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0 | 10026165 | [
{
"id": "1",
"type": "",
"text": [
"3,4-Dihydroxyphenylalanine (Dopa) decarboxylase is a stereospecific pyridoxal 5'-phosphate (PLP)-dependent alpha-decarboxylase that converts L-aromatic amino acids into their corresponding amines. We now report that reaction of the enzyme with D-5-hydroxytryptophan or D-Dopa results in a time-dependent inactivation and conversion of the PLP coenzyme to pyridoxamine 5'-phosphate and PLP-D-amino acid Pictet-Spengler adducts, which have been identified by high performance liquid chromatography. We also show that the reaction specificity of Dopa decarboxylase toward aromatic amines depends on the experimental conditions. Whereas oxidative deamination occurs under aerobic conditions (Bertoldi, M., Moore, P. S., Maras, B., Dominici, P., and Borri Voltattorni, C. (1996) J. Biol. Chem. 271, 23954-23959; Bertoldi, M., Dominici, P., Moore, P. S., Maras, B., and Borri Voltattorni, C. (1998) Biochemistry 37, 6552-6561), half-transamination and Pictet-Spengler reactions take place under anaerobic conditions. Moreover, we examined the reaction specificity of nicked Dopa decarboxylase, obtained by selective tryptic cleavage of the native enzyme between Lys334 and His335. Although this enzymatic species does not exhibit either decarboxylase or oxidative deamination activities, it retains a large percentage of the native transaminase activity toward D-aromatic amino acids and displays a slow transaminase activity toward aromatic amines. These transamination reactions occur concomitantly with the formation of cyclic coenzyme-substrate adducts. Together with additional data, we thus suggest that native Dopa decarboxylase can exist as an equilibrium among \"open,\" \"half-open,\" and \"closed\" forms. \n"
],
"offsets": [
[
0,
1710
]
]
}
] | [
{
"id": "1_T4",
"type": "Protein",
"text": [
"3,4-Dihydroxyphenylalanine (Dopa) decarboxylase"
],
"offsets": [
[
0,
47
]
],
"normalized": []
},
{
"id": "1_T7",
"type": "Protein",
"text": [
"alpha-decarboxylase"
],
"offsets": [
[
107,
126
]
],
"normalized": []
},
{
"id": "1_T9",
"type": "Chemical",
"text": [
"L-aromatic amino acids"
],
"offsets": [
[
141,
163
]
],
"normalized": []
},
{
"id": "1_T11",
"type": "Chemical",
"text": [
"amines"
],
"offsets": [
[
189,
195
]
],
"normalized": []
},
{
"id": "1_T10",
"type": "Chemical",
"text": [
"D-5-hydroxytryptophan"
],
"offsets": [
[
245,
266
]
],
"normalized": []
},
{
"id": "1_T12",
"type": "Protein",
"text": [
"enzyme"
],
"offsets": [
[
232,
240
]
],
"normalized": []
},
{
"id": "1_T13",
"type": "Chemical",
"text": [
"D-Dopa"
],
"offsets": [
[
270,
276
]
],
"normalized": []
},
{
"id": "1_T14",
"type": "Chemical",
"text": [
"PLP"
],
"offsets": [
[
340,
343
]
],
"normalized": []
},
{
"id": "1_T15",
"type": "Biological_Activity",
"text": [
"coenzyme"
],
"offsets": [
[
344,
352
]
],
"normalized": []
},
{
"id": "1_T16",
"type": "Chemical",
"text": [
"pyridoxamine 5'-phosphate"
],
"offsets": [
[
356,
381
]
],
"normalized": []
},
{
"id": "1_T17",
"type": "Chemical",
"text": [
"PLP-D-amino acid Pictet-Spengler adducts"
],
"offsets": [
[
386,
427
]
],
"normalized": []
},
{
"id": "1_T18",
"type": "Chemical",
"text": [
"PLP-D-amino acid"
],
"offsets": [
[
386,
402
]
],
"normalized": []
},
{
"id": "1_T19",
"type": "Protein",
"text": [
"Dopa decarboxylase"
],
"offsets": [
[
545,
563
]
],
"normalized": []
},
{
"id": "1_T21",
"type": "Chemical",
"text": [
"aromatic amines"
],
"offsets": [
[
572,
587
]
],
"normalized": []
},
{
"id": "1_T22",
"type": "Protein",
"text": [
"Dopa decarboxylase"
],
"offsets": [
[
1072,
1090
]
],
"normalized": []
},
{
"id": "1_T24",
"type": "Biological_Activity",
"text": [
"decarboxylase"
],
"offsets": [
[
1235,
1248
]
],
"normalized": []
},
{
"id": "1_T25",
"type": "Biological_Activity",
"text": [
"oxidative deamination"
],
"offsets": [
[
1252,
1273
]
],
"normalized": []
},
{
"id": "1_T26",
"type": "Biological_Activity",
"text": [
"transaminase"
],
"offsets": [
[
1330,
1342
]
],
"normalized": []
},
{
"id": "1_T27",
"type": "Chemical",
"text": [
"D-aromatic amino acids"
],
"offsets": [
[
1359,
1381
]
],
"normalized": []
},
{
"id": "1_T28",
"type": "Biological_Activity",
"text": [
"transaminase"
],
"offsets": [
[
1402,
1414
]
],
"normalized": []
},
{
"id": "1_T29",
"type": "Chemical",
"text": [
"aromatic amines."
],
"offsets": [
[
1431,
1447
]
],
"normalized": []
},
{
"id": "1_T30",
"type": "Chemical",
"text": [
"coenzyme-substrate adduct"
],
"offsets": [
[
1528,
1553
]
],
"normalized": []
},
{
"id": "1_T31",
"type": "Protein",
"text": [
"Dopa decarboxylase"
],
"offsets": [
[
1615,
1633
]
],
"normalized": []
},
{
"id": "1_T33",
"type": "Protein",
"text": [
"pyridoxal 5'-phosphate (PLP)-dependent alpha-decarboxylase"
],
"offsets": [
[
68,
126
]
],
"normalized": []
},
{
"id": "1_T1",
"type": "Chemical",
"text": [
"pyridoxal 5'-phosphate"
],
"offsets": [
[
68,
90
]
],
"normalized": []
},
{
"id": "1_T2",
"type": "Chemical",
"text": [
"PLP"
],
"offsets": [
[
92,
95
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "1_R4",
"type": "Associated_With",
"arg1_id": "1_T14",
"arg2_id": "1_T15",
"normalized": []
}
] |
2 | 10027587 | [
{
"id": "3",
"type": "",
"text": [
"Extracts of the creosote bush (Larrea tridentata, family Zygophyllaceae) have long been used as a folk remedy for Type II (non-insulin-dependent) diabetes by native Americans in southwestern North America. In this study we have evaluated the metabolic effects of masoprocol, a pure compound isolated from the creosote bush, in a rat model of Type II diabetes. Animals were fed a 20% fat (by weight) diet for 2 weeks prior to intravenous injection with streptozotocin (STZ, 0.19 mmol/kg). Diabetic animals (glucose 16-33 mmol/l) were treated with vehicle, metformin (0.83 mmol/kg body weight) or masoprocol (0.83 mmol/kg body weight) twice a day for 4 days. Masoprocol treatment lowered glucose concentrations an average of 35% compared with vehicle (14.2+/-1.1 vs 21.7+/-1.0 mmol/l, p < 0.001), a reduction similar to metformin treatment (12.8+/-0.9 mmol/l), without any change in insulin concentration. Masoprocol treatment also lowered triglyceride concentrations 80% compared with vehicle (1.0+/-0.1 vs 4.8+/-0.3 mmol/l, p < 0.001), a reduction far greater than following metformin treatment (3.6+/-0.3 mmol/l). Non-esterified fatty acid and glycerol concentration were decreased by approximately 65% by masoprocol compared with vehicle, a reduction approximately twice as great as seen with metformin (p < 0.001). The effect of masoprocol on in vivo insulin-mediated glucose disposal was evaluated by infusing fat-fed/STZ rats with glucose (0.22 mmol kg x min(-1)) and insulin (30 pmol x kg x min(-1)) for 5 h. In response to the infusion, steady-state plasma glucose concentrations were reduced 30% in masoprocol-treated animals compared with vehicle controls (p < 0.05) with no change noted in rats treated with metformin. The effect of masoprocol treatment was also tested in primary adipocytes isolated from normal animals. Adipocytes treated with masoprocol (30 micromol/l) had higher basal and insulin-stimulated glucose clearance than did adipocytes treated with vehicle (p <0.05). These data show that masoprocol decreases both plasma glucose and triglyceride concentrations in fat-fed/STZ rats, presumably as a result of its ability to both increase glucose disposal and decrease lipolysis. \n"
],
"offsets": [
[
0,
2208
]
]
}
] | [
{
"id": "3_T1",
"type": "Species",
"text": [
"creosote bush"
],
"offsets": [
[
16,
29
]
],
"normalized": []
},
{
"id": "3_T2",
"type": "Species",
"text": [
"Larrea tridentata"
],
"offsets": [
[
31,
48
]
],
"normalized": []
},
{
"id": "3_T4",
"type": "Metabolite",
"text": [
"masoprocol"
],
"offsets": [
[
263,
273
]
],
"normalized": []
},
{
"id": "3_T5",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
263,
273
]
],
"normalized": []
},
{
"id": "3_T6",
"type": "Species",
"text": [
"creosote bush"
],
"offsets": [
[
309,
322
]
],
"normalized": []
},
{
"id": "3_T7",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
329,
332
]
],
"normalized": []
},
{
"id": "3_T8",
"type": "Chemical",
"text": [
"streptozotocin"
],
"offsets": [
[
453,
467
]
],
"normalized": []
},
{
"id": "3_T9",
"type": "Chemical",
"text": [
"metformin"
],
"offsets": [
[
556,
565
]
],
"normalized": []
},
{
"id": "3_T10",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
596,
606
]
],
"normalized": []
},
{
"id": "3_T11",
"type": "Chemical",
"text": [
"Masoprocol"
],
"offsets": [
[
658,
668
]
],
"normalized": []
},
{
"id": "3_T12",
"type": "Chemical",
"text": [
"glucose"
],
"offsets": [
[
687,
694
]
],
"normalized": []
},
{
"id": "3_T14",
"type": "Chemical",
"text": [
"metformin"
],
"offsets": [
[
819,
828
]
],
"normalized": []
},
{
"id": "3_T15",
"type": "Protein",
"text": [
"insulin"
],
"offsets": [
[
882,
889
]
],
"normalized": []
},
{
"id": "3_T16",
"type": "Chemical",
"text": [
"Masoprocol"
],
"offsets": [
[
905,
915
]
],
"normalized": []
},
{
"id": "3_T17",
"type": "Chemical",
"text": [
"triglyceride"
],
"offsets": [
[
939,
951
]
],
"normalized": []
},
{
"id": "3_T18",
"type": "Chemical",
"text": [
"metformin"
],
"offsets": [
[
1076,
1085
]
],
"normalized": []
},
{
"id": "3_T19",
"type": "Chemical",
"text": [
"Non-esterified fatty acid"
],
"offsets": [
[
1116,
1141
]
],
"normalized": []
},
{
"id": "3_T20",
"type": "Chemical",
"text": [
"glycerol"
],
"offsets": [
[
1146,
1154
]
],
"normalized": []
},
{
"id": "3_T21",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
1208,
1218
]
],
"normalized": []
},
{
"id": "3_T22",
"type": "Chemical",
"text": [
"metformin"
],
"offsets": [
[
1296,
1305
]
],
"normalized": []
},
{
"id": "3_T23",
"type": "Metabolite",
"text": [
"masoprocol"
],
"offsets": [
[
1333,
1343
]
],
"normalized": []
},
{
"id": "3_T24",
"type": "Protein",
"text": [
"insulin"
],
"offsets": [
[
1355,
1362
]
],
"normalized": []
},
{
"id": "3_T25",
"type": "Chemical",
"text": [
"glucose"
],
"offsets": [
[
1372,
1379
]
],
"normalized": []
},
{
"id": "3_T26",
"type": "Chemical",
"text": [
"STZ"
],
"offsets": [
[
1423,
1426
]
],
"normalized": []
},
{
"id": "3_T27",
"type": "Chemical",
"text": [
"STZ"
],
"offsets": [
[
469,
472
]
],
"normalized": []
},
{
"id": "3_T28",
"type": "Chemical",
"text": [
"glucose"
],
"offsets": [
[
1437,
1444
]
],
"normalized": []
},
{
"id": "3_T29",
"type": "Protein",
"text": [
"insulin"
],
"offsets": [
[
1474,
1481
]
],
"normalized": []
},
{
"id": "3_T30",
"type": "Chemical",
"text": [
"glucose"
],
"offsets": [
[
1566,
1573
]
],
"normalized": []
},
{
"id": "3_T31",
"type": "Metabolite",
"text": [
"masoprocol"
],
"offsets": [
[
1609,
1619
]
],
"normalized": []
},
{
"id": "3_T32",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1427,
1431
]
],
"normalized": []
},
{
"id": "3_T33",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1702,
1706
]
],
"normalized": []
},
{
"id": "3_T34",
"type": "Chemical",
"text": [
"metformin"
],
"offsets": [
[
1720,
1729
]
],
"normalized": []
},
{
"id": "3_T35",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
1746,
1756
]
],
"normalized": []
},
{
"id": "3_T36",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
1859,
1869
]
],
"normalized": []
},
{
"id": "3_T37",
"type": "Protein",
"text": [
"insulin"
],
"offsets": [
[
1907,
1914
]
],
"normalized": []
},
{
"id": "3_T38",
"type": "Chemical",
"text": [
"glucose"
],
"offsets": [
[
1926,
1933
]
],
"normalized": []
},
{
"id": "3_T39",
"type": "Protein",
"text": [
"insulin"
],
"offsets": [
[
127,
134
]
],
"normalized": []
},
{
"id": "3_T40",
"type": "Chemical",
"text": [
"glucose"
],
"offsets": [
[
2050,
2057
]
],
"normalized": []
},
{
"id": "3_T41",
"type": "Chemical",
"text": [
"triglyceride"
],
"offsets": [
[
2062,
2074
]
],
"normalized": []
},
{
"id": "3_T42",
"type": "Chemical",
"text": [
"STZ"
],
"offsets": [
[
2101,
2104
]
],
"normalized": []
},
{
"id": "3_T43",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
2105,
2109
]
],
"normalized": []
},
{
"id": "3_T44",
"type": "Chemical",
"text": [
"glucose"
],
"offsets": [
[
2166,
2173
]
],
"normalized": []
},
{
"id": "3_T46",
"type": "Species",
"text": [
"native Americans"
],
"offsets": [
[
158,
174
]
],
"normalized": []
},
{
"id": "3_T47",
"type": "Metabolite",
"text": [
"masoprocol"
],
"offsets": [
[
596,
606
]
],
"normalized": []
},
{
"id": "3_T48",
"type": "Metabolite",
"text": [
"Masoprocol"
],
"offsets": [
[
658,
668
]
],
"normalized": []
},
{
"id": "3_T50",
"type": "Metabolite",
"text": [
"Masoprocol"
],
"offsets": [
[
905,
915
]
],
"normalized": []
},
{
"id": "3_T52",
"type": "Metabolite",
"text": [
"masoprocol"
],
"offsets": [
[
1746,
1756
]
],
"normalized": []
},
{
"id": "3_T53",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
1609,
1619
]
],
"normalized": []
},
{
"id": "3_T54",
"type": "Metabolite",
"text": [
"masoprocol"
],
"offsets": [
[
1859,
1869
]
],
"normalized": []
},
{
"id": "3_T55",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
2017,
2027
]
],
"normalized": []
},
{
"id": "3_T56",
"type": "Metabolite",
"text": [
"masoprocol"
],
"offsets": [
[
2017,
2027
]
],
"normalized": []
},
{
"id": "3_T57",
"type": "Metabolite",
"text": [
"triglyceride"
],
"offsets": [
[
939,
951
]
],
"normalized": []
},
{
"id": "3_T61",
"type": "Chemical",
"text": [
"masoprocol"
],
"offsets": [
[
1333,
1343
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "3_R1",
"type": "Isolated_From",
"arg1_id": "3_T4",
"arg2_id": "3_T2",
"normalized": []
},
{
"id": "3_R2",
"type": "Isolated_From",
"arg1_id": "3_T4",
"arg2_id": "3_T1",
"normalized": []
},
{
"id": "3_R3",
"type": "Isolated_From",
"arg1_id": "3_T4",
"arg2_id": "3_T6",
"normalized": []
},
{
"id": "3_R4",
"type": "Isolated_From",
"arg1_id": "3_T47",
"arg2_id": "3_T6",
"normalized": []
}
] |
4 | 10027798 | [
{
"id": "5",
"type": "",
"text": [
"Recently, it was shown that diclofenac was metabolized in rats to reactive benzoquinone imines via cytochrome P450-catalyzed oxidation. These metabolites also were detected in human hepatocyte cultures in the form of glutathione (GSH) adducts. This report describes the results of further studies aimed at characterizing the human hepatic P450-mediated bioactivation of diclofenac. The reactive metabolites formed in vitro were trapped by GSH and analyzed by LC/MS/MS. Thus, three GSH adducts, namely, 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified in incubations of diclofenac with human liver microsomes in the presence of NADPH and GSH. The formation of the adducts was taken to reflect the intermediacy of the corresponding putative benzoquinone imines. While M2 was the dominant metabolite over a substrate concentration range of 10-50 microM, M1 and M3 became equally important products at >/=100 microM diclofenac. The formation of M2 was inhibited by sulfaphenazole or an anti-P450 2C9 antibody (5-10% of control values). The formation of M1 and M3 was inhibited by troleandomycin, ketoconazole, or an anti-P450 3A4 antibody (30-50% of control values). In studies in which recombinant P450 isoforms were used, M2 was generated only by P450 2C9-catalyzed reaction, while M1 and M3 were produced by P450 3A4-catalyzed reaction. Good correlations were established between the extent of formation of M2 and P450 2C9 activities (r = 0.93, n = 10) and between the extent of formation of M1 and M3 and P450 3A4 activities (r = 0.98, n = 10) in human liver microsomal incubations. Taken together, the data suggest that the biotransformation of diclofenac to M2 is P450 2C9-dependent, whereas metabolism of the drug to M1 and M3 involves mainly P450 3A4. Although P450s 2C9 and 3A4 both catalyze the bioactivation of diclofenac, P450 2C9 is capable of producing the benzoquinone imine intermediate at lower drug concentrations which may be more clinically relevant. \n"
],
"offsets": [
[
0,
2084
]
]
}
] | [
{
"id": "5_T1",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
28,
38
]
],
"normalized": []
},
{
"id": "5_T2",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
58,
62
]
],
"normalized": []
},
{
"id": "5_T3",
"type": "Chemical",
"text": [
"benzoquinone imines"
],
"offsets": [
[
75,
94
]
],
"normalized": []
},
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851,
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878,
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"Recently, it was shown that diclofenac was metabolized in rats to reactive benzoquinone imines via cytochrome P450-catalyzed oxidation. These metabolites also were detected in human hepatocyte cultures in the form of glutathione (GSH) adducts. This report describes the results of further studies aimed at characterizing the human hepatic P450-mediated bioactivation of diclofenac. The reactive metabolites formed in vitro were trapped by GSH and analyzed by LC/MS/MS. Thus, three GSH adducts, namely, 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified in incubations of diclofenac with human liver microsomes in the presence of NADPH and GSH. The formation of the adducts was taken to reflect the intermediacy of the corresponding putative benzoquinone imines. While M2 was the dominant metabolite over a substrate concentration range of 10-50 microM, M1 and M3 became equally important products at >/=100 microM diclofenac. The formation of M2 was inhibited by sulfaphenazole or an anti-P450 2C9 antibody (5-10% of control values). The formation of M1 and M3 was inhibited by troleandomycin, ketoconazole, or an anti-P450 3A4 antibody (30-50% of control values). In studies in which recombinant P450 isoforms were used, M2 was generated only by P450 2C9-catalyzed reaction, while M1 and M3 were produced by P450 3A4-catalyzed reaction. Good correlations were established between the extent of formation of M2 and P450 2C9 activities (r = 0.93, n = 10) and between the extent of formation of M1 and M3 and P450 3A4 activities (r = 0.98, n = 10) in human liver microsomal incubations. Taken together, the data suggest that the biotransformation of diclofenac to M2 is P450 2C9-dependent, whereas metabolism of the drug to M1 and M3 involves mainly P450 3A4. Although P450s 2C9 and 3A4 both catalyze the bioactivation of diclofenac, P450 2C9 is capable of producing the benzoqu"
