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 hours after the dosing. Compared with placebo, itraconazole treatment significantly increased the peak plasma concentration (Cmax) of paroxetine by 1.3 fold (6.7 +/- 2.5 versus 9.0 +/- 3.3 ng/mL, P < 0.05) and the area under the plasma concentration-time curve from zero to 48 hours [AUC (0-48)] of paroxetine by 1.5 fold (137 +/- 73 versus 199 +/- 91 ng*h/mL, P < 0.01). Although elimination half-life differed significantly (16.1 +/- 3.4 versus 18.8 +/- 5.9 hours, P < 0.05), the alteration was small (1.1 fold). The present study demonstrated that the bioavailability of paroxetine was increased by itraconazole, suggesting a possible involvement of P-glycoprotein in the pharmacokinetics of paroxetine."
],
"offsets": [
[
88,
1406
]
]
}
] | [
{
"id": "1543",
"type": "Chemicals & Drugs",
"text": [
"itraconazole"
],
"offsets": [
[
10,
22
]
],
"normalized": []
},
{
"id": "1544",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
46,
56
]
],
"normalized": []
},
{
"id": "1545",
"type": "Genes & Molecular Sequences",
"text": [
"gut transporters"
],
"offsets": [
[
70,
86
]
],
"normalized": []
},
{
"id": "1546",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
127,
137
]
],
"normalized": []
},
{
"id": "1547",
"type": "Genes & Molecular Sequences",
"text": [
"P-glycoprotein"
],
"offsets": [
[
156,
170
]
],
"normalized": []
},
{
"id": "1548",
"type": "Genes & Molecular Sequences",
"text": [
"P-glycoprotein"
],
"offsets": [
[
244,
258
]
],
"normalized": []
},
{
"id": "1549",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
286,
296
]
],
"normalized": []
},
{
"id": "1550",
"type": "Chemicals & Drugs",
"text": [
"itraconazole"
],
"offsets": [
[
350,
362
]
],
"normalized": []
},
{
"id": "1551",
"type": "Chemicals & Drugs",
"text": [
"P-glycoprotein inhibitor"
],
"offsets": [
[
366,
390
]
],
"normalized": []
},
{
"id": "1552",
"type": "Genes & Molecular Sequences",
"text": [
"P-glycoprotein inhibitor"
],
"offsets": [
[
366,
390
]
],
"normalized": []
},
{
"id": "1553",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
419,
429
]
],
"normalized": []
},
{
"id": "1554",
"type": "Chemicals & Drugs",
"text": [
"itraconazole"
],
"offsets": [
[
466,
478
]
],
"normalized": []
},
{
"id": "1555",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
603,
613
]
],
"normalized": []
},
{
"id": "1556",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
665,
675
]
],
"normalized": []
},
{
"id": "1557",
"type": "Chemicals & Drugs",
"text": [
"itraconazole"
],
"offsets": [
[
747,
759
]
],
"normalized": []
},
{
"id": "1558",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
834,
844
]
],
"normalized": []
},
{
"id": "1559",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
999,
1009
]
],
"normalized": []
},
{
"id": "1560",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
1274,
1284
]
],
"normalized": []
},
{
"id": "1561",
"type": "Chemicals & Drugs",
"text": [
"itraconazole"
],
"offsets": [
[
1302,
1314
]
],
"normalized": []
},
{
"id": "1562",
"type": "Genes & Molecular Sequences",
"text": [
"P-glycoprotein"
],
"offsets": [
[
1353,
1367
]
],
"normalized": []
},
{
"id": "1563",
"type": "Chemicals & Drugs",
"text": [
"paroxetine"
],
"offsets": [
[
1395,
1405
]
],
"normalized": []
},
{
"id": "1564",
"type": "",
"text": [
"paroxetine"
],
"offsets": [
[
127,
137
]
],
"normalized": []
},
{
"id": "1565",
"type": "",
"text": [
"P-glycoprotein"
],
"offsets": [
[
156,
170
]
],
"normalized": []
},
{
"id": "1567",
"type": "",
"text": [
"paroxetine"
],
"offsets": [
[
286,
296
]
],
"normalized": []