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"id": "5_R17",
"type": "Associated_With",
"arg1_id": "5_T22",
"arg2_id": "5_T87",
"normalized": []
},
{
"id": "5_R18",
"type": "Associated_With",
"arg1_id": "5_T25",
"arg2_id": "5_T87",
"normalized": []
}
] |
6 | 10027801 | [
{
"id": "7",
"type": "",
"text": [
"Cytochrome P450 2C11 in rats was recently found to metabolize diclofenac into a highly reactive product that covalently bound to this enzyme before it could diffuse away and react with other proteins. To determine whether cytochromes P450 in human liver could catalyze a similar reaction, we have studied the covalent binding of diclofenac in vitro to liver microsomes of 16 individuals. Only three of 16 samples were found by immunoblot analysis to activate diclofenac appreciably to form protein adducts in a NADPH-dependent pathway. Cytochrome P450 2C9, which catalyzes the major route of oxidative metabolism of diclofenac to produce 4'-hydroxydiclofenac, did not appear to be responsible for the formation of the protein adducts, because sulfaphenazole, an inhibitor of this enzyme, did not affect protein adduct formation. In contrast, troleandomycin, an inhibitor of P450 3A4, inhibited both protein adduct formation and 5-hydroxylation of diclofenac. These findings were confirmed with the use of baculovirus-expressed human P450 2C9 and P450 3A4. One possible reactive intermediate that would be expected to bind covalently to liver proteins was the p-benzoquinone imine derivative of 5-hydroxydiclofenac. This product was formed by an apparent metal-catalyzed oxidation of 5-hydroxydiclofenac that was inhibited by EDTA, glutathione, and NADPH. The p-benzoquinone imine decomposition product bound covalently to human liver microsomes in vitro in a reaction that was inhibited by GSH. In contrast, GSH did not prevent the covalent binding of diclofenac to human liver microsomes. These results suggest that for appreciable P450-mediated bioactivation of diclofenac to occur in vivo, an individual may have to have both high activities of P450 3A4 and perhaps low activities of other enzymes that catalyze competing pathways of metabolism of diclofenac. Moreover, the p-benzoquinone imine derivative of 5-hydroxydiclofenac probably has a role in covalent binding in the liver only under the conditions where levels of NADPH, GSH, and other reducing agents would be expected to be low. \n"
],
"offsets": [
[
0,
2098
]
]
}
] | [
{
"id": "7_T1",
"type": "Protein",
"text": [
"Cytochrome P450 2C11"
],
"offsets": [
[
0,
20
]
],
"normalized": []
},
{
"id": "7_T2",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
24,
28
]
],
"normalized": []
},
{
"id": "7_T3",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
62,
72
]
],
"normalized": []
},
{
"id": "7_T4",
"type": "Protein",
"text": [
"cytochromes P450"
],
"offsets": [
[
222,
238
]
],
"normalized": []
},
{
"id": "7_T5",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
242,
247
]
],
"normalized": []
},
{
"id": "7_T6",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
329,
339
]
],
"normalized": []
},
{
"id": "7_T7",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
460,
470
]
],
"normalized": []
},
{
"id": "7_T8",
"type": "Chemical",
"text": [
"NADPH"
],
"offsets": [
[
512,
517
]
],
"normalized": []
},
{
"id": "7_T9",
"type": "Protein",
"text": [
"Cytochrome P450 2C9"
],
"offsets": [
[
537,
556
]
],
"normalized": []
},
{
"id": "7_T10",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
617,
627
]
],
"normalized": []
},
{
"id": "7_T11",
"type": "Biological_Activity",
"text": [
"metabolism"
],
"offsets": [
[
603,
613
]
],
"normalized": []
},
{
"id": "7_T12",
"type": "Metabolite",
"text": [
"4'-hydroxydiclofenac"
],
"offsets": [
[
639,
659
]
],
"normalized": []
},
{
"id": "7_T13",
"type": "Chemical",
"text": [
"4'-hydroxydiclofenac"
],
"offsets": [
[
639,
659
]
],
"normalized": []
},
{
"id": "7_T14",
"type": "Chemical",
"text": [
"sulfaphenazole"
],
"offsets": [
[
745,
759
]
],
"normalized": []
},
{
"id": "7_T16",
"type": "Chemical",
"text": [
"troleandomycin"
],
"offsets": [
[
845,
859
]
],
"normalized": []
},
{
"id": "7_T17",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
864,
873
]
],
"normalized": []
},
{
"id": "7_T18",
"type": "Chemical",
"text": [
"5-hydroxylation of",
"diclofenac"
],
"offsets": [
[
931,
949
],
[
950,
960
]
],
"normalized": []
},
{
"id": "7_T19",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
1030,
1035
]
],
"normalized": []
},
{
"id": "7_T20",
"type": "Protein",
"text": [
"P450 2C9"
],
"offsets": [
[
1036,
1044
]
],
"normalized": []
},
{
"id": "7_T21",
"type": "Protein",
"text": [
"P450 3A4"
],
"offsets": [
[
1049,
1057
]
],
"normalized": []
},
{
"id": "7_T23",
"type": "Chemical",
"text": [
"p-benzoquinone imine derivative of 5-hydroxydiclofenac"
],
"offsets": [
[
1162,
1216
]
],
"normalized": []
},
{
"id": "7_T22",
"type": "Chemical",
"text": [
"5-hydroxydiclofenac"
],
"offsets": [
[
1286,
1305
]
],
"normalized": []
},
{
"id": "7_T24",
"type": "Metabolite",
"text": [
"5-hydroxydiclofenac"
],
"offsets": [
[
1286,
1305
]
],
"normalized": []
},
{
"id": "7_T25",
"type": "Chemical",
"text": [
"EDTA"
],
"offsets": [
[
1328,
1332
]
],
"normalized": []
},
{
"id": "7_T26",
"type": "Chemical",
"text": [
"glutathione"
],
"offsets": [
[
1334,
1345
]
],
"normalized": []
},
{
"id": "7_T27",
"type": "Chemical",
"text": [
"NADPH"
],
"offsets": [
[
1351,
1356
]
],
"normalized": []
},
{
"id": "7_T28",
"type": "Chemical",
"text": [
"metal"
],
"offsets": [
[
1257,
1262
]
],
"normalized": []
},
{
"id": "7_T29",
"type": "Chemical",
"text": [
"p-benzoquinone imine"
],
"offsets": [
[
1362,
1382
]
],
"normalized": []
},
{
"id": "7_T30",
"type": "Chemical",
"text": [
"GSH"
],
"offsets": [
[
1493,
1496
]
],
"normalized": []
},
{
"id": "7_T32",
"type": "Chemical",
"text": [
"GSH"
],
"offsets": [
[
1511,
1514
]
],
"normalized": []
},
{
"id": "7_T33",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
1555,
1565
]
],
"normalized": []
},
{
"id": "7_T34",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
1569,
1574
]
],
"normalized": []
},
{
"id": "7_T35",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
1425,
1430
]
],
"normalized": []
},
{
"id": "7_T36",
"type": "Protein",
"text": [
"P450"
],
"offsets": [
[
1636,
1640
]
],
"normalized": []
},
{
"id": "7_T37",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
1667,
1677
]
],
"normalized": []
},
{
"id": "7_T38",
"type": "Protein",
"text": [
"P450 3A4"
],
"offsets": [
[
1751,
1759
]
],
"normalized": []
},
{
"id": "7_T39",
"type": "Chemical",
"text": [
"diclofenac"
],
"offsets": [
[
1854,
1864
]
],
"normalized": []
},
{
"id": "7_T40",
"type": "Chemical",
"text": [
"p-benzoquinone imine",
"5-hydroxydiclofenac"
],
"offsets": [
[
1880,
1900
],
[
1915,
1934
]
],
"normalized": []
},
{
"id": "7_T41",
"type": "Chemical",
"text": [
"5-hydroxydiclofenac"
],
"offsets": [
[
1915,
1934
]
],
"normalized": []
},
{
"id": "7_T42",
"type": "Chemical",
"text": [
"NADPH"
],
"offsets": [
[
2030,
2035
]
],
"normalized": []
},
{
"id": "7_T43",
"type": "Chemical",
"text": [
"GSH"
],
"offsets": [
[
2037,
2040
]
],
"normalized": []
},
{
"id": "7_T44",
"type": "Chemical",
"text": [
"reducing agents"
],
"offsets": [
[
2052,
2067
]
],
"normalized": []
},
{
"id": "7_T45",
"type": "Protein",
"text": [
"enzyme"
],
"offsets": [
[
134,
140
]
],
"normalized": []
},
{
"id": "7_T46",
"type": "Protein",
"text": [
"protein adducts"
],
"offsets": [
[
491,
506
]
],
"normalized": []
},
{
"id": "7_T47",
"type": "Protein",
"text": [
"protein adducts"
],
"offsets": [
[
720,
735
]
],
"normalized": []
},
{
"id": "7_T48",
"type": "Protein",
"text": [
"protein adduct"
],
"offsets": [
[
806,
820
]
],
"normalized": []
},
{
"id": "7_T49",
"type": "Protein",
"text": [
"protein adduc"
],
"offsets": [
[
902,
915
]
],
"normalized": []
},
{
"id": "7_T50",
"type": "Protein",
"text": [
"proteins"
],
"offsets": [
[
1145,
1153
]
],
"normalized": []
},
{
"id": "7_T51",
"type": "Chemical",
"text": [
"5-hydroxydiclofenac"
],
"offsets": [
[
1197,
1216
]
],
"normalized": []
},
{
"id": "7_T52",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
764,
773
]
],
"normalized": []
},
{
"id": "7_T54",
"type": "Protein",
"text": [
"P450 3A4"
],
"offsets": [
[
877,
885
]
],
"normalized": []
},
{
"id": "7_T31",
"type": "Protein",
"text": [
"enzymes"
],
"offsets": [
[
1796,
1803
]
],
"normalized": []
},
{
"id": "7_T15",
"type": "Biological_Activity",
"text": [
"inhibited"
],
"offsets": [
[
1315,
1324
]
],
"normalized": []
},
{
"id": "7_T53",
"type": "Biological_Activity",
"text": [
"inhibited"
],
"offsets": [
[
1480,
1489
]
],
"normalized": []
},
{
"id": "7_T55",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
318,
325
]
],
"normalized": []
},
{
"id": "7_T56",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
1544,
1551
]
],
"normalized": []
},
{
"id": "7_T57",
"type": "Biological_Activity",
"text": [
"metabolism"
],
"offsets": [
[
1840,
1850
]
],
"normalized": []
},
{
"id": "7_T58",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
1967,
1974
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "7_R1",
"type": "Metabolite_Of",
"arg1_id": "7_T12",
"arg2_id": "7_T10",
"normalized": []
},
{
"id": "7_R2",
"type": "Associated_With",
"arg1_id": "7_T14",
"arg2_id": "7_T52",
"normalized": []
},
{
"id": "7_R5",
"type": "Binds_With",
"arg1_id": "7_T14",
"arg2_id": "7_T9",
"normalized": []
},
{
"id": "7_R3",
"type": "Associated_With",
"arg1_id": "7_T16",
"arg2_id": "7_T17",
"normalized": []
},
{
"id": "7_R6",
"type": "Binds_With",
"arg1_id": "7_T16",
"arg2_id": "7_T54",
"normalized": []
},
{
"id": "7_R4",
"type": "Associated_With",
"arg1_id": "7_T25",
"arg2_id": "7_T15",
"normalized": []
},
{
"id": "7_R7",
"type": "Associated_With",
"arg1_id": "7_T26",
"arg2_id": "7_T15",
"normalized": []
},
{
"id": "7_R8",
"type": "Associated_With",
"arg1_id": "7_T27",
"arg2_id": "7_T15",
"normalized": []
},
{
"id": "7_R9",
"type": "Associated_With",
"arg1_id": "7_T30",
"arg2_id": "7_T53",
"normalized": []
},
{
"id": "7_R10",
"type": "Associated_With",
"arg1_id": "7_T6",
"arg2_id": "7_T55",
"normalized": []
},
{
"id": "7_R11",
"type": "Associated_With",
"arg1_id": "7_T33",
"arg2_id": "7_T56",
"normalized": []
},
{
"id": "7_R12",
"type": "Associated_With",
"arg1_id": "7_T10",
"arg2_id": "7_T11",
"normalized": []
},
{
"id": "7_R13",
"type": "Associated_With",
"arg1_id": "7_T39",
"arg2_id": "7_T57",
"normalized": []
},
{
"id": "7_R14",
"type": "Associated_With",
"arg1_id": "7_T40",
"arg2_id": "7_T58",
"normalized": []
}
] |
8 | 10027870 | [
{
"id": "9",
"type": "",
"text": [
"The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo. \n"
],
"offsets": [
[
0,
1750
]
]
}
] | [
{
"id": "9_T1",
"type": "Biological_Activity",
"text": [
"analgesic"
],
"offsets": [
[
11,
20
]
],
"normalized": []
},
{
"id": "9_T2",
"type": "Chemical",
"text": [
"ketorolac"
],
"offsets": [
[
33,
42
]
],
"normalized": []
},
{
"id": "9_T3",
"type": "Species",
"text": [
"humans"
],
"offsets": [
[
46,
52
]
],
"normalized": []
},
{
"id": "9_T4",
"type": "Chemical",
"text": [
"nonsteroidal anti-inflammatory drugs"
],
"offsets": [
[
72,
108
]
],
"normalized": []
},
{
"id": "9_T5",
"type": "Biological_Activity",
"text": [
"anti-inflammatory"
],
"offsets": [
[
85,
102
]
],
"normalized": []
},
{
"id": "9_T6",
"type": "Chemical",
"text": [
"NSAIDs"
],
"offsets": [
[
110,
116
]
],
"normalized": []
},
{
"id": "9_T7",
"type": "Biological_Activity",
"text": [
"analgesic"
],
"offsets": [
[
209,
218
]
],
"normalized": []
},
{
"id": "9_T8",
"type": "Chemical",
"text": [
"NSAID"
],
"offsets": [
[
172,
177
]
],
"normalized": []
},
{
"id": "9_T9",
"type": "Chemical",
"text": [
"(R,S)-ketorolac"
],
"offsets": [
[
275,
290
]
],
"normalized": []
},
{
"id": "9_T11",
"type": "Protein",
"text": [
"cyclooxygenase"
],
"offsets": [
[
364,
378
]
],
"normalized": []
},
{
"id": "9_T13",
"type": "Protein",
"text": [
"COX"
],
"offsets": [
[
380,
383
]
],
"normalized": []
},
{
"id": "9_T14",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
385,
394
]
],
"normalized": []
},
{
"id": "9_T15",
"type": "Chemical",
"text": [
"indomethacin"
],
"offsets": [
[
397,
409
]
],
"normalized": []
},
{
"id": "9_T16",
"type": "Chemical",
"text": [
"INDO"
],
"offsets": [
[
411,
415
]
],
"normalized": []
},
{
"id": "9_T17",
"type": "Chemical",
"text": [
"diclofenac sodium"
],
"offsets": [
[
421,
438
]
],
"normalized": []
},
{
"id": "9_T18",
"type": "Chemical",
"text": [
"DS"
],
"offsets": [
[
440,
442
]
],
"normalized": []
},
{
"id": "9_T19",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
476,
485
]
],
"normalized": []
},
{
"id": "9_T20",
"type": "Chemical",
"text": [
"celecoxib"
],
"offsets": [
[
487,
496
]
],
"normalized": []
},
{
"id": "9_T21",
"type": "Protein",
"text": [
"COX-2"
],
"offsets": [
[
470,
475
]
],
"normalized": []
},
{
"id": "9_T23",
"type": "Chemical",
"text": [
"(R,S)-ketorolac"
],
"offsets": [
[
536,
551
]
],
"normalized": []
},
{
"id": "9_T24",
"type": "Chemical",
"text": [
"acetic acid"
],
"offsets": [
[
576,
587
]
],
"normalized": []
},
{
"id": "9_T25",
"type": "Chemical",
"text": [
"carrageenan"
],
"offsets": [
[
606,
617
]
],
"normalized": []
},
{
"id": "9_T27",
"type": "Chemical",
"text": [
"carrageenan"
],
"offsets": [
[
648,
659
]
],
"normalized": []
},
{
"id": "9_T29",
"type": "Species",
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10 | 10027962 | [
{
"id": "11",
"type": "",
"text": [
"Diazaborine and isoniazid are, at first sight, unrelated anti-bacterial agents that inhibit the enoyl-ACP reductase (ENR) of Escherichia coli and Mycobacterium tuberculosis respectively. The crystal structures of these enzymes including that of the diazaborine-inhibited E. coli ENR have been obtained at high resolution. Site-directed mutagenesis was used to study the importance of amino acid residues in diazaborine susceptibility and enzyme function. The results show that drug binding and inhibition require the presence of a glycine residue at position 93 of E. coli ENR or at the structurally equivalent position in the plant homologue, which is naturally resistant to the drug. The data confirm the hypothesis that any amino acid side-chain other than hydrogen at this position within the three-dimensional structure of these enzymes will affect diazaborine resistance by encroaching into the drug binding site. Substitutions of Gly-93 by amino acids with small side-chains, such as serine, alanine, cysteine and valine, hardly affected the catalytic parameters and rendered the bacterial host resistant to the drug. Larger amino acid side-chains, such as that of arginine, histidine, lysine and glutamine, completely inactivated the activity of the enzyme. \n"
],
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"text": [
"drug"
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[
478,
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],
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}
] | [] | [] | [
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] |
12 | 10028198 | [
{
"id": "13",
"type": "",
"text": [
"The aim of this study was to investigate the distribution, excretion and metabolism of 1,2-dimethylnaphthalene-[ring-U-3H] in rats. The experiments were performed on 54 male outbred IMP:Wist rats with body weight of 200 g +/- 20%. The compound was given i.p. in olive oil in a single dose of 28 mg/kg (about 6.2 MBq per animal). 3H radioactivity was traced in selected organs and tissues, blood, urine and faeces, 1-72 h following the administration. The main metabolites were isolated from urine and identified by the GC-MS method. Faeces and urine proved to be the main route of tritium elimination. Over 93% of the given compound was excreted during the first 72 h. Maximum level of tritium in plasma was observed during the 4th h after the compound administration. The accretion of 3H proceeded with kinetic constant of 0.7 h, followed by monophasic decline with the half-life of about 19h. In organs and tissue, the highest concentration during the first hours after administration were detected in the fat, adrenals, liver, spleen and kidneys. Then gradual decline of tritium was noticed in all examined tissues. The following urinary metabolites were identified: 1. 1,2-dimethylthionaphthalene, 2. 1,2-dimethylnaphthol, 3. 1-methylnaphthalene-2-methanol, 4. 1-methyl-2-naphthoic acid and 5. 1,2-dimethylmethylthionaphthalene. In conclusion, 1,2-dimethylnaphthalene has a relatively rapid turnover rate in the rat organism and does not form deposits in the tissue. The metabolism encompasses ring hydroxylation and glutathione conjugation leading to thionaphthol and oxygenation, and then to naphthoic acid. \n"
],
"offsets": [
[
0,
1620
]
]
}
] | [
{
"id": "13_T1",
"type": "Chemical",
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"1,2-dimethylnaphthalene"
],
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[
87,
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]
],
"normalized": []
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{
"id": "13_T2",
"type": "Chemical",
"text": [
"1,2-dimethylnaphthalene-[ring-U-3H]"
],
"offsets": [
[
87,
122
]
],
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},
{
"id": "13_T3",
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"rats"
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126,
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},
{
"id": "13_T4",
"type": "Species",
"text": [
"rats"
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"offsets": [
[
191,
195
]
],
"normalized": []
},
{
"id": "13_T5",
"type": "Chemical",
"text": [
"olive oil"
],
"offsets": [
[
262,
271
]
],
"normalized": []
},
{
"id": "13_T7",
"type": "Spectral_Data",
"text": [
"GC-MS"
],
"offsets": [
[
521,
526
]
],
"normalized": []
},
{
"id": "13_T8",
"type": "Chemical",
"text": [
"tritium"
],
"offsets": [
[
583,
590
]
],
"normalized": []
},
{
"id": "13_T9",
"type": "Chemical",
"text": [
"3H"
],
"offsets": [
[
330,
332
]
],
"normalized": []
},
{
"id": "13_T10",
"type": "Chemical",
"text": [
"3H"
],
"offsets": [
[
788,
790
]
],
"normalized": []
},
{
"id": "13_T11",
"type": "Chemical",
"text": [
"tritium"
],
"offsets": [
[
1077,
1084
]
],
"normalized": []
},
{
"id": "13_T12",
"type": "Chemical",
"text": [
"1,2-dimethylthionaphthalene"
],
"offsets": [
[
1176,
1203
]
],
"normalized": []
},
{
"id": "13_T13",
"type": "Chemical",
"text": [
"1,2-dimethylnaphthol"
],
"offsets": [
[
1208,
1228
]
],
"normalized": []
},
{
"id": "13_T14",
"type": "Metabolite",
"text": [
"1,2-dimethylnaphthol"
],
"offsets": [
[
1208,
1228
]
],
"normalized": []
},
{
"id": "13_T15",
"type": "Chemical",
"text": [
"1-methylnaphthalene-2-methanol"
],
"offsets": [
[
1233,
1263
]
],
"normalized": []
},
{
"id": "13_T16",
"type": "Metabolite",
"text": [
"1-methylnaphthalene-2-methanol"
],
"offsets": [
[
1233,
1263
]
],
"normalized": []
},
{
"id": "13_T17",
"type": "Chemical",
"text": [
"1-methyl-2-naphthoic acid"
],
"offsets": [
[
1268,
1294
]
],
"normalized": []
},
{
"id": "13_T18",
"type": "Metabolite",
"text": [
"1-methyl-2-naphthoic acid"
],
"offsets": [
[
1268,
1294
]
],
"normalized": []
},
{
"id": "13_T19",
"type": "Chemical",
"text": [
"1,2-dimethylmethylthionaphthalene"
],
"offsets": [
[
1302,
1335
]
],
"normalized": []
},
{
"id": "13_T20",
"type": "Metabolite",
"text": [
"1,2-dimethylmethylthionaphthalene"
],
"offsets": [
[
1302,
1335
]
],
"normalized": []
},
{
"id": "13_T21",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
1420,
1423
]
],
"normalized": []
},
{
"id": "13_T22",
"type": "Chemical",
"text": [
"1,2-dimethylnaphthalene"
],
"offsets": [
[
1352,
1375
]
],
"normalized": []
},
{
"id": "13_T23",
"type": "Chemical",
"text": [
"glutathione"
],
"offsets": [
[
1526,
1537
]
],
"normalized": []
},
{
"id": "13_T24",
"type": "Chemical",
"text": [
"thionaphthol"
],
"offsets": [
[
1561,
1573
]
],
"normalized": []
},
{
"id": "13_T25",
"type": "Chemical",
"text": [
"naphthoic acid"
],
"offsets": [
[
1603,
1617
]
],
"normalized": []
},
{
"id": "13_T26",
"type": "Biological_Activity",
"text": [
"oxygenation"
],
"offsets": [
[
1578,
1589
]
],
"normalized": []
},
{
"id": "13_T27",
"type": "Metabolite",
"text": [
"1,2-dimethylthionaphthalene"
],
"offsets": [
[
1176,
1203
]
],
"normalized": []
},
{
"id": "13_T6",
"type": "Chemical",
"text": [
"tritium"
],
"offsets": [
[
688,
695
]
],
"normalized": []
},
{
"id": "13_T28",
"type": "Biological_Activity",
"text": [
"metabolism"
],
"offsets": [
[
73,
83
]
],
"normalized": []
},
{
"id": "13_T29",
"type": "Biological_Activity",
"text": [
"metabolism"
],
"offsets": [
[
1480,
1490
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "13_R1",
"type": "Associated_With",
"arg1_id": "13_T14",
"arg2_id": "13_T7",
"normalized": []
},
{
"id": "13_R2",
"type": "Associated_With",
"arg1_id": "13_T16",
"arg2_id": "13_T7",
"normalized": []
},
{
"id": "13_R3",
"type": "Associated_With",
"arg1_id": "13_T18",
"arg2_id": "13_T7",
"normalized": []
},
{
"id": "13_R4",
"type": "Associated_With",
"arg1_id": "13_T20",
"arg2_id": "13_T7",
"normalized": []
},
{
"id": "13_R5",
"type": "Associated_With",
"arg1_id": "13_T27",
"arg2_id": "13_T7",
"normalized": []
},
{
"id": "13_R6",
"type": "Associated_With",
"arg1_id": "13_T24",
"arg2_id": "13_T26",
"normalized": []
},
{
"id": "13_R7",
"type": "Metabolite_Of",
"arg1_id": "13_T20",
"arg2_id": "13_T1",
"normalized": []
},
{
"id": "13_R8",
"type": "Metabolite_Of",
"arg1_id": "13_T18",
"arg2_id": "13_T1",
"normalized": []
},
{
"id": "13_R9",
"type": "Metabolite_Of",
"arg1_id": "13_T16",
"arg2_id": "13_T1",
"normalized": []
},
{
"id": "13_R10",
"type": "Metabolite_Of",
"arg1_id": "13_T14",
"arg2_id": "13_T1",
"normalized": []
},
{
"id": "13_R11",
"type": "Metabolite_Of",
"arg1_id": "13_T27",
"arg2_id": "13_T1",
"normalized": []
}
] |
14 | 10028199 | [
{
"id": "15",
"type": "",
"text": [
"Trimethylbenzene isomers (TMBs): 1,2,4-TMB (pseudocumene--PS), 1,2,3-TMB (hemimellitene--HM) and 1,3,5-TMB (mesitylene--MES) are important constituents of solvent mixtures. In the US, the adopted TLV-TWA value for TMBs is 125 mg/m3 or 25 ppm (ACGIH 1996). Recent experiments at our laboratory have revealed an impaired learning of passive and active avoidance responses and a longer persistence of an effect of footshock (increase in latency of the paw-lick response to heat) in rats tested several weeks after a four-week inhalation exposure (6h/day, five days/week) to PS at a concentration of 100 or 250 ppm (15). The concentration-effect relationship appeared to be nonlinear; the effect of 100 ppm HM was more pronounced than that of 250 ppm. In the present experiment we investigated the effects of a repeated four-week (6h/day, 5 days/week) inhalation exposure to HM at concentrations of 0, 25, 100 or 250 ppm on radial-maze performance, open-field activity, passive and active avoidance learning, and on the shock-induced changes in latency of the paw-lick response to heat (hot-plate test). The tests were performed between days 14 and 61 after the last exposure. No significant effects on radial-maze performance and open-field activity were noted in any of the dose groups. In the remaining tests effects of exposure were noted but, similarly as in the case of PS exposure, the concentration-effect relationship was not linear. In rats exposed to HM at 25 or 100 ppm, but not 250 ppm, learning of the passive avoidance, i.e. refraining from performance of a punished response (stepping off an elevated platform) was significantly impaired. Moreover, in rats exposed to 100, but not 250 ppm of HM, acquisition of the two-way active avoidance in the shuttle-box was slower and the footshock-induced increase in latency of the paw-lick response to heat persisted longer than in the unexposed animals. The results suggest that a low-level inhalation exposure to HM, just like low-level exposure to PS, may lead to long-lasting disturbances in the CNS functions. The nonlinear concentration-effect relationship observed in the case of both TMB-s requires clarification in further studies. \n"
],
"offsets": [
[
0,
2202
]
]
}
] | [
{
"id": "15_T1",
"type": "Chemical",
"text": [
"Trimethylbenzene"
],
"offsets": [
[
0,
16
]
],
"normalized": []
},
{
"id": "15_T2",
"type": "Chemical",
"text": [
"TMBs"
],
"offsets": [
[
26,
30
]
],
"normalized": []
},
{
"id": "15_T3",
"type": "Chemical",
"text": [
"1,2,4-TMB"
],
"offsets": [
[
33,
42
]
],
"normalized": []
},
{
"id": "15_T4",
"type": "Chemical",
"text": [
"pseudocumene"
],
"offsets": [
[
44,
56
]
],
"normalized": []
},
{
"id": "15_T5",
"type": "Chemical",
"text": [
"PS"
],
"offsets": [
[
58,
60
]
],
"normalized": []
},
{
"id": "15_T6",
"type": "Chemical",
"text": [
"1,2,3-TMB"
],
"offsets": [
[
63,
72
]
],
"normalized": []
},
{
"id": "15_T7",
"type": "Chemical",
"text": [
"hemimellitene"
],
"offsets": [
[
74,
87
]
],
"normalized": []
},
{
"id": "15_T8",
"type": "Chemical",
"text": [
"HM"
],
"offsets": [
[
89,
91
]
],
"normalized": []
},
{
"id": "15_T9",
"type": "Chemical",
"text": [
"1,3,5-TMB"
],
"offsets": [
[
97,
106
]
],
"normalized": []
},
{
"id": "15_T10",
"type": "Chemical",
"text": [
"mesitylene"
],
"offsets": [
[
108,
118
]
],
"normalized": []
},
{
"id": "15_T11",
"type": "Chemical",
"text": [
"MES"
],
"offsets": [
[
120,
123
]
],
"normalized": []
},
{
"id": "15_T12",
"type": "Chemical",
"text": [
"TMBs"
],
"offsets": [
[
214,
218
]
],
"normalized": []
},
{
"id": "15_T16",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
479,
483
]
],
"normalized": []
},
{
"id": "15_T17",
"type": "Chemical",
"text": [
"PS"
],
"offsets": [
[
571,
573
]
],
"normalized": []
},
{
"id": "15_T18",
"type": "Chemical",
"text": [
"HM"
],
"offsets": [
[
704,
706
]
],
"normalized": []
},
{
"id": "15_T19",
"type": "Chemical",
"text": [
"HM"
],
"offsets": [
[
872,
874
]
],
"normalized": []
},
{
"id": "15_T22",
"type": "Chemical",
"text": [
"PS"
],
"offsets": [
[
1375,
1377
]
],
"normalized": []
},
{
"id": "15_T23",
"type": "Chemical",
"text": [
"HM"
],
"offsets": [
[
1461,
1463
]
],
"normalized": []
},
{
"id": "15_T25",
"type": "Chemical",
"text": [
"HM"
],
"offsets": [
[
1708,
1710
]
],
"normalized": []
},
{
"id": "15_T28",
"type": "Chemical",
"text": [
"HM"
],
"offsets": [
[
1975,
1977
]
],
"normalized": []
},
{
"id": "15_T29",
"type": "Chemical",
"text": [
"PS"
],
"offsets": [
[
2011,
2013
]
],
"normalized": []
},
{
"id": "15_T31",
"type": "Chemical",
"text": [
"TMB-s"
],
"offsets": [
[
2152,
2157
]
],
"normalized": []
},
{
"id": "15_T13",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1445,
1449
]
],
"normalized": []
},
{
"id": "15_T14",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1668,
1672
]
],
"normalized": []
}
] | [] | [] | [] |
16 | 10029225 | [
{
"id": "17",
"type": "",
"text": [
"OBJECTIVE: To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). METHODS: A population of 111 workers from 2 condenser plants (A and B) using epoxy resin with MTHPA underwent a questionnaire survey and serology investigations, and data obtained on 95 subjects in assembly and inspection lines were analyzed for this study. RESULTS: In all, 24 (65%) of 37 workers in plant A and 38 (66%) of 58 workers in plant B had positive MTHPA-specific IgE. The air levels of MTHPA detected in assembly and inspection lines were higher in plant A than in plant B (geometric mean 25.5-63.9 and 4.93-5.49 microg/m3, respectively). IgE-sensitized workers in each plant had significantly (P < 0.05) more complaints regarding the eyes and nose than did unsensitized workers, suggesting that there is an IgE-mediated mechanism in most of these symptoms. The sensitized workers in plant A had higher frequencies for symptoms of the eyes, nose, and pharynx than did those in plant B (P < 0.02). Furthermore, only 15% of persons often displayed work-related symptoms among the 20 symptomatic workers in plant B as compared with 73% of the 26 symptomatic workers in plant A (P < 0.0001). These results can be explained by the difference in the MTHPA levels measured in the lines between the two plants. In plant B the minimal level of MTHPA that was associated with work-related symptoms was 15-22 microg/m3, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. CONCLUSIONS: These results suggest that MTHPA exposure at levels above 15 microg/m3 should be avoided to prevent the development of occupational allergic diseases in most workers. \n"
],
"offsets": [
[
0,
1780
]
]
}
] | [
{
"id": "17_T1",
"type": "Chemical",
"text": [
"methyltetrahydrophthalic anhydride"
],
"offsets": [
[
130,
164
]
],
"normalized": []
},
{
"id": "17_T2",
"type": "Chemical",
"text": [
"MTHPA"
],
"offsets": [
[
166,
171
]
],
"normalized": []
},
{
"id": "17_T3",
"type": "Species",
"text": [
"workers"
],
"offsets": [
[
111,
118
]
],
"normalized": []
},
{
"id": "17_T4",
"type": "Species",
"text": [
"workers"
],
"offsets": [
[
203,
210
]
],
"normalized": []
},
{
"id": "17_T5",
"type": "Chemical",
"text": [
"epoxy resin"
],
"offsets": [
[
251,
262
]
],
"normalized": []
},
{
"id": "17_T6",
"type": "Chemical",
"text": [
"MTHPA"
],
"offsets": [
[
268,
273
]
],
"normalized": []
},
{
"id": "17_T7",
"type": "Protein",
"text": [
"IgE"
],
"offsets": [
[
549,
552
]
],
"normalized": []
},
{
"id": "17_T8",
"type": "Chemical",
"text": [
"MTHPA"
],
"offsets": [
[
534,
539
]
],
"normalized": []
},
{
"id": "17_T9",
"type": "Chemical",
"text": [
"MTHPA"
],
"offsets": [
[
572,
577
]
],
"normalized": []
},
{
"id": "17_T10",
"type": "Protein",
"text": [
"IgE"
],
"offsets": [
[
725,
728
]
],
"normalized": []
},
{
"id": "17_T11",
"type": "Protein",
"text": [
"IgE"
],
"offsets": [
[
894,
897
]
],
"normalized": []
},
{
"id": "17_T12",
"type": "Chemical",
"text": [
"MTHPA"
],
"offsets": [
[
1332,
1337
]
],
"normalized": []
},
{
"id": "17_T13",
"type": "Chemical",
"text": [
"MTHPA"
],
"offsets": [
[
1424,
1429
]
],
"normalized": []
},
{
"id": "17_T14",
"type": "Chemical",
"text": [
"MTHPA"
],
"offsets": [
[
1639,
1644
]
],
"normalized": []
},
{
"id": "17_T16",
"type": "Species",
"text": [
"workers"
],
"offsets": [
[
502,
509
]
],
"normalized": []
},
{
"id": "17_T17",
"type": "Species",
"text": [
"workers"
],
"offsets": [
[
740,
747
]
],
"normalized": []
},
{
"id": "17_T18",
"type": "Species",
"text": [
"workers"
],
"offsets": [
[
960,
967
]
],
"normalized": []
},
{
"id": "17_T19",
"type": "Species",
"text": [
"persons"
],
"offsets": [
[
1109,
1116
]
],
"normalized": []
},
{
"id": "17_T20",
"type": "Species",
"text": [
"workers"
],
"offsets": [
[
1770,
1777
]
],
"normalized": []
},
{
"id": "17_T21",
"type": "Species",
"text": [
"workers"
],
"offsets": [
[
1181,
1188
]
],
"normalized": []
}
] | [] | [] | [] |
18 | 1002932 | [
{
"id": "19",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
20 | 10030438 | [
{
"id": "21",
"type": "",
"text": [
"All the benzodiazepines (BZDs) in clinical use have the capacity to promote the binding of the major inhibitory neurotransmitter, gamma-amino-butyric acid (GABA), to sub-types of GABA receptors which exist as multi-subunit ligand-gated chloride channels. Thus, the BZDs facilitate the actions of GABA in the brain. The BZDs in use as antiepileptic drugs are diazepam, clonazepam, clobazam, nitrazepam, and lately, also lorazepam and midazolam as emergency therapy. The BZDs have a wide-spectrum of proven clinical efficacy in the prevention of different kind of seizures. Clonazepam and clobazam, as well as nitrazepam in some cases, can be useful as an adjunct treatment in refractory epilepsies. However, the clinical use of BZDs for the prophylactic treatment of epilepsy is associated with two major problems which have limited the long-term use of these drugs: the potential for side-effects, especially sedative effects, and the high risk of development of tolerance. Despite the limitations of BZDs in the prophylactic treatment of epilepsies, these drugs play a prominent role in clinical practice in the emergency management of acute seizures and status epilepticus. Diazepam, clonazepam and lorazepam are all considered first-line agents in the emergency management of acute seizures and status epilepticus. Furthermore, the value of midazolam as an emergency therapy in epilepsy has been increasingly recognized in recent years. \n"
],
"offsets": [
[
0,
1445
]
]
}
] | [
{
"id": "21_T1",
"type": "Chemical",
"text": [
"benzodiazepines"
],
"offsets": [
[
8,
23
]
],
"normalized": []
},
{
"id": "21_T2",
"type": "Chemical",
"text": [
"gamma-amino-butyric acid"
],
"offsets": [
[
130,
154
]
],
"normalized": []
},
{
"id": "21_T3",
"type": "Biological_Activity",
"text": [
"neurotransmitter"
],
"offsets": [
[
112,
128
]
],
"normalized": []
},
{
"id": "21_T4",
"type": "Chemical",
"text": [
"GABA"
],
"offsets": [
[
156,
160
]
],
"normalized": []
},
{
"id": "21_T5",
"type": "Chemical",
"text": [
"BZDs"
],
"offsets": [
[
266,
270
]
],
"normalized": []
},
{
"id": "21_T6",
"type": "Chemical",
"text": [
"BZDs"
],
"offsets": [
[
25,
29
]
],
"normalized": []
},
{
"id": "21_T7",
"type": "Chemical",
"text": [
"GABA"
],
"offsets": [
[
297,
301
]
],
"normalized": []
},
{
"id": "21_T8",
"type": "Chemical",
"text": [
"BZDs"
],
"offsets": [
[
320,
324
]
],
"normalized": []
},
{
"id": "21_T9",
"type": "Biological_Activity",
"text": [
"antiepileptic"
],
"offsets": [
[
335,
348
]
],
"normalized": []
},
{
"id": "21_T10",
"type": "Chemical",
"text": [
"diazepam"
],
"offsets": [
[
359,
367
]
],
"normalized": []
},
{
"id": "21_T11",
"type": "Chemical",
"text": [
"clonazepam"
],
"offsets": [
[
369,
379
]
],
"normalized": []
},
{
"id": "21_T12",
"type": "Chemical",
"text": [
"clobazam"
],
"offsets": [
[
381,
389
]
],
"normalized": []
},
{
"id": "21_T13",
"type": "Chemical",
"text": [
"nitrazepam"
],
"offsets": [
[
391,
401
]
],
"normalized": []
},
{
"id": "21_T14",
"type": "Chemical",
"text": [
"lorazepam"
],
"offsets": [
[
420,
429
]
],
"normalized": []
},
{
"id": "21_T15",
"type": "Chemical",
"text": [
"midazolam"
],
"offsets": [
[
434,
443
]
],
"normalized": []
},
{
"id": "21_T18",
"type": "Chemical",
"text": [
"BZDs"
],
"offsets": [
[
470,
474
]
],
"normalized": []
},
{
"id": "21_T20",
"type": "Chemical",
"text": [
"Clonazepam"
],
"offsets": [
[
573,
583
]
],
"normalized": []
},
{
"id": "21_T21",
"type": "Chemical",
"text": [
"clobazam"
],
"offsets": [
[
588,
596
]
],
"normalized": []
},
{
"id": "21_T22",
"type": "Chemical",
"text": [
"nitrazepam"
],
"offsets": [
[
609,
619
]
],
"normalized": []
},
{
"id": "21_T24",
"type": "Chemical",
"text": [
"BZDs"
],
"offsets": [
[
728,
732
]
],
"normalized": []
},
{
"id": "21_T26",
"type": "Chemical",
"text": [
"drugs"
],
"offsets": [
[
861,
866
]
],
"normalized": []
},
{
"id": "21_T27",
"type": "Biological_Activity",
"text": [
"sedative"
],
"offsets": [
[
911,
919
]
],
"normalized": []
},
{
"id": "21_T28",
"type": "Chemical",
"text": [
"BZDs"
],
"offsets": [
[
1004,
1008
]
],
"normalized": []
},
{
"id": "21_T30",
"type": "Chemical",
"text": [
"Diazepam"
],
"offsets": [
[
1179,
1187
]
],
"normalized": []
},
{
"id": "21_T31",
"type": "Chemical",
"text": [
"clonazepam"
],
"offsets": [
[
1189,
1199
]
],
"normalized": []
},
{
"id": "21_T32",
"type": "Chemical",
"text": [
"lorazepam"
],
"offsets": [
[
1204,
1213
]
],
"normalized": []
},
{
"id": "21_T35",
"type": "Chemical",
"text": [
"midazolam"
],
"offsets": [
[
1347,
1356
]