},
{
"id": "1568",
"type": "",
"text": [
"P-glycoprotein"
],
"offsets": [
[
244,
258
]
],
"normalized": []
},
{
"id": "1570",
"type": "",
"text": [
"paroxetine"
],
"offsets": [
[
1395,
1405
]
],
"normalized": []
},
{
"id": "1571",
"type": "",
"text": [
"P-glycoprotein"
],
"offsets": [
[
1353,
1367
]
],
"normalized": []
},
{
"id": "1573",
"type": "",
"text": [
"itraconazole"
],
"offsets": [
[
10,
22
]
],
"normalized": []
},
{
"id": "1574",
"type": "",
"text": [
"gut transporters"
],
"offsets": [
[
70,
86
]
],
"normalized": []
},
{
"id": "1576",
"type": "",
"text": [
"paroxetine"
],
"offsets": [
[
46,
56
]
],
"normalized": []
},
{
"id": "1577",
"type": "",
"text": [
"gut transporters"
],
"offsets": [
[
70,
86
]
],
"normalized": []
},
{
"id": "1579",
"type": "",
"text": [
"itraconazole"
],
"offsets": [
[
350,
362
]
],
"normalized": []
},
{
"id": "1580",
"type": "",
"text": [
"P-glycoprotein inhibitor"
],
"offsets": [
[
366,
390
]
],
"normalized": []
},
{
"id": "1582",
"type": "",
"text": [
"paroxetine"
],
"offsets": [
[
419,
429
]
],
"normalized": []
},
{
"id": "1583",
"type": "",
"text": [
"P-glycoprotein inhibitor"
],
"offsets": [
[
366,
390
]
],
"normalized": []
},
{
"id": "1585",
"type": "",
"text": [
"itraconazole"
],
"offsets": [
[
1302,
1314
]
],
"normalized": []
},
{
"id": "1586",
"type": "",
"text": [
"P-glycoprotein"
],
"offsets": [
[
1353,
1367
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1566",
"type": "PA",
"arg1_id": "1564",
"arg2_id": "1565",
"normalized": []
},
{
"id": "1569",
"type": "SA",
"arg1_id": "1567",
"arg2_id": "1568",
"normalized": []
},
{
"id": "1572",
"type": "SA",
"arg1_id": "1570",
"arg2_id": "1571",
"normalized": []
},
{
"id": "1575",
"type": "PA",
"arg1_id": "1573",
"arg2_id": "1574",
"normalized": []
},
{
"id": "1578",
"type": "PA",
"arg1_id": "1576",
"arg2_id": "1577",
"normalized": []
},
{
"id": "1581",
"type": "PA",
"arg1_id": "1579",
"arg2_id": "1580",
"normalized": []
},
{
"id": "1584",
"type": "PA",
"arg1_id": "1582",
"arg2_id": "1583",
"normalized": []
},
{
"id": "1587",
"type": "PA",
"arg1_id": "1585",
"arg2_id": "1586",
"normalized": []
}
] |
1589 | 1589 | [
{
"id": "1590",
"type": "title",
"text": [
"A facile lentiviral vector system for expression of doxycycline-inducible shRNAs: knockdown of the pre-miRNA processing enzyme Drosha."
],
"offsets": [
[
0,
134
]
]
},
{
"id": "1591",
"type": "abstract",
"text": [
"RNA interference (RNAi) is a powerful genetic tool for loss-of-function studies in mammalian cells and is also considered a potentially powerful therapeutic modality for the treatment of a variety of human diseases. During the past 3 years a number of systems for conditional RNAi have been developed that allow controlled expression of short hairpin RNA (shRNA) triggers of RNAi. The simplest strategy relies on tet-operable polymerase III-promoted shRNAs and co-expression of the tetracycline regulatory protein, TetR. In this study we have combined these features into a single lentiviral vector that upon delivery to target cells allows robust induction of shRNAs, even with low levels of doxycycline; importantly, we show minimal leakiness in the absence of inducer. We have exploited the regulatory properties of our system by targeting an essential cellular gene, the nuclear RNaseIII endonuclease Drosha. Drosha is the core catalytic component of the \"microprocessor complex\" and cleaves the primary microRNA (miRNA) transcripts into their pre-miRNA hairpin intermediates. We anticipate that our vector will facilitate functional studies of miRNA biogenesis."