],
"normalized": []
},
{
"id": "21_T38",
"type": "Metabolite",
"text": [
"gamma-amino-butyric acid"
],
"offsets": [
[
130,
154
]
],
"normalized": []
},
{
"id": "21_T39",
"type": "Protein",
"text": [
"GABA receptors"
],
"offsets": [
[
179,
193
]
],
"normalized": []
},
{
"id": "21_T40",
"type": "Protein",
"text": [
"ligand-gated chloride channels"
],
"offsets": [
[
223,
254
]
],
"normalized": []
},
{
"id": "21_T41",
"type": "Metabolite",
"text": [
"GABA"
],
"offsets": [
[
297,
301
]
],
"normalized": []
},
{
"id": "21_T44",
"type": "Metabolite",
"text": [
"GABA"
],
"offsets": [
[
156,
160
]
],
"normalized": []
},
{
"id": "21_T16",
"type": "Chemical",
"text": [
"drugs"
],
"offsets": [
[
349,
354
]
],
"normalized": []
},
{
"id": "21_T17",
"type": "Chemical",
"text": [
"drugs"
],
"offsets": [
[
1060,
1065
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "21_R1",
"type": "Associated_With",
"arg1_id": "21_T10",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R2",
"type": "Associated_With",
"arg1_id": "21_T11",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R3",
"type": "Associated_With",
"arg1_id": "21_T12",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R4",
"type": "Associated_With",
"arg1_id": "21_T13",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R5",
"type": "Associated_With",
"arg1_id": "21_T14",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R6",
"type": "Associated_With",
"arg1_id": "21_T15",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R10",
"type": "Associated_With",
"arg1_id": "21_T10",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R11",
"type": "Associated_With",
"arg1_id": "21_T11",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R12",
"type": "Associated_With",
"arg1_id": "21_T12",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R13",
"type": "Associated_With",
"arg1_id": "21_T13",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R14",
"type": "Associated_With",
"arg1_id": "21_T14",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R15",
"type": "Associated_With",
"arg1_id": "21_T15",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R20",
"type": "Associated_With",
"arg1_id": "21_T38",
"arg2_id": "21_T3",
"normalized": []
},
{
"id": "21_R21",
"type": "Associated_With",
"arg1_id": "21_T38",
"arg2_id": "21_T3",
"normalized": []
},
{
"id": "21_R9",
"type": "Binds_With",
"arg1_id": "21_T4",
"arg2_id": "21_T39",
"normalized": []
},
{
"id": "21_R16",
"type": "Binds_With",
"arg1_id": "21_T44",
"arg2_id": "21_T39",
"normalized": []
},
{
"id": "21_R7",
"type": "Binds_With",
"arg1_id": "21_T2",
"arg2_id": "21_T39",
"normalized": []
},
{
"id": "21_R8",
"type": "Binds_With",
"arg1_id": "21_T38",
"arg2_id": "21_T39",
"normalized": []
},
{
"id": "21_R17",
"type": "Associated_With",
"arg1_id": "21_T24",
"arg2_id": "21_T27",
"normalized": []
}
] |
22 | 1003703 | [
{
"id": "23",
"type": "",
"text": [
"Anti-ulcer effects of cetraxate, a new compound possessing anti-plasmin, anti-casein and anti-trypsin actions were investigated by using experimental gastric ulcer models in rats. Cetraxate, 300 mg/kg p.o. showed significant inhibitory effects of 65.3%, 70.0%, 30.2%, and 67.1% against aucte types of ulcers producing by aspirin, phenylbutazone, indomethacin, and pyloric ligature (Shay's ulcer), respectively. These effects were greater than those obtained by gefarnate and aluminum sucrose sulfate may be mainly attributed to the protecting action of this drug on gastric mucosa. Ctraxate further revealed remarkable inhibitory effects on chronic types of ulcers produced by acetic acid, clamping, and clamping-cortisone. In acetic acid ulcer in particular, cetraxate was found to have a dose-dependent inhibitory effect at doses over 50 mg/kg. Of test drugs including L-glutamine and methylmethionine sulfonium chloride, cetraxate showed the most remarkable inhibitory effect on beta-glucuronidase activity in ulcer tissue of these three types of ulcers. These findings suggest that cetraxate may prevent the connective tissue in the ulcer location from decomposition due to lysosomal enzymes such as beta-glucuronidase, thereby accelerating the recovery from ulcer. \n"
],
"offsets": [
[
0,
1274
]
]
}
] | [
{
"id": "23_T1",
"type": "Biological_Activity",
"text": [
"Anti-ulcer"
],
"offsets": [
[
0,
10
]
],
"normalized": []
},
{
"id": "23_T2",
"type": "Chemical",
"text": [
"cetraxate"
],
"offsets": [
[
22,
31
]
],
"normalized": []
},
{
"id": "23_T3",
"type": "Biological_Activity",
"text": [
"anti-plasmin"
],
"offsets": [
[
59,
71
]
],
"normalized": []
},
{
"id": "23_T4",
"type": "Biological_Activity",
"text": [
"anti-casein"
],
"offsets": [
[
73,
84
]
],
"normalized": []
},
{
"id": "23_T5",
"type": "Biological_Activity",
"text": [
"anti-trypsin"
],
"offsets": [
[
89,
101
]
],
"normalized": []
},
{
"id": "23_T6",
"type": "Protein",
"text": [
"plasmin"
],
"offsets": [
[
64,
71
]
],
"normalized": []
},
{
"id": "23_T9",
"type": "Protein",
"text": [
"trypsin"
],
"offsets": [
[
94,
101
]
],
"normalized": []
},
{
"id": "23_T11",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
174,
178
]
],
"normalized": []
},
{
"id": "23_T12",
"type": "Chemical",
"text": [
"Cetraxate"
],
"offsets": [
[
180,
189
]
],
"normalized": []
},
{
"id": "23_T13",
"type": "Biological_Activity",
"text": [
"inhibitory"
],
"offsets": [
[
225,
235
]
],
"normalized": []
},
{
"id": "23_T14",
"type": "Chemical",
"text": [
"aspirin"
],
"offsets": [
[
321,
328
]
],
"normalized": []
},
{
"id": "23_T15",
"type": "Chemical",
"text": [
"phenylbutazone"
],
"offsets": [
[
330,
344
]
],
"normalized": []
},
{
"id": "23_T16",
"type": "Chemical",
"text": [
"indomethacin"
],
"offsets": [
[
346,
358
]
],
"normalized": []
},
{
"id": "23_T17",
"type": "Chemical",
"text": [
"gefarnate"
],
"offsets": [
[
461,
470
]
],
"normalized": []
},
{
"id": "23_T18",
"type": "Chemical",
"text": [
"aluminum sucrose sulfate"
],
"offsets": [
[
475,
499
]
],
"normalized": []
},
{
"id": "23_T19",
"type": "Chemical",
"text": [
"Ctraxate"
],
"offsets": [
[
582,
590
]
],
"normalized": []
},
{
"id": "23_T21",
"type": "Chemical",
"text": [
"acetic acid"
],
"offsets": [
[
677,
688
]
],
"normalized": []
},
{
"id": "23_T22",
"type": "Chemical",
"text": [
"cortisone"
],
"offsets": [
[
714,
723
]
],
"normalized": []
},
{
"id": "23_T23",
"type": "Chemical",
"text": [
"acetic acid"
],
"offsets": [
[
728,
739
]
],
"normalized": []
},
{
"id": "23_T24",
"type": "Chemical",
"text": [
"cetraxate"
],
"offsets": [
[
761,
770
]
],
"normalized": []
},
{
"id": "23_T25",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
806,
815
]
],
"normalized": []
},
{
"id": "23_T26",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
619,
628
]
],
"normalized": []
},
{
"id": "23_T20",
"type": "Chemical",
"text": [
"L-glutamine"
],
"offsets": [
[
873,
884
]
],
"normalized": []
},
{
"id": "23_T28",
"type": "Chemical",
"text": [
"methylmethionine sulfonium chloride"
],
"offsets": [
[
889,
924
]
],
"normalized": []
},
{
"id": "23_T29",
"type": "Chemical",
"text": [
"cetraxate"
],
"offsets": [
[
926,
935
]
],
"normalized": []
},
{
"id": "23_T31",
"type": "Protein",
"text": [
"beta-glucuronidase"
],
"offsets": [
[
984,
1002
]
],
"normalized": []
},
{
"id": "23_T33",
"type": "Chemical",
"text": [
"cetraxate"
],
"offsets": [
[
1088,
1097
]
],
"normalized": []
},
{
"id": "23_T35",
"type": "Protein",
"text": [
"beta-glucuronidase"
],
"offsets": [
[
1207,
1225
]
],
"normalized": []
},
{
"id": "23_T38",
"type": "Protein",
"text": [
"lysosomal enzymes"
],
"offsets": [
[
1181,
1198
]
],
"normalized": []
},
{
"id": "23_T39",
"type": "Protein",
"text": [
"casein"
],
"offsets": [
[
78,
84
]
],
"normalized": []
},
{
"id": "23_T40",
"type": "Biological_Activity",
"text": [
"protecting"
],
"offsets": [
[
532,
542
]
],
"normalized": []
},
{
"id": "23_T43",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
963,
972
]
],
"normalized": []
},
{
"id": "23_T7",
"type": "Chemical",
"text": [
"drug"
],
"offsets": [
[
558,
562
]
],
"normalized": []
},
{
"id": "23_T8",
"type": "Chemical",
"text": [
"drugs"
],
"offsets": [
[
856,
863
]
],
"normalized": []
},
{
"id": "23_T10",
"type": "Biological_Activity",
"text": [
"glucuronidase"
],
"offsets": [
[
989,
1002
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "23_R1",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T1",
"normalized": []
},
{
"id": "23_R2",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T3",
"normalized": []
},
{
"id": "23_R3",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T4",
"normalized": []
},
{
"id": "23_R4",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T5",
"normalized": []
},
{
"id": "23_R5",
"type": "Associated_With",
"arg1_id": "23_T12",
"arg2_id": "23_T13",
"normalized": []
},
{
"id": "23_R9",
"type": "Associated_With",
"arg1_id": "23_T17",
"arg2_id": "23_T13",
"normalized": []
},
{
"id": "23_R10",
"type": "Associated_With",
"arg1_id": "23_T18",
"arg2_id": "23_T13",
"normalized": []
},
{
"id": "23_R11",
"type": "Associated_With",
"arg1_id": "23_T19",
"arg2_id": "23_T26",
"normalized": []
},
{
"id": "23_R14",
"type": "Associated_With",
"arg1_id": "23_T24",
"arg2_id": "23_T25",
"normalized": []
},
{
"id": "23_R16",
"type": "Associated_With",
"arg1_id": "23_T12",
"arg2_id": "23_T40",
"normalized": []
},
{
"id": "23_R15",
"type": "Associated_With",
"arg1_id": "23_T29",
"arg2_id": "23_T43",
"normalized": []
},
{
"id": "23_R17",
"type": "Binds_With",
"arg1_id": "23_T2",
"arg2_id": "23_T6",
"normalized": []
},
{
"id": "23_R24",
"type": "Binds_With",
"arg1_id": "23_T2",
"arg2_id": "23_T39",
"normalized": []
},
{
"id": "23_R28",
"type": "Binds_With",
"arg1_id": "23_T2",
"arg2_id": "23_T9",
"normalized": []
},
{
"id": "23_R6",
"type": "Binds_With",
"arg1_id": "23_T20",
"arg2_id": "23_T31",
"normalized": []
},
{
"id": "23_R12",
"type": "Binds_With",
"arg1_id": "23_T28",
"arg2_id": "23_T31",
"normalized": []
},
{
"id": "23_R13",
"type": "Binds_With",
"arg1_id": "23_T29",
"arg2_id": "23_T31",
"normalized": []
}
] |
24 | 10037325 | [
{
"id": "25",
"type": "",
"text": [
"The induction of micronucleated erythrocytes by diisopropylcarbodiimide (DIC) and dicyclohexylcarbodiimide (DCC) was investigated as part of a U.S. National Toxicology Program (NTP) evaluation of the subchronic toxicity of these chemicals. Analysis of peripheral blood smears from male and female B6C3F1 mice exposed to 17.5-140.0 mg DIC/kg/day by skin painting for 13 weeks revealed dose-related increases in the frequency of micronucleated normochromatic erythrocytes (MN-NCE) in both sexes. Results of a similar 13-week peripheral blood micronucleus (MN) test with DCC (1.5-12.0 mg/kg/day) were also positive, although the increases in MN-NCE were not as great as those observed with DIC. In contrast to the positive results of the subchronic skin-painting studies in mice, acute bone marrow MN studies with DIC and DCC in male F344 rats, using intraperitoneal (i.p.) injection, yielded negative results. Both the acute and the subchronic exposures included doses that produced clinical signs of toxicity. Acute mouse bone marrow MN tests with DIC administered in single or triple i.p. injection protocols were subsequently conducted to determine if the differing responses between mice and rats were due to species or protocol differences. The results of these acute tests were negative or equivocal. Because the subchronic studies produced positive results, it was hypothesized that these carbodiimides required multiple treatments over an extended period of time to produce an increase in MN-erythrocytes. To confirm the original response, a second dermal subchronic study was conducted with DIC; the protocol was modified to include sequential blood samplings to permit monitoring MN frequencies over time. The data demonstrated a small but consistent induction of micronucleated erythrocytes in mice treated with DIC by skin painting. \n"
],
"offsets": [
[
0,
1845
]
]
}
] | [
{
"id": "25_T1",
"type": "Chemical",
"text": [
"diisopropylcarbodiimide"
],
"offsets": [
[
48,
71
]
],
"normalized": []
},
{
"id": "25_T2",
"type": "Chemical",
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"DIC"
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73,
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"id": "25_T3",
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"dicyclohexylcarbodiimide"
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82,
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108,
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"id": "25_T5",
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"toxicity"
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211,
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"id": "25_T7",
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"B6C3F1 mice"
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297,
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"id": "25_T9",
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"DCC"
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568,
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"DIC"
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687,
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"DIC"
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"F344 rats"
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831,
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"id": "25_T14",
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"toxicity"
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999,
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"id": "25_T15",
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"mouse"
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1015,
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"DIC"
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"mice"
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1185,
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"id": "25_T18",
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"rats"
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1194,
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"mice"
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771,
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"type": "Biological_Activity",
"text": [
"induction"
],
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[
1760,
1769
]
],
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}
] | [] | [] | [
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"id": "25_R6",
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}
] |
26 | 10037456 | [
{
"id": "27",
"type": "",
"text": [
"We investigated the protective effect of fluvastatin sodium on the oxidation of low-density lipoprotein (LDL) induced in vitro by copper ions. The extent of lipid peroxidation was assessed by monitoring the increase of UV absorbance at 234 nm, which is the peak absorbance of a conjugated diene. Fluvastatin sodium (1-30 microM) not only prolonged the lag time of oxidation in the initiation step, but also decreased the rate of oxidation in the propagation step, both concentration dependently. Fluvastatin sodium and alpha-tocopherol showed an additive effect when both compounds were added before oxidation. However, when the lag time was prolonged initially by alpha-tocopherol, and fluvastatin sodium and alpha-tocopherol, were further added into the reaction mixture at the end point of the lag phase, fluvastatin sodium still showed an antioxidative effect, whereas alpha-tocopherol showed a pro-oxidative effect. Therefore, the antioxidative property of fluvastatin sodium differs from that of alpha-tocopherol. In this experiment, as neither the double bond-reduced derivative of fluvastatin sodium nor pravastatin sodium showed any protective effect, we concluded that the antioxidative effect of fluvastatin sodium is not a common property of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but may be derived from its unique chemical structure. Since the oxidative modification of LDL plays an important role in the genesis of atherosclerosis, fluvastatin sodium may help reduce the risk of atherosclerosis, not only by reducing plasma LDL levels but also by protecting LDL from oxidative modification. \n"
],
"offsets": [
[
0,
1642
]
]
}
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"id": "27_T1",
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"fluvastatin sodium"
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41,
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"copper ion"
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130,
140
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"Fluvastatin sodium"
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296,
314
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"id": "27_T6",
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"Fluvastatin sodium"
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496,
514
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"id": "27_T7",
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"alpha-tocopherol"
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[
519,
535
]
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"id": "27_T8",
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"alpha-tocopherol"
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665,
681
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"id": "27_T9",
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"fluvastatin sodium"
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[
687,
705
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"id": "27_T10",
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"alpha-tocopherol"
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[
711,
727
]
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"fluvastatin sodium"
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809,
827
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"id": "27_T12",
"type": "Biological_Activity",
"text": [
"antioxidative"
],
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[
844,
857
]
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{
"id": "27_T13",
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"alpha-tocopherol"
],
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[
875,
891
]
],
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{
"id": "27_T14",
"type": "Biological_Activity",
"text": [
"pro-oxidative"
],
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[
901,
914
]
],
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},
{
"id": "27_T15",
"type": "Biological_Activity",
"text": [
"antioxidative"
],
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[
938,
951
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"id": "27_T16",
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"text": [
"fluvastatin sodium"
],
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[
964,
982
]
],
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},
{
"id": "27_T17",
"type": "Chemical",
"text": [
"alpha-tocopherol"
],
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[
1004,
1020
]
],
"normalized": []
},
{
"id": "27_T18",
"type": "Chemical",
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"double bond-reduced derivative of fluvastatin sodium"
],
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[
1057,
1109
]
],
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"id": "27_T20",
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"pravastatin sodium"
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1114,
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"id": "27_T21",
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"antioxidative"
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1185,
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"id": "27_T22",
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"fluvastatin sodium"
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1209,
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"id": "27_T23",
"type": "Protein",
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],
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1256,
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]
],
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},
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"id": "27_T26",
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"text": [
"inhibitor"
],
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[
1314,
1323
]
],
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},
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"id": "27_T28",
"type": "Protein",
"text": [
"low-density lipoprotein"
],
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[
80,
103
]
],
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"id": "27_T29",
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"LDL"
],
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105,
108
]
],
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},
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"id": "27_T30",
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"LDL"
],
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1417,
1420
]
],
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"id": "27_T31",
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],
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1480,
1498
]
],
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},
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"id": "27_T32",
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],
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1573,
1576
]
],
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},
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"id": "27_T33",
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"LDL"
],
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1607,
1610
]
],
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},
{
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1596,
1606
]
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"id": "27_T36",
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219,
232
]
],
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"id": "27_T37",
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],
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278,
294
]
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"protective"
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[
20,
30
]
],
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},
{
"id": "27_T24",
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"text": [
"protective"
],
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1144,
1154
]
],
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"id": "27_T3",
"type": "Biological_Activity",
"text": [
"oxidative"
],
"offsets": [
[
1391,
1400
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "27_R2",
"type": "Associated_With",
"arg1_id": "27_T11",
"arg2_id": "27_T12",
"normalized": []
},
{
"id": "27_R3",
"type": "Associated_With",
"arg1_id": "27_T13",
"arg2_id": "27_T14",
"normalized": []
},
{
"id": "27_R4",
"type": "Associated_With",
"arg1_id": "27_T16",
"arg2_id": "27_T15",
"normalized": []
},
{
"id": "27_R5",
"type": "Associated_With",
"arg1_id": "27_T22",
"arg2_id": "27_T21",
"normalized": []
},
{
"id": "27_R6",
"type": "Associated_With",
"arg1_id": "27_T22",
"arg2_id": "27_T26",
"normalized": []
},
{
"id": "27_R7",
"type": "Associated_With",
"arg1_id": "27_T31",
"arg2_id": "27_T34",
"normalized": []
},
{
"id": "27_R8",
"type": "Associated_With",
"arg1_id": "27_T37",
"arg2_id": "27_T36",
"normalized": []
},
{
"id": "27_R9",
"type": "Associated_With",
"arg1_id": "27_T17",
"arg2_id": "27_T15",
"normalized": []
},
{
"id": "27_R11",
"type": "Associated_With",
"arg1_id": "27_T1",
"arg2_id": "27_T19",
"normalized": []
}
] |
28 | 10048024 | [
{
"id": "29",
"type": "",
"text": [
"Sequence analysis reveals that the Bacillus subtilis 168 tuaABCDEFGH operon encodes enzymes required for the polymerization of teichuronic acid as well as for the synthesis of one of its precursors, the UDP-glucuronate. Mutants deficient in any of the tua genes, grown in batch cultures under conditions of phosphate limitation, were characterized by reduced amounts of uronate in their cell walls. The teichuronic acid operon belongs to the Pho regulon, as phosphate limitation induces its transcription. Placing the tuaABCDEFGH operon under the control of the inducible Pspac promoter allowed its constitutive expression independently of the phosphate concentration in the medium; the level of uronic acid in cell walls was dependent on the concentration of the inducer. Apparently, owing to an interdependence between teichoic and teichuronic acid incorporation into the cell wall, in examined growth conditions, the balance between the two polymers is maintained in order to insure a constant level of the wall negative charge. \n"
],
"offsets": [
[
0,
1034
]
]
}
] | [
{
"id": "29_T1",
"type": "Species",
"text": [
"Bacillus subtilis 168"
],
"offsets": [
[
35,
56
]
],
"normalized": []
},
{
"id": "29_T2",
"type": "Chemical",
"text": [
"teichuronic acid"
],
"offsets": [
[
127,
143
]
],
"normalized": []
},
{
"id": "29_T3",
"type": "Chemical",
"text": [
"UDP-glucuronate"
],
"offsets": [
[
203,
218
]
],
"normalized": []
},
{
"id": "29_T4",
"type": "Chemical",
"text": [
"phosphate"
],
"offsets": [
[
307,
316
]
],
"normalized": []
},
{
"id": "29_T5",
"type": "Chemical",
"text": [
"uronate"
],
"offsets": [
[
370,
377
]
],
"normalized": []
},
{
"id": "29_T7",
"type": "Chemical",
"text": [
"phosphate"
],
"offsets": [
[
458,
469
]
],
"normalized": []
},
{
"id": "29_T8",
"type": "Chemical",
"text": [
"phosphate"
],
"offsets": [
[
645,
654
]
],
"normalized": []
},
{
"id": "29_T9",
"type": "Metabolite",
"text": [
"uronic acid"
],
"offsets": [
[
697,
708
]
],
"normalized": []
},
{
"id": "29_T10",
"type": "Chemical",
"text": [
"teichoic",
"acid"
],
"offsets": [
[
822,
830
],
[
847,
851
]
],
"normalized": []
},
{
"id": "29_T11",
"type": "Chemical",
"text": [
"teichuronic acid"
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835,
851
]
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},
{
"id": "29_T12",
"type": "Metabolite",
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"teichuronic acid"
],
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[
127,
143
]
],
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},
{
"id": "29_T13",
"type": "Metabolite",
"text": [
"UDP-glucuronate"
],
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[
203,
218
]
],
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},
{
"id": "29_T14",
"type": "Metabolite",
"text": [
"teichoic",
"acid"
],
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[
822,
830
],
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847,
851
]
],
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},
{
"id": "29_T15",
"type": "Metabolite",
"text": [
"teichuronic acid"
],
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[
835,
851
]
],
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{
"id": "29_T6",
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"text": [
"uronic acid"
],
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[
697,
708
]
],
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},
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"id": "29_T16",
"type": "Chemical",
"text": [
"polymers"
],
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[
945,
953
]
],
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},
{
"id": "29_T17",
"type": "Biological_Activity",
"text": [
"inducer"
],
"offsets": [
[
765,
772
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "29_R1",
"type": "Isolated_From",
"arg1_id": "29_T13",
"arg2_id": "29_T1",
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"id": "29_R2",
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"arg1_id": "29_T12",
"arg2_id": "29_T1",
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},
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"id": "29_R3",
"type": "Metabolite_Of",
"arg1_id": "29_T12",
"arg2_id": "29_T3",
"normalized": []
}
] |
30 | 10048138 | [
{
"id": "31",
"type": "",
"text": [
"Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormaplatin (2 mg/kg) were administered i.p. twice weekly for 4.5 weeks. Lactose injections (0.9%) were used as a control for oxaliplatin and 0.9% saline injections were used as a control for cisplatin and ormaplatin. Morphometric changes to dorsal root ganglia L4-L6 were quantitated as a measure of neurotoxicity. Drug treatment resulted in a decrease in cell and nuclear area and an increase in the percentage of cells with eccentric nucleoli for neuronal cell bodies in the DRG. Immediately following treatment the order of morphometric changes was ormaplatin > cisplatin > or = oxaliplatin. The accumulation of platinum in the DRG was measured by inductively coupled plasma mass spectrometry. The order of accumulation was cisplatin > oxaliplatin > ormaplatin. Following an 8-week recovery period the order of morphometric changes to the DRG was ormaplatin approximately equal to oxaliplatin > cisplatin. This correlated with a greater retention of platinum by the DRG for ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wistar rat model. However, following an 8-week recovery period both ormaplatin and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG. \n"
],
"offsets": [
[
0,
1409
]
]
}
] | [
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11
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23,
32
]
],
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56,
64
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"ormaplatin"
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70,
82
]
],
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143,
150
]
],
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[
196,
207
]
],
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"saline"
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217,
223
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],
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},
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"cisplatin"
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262,
271
]
],
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},
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"id": "31_T9",
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"text": [
"ormaplatin"
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276,
286
]
],
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},
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"id": "31_T10",
"type": "Biological_Activity",
"text": [
"neurotoxicity"
],
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[
371,
384
]
],
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},
{
"id": "31_T11",
"type": "Chemical",
"text": [
"ormaplatin"
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[
623,
633
]
],
"normalized": []
},
{
"id": "31_T12",
"type": "Chemical",
"text": [
"cisplatin"
],
"offsets": [
[
636,
645
]
],
"normalized": []
},
{
"id": "31_T13",
"type": "Chemical",
"text": [
"oxaliplatin"
],
"offsets": [
[
654,
665
]
],
"normalized": []
},
{
"id": "31_T14",
"type": "Chemical",
"text": [
"platinum"
],
"offsets": [
[
687,
695
]
],
"normalized": []
},
{
"id": "31_T15",
"type": "Chemical",
"text": [
"cisplatin"
],
"offsets": [
[
799,
808
]
],
"normalized": []
},
{
"id": "31_T16",
"type": "Chemical",
"text": [
"oxaliplatin"
],
"offsets": [
[
811,
822
]
],
"normalized": []
},
{
"id": "31_T17",
"type": "Chemical",
"text": [
"ormaplatin"
],
"offsets": [
[
825,
835
]
],
"normalized": []
},
{
"id": "31_T18",
"type": "Chemical",
"text": [
"ormaplatin"
],
"offsets": [
[
922,
932
]
],
"normalized": []
},
{
"id": "31_T19",
"type": "Chemical",
"text": [
"oxaliplatin"
],
"offsets": [
[
956,
967
]
],
"normalized": []
},
{
"id": "31_T20",
"type": "Chemical",
"text": [
"cisplatin"
],
"offsets": [
[
970,
979
]
],
"normalized": []
},
{
"id": "31_T21",
"type": "Chemical",
"text": [
"platinum"
],
"offsets": [
[
1025,
1033
]
],
"normalized": []
},
{
"id": "31_T22",
"type": "Chemical",
"text": [
"ormaplatin"
],
"offsets": [
[
1050,
1060
]
],
"normalized": []
},
{
"id": "31_T23",
"type": "Chemical",
"text": [
"oxaliplatin"
],
"offsets": [
[
1065,
1076
]
],
"normalized": []
},
{
"id": "31_T24",
"type": "Chemical",
"text": [
"cisplatin"
],
"offsets": [
[
1086,
1095
]
],
"normalized": []
},
{
"id": "31_T25",
"type": "Chemical",
"text": [
"ormaplatin"
],
"offsets": [
[
1122,
1132
]
],
"normalized": []
},
{
"id": "31_T26",
"type": "Biological_Activity",
"text": [
"neurotoxic"
],
"offsets": [
[
1145,
1155
]
],
"normalized": []
},
{
"id": "31_T27",
"type": "Species",
"text": [
"Wistar rat"
],
"offsets": [
[
1195,
1205
]
],
"normalized": []
},
{
"id": "31_T28",
"type": "Chemical",
"text": [
"ormaplatin"
],
"offsets": [
[
1263,
1273
]
],
"normalized": []
},
{
"id": "31_T29",
"type": "Chemical",
"text": [
"oxaliplatin"
],
"offsets": [
[
1278,
1289
]
],
"normalized": []
},
{
"id": "31_T30",
"type": "Biological_Activity",
"text": [
"neurotoxic"
],
"offsets": [
[
1299,
1309
]
],
"normalized": []
},
{
"id": "31_T31",
"type": "Chemical",
"text": [
"cisplatin"
],
"offsets": [
[
1315,
1324
]
],
"normalized": []
},
{
"id": "31_T32",
"type": "Biological_Activity",
"text": [
"neurotoxicity"
],
"offsets": [
[
1334,
1347
]
],
"normalized": []
},
{
"id": "31_T33",
"type": "Chemical",
"text": [
"platinum"
],
"offsets": [
[
1387,
1395
]
],
"normalized": []
},
{
"id": "31_T35",
"type": "Spectral_Data",
"text": [
"mass spectrometry"
],
"offsets": [
[
750,
767
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "31_R1",
"type": "Associated_With",
"arg1_id": "31_T11",
"arg2_id": "31_T10",
"normalized": []
},
{
"id": "31_R2",
"type": "Associated_With",
"arg1_id": "31_T12",
"arg2_id": "31_T10",
"normalized": []
},
{
"id": "31_R3",
"type": "Associated_With",
"arg1_id": "31_T13",
"arg2_id": "31_T10",
"normalized": []
},
{
"id": "31_R4",
"type": "Associated_With",
"arg1_id": "31_T25",
"arg2_id": "31_T26",
"normalized": []
},
{
"id": "31_R5",
"type": "Associated_With",
"arg1_id": "31_T28",
"arg2_id": "31_T30",
"normalized": []
},
{
"id": "31_R6",
"type": "Associated_With",
"arg1_id": "31_T29",
"arg2_id": "31_T30",
"normalized": []
},
{
"id": "31_R7",
"type": "Associated_With",
"arg1_id": "31_T31",
"arg2_id": "31_T30",
"normalized": []
},
{
"id": "31_R11",
"type": "Associated_With",
"arg1_id": "31_T14",
"arg2_id": "31_T35",
"normalized": []
}
] |
32 | 10048141 | [
{
"id": "33",
"type": "",
"text": [