],
"offsets": [
[
135,
1301
]
]
}
] | [
{
"id": "1592",
"type": "Chemicals & Drugs",
"text": [
"doxycycline"
],
"offsets": [
[
52,
63
]
],
"normalized": []
},
{
"id": "1593",
"type": "Genes & Molecular Sequences",
"text": [
"shRNAs"
],
"offsets": [
[
74,
80
]
],
"normalized": []
},
{
"id": "1594",
"type": "Genes & Molecular Sequences",
"text": [
"miRNA"
],
"offsets": [
[
103,
108
]
],
"normalized": []
},
{
"id": "1595",
"type": "Genes & Molecular Sequences",
"text": [
"Drosha"
],
"offsets": [
[
127,
133
]
],
"normalized": []
},
{
"id": "1596",
"type": "Chemicals & Drugs",
"text": [
"RNA interference"
],
"offsets": [
[
135,
151
]
],
"normalized": []
},
{
"id": "1597",
"type": "Chemicals & Drugs",
"text": [
"RNAi"
],
"offsets": [
[
153,
157
]
],
"normalized": []
},
{
"id": "1598",
"type": "Chemicals & Drugs",
"text": [
"RNAi"
],
"offsets": [
[
411,
415
]
],
"normalized": []
},
{
"id": "1599",
"type": "Genes & Molecular Sequences",
"text": [
"short hairpin RNA"
],
"offsets": [
[
472,
489
]
],
"normalized": []
},
{
"id": "1600",
"type": "Genes & Molecular Sequences",
"text": [
"shRNA"
],
"offsets": [
[
491,
496
]
],
"normalized": []
},
{
"id": "1601",
"type": "Chemicals & Drugs",
"text": [
"RNAi"
],
"offsets": [
[
510,
514
]
],
"normalized": []
},
{
"id": "1602",
"type": "Genes & Molecular Sequences",
"text": [
"tet-operable polymerase III"
],
"offsets": [
[
548,
575
]
],
"normalized": []
},
{
"id": "1603",
"type": "Genes & Molecular Sequences",
"text": [
"shRNAs"
],
"offsets": [
[
585,
591
]
],
"normalized": []
},
{
"id": "1604",
"type": "Genes & Molecular Sequences",
"text": [
"tetracycline regulatory protein"
],
"offsets": [
[
617,
648
]
],
"normalized": []
},
{
"id": "1605",
"type": "Chemicals & Drugs",
"text": [
"tetracycline regulatory protein"
],
"offsets": [
[
617,
648
]
],
"normalized": []
},
{
"id": "1606",
"type": "Genes & Molecular Sequences",
"text": [
"TetR"
],
"offsets": [
[
650,
654
]
],
"normalized": []
},
{
"id": "1607",
"type": "Genes & Molecular Sequences",
"text": [
"shRNAs"
],
"offsets": [
[
796,
802
]
],
"normalized": []
},
{
"id": "1608",
"type": "Chemicals & Drugs",
"text": [
"doxycycline"
],
"offsets": [
[
828,
839
]
],
"normalized": []
},
{
"id": "1609",
"type": "Genes & Molecular Sequences",
"text": [
"nuclear RNaseIII endonuclease Drosha"
],
"offsets": [
[
1010,
1046
]
],
"normalized": []
},
{
"id": "1610",
"type": "Genes & Molecular Sequences",
"text": [
"RNaseIII endonuclease"
],
"offsets": [
[
1018,
1039
]
],
"normalized": []
},
{
"id": "1611",
"type": "Genes & Molecular Sequences",
"text": [
"Drosha"
],
"offsets": [
[
1048,
1054
]
],
"normalized": []
},
{
"id": "1612",
"type": "Genes & Molecular Sequences",
"text": [
"microRNA"
],
"offsets": [
[
1143,
1151
]
],
"normalized": []
},
{
"id": "1613",
"type": "Genes & Molecular Sequences",
"text": [
"miRNA"
],
"offsets": [
[
1153,
1158
]
],
"normalized": []
},
{
"id": "1614",
"type": "Genes & Molecular Sequences",
"text": [
"miRNA"
],
"offsets": [
[
1187,
1192
]
],
"normalized": []
},
{
"id": "1615",
"type": "Genes & Molecular Sequences",
"text": [
"miRNA"
],
"offsets": [
[
1284,
1289
]
],
"normalized": []
},
{
"id": "1616",
"type": "",
"text": [
"RNAi"
],
"offsets": [
[
510,
514
]
],
"normalized": []
},
{
"id": "1617",
"type": "",
"text": [
"short hairpin RNA"
],
"offsets": [
[
472,
489
]
],
"normalized": []
},
{
"id": "1619",
"type": "",
"text": [
"RNAi"
],
"offsets": [
[
510,
514
]
],
"normalized": []
},
{
"id": "1620",
"type": "",
"text": [
"shRNA"
],
"offsets": [
[
491,
496
]
],
"normalized": []
},
{
"id": "1622",
"type": "",
"text": [
"doxycycline"
],
"offsets": [
[
828,
839
]
],
"normalized": []
},
{
"id": "1623",
"type": "",
"text": [
"shRNAs"
],
"offsets": [
[
796,
802
]
],
"normalized": []