"1,2-Dichlorobenzene (1,2-DCB) is a potent hepatotoxicant in male Fischer 344 (F344) rats and previous studies have suggested that reactive oxygen species may play a role in the development of hepatotoxicity. Since reactive oxygen species can damage lipid membranes, this study was conducted to determine the extent of lipid peroxidation after administration of 1,2-DCB by immuno-histochemical analysis of 4-hydroxynonenal (4-HNE) protein adduct formation in liver and conjugated diene formation in liver and serum. The contribution of Kupffer cells to the lipid peroxidation was also investigated. Male F344 rats were administered 1,2-DCB (3.6 mmol/kg i.p. in corn oil) and killed at selected times between 3 and 48 h. Time course studies revealed the greatest abundance of 4-HNE protein adducts in the centrilobular regions of the liver 24 h after 1,2-DCB administration, with much lower levels at 16 h. Adducts were present in necrotic and vacuolized centrilobular hepatocytes of 1,2-DCB treated rats but not in livers of controls. Further, conjugated dienes were significantly increased in liver and serum 16 and 24 h after 1,2-DCB administration, peaking at 24 h. These data correlated with hepatocellular injury, determined by serum alanine aminotransferase activity and histopathological evaluation, which was markedly elevated within 16 h and peaked at 24 h. When rats were pretreated with gadolinium chloride (GdCl3; 10 mg/kg i.v. 24 h prior to 1,2-DCB), an inhibitor of Kupffer cells, hepatotoxicity was decreased by 89 and 86%, at 16 and 24 h, respectively. Conjugated diene concentrations were decreased to control values at these times after 1,2-DCB administration. Moreover, no 4-HNE protein adducts were detected in livers of 1,2-DCB-treated rats pretreated with GdCl3. Finally, Kupffer cells isolated from 1,2-DCB-treated rats produced significantly more superoxide anion than Kupffer cells isolated from vehicle controls. These data, along with previous findings, suggest that lipid peroxidation associated with 1,2-DCB is mediated in part by Kupffer cell-derived reactive oxygen species. \n"
],
"offsets": [
[
0,
2110
]
]
}
] | [
{
"id": "33_T1",
"type": "Chemical",
"text": [
"1,2-Dichlorobenzene"
],
"offsets": [
[
0,
19
]
],
"normalized": []
},
{
"id": "33_T2",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
21,
28
]
],
"normalized": []
},
{
"id": "33_T3",
"type": "Biological_Activity",
"text": [
"hepatotoxic"
],
"offsets": [
[
42,
53
]
],
"normalized": []
},
{
"id": "33_T4",
"type": "Species",
"text": [
"Fischer 344",
"rats"
],
"offsets": [
[
65,
76
],
[
84,
88
]
],
"normalized": []
},
{
"id": "33_T5",
"type": "Chemical",
"text": [
"reactive oxygen species"
],
"offsets": [
[
130,
153
]
],
"normalized": []
},
{
"id": "33_T6",
"type": "Biological_Activity",
"text": [
"hepatotoxicity"
],
"offsets": [
[
193,
207
]
],
"normalized": []
},
{
"id": "33_T7",
"type": "Chemical",
"text": [
"reactive oxygen species"
],
"offsets": [
[
215,
238
]
],
"normalized": []
},
{
"id": "33_T8",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
362,
369
]
],
"normalized": []
},
{
"id": "33_T9",
"type": "Chemical",
"text": [
"4-hydroxynonenal"
],
"offsets": [
[
406,
422
]
],
"normalized": []
},
{
"id": "33_T10",
"type": "Chemical",
"text": [
"4-HNE"
],
"offsets": [
[
424,
429
]
],
"normalized": []
},
{
"id": "33_T11",
"type": "Chemical",
"text": [
"conjugated diene"
],
"offsets": [
[
469,
485
]
],
"normalized": []
},
{
"id": "33_T12",
"type": "Species",
"text": [
"F344 rats"
],
"offsets": [
[
605,
614
]
],
"normalized": []
},
{
"id": "33_T13",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
633,
640
]
],
"normalized": []
},
{
"id": "33_T14",
"type": "Chemical",
"text": [
"corn oil"
],
"offsets": [
[
662,
670
]
],
"normalized": []
},
{
"id": "33_T15",
"type": "Chemical",
"text": [
"4-HNE"
],
"offsets": [
[
776,
781
]
],
"normalized": []
},
{
"id": "33_T16",
"type": "Protein",
"text": [
"protein"
],
"offsets": [
[
431,
438
]
],
"normalized": []
},
{
"id": "33_T17",
"type": "Protein",
"text": [
"protein"
],
"offsets": [
[
782,
789
]
],
"normalized": []
},
{
"id": "33_T18",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
851,
858
]
],
"normalized": []
},
{
"id": "33_T19",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
985,
992
]
],
"normalized": []
},
{
"id": "33_T20",
"type": "Chemical",
"text": [
"conjugated dienes"
],
"offsets": [
[
1046,
1063
]
],
"normalized": []
},
{
"id": "33_T21",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
1130,
1137
]
],
"normalized": []
},
{
"id": "33_T23",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1375,
1379
]
],
"normalized": []
},
{
"id": "33_T24",
"type": "Chemical",
"text": [
"gadolinium chloride"
],
"offsets": [
[
1401,
1420
]
],
"normalized": []
},
{
"id": "33_T25",
"type": "Chemical",
"text": [
"GdCl3"
],
"offsets": [
[
1422,
1427
]
],
"normalized": []
},
{
"id": "33_T26",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
1457,
1464
]
],
"normalized": []
},
{
"id": "33_T27",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
1470,
1479
]
],
"normalized": []
},
{
"id": "33_T28",
"type": "Biological_Activity",
"text": [
"hepatotoxicity"
],
"offsets": [
[
1498,
1512
]
],
"normalized": []
},
{
"id": "33_T29",
"type": "Chemical",
"text": [
"Conjugated diene"
],
"offsets": [
[
1572,
1588
]
],
"normalized": []
},
{
"id": "33_T30",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
1658,
1665
]
],
"normalized": []
},
{
"id": "33_T31",
"type": "Chemical",
"text": [
"4-HNE"
],
"offsets": [
[
1695,
1700
]
],
"normalized": []
},
{
"id": "33_T32",
"type": "Protein",
"text": [
"protein"
],
"offsets": [
[
1701,
1708
]
],
"normalized": []
},
{
"id": "33_T33",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
1744,
1751
]
],
"normalized": []
},
{
"id": "33_T34",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1760,
1764
]
],
"normalized": []
},
{
"id": "33_T35",
"type": "Chemical",
"text": [
"GdCl3"
],
"offsets": [
[
1781,
1786
]
],
"normalized": []
},
{
"id": "33_T36",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
1825,
1832
]
],
"normalized": []
},
{
"id": "33_T37",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1841,
1845
]
],
"normalized": []
},
{
"id": "33_T38",
"type": "Chemical",
"text": [
"superoxide anion"
],
"offsets": [
[
1874,
1890
]
],
"normalized": []
},
{
"id": "33_T39",
"type": "Chemical",
"text": [
"1,2-DCB"
],
"offsets": [
[
2032,
2039
]
],
"normalized": []
},
{
"id": "33_T40",
"type": "Chemical",
"text": [
"reactive oxygen species"
],
"offsets": [
[
2084,
2107
]
],
"normalized": []
},
{
"id": "33_T45",
"type": "Species",
"text": [
"F344",
"rats"
],
"offsets": [
[
78,
82
],
[
84,
88
]
],
"normalized": []
},
{
"id": "33_T46",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
1001,
1005
]
],
"normalized": []
},
{
"id": "33_T22",
"type": "Biological_Activity",
"text": [
"aminotransferase"
],
"offsets": [
[
1250,
1266
]
],
"normalized": []
},
{
"id": "33_T41",
"type": "Protein",
"text": [
"alanine aminotransferase"
],
"offsets": [
[
1242,
1266
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "33_R1",
"type": "Associated_With",
"arg1_id": "33_T1",
"arg2_id": "33_T3",
"normalized": []
},
{
"id": "33_R2",
"type": "Associated_With",
"arg1_id": "33_T2",
"arg2_id": "33_T3",
"normalized": []
},
{
"id": "33_R3",
"type": "Associated_With",
"arg1_id": "33_T5",
"arg2_id": "33_T6",
"normalized": []
},
{
"id": "33_R8",
"type": "Associated_With",
"arg1_id": "33_T24",
"arg2_id": "33_T27",
"normalized": []
},
{
"id": "33_R9",
"type": "Associated_With",
"arg1_id": "33_T25",
"arg2_id": "33_T27",
"normalized": []
}
] |
34 | 10048179 | [
{
"id": "35",
"type": "",
"text": [
"The crystal structure of gliclazide, N-[(perhydrocyclopenta [c]pyrrol-2-yl)aminocarbonyl]-p-toluenesulfonamide, C15H21B3O3S, a second-generation oral hypoglycemic agent, contains discrete molecules with normal molecular dimensions. Both of the five-membered fused rings adopt envelope conformations. The molecules are linked into chains by intermolecular hydrogen bonds involving amino-H atoms, with N...O separations of 2.967 (3) and 2.949 (3) A. \n"
],
"offsets": [
[
0,
450
]
]
}
] | [
{
"id": "35_T1",
"type": "Chemical",
"text": [
"gliclazide"
],
"offsets": [
[
25,
35
]
],
"normalized": []
},
{
"id": "35_T2",
"type": "Chemical",
"text": [
"N-[(perhydrocyclopenta [c]pyrrol-2-yl)aminocarbonyl]-p-toluenesulfonamide"
],
"offsets": [
[
37,
110
]
],
"normalized": []
},
{
"id": "35_T3",
"type": "Biological_Activity",
"text": [
"hypoglycemic"
],
"offsets": [
[
150,
162
]
],
"normalized": []
},
{
"id": "35_T4",
"type": "Chemical",
"text": [
"molecules"
],
"offsets": [
[
304,
313
]
],
"normalized": []
},
{
"id": "35_T5",
"type": "Spectral_Data",
"text": [
"crystal structure"
],
"offsets": [
[
4,
21
]
],
"normalized": []
},
{
"id": "35_T6",
"type": "Chemical",
"text": [
"molecules"
],
"offsets": [
[
188,
197
]
],
"normalized": []
},
{
"id": "35_T7",
"type": "Chemical",
"text": [
"amino"
],
"offsets": [
[
380,
385
]
],
"normalized": []
},
{
"id": "35_T8",
"type": "Chemical",
"text": [
"H"
],
"offsets": [
[
386,
387
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "35_R1",
"type": "Associated_With",
"arg1_id": "35_T1",
"arg2_id": "35_T3",
"normalized": []
},
{
"id": "35_R2",
"type": "Associated_With",
"arg1_id": "35_T2",
"arg2_id": "35_T3",
"normalized": []
},
{
"id": "35_R3",
"type": "Associated_With",
"arg1_id": "35_T1",
"arg2_id": "35_T5",
"normalized": []
},
{
"id": "35_R4",
"type": "Associated_With",
"arg1_id": "35_T2",
"arg2_id": "35_T5",
"normalized": []
}
] |
36 | 10048567 | [
{
"id": "37",
"type": "",
"text": [
"Antibacterial antibiotics, diperamycin (1) was produced in the culture broth of Streptomyces griseoaurantiacus MK393-AF2. Various spectroscopic analyses of 1 suggested that 1 belonged to a member of cyclic hexadepsipeptide antibiotic. Antibiotic 1 had potent inhibitory activity against various Gram-positive bacteria including Enterococcus seriolicida and methicillin-resistant Staphylococcus aureus. \n"
],
"offsets": [
[
0,
403
]
]
}
] | [
{
"id": "37_T1",
"type": "Biological_Activity",
"text": [
"Antibacterial",
"antibiotics"
],
"offsets": [
[
0,
13
],
[
14,
25
]
],
"normalized": []
},
{
"id": "37_T2",
"type": "Biological_Activity",
"text": [
"antibiotics"
],
"offsets": [
[
14,
25
]
],
"normalized": []
},
{
"id": "37_T3",
"type": "Chemical",
"text": [
"diperamycin"
],
"offsets": [
[
27,
38
]
],
"normalized": []
},
{
"id": "37_T4",
"type": "Species",
"text": [
"Streptomyces griseoaurantiacus MK393-AF2"
],
"offsets": [
[
80,
120
]
],
"normalized": []
},
{
"id": "37_T5",
"type": "Chemical",
"text": [
"cyclic hexadepsipeptide antibiotic"
],
"offsets": [
[
199,
233
]
],
"normalized": []
},
{
"id": "37_T9",
"type": "Biological_Activity",
"text": [
"Antibiotic"
],
"offsets": [
[
235,
245
]
],
"normalized": []
},
{
"id": "37_T10",
"type": "Chemical",
"text": [
"1"
],
"offsets": [
[
246,
247
]
],
"normalized": []
},
{
"id": "37_T11",
"type": "Biological_Activity",
"text": [
"inhibitory"
],
"offsets": [
[
259,
269
]
],
"normalized": []
},
{
"id": "37_T12",
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"Enterococcus seriolicida"
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"id": "37_T13",
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"id": "37_T14",
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"text": [
"methicillin"
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357,
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"id": "37_T15",
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"diperamycin"
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"id": "37_T18",
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"antibiotic"
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"id": "37_T20",
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"1"
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"id": "37_T21",
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"id": "37_T7",
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"id": "37_T6",
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"text": [
"antibiotics"
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14,
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] | [] | [] | [
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"id": "37_R1",
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},
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"id": "37_R2",
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},
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"type": "Associated_With",
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"arg2_id": "37_T11",
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}
] |
38 | 10048572 | [
{
"id": "39",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
40 | 10048707 | [
{
"id": "41",
"type": "",
"text": [
"By assaying lactate dehydrogenase and malondialdehyde leakage from LLC-PK1 cells in culture, a study was conducted to clarify whether flavonoid compounds ameliorate renal cellular injury. The cells were cultured with various concentrations of samples under routine conditions. The results demonstrated that baicalin, cirsimaritin, 6-hydroxyluteolin, luteolin, plantaginin, rhoifolin, sorbarin, afzelin, hyperin, isoquercitrin, isorhamnetin, kaempferitrin, kaempferol-7-glucoside, oxyayanin A, quercetin, quercitrin, rhamnetin and rutin exerted marked protective effects on the cells, whereas acacetin, apigenin, apiin, cirsilineol, genkwanin, pectolinarin and tetramethylquercitin had virtually no effect. In the light of these findings, we propose that the general capability of these compounds is largely decided by the number and position of phenolic hydroxyl groups linked to the structural backbone. \n"
],
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0,
908
]
]
}
] | [
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],
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38,
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],
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},
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"id": "41_T4",
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135,
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],
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"id": "41_T6",
"type": "Chemical",
"text": [
"baicalin"
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308,
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]
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},
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"id": "41_T7",
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"cirsimaritin"
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318,
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],
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"id": "41_T8",
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"6-hydroxyluteolin"
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332,
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]
],
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},
{
"id": "41_T9",
"type": "Chemical",
"text": [
"luteolin"
],
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351,
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]
],
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"id": "41_T10",
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"plantaginin"
],
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361,
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],
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"id": "41_T11",
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"rhoifolin"
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374,
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]
],
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"id": "41_T12",
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"sorbarin"
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385,
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]
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"id": "41_T13",
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"afzelin"
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395,
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]
],
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},
{
"id": "41_T14",
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"hyperin"
],
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404,
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]
],
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},
{
"id": "41_T15",
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413,
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],
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},
{
"id": "41_T16",
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"text": [
"isorhamnetin"
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[
428,
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]
],
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},
{
"id": "41_T17",
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442,
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],
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"id": "41_T18",
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],
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457,
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]
],
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},
{
"id": "41_T19",
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"oxyayanin A"
],
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481,
492
]
],
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},
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"id": "41_T20",
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"quercetin"
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494,
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"id": "41_T21",
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"quercitrin"
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505,
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]
],
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{
"id": "41_T22",
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"rhamnetin"
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517,
526
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],
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{
"id": "41_T23",
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"rutin"
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531,
536
]
],
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},
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"id": "41_T24",
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"acacetin"
],
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593,
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]
],
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{
"id": "41_T25",
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"apigenin"
],
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603,
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],
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},
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"id": "41_T26",
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"apiin"
],
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613,
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]
],
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},
{
"id": "41_T27",
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"cirsilineol"
],
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620,
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]
],
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},
{
"id": "41_T28",
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"genkwanin"
],
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[
633,
642
]
],
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},
{
"id": "41_T29",
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"text": [
"pectolinarin"
],
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644,
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]
],
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},
{
"id": "41_T30",
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],
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[
661,
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]
],
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},
{
"id": "41_T31",
"type": "Chemical",
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"phenolic hydroxyl groups"
],
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[
847,
871
]
],
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},
{
"id": "41_T32",
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"LLC-PK1"
],
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67,
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]
],
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},
{
"id": "41_T2",
"type": "Biological_Activity",
"text": [
"protective"
],
"offsets": [
[
552,
562
]
],
"normalized": []
}
] | [] | [] | [
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"id": "41_R19",
"type": "Associated_With",
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},
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"id": "41_R20",
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},
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"id": "41_R21",
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},
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"id": "41_R22",
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"arg1_id": "41_T9",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R23",
"type": "Associated_With",
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"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R24",
"type": "Associated_With",
"arg1_id": "41_T11",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R25",
"type": "Associated_With",
"arg1_id": "41_T12",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R26",
"type": "Associated_With",
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"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R27",
"type": "Associated_With",
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"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R28",
"type": "Associated_With",
"arg1_id": "41_T15",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R29",
"type": "Associated_With",
"arg1_id": "41_T16",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R30",
"type": "Associated_With",
"arg1_id": "41_T17",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R31",
"type": "Associated_With",
"arg1_id": "41_T18",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R32",
"type": "Associated_With",
"arg1_id": "41_T19",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R33",
"type": "Associated_With",
"arg1_id": "41_T20",
"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R34",
"type": "Associated_With",
"arg1_id": "41_T21",
"arg2_id": "41_T2",
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},
{
"id": "41_R35",
"type": "Associated_With",
"arg1_id": "41_T23",
"arg2_id": "41_T2",
"normalized": []
}
] |
42 | 100496 | [
{
"id": "43",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
44 | 10049714 | [
{
"id": "45",
"type": "",
"text": [
"Dopamine D4-like binding sites are abundant in human cerebral cortex as detected by [3H]nemonapride. The extremely low density of D4 mRNA in human cerebral cortex is inconsistent with the high amount of D4-like binding sites. To investigate the nature of the D4-like receptors, [3H]nemonapride binding sites in the nonhuman primate cerebral cortex were characterized. Although [3H]nemonapride binding sites were D4-like, displaceable by clozapine but not raclopride, [3H]nemonapride binding was not displaced by selective D4 antagonists but was displaced by the selective 5-HT2A antagonist MDL100907. Using [3H]ketanserin as a 5-HT2A ligand, nemonapride showed high affinity for monkey (Ki = 10.4 nM) and cloned human (Ki = 9.4 nM) 5-HT2A receptors, while its affinity for rat receptors was lower (Ki = 140 nM). The present study demonstrates that cerebral cortical D4-like binding sites labeled by [3H]nemonapride in nonhuman primates consist of a very small portion of D4, but a substantial portion of 5-HT2A receptors. The unexpectedly high affinity of nemonapride for primate 5-HT2A receptor suggests reconsidering previous data from other studies using [3H]nemonapride, particularly those on D4-like receptors. \n"
],
"offsets": [
[
0,
1218
]
]
}
] | [
{
"id": "45_T1",
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],
"offsets": [
[
0,
30
]
],
"normalized": []
},
{
"id": "45_T3",
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"[3H]nemonapride"
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85,
100
]
],
"normalized": []
},
{
"id": "45_T6",
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"[3H]nemonapride"
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279,
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]
],
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},
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"id": "45_T7",
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],
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316,
332
]
],
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},
{
"id": "45_T8",
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"text": [
"[3H]nemonapride"
],
"offsets": [
[
378,
393
]
],
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},
{
"id": "45_T11",
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],
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438,
447
]
],
"normalized": []
},
{
"id": "45_T12",
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],
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456,
466
]
],
"normalized": []
},
{
"id": "45_T13",
"type": "Chemical",
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"[3H]nemonapride"
],
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[
468,
483
]
],
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},
{
"id": "45_T14",
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],
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526,
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]
],
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},
{
"id": "45_T15",
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580,
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]
],
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{
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591,
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]
],
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608,
622
]
],
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},
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643,
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],
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680,
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]
],
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},
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713,
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]
],
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"id": "45_T23",
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],
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573,
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]
],
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},
{
"id": "45_T24",
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],
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628,
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]
],
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774,
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900,
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],
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},
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"id": "45_T29",
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"D4"
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1012,
1021
],
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972,
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],
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},
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"id": "45_T31",
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],
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1005,
1011
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],
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},
{
"id": "45_T33",
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"D4 antagonists"
],
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523,
537
]
],
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},
{
"id": "45_T35",
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"text": [
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],
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[
260,
277
]
],
"normalized": []
},
{
"id": "45_T36",
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"text": [
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],
"offsets": [
[
280,
308
]
],
"normalized": []
},
{
"id": "45_T37",
"type": "Protein",
"text": [
"5-HT2A"
],
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[
733,
739
]
],
"normalized": []
},
{
"id": "45_T38",
"type": "Protein",
"text": [
"D4"
],
"offsets": [
[
131,
133
]
],
"normalized": []
},
{
"id": "45_T39",
"type": "Protein",
"text": [
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],
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[
1081,
1096
]
],
"normalized": []
},
{
"id": "45_T40",
"type": "Protein",
"text": [
"5-HT2A"
],
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1081,
1087
]
],
"normalized": []
},
{
"id": "45_T42",
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],
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[
733,
749
]
],
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},
{
"id": "45_T43",
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"text": [
"5-HT2A receptors"
],
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[
1005,
1021
]
],
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},
{
"id": "45_T44",
"type": "Species",
"text": [
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],
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919,
936
]
],
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},
{
"id": "45_T45",
"type": "Species",
"text": [
"human"
],
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[
47,
52
]
],
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},
{
"id": "45_T46",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
484,
491
]
],
"normalized": []
},
{
"id": "45_T48",
"type": "Protein",
"text": [
"cerebral cortical D4-like binding sites"
],
"offsets": [
[
849,
888
]
],
"normalized": []
},
{
"id": "45_T49",
"type": "Chemical",
"text": [
"nemonapride"
],
"offsets": [
[
1057,
1068
]
],
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},
{
"id": "45_T50",
"type": "Species",
"text": [
"primate"
],
"offsets": [
[
1073,
1080
]
],
"normalized": []
},
{
"id": "45_T51",
"type": "Chemical",
"text": [
"[3H]nemonapride"
],
"offsets": [
[
1159,
1174
]
],
"normalized": []
},
{
"id": "45_T52",
"type": "Protein",
"text": [
"D4-like receptors"
],
"offsets": [
[
1198,
1215
]
],
"normalized": []
},
{
"id": "45_T54",
"type": "Protein",
"text": [
"D4-like binding sites"
],
"offsets": [
[
204,
225
]
],
"normalized": []
},
{
"id": "45_T55",
"type": "Protein",
"text": [
"[3H]nemonapride binding sites"
],
"offsets": [
[
378,
407
]
],
"normalized": []
},
{
"id": "45_T56",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
142,
147
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "45_R2",
"type": "Associated_With",
"arg1_id": "45_T16",
"arg2_id": "45_T15",
"normalized": []
},
{
"id": "45_R3",
"type": "Binds_With",
"arg1_id": "45_T3",
"arg2_id": "45_T1",
"normalized": []
},
{
"id": "45_R5",
"type": "Binds_With",
"arg1_id": "45_T16",
"arg2_id": "45_T55",
"normalized": []
},
{
"id": "45_R4",
"type": "Binds_With",
"arg1_id": "45_T11",
"arg2_id": "45_T55",
"normalized": []
},
{
"id": "45_R1",
"type": "Associated_With",
"arg1_id": "45_T13",
"arg2_id": "45_T46",
"normalized": []
},
{
"id": "45_R6",
"type": "Binds_With",
"arg1_id": "45_T16",
"arg2_id": "45_T23",
"normalized": []
},
{
"id": "45_R8",
"type": "Binds_With",
"arg1_id": "45_T19",
"arg2_id": "45_T42",
"normalized": []
},
{
"id": "45_R7",
"type": "Binds_With",
"arg1_id": "45_T49",
"arg2_id": "45_T39",
"normalized": []
}
] |
46 | 10052027 | [
{
"id": "47",
"type": "",
"text": [
"The concentrations of adrenaline, noradrenaline, dopamine, aldosterone, the atrial natriuretic hormone, and plasma renin activity were investigated in 50 patients with mild chronic heart failure. The patients received oral digoxin chronically in a daily dose of 0.125 mg. On the basis of the estimate of the dosing of digoxin these patients were divided into two groups: the first with therapeutic and the second with subtherapeutic concentrations of digoxin in serum. The therapeutic concentration of digoxin in serum was found in 23 patients (46%), while subtherapeutic levels were found in 27 patients (54%). The concentrations of noradrenaline, dopamine, the renin activity of plasma, aldosterone and the atrial natriuretic hormone in the blood serum in the group of patients in whom the presence of subtherapeutic concentrations of digoxin was found, did not differ essentially from the concentration that was observed in the group with therapeutic concentrations. Only the concentration of adrenaline was higher (p < 0.05) in the group of patients with therapeutic concentrations of digoxin. The above results reveal that the neuroendocrine activity of plasma (except for the concentration of adrenaline) is alike in both ranges of digoxin concentrations in serum. \n"
],
"offsets": [
[
0,
1272
]
]
}
] | [
{
"id": "47_T1",
"type": "Chemical",
"text": [
"adrenaline"
],
"offsets": [
[
22,
32
]
],
"normalized": []
},
{
"id": "47_T2",
"type": "Chemical",
"text": [
"noradrenaline"
],
"offsets": [
[
34,
47
]
],
"normalized": []
},
{
"id": "47_T3",
"type": "Chemical",
"text": [
"dopamine"
],
"offsets": [
[
49,
57
]
],
"normalized": []
},
{
"id": "47_T4",
"type": "Chemical",
"text": [
"aldosterone"
],
"offsets": [
[
59,
70
]
],
"normalized": []
},
{
"id": "47_T8",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
154,
162
]
],
"normalized": []
},
{
"id": "47_T9",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
200,
208
]
],
"normalized": []
},
{
"id": "47_T10",
"type": "Chemical",
"text": [
"digoxin"
],
"offsets": [
[
223,
230
]
],
"normalized": []
},
{
"id": "47_T5",
"type": "Biological_Activity",
"text": [
"hormone"
],
"offsets": [
[
95,
102
]
],
"normalized": []
},
{
"id": "47_T7",
"type": "Metabolite",
"text": [
"adrenaline"
],
"offsets": [
[
22,
32
]
],
"normalized": []
},
{
"id": "47_T12",
"type": "Metabolite",
"text": [
"noradrenaline"
],
"offsets": [
[
34,
47
]
],
"normalized": []
},
{
"id": "47_T13",
"type": "Metabolite",
"text": [
"dopamine"
],
"offsets": [
[
49,
57
]
],
"normalized": []
},
{
"id": "47_T14",
"type": "Metabolite",
"text": [
"aldosterone"
],
"offsets": [
[
59,
70
]
],
"normalized": []
},
{
"id": "47_T15",
"type": "Chemical",
"text": [
"digoxin"
],
"offsets": [
[
318,
325
]
],
"normalized": []
},
{
"id": "47_T16",
"type": "Chemical",
"text": [
"digoxin"
],
"offsets": [
[
451,
458
]
],
"normalized": []
},
{
"id": "47_T17",
"type": "Chemical",
"text": [
"digoxin"
],
"offsets": [
[
502,
509
]
],
"normalized": []
},
{
"id": "47_T18",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
332,
340
]
],
"normalized": []
},
{
"id": "47_T19",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
535,
543
]
],
"normalized": []
},
{
"id": "47_T20",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
596,
604
]
],
"normalized": []
},
{
"id": "47_T21",
"type": "Chemical",
"text": [
"noradrenaline"
],
"offsets": [
[
634,
647
]
],
"normalized": []
},
{
"id": "47_T22",
"type": "Metabolite",
"text": [
"noradrenaline"
],
"offsets": [
[
634,
647
]
],
"normalized": []
},
{
"id": "47_T23",
"type": "Metabolite",
"text": [
"dopamine"
],
"offsets": [
[
649,
657
]
],
"normalized": []
},
{
"id": "47_T24",
"type": "Chemical",
"text": [
"dopamine"
],
"offsets": [
[
649,
657
]
],
"normalized": []
},
{
"id": "47_T25",
"type": "Protein",
"text": [
"renin"
],
"offsets": [
[
663,
668
]
],
"normalized": []
},
{
"id": "47_T27",
"type": "Chemical",
"text": [
"aldosterone"
],
"offsets": [
[
689,
700
]
],
"normalized": []
},
{
"id": "47_T28",