},
{
"id": "1625",
"type": "",
"text": [
"doxycycline"
],
"offsets": [
[
52,
63
]
],
"normalized": []
},
{
"id": "1626",
"type": "",
"text": [
"Drosha"
],
"offsets": [
[
127,
133
]
],
"normalized": []
},
{
"id": "1628",
"type": "",
"text": [
"doxycycline"
],
"offsets": [
[
52,
63
]
],
"normalized": []
},
{
"id": "1629",
"type": "",
"text": [
"shRNAs"
],
"offsets": [
[
74,
80
]
],
"normalized": []
},
{
"id": "1631",
"type": "",
"text": [
"tetracycline regulatory protein"
],
"offsets": [
[
617,
648
]
],
"normalized": []
},
{
"id": "1632",
"type": "",
"text": [
"TetR"
],
"offsets": [
[
650,
654
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1618",
"type": "PA",
"arg1_id": "1616",
"arg2_id": "1617",
"normalized": []
},
{
"id": "1621",
"type": "PA",
"arg1_id": "1619",
"arg2_id": "1620",
"normalized": []
},
{
"id": "1624",
"type": "PA",
"arg1_id": "1622",
"arg2_id": "1623",
"normalized": []
},
{
"id": "1627",
"type": "PA",
"arg1_id": "1625",
"arg2_id": "1626",
"normalized": []
},
{
"id": "1630",
"type": "PA",
"arg1_id": "1628",
"arg2_id": "1629",
"normalized": []
},
{
"id": "1633",
"type": "PA",
"arg1_id": "1631",
"arg2_id": "1632",
"normalized": []
}
] |
End of preview. Expand
in Dataset Viewer.
Dataset Card for EU-ADR
Corpora with specific entities and relationships annotated are essential to train and evaluate text-mining systems that are developed to extract specific structured information from a large corpus. In this paper we describe an approach where a named-entity recognition system produces a first annotation and annotators revise this annotation using a web-based interface. The agreement figures achieved show that the inter-annotator agreement is much better than the agreement with the system provided annotations. The corpus has been annotated for drugs, disorders, genes and their inter-relationships. For each of the drug-disorder, drug-target, and target-disorder relations three experts have annotated a set of 100 abstracts. These annotated relationships will be used to train and evaluate text-mining software to capture these relationships in texts.
Citation Information
@article{VANMULLIGEN2012879,
title = {The EU-ADR corpus: Annotated drugs, diseases, targets, and their relationships},
journal = {Journal of Biomedical Informatics},
volume = {45},
number = {5},
pages = {879-884},
year = {2012},
note = {Text Mining and Natural Language Processing in Pharmacogenomics},
issn = {1532-0464},
doi = {https://doi.org/10.1016/j.jbi.2012.04.004},
url = {https://www.sciencedirect.com/science/article/pii/S1532046412000573},
author = {Erik M. {van Mulligen} and Annie Fourrier-Reglat and David Gurwitz and Mariam Molokhia and Ainhoa Nieto and Gianluca Trifiro and Jan A. Kors and Laura I. Furlong},
keywords = {Text mining, Corpus development, Machine learning, Adverse drug reactions},
abstract = {Corpora with specific entities and relationships annotated are essential to train and evaluate text-mining systems that are developed to extract specific structured information from a large corpus. In this paper we describe an approach where a named-entity recognition system produces a first annotation and annotators revise this annotation using a web-based interface. The agreement figures achieved show that the inter-annotator agreement is much better than the agreement with the system provided annotations. The corpus has been annotated for drugs, disorders, genes and their inter-relationships. For each of the drug–disorder, drug–target, and target–disorder relations three experts have annotated a set of 100 abstracts. These annotated relationships will be used to train and evaluate text-mining software to capture these relationships in texts.}
}
- Downloads last month
- 24