"type": "Metabolite",
"text": [
"aldosterone"
],
"offsets": [
[
689,
700
]
],
"normalized": []
},
{
"id": "47_T29",
"type": "Chemical",
"text": [
"atrial natriuretic hormone"
],
"offsets": [
[
709,
735
]
],
"normalized": []
},
{
"id": "47_T30",
"type": "Biological_Activity",
"text": [
"hormone"
],
"offsets": [
[
728,
735
]
],
"normalized": []
},
{
"id": "47_T31",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
771,
779
]
],
"normalized": []
},
{
"id": "47_T33",
"type": "Chemical",
"text": [
"adrenaline"
],
"offsets": [
[
996,
1006
]
],
"normalized": []
},
{
"id": "47_T34",
"type": "Metabolite",
"text": [
"adrenaline"
],
"offsets": [
[
996,
1006
]
],
"normalized": []
},
{
"id": "47_T35",
"type": "Chemical",
"text": [
"digoxin"
],
"offsets": [
[
1089,
1096
]
],
"normalized": []
},
{
"id": "47_T37",
"type": "Metabolite",
"text": [
"adrenaline"
],
"offsets": [
[
1199,
1209
]
],
"normalized": []
},
{
"id": "47_T38",
"type": "Chemical",
"text": [
"adrenaline"
],
"offsets": [
[
1199,
1209
]
],
"normalized": []
},
{
"id": "47_T39",
"type": "Chemical",
"text": [
"digoxin"
],
"offsets": [
[
1238,
1245
]
],
"normalized": []
},
{
"id": "47_T40",
"type": "Chemical",
"text": [
"digoxin"
],
"offsets": [
[
837,
844
]
],
"normalized": []
},
{
"id": "47_T11",
"type": "Chemical",
"text": [
"atrial natriuretic hormone"
],
"offsets": [
[
76,
102
]
],
"normalized": []
},
{
"id": "47_T32",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
1045,
1053
]
],
"normalized": []
},
{
"id": "47_T41",
"type": "Protein",
"text": [
"renin"
],
"offsets": [
[
115,
120
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "47_R1",
"type": "Isolated_From",
"arg1_id": "47_T7",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R2",
"type": "Isolated_From",
"arg1_id": "47_T12",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R3",
"type": "Isolated_From",
"arg1_id": "47_T13",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R4",
"type": "Isolated_From",
"arg1_id": "47_T14",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R5",
"type": "Isolated_From",
"arg1_id": "47_T22",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R6",
"type": "Isolated_From",
"arg1_id": "47_T23",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R7",
"type": "Isolated_From",
"arg1_id": "47_T28",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R8",
"type": "Isolated_From",
"arg1_id": "47_T29",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R9",
"type": "Isolated_From",
"arg1_id": "47_T34",
"arg2_id": "47_T32",
"normalized": []
}
] |
48 | 10052973 | [
{
"id": "49",
"type": "",
"text": [
"Three series of cycloalkanecarboxylic esters derived from the naturally occurring clavine alkaloids lysergol, dihydrolysergol-I, and elymoclavine were synthesized to study their interaction with 5-HT2A receptors and alpha1-adrenoceptors in rat tail artery and aorta, respectively. Especially cycloalkanecarboxylic esters derived from lysergol showed complex behavior as partial agonists and antagonists of the contractile effect of 5-HT. Within this group, partial 5-HT2A receptor agonist activity was most potent for cyclopropanecarboxylic ester 6a (pKP = 7.67, alpha = 0.21) and decreased as the volume requirement of the alicyclic ring increased. This tendency was echoed in experiments where the compounds were used as antagonists of the contractile effect of 5-HT. From the structure-activity study, the N-1-isopropyl homologue of 6a, compound 6b, emerged as the ligand with the highest affinity for rat 5-HT2A receptors (pA2 = 8.74). For cycloalkanecarboxylic esters derived from dihydrolysergol-I and elymoclavine, no clear structure-affinity relationship could be deduced, although those compounds that had smaller cycloalkyl rings in the acyl portion and an isopropyl substituent at N-1 showed the highest 5-HT2A receptor affinity. On the other hand, cycloalkanecarboxylic esters derived from lysergol, dihydrolysergol-I, and elymoclavine displayed low or marginal affinity at alpha1-adrenoceptors. A further aim of the study was to examine to what extent the complete removal of the acyl portion of the esters would affect 5-HT2A receptor affinity. The parent alcohols of the three series of N-1-isopropyl homologues, 1-isopropyllysergol (1b), 1-isopropyldihydrolysergol-I (2b), and 1-isopropylelymoclavine (3b), displayed higher affinity for 5-HT2A receptors (pA2 = 9.15, 8.50, 9.14) than the corresponding esters. Compounds 1b-3b had no contractile effects by themselves and displayed low affinity at guinea-pig 5-HT1B receptors and rat alpha1-adrenoceptors. The high affinity for rat 5-HT2A receptors was retained when clavines even more simple in structure than 1b-3b, compounds 4b and 5b, were examined as 5-HT2A receptor antagonists. The nanomolar antagonist activity of simple clavines (1b-5b) in the rat suggests that the indolo[4,3-fg]quinoline system of the ergolines is the molecular fragment that is responsible for 5-HT2A receptor affinity, and not the substituent at position C-8. \n"
],
"offsets": [
[
0,
2415
]
]
}
] | [
{
"id": "49_T1",
"type": "Chemical",
"text": [
"lysergol",
"dihydrolysergol-I",
"elymoclavine",
"cycloalkanecarboxylic esters"
],
"offsets": [
[
100,
108
],
[
110,
127
],
[
133,
145
],
[
16,
44
]
],
"normalized": []
},
{
"id": "49_T2",
"type": "Chemical",
"text": [
"clavine alkaloids"
],
"offsets": [
[
82,
99
]
],
"normalized": []
},
{
"id": "49_T3",
"type": "Chemical",
"text": [
"lysergol"
],
"offsets": [
[
100,
108
]
],
"normalized": []
},
{
"id": "49_T4",
"type": "Chemical",
"text": [
"dihydrolysergol-I"
],
"offsets": [
[
110,
127
]
],
"normalized": []
},
{
"id": "49_T5",
"type": "Chemical",
"text": [
"elymoclavine"
],
"offsets": [
[
133,
145
]
],
"normalized": []
},
{
"id": "49_T6",
"type": "Metabolite",
"text": [
"lysergol"
],
"offsets": [
[
100,
108
]
],
"normalized": []
},
{
"id": "49_T7",
"type": "Metabolite",
"text": [
"dihydrolysergol-I"
],
"offsets": [
[
110,
127
]
],
"normalized": []
},
{
"id": "49_T8",
"type": "Metabolite",
"text": [
"elymoclavine"
],
"offsets": [
[
133,
145
]
],
"normalized": []
},
{
"id": "49_T9",
"type": "Protein",
"text": [
"5-HT2A receptors"
],
"offsets": [
[
196,
212
]
],
"normalized": []
},
{
"id": "49_T11",
"type": "Protein",
"text": [
"alpha1-adrenoceptors"
],
"offsets": [
[
217,
237
]
],
"normalized": []
},
{
"id": "49_T13",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
241,
244
]
],
"normalized": []
},
{
"id": "49_T14",
"type": "Chemical",
"text": [
"cycloalkanecarboxylic esters",
"lysergol"
],
"offsets": [
[
294,
322
],
[
336,
344
]
],
"normalized": []
},
{
"id": "49_T15",
"type": "Chemical",
"text": [
"lysergol"
],
"offsets": [
[
336,
344
]
],
"normalized": []
},
{
"id": "49_T16",
"type": "Metabolite",
"text": [
"lysergol"
],
"offsets": [
[
336,
344
]
],
"normalized": []
},
{
"id": "49_T17",
"type": "Biological_Activity",
"text": [
"agonists"
],
"offsets": [
[
380,
388
]
],
"normalized": []
},
{
"id": "49_T18",
"type": "Biological_Activity",
"text": [
"antagonists"
],
"offsets": [
[
393,
404
]
],
"normalized": []
},
{
"id": "49_T19",
"type": "Chemical",
"text": [
"5-HT"
],
"offsets": [
[
434,
438
]
],
"normalized": []
},
{
"id": "49_T20",
"type": "Biological_Activity",
"text": [
"agonist"
],
"offsets": [
[
483,
490
]
],
"normalized": []
},
{
"id": "49_T22",
"type": "Protein",
"text": [
"5-HT2A receptor"
],
"offsets": [
[
467,
482
]
],
"normalized": []
},
{
"id": "49_T23",
"type": "Chemical",
"text": [
"cyclopropanecarboxylic ester 6a"
],
"offsets": [
[
520,
551
]
],
"normalized": []
},
{
"id": "49_T24",
"type": "Chemical",
"text": [
"alicyclic ring"
],
"offsets": [
[
626,
640
]
],
"normalized": []
},
{
"id": "49_T25",
"type": "Biological_Activity",
"text": [
"antagonists"
],
"offsets": [
[
726,
737
]
],
"normalized": []
},
{
"id": "49_T26",
"type": "Chemical",
"text": [
"5-HT"
],
"offsets": [
[
767,
771
]
],
"normalized": []
},
{
"id": "49_T27",
"type": "Chemical",
"text": [
"N-1-isopropyl homologue of 6a"
],
"offsets": [
[
812,
841
]
],
"normalized": []
},
{
"id": "49_T29",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
908,
911
]
],
"normalized": []
},
{
"id": "49_T31",
"type": "Protein",
"text": [
"5-HT2A receptors"
],
"offsets": [
[
912,
928
]
],
"normalized": []
},
{
"id": "49_T33",
"type": "Chemical",
"text": [
"cycloalkanecarboxylic esters"
],
"offsets": [
[
947,
975
]
],
"normalized": []
},
{
"id": "49_T34",
"type": "Metabolite",
"text": [
"dihydrolysergol-I"
],
"offsets": [
[
989,
1006
]
],
"normalized": []
},
{
"id": "49_T35",
"type": "Metabolite",
"text": [
"elymoclavine"
],
"offsets": [
[
1011,
1023
]
],
"normalized": []
},
{
"id": "49_T36",
"type": "Chemical",
"text": [
"dihydrolysergol-I"
],
"offsets": [
[
989,
1006
]
],
"normalized": []
},
{
"id": "49_T37",
"type": "Chemical",
"text": [
"elymoclavine"
],
"offsets": [
[
1011,
1023
]
],
"normalized": []
},
{
"id": "49_T38",
"type": "Chemical",
"text": [
"cycloalkanecarboxylic esters derived from dihydrolysergol-I and elymoclavine"
],
"offsets": [
[
947,
1023
]
],
"normalized": []
},
{
"id": "49_T39",
"type": "Chemical",
"text": [
"cycloalkyl ring"
],
"offsets": [
[
1128,
1143
]
],
"normalized": []
},
{
"id": "49_T40",
"type": "Chemical",
"text": [
"acyl portion"
],
"offsets": [
[
1152,
1164
]
],
"normalized": []
},
{
"id": "49_T41",
"type": "Chemical",
"text": [
"isopropyl substituent"
],
"offsets": [
[
1172,
1193
]
],
"normalized": []
},
{
"id": "49_T42",
"type": "Protein",
"text": [
"5-HT2A receptor"
],
"offsets": [
[
1220,
1235
]
],
"normalized": []
},
{
"id": "49_T45",
"type": "Chemical",
"text": [
"cycloalkanecarboxylic esters",
"lysergol",
"dihydrolysergol-I",
"elymoclavine"
],
"offsets": [
[
1265,
1293
],
[
1307,
1315
],
[
1317,
1334
],
[
1341,
1353
]
],
"normalized": []
},
{
"id": "49_T46",
"type": "Metabolite",
"text": [
"lysergol"
],
"offsets": [
[
1307,
1315
]
],
"normalized": []
},
{
"id": "49_T47",
"type": "Metabolite",
"text": [
"dihydrolysergol-I"
],
"offsets": [
[
1317,
1334
]
],
"normalized": []
},
{
"id": "49_T48",
"type": "Metabolite",
"text": [
"elymoclavine"
],
"offsets": [
[
1341,
1353
]
],
"normalized": []
},
{
"id": "49_T49",
"type": "Chemical",
"text": [
"lysergol"
],
"offsets": [
[
1307,
1315
]
],
"normalized": []
},
{
"id": "49_T50",
"type": "Chemical",
"text": [
"dihydrolysergol-I"
],
"offsets": [
[
1317,
1334
]
],
"normalized": []
},
{
"id": "49_T51",
"type": "Chemical",
"text": [
"elymoclavine"
],
"offsets": [
[
1341,
1353
]
],
"normalized": []
},
{
"id": "49_T52",
"type": "Chemical",
"text": [
"cycloalkanecarboxylic esters derived from lysergol, dihydrolysergol-I, and elymoclavine"
],
"offsets": [
[
1265,
1353
]
],
"normalized": []
},
{
"id": "49_T54",
"type": "Protein",
"text": [
"alpha1-adrenoceptors"
],
"offsets": [
[
1392,
1412
]
],
"normalized": []
},
{
"id": "49_T55",
"type": "Chemical",
"text": [
"acyl"
],
"offsets": [
[
1499,
1503
]
],
"normalized": []
},
{
"id": "49_T56",
"type": "Chemical",
"text": [
"esters"
],
"offsets": [
[
1519,
1525
]
],
"normalized": []
},
{
"id": "49_T58",
"type": "Protein",
"text": [
"5-HT2A receptor"
],
"offsets": [
[
1539,
1554
]
],
"normalized": []
},
{
"id": "49_T62",
"type": "Chemical",
"text": [
"parent alcohols",
"of N-1-isopropyl homologues"
],
"offsets": [
[
1569,
1585
],
[
1606,
1633
]
],
"normalized": []
},
{
"id": "49_T63",
"type": "Chemical",
"text": [
"1-isopropyllysergol"
],
"offsets": [
[
1635,
1654
]
],
"normalized": []
},
{
"id": "49_T64",
"type": "Chemical",
"text": [
"1-isopropyldihydrolysergol-I"
],
"offsets": [
[
1661,
1689
]
],
"normalized": []
},
{
"id": "49_T65",
"type": "Chemical",
"text": [
"1-isopropylelymoclavine"
],
"offsets": [
[
1700,
1723
]
],
"normalized": []
},
{
"id": "49_T66",
"type": "Protein",
"text": [
"5-HT2A receptors"
],
"offsets": [
[
1760,
1776
]
],
"normalized": []
},
{
"id": "49_T69",
"type": "Species",
"text": [
"guinea-pig"
],
"offsets": [
[
1921,
1931
]
],
"normalized": []
},
{
"id": "49_T70",
"type": "Protein",
"text": [
"5-HT1B receptor"
],
"offsets": [
[
1932,
1947
]
],
"normalized": []
},
{
"id": "49_T72",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
1953,
1956
]
],
"normalized": []
},
{
"id": "49_T75",
"type": "Protein",
"text": [
"alpha1-adrenoceptors"
],
"offsets": [
[
1957,
1977
]
],
"normalized": []
},
{
"id": "49_T77",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
2001,
2004
]
],
"normalized": []
},
{
"id": "49_T79",
"type": "Protein",
"text": [
"5-HT2A receptors"
],
"offsets": [
[
2005,
2021
]
],
"normalized": []
},
{
"id": "49_T80",
"type": "Metabolite",
"text": [
"clavines"
],
"offsets": [
[
2040,
2048
]
],
"normalized": []
},
{
"id": "49_T84",
"type": "Chemical",
"text": [
"1b"
],
"offsets": [
[
1656,
1658
]
],
"normalized": []
},
{
"id": "49_T85",
"type": "Chemical",
"text": [
"2b"
],
"offsets": [
[
1691,
1693
]
],
"normalized": []
},
{
"id": "49_T86",
"type": "Chemical",
"text": [
"3b"
],
"offsets": [
[
1725,
1727
]
],
"normalized": []
},
{
"id": "49_T87",
"type": "Chemical",
"text": [
"Compounds 1b",
"3b"
],
"offsets": [
[
1834,
1846
],
[
1847,
1849
]
],
"normalized": []
},
{
"id": "49_T89",
"type": "Chemical",
"text": [
"clavines"
],
"offsets": [
[
2040,
2048
]
],
"normalized": []
},
{
"id": "49_T90",
"type": "Chemical",
"text": [
"1b",
"3b"
],
"offsets": [
[
2084,
2086
],
[
2087,
2089
]
],
"normalized": []
},
{
"id": "49_T92",
"type": "Chemical",
"text": [
"compound",
"4b"
],
"offsets": [
[
2091,
2099
],
[
2101,
2103
]
],
"normalized": []
},
{
"id": "49_T94",
"type": "Protein",
"text": [
"5-HT2A receptor"
],
"offsets": [
[
2129,
2144
]
],
"normalized": []
},
{
"id": "49_T95",
"type": "Biological_Activity",
"text": [
"antagonists"
],
"offsets": [
[
2145,
2156
]
],
"normalized": []
},
{
"id": "49_T96",
"type": "Biological_Activity",
"text": [
"antagonist"
],
"offsets": [
[
2172,
2182
]
],
"normalized": []
},
{
"id": "49_T97",
"type": "Chemical",
"text": [
"clavines"
],
"offsets": [
[
2202,
2210
]
],
"normalized": []
},
{
"id": "49_T99",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
2226,
2229
]
],
"normalized": []
},
{
"id": "49_T100",
"type": "Chemical",
"text": [
"1b",
"5b"
],
"offsets": [
[
2212,
2214
],
[
2215,
2217
]
],
"normalized": []
},
{
"id": "49_T101",
"type": "Chemical",
"text": [
"indolo[4,3-fg]quinoline"
],
"offsets": [
[
2248,
2271
]
],
"normalized": []
},
{
"id": "49_T102",
"type": "Chemical",
"text": [
"ergolines"
],
"offsets": [
[
2286,
2295
]
],
"normalized": []
},
{
"id": "49_T103",
"type": "Metabolite",
"text": [
"ergolines"
],
"offsets": [
[
2286,
2295
]
],
"normalized": []
},
{
"id": "49_T104",
"type": "Chemical",
"text": [
"indolo[4,3-fg]quinoline system of the ergolines"
],
"offsets": [
[
2248,
2295
]
],
"normalized": []
},
{
"id": "49_T106",
"type": "Metabolite",
"text": [
"clavine alkaloids"
],
"offsets": [
[
82,
99
]
],
"normalized": []
},
{
"id": "49_T81",
"type": "Chemical",
"text": [
"compound",
"5b"
],
"offsets": [
[
2091,
2099
],
[
2108,
2110
]
],
"normalized": []
},
{
"id": "49_T28",
"type": "Protein",
"text": [
"5-HT2A receptor"
],
"offsets": [
[
2346,
2362
]
],
"normalized": []
},
{
"id": "49_T10",
"type": "Chemical",
"text": [
"compound 6b"
],
"offsets": [
[
843,
854
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "49_R1",
"type": "Associated_With",
"arg1_id": "49_T23",
"arg2_id": "49_T20",
"normalized": []
},
{
"id": "49_R16",
"type": "Associated_With",
"arg1_id": "49_T81",
"arg2_id": "49_T95",
"normalized": []
},
{
"id": "49_R17",
"type": "Associated_With",
"arg1_id": "49_T92",
"arg2_id": "49_T95",
"normalized": []
},
{
"id": "49_R18",
"type": "Binds_With",
"arg1_id": "49_T23",
"arg2_id": "49_T22",
"normalized": []
},
{
"id": "49_R10",
"type": "Binds_With",
"arg1_id": "49_T27",
"arg2_id": "49_T31",
"normalized": []
},
{
"id": "49_R2",
"type": "Binds_With",
"arg1_id": "49_T10",
"arg2_id": "49_T31",
"normalized": []
},
{
"id": "49_R3",
"type": "Binds_With",
"arg1_id": "49_T86",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R4",
"type": "Binds_With",
"arg1_id": "49_T65",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R5",
"type": "Binds_With",
"arg1_id": "49_T85",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R6",
"type": "Binds_With",
"arg1_id": "49_T64",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R11",
"type": "Binds_With",
"arg1_id": "49_T84",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R13",
"type": "Binds_With",
"arg1_id": "49_T63",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R14",
"type": "Binds_With",
"arg1_id": "49_T81",
"arg2_id": "49_T94",
"normalized": []
},
{
"id": "49_R19",
"type": "Binds_With",
"arg1_id": "49_T92",
"arg2_id": "49_T94",
"normalized": []
}
] |
50 | 100603 | [
{
"id": "51",
"type": "",
"text": [
"Subcutaneous tumor induction with three dose levels of 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), and 7,12-dimethylbenz[a]anthracene (DMBA) in two vehicles was studied in C3H/Anf Cum, C57BL/6 Cum, DBA/2J, and (C57BLXC3H/Anf)F1 (BC3F1/Cum) mice. Median tumor dose levels were significantly lower when the three carcinogens were suspended in trioctanoin. When beeswax: trioctanoin (B:T) was used as a vehicle, the three carcinogens differed in their abilities to be absorbed or solubilized from the vehicle by the three strains of mice and the hybrid. In C3H/Anf mice, BP in B:T failed to produce tumors. In BC3F1 mice, no tumors were produced by MCA, BP, or DMBA in B:T. In C57BL/6 mice, no tumors were produced with DMBA or MCA in B:T. In DBA/2 mice, no tumors were produced by BP or MCA in B:T. These results indicated that the interpretation of tumor induction results obtained with B:T vehicle may be related to the conditions of bioassay rather than to the carcinogenic potential of a compound. \n"
],
"offsets": [
[
0,
1008
]
]
}
] | [
{
"id": "51_T2",
"type": "Chemical",
"text": [
"3-methylcholanthrene"
],
"offsets": [
[
55,
75
]
],
"normalized": []
},
{
"id": "51_T3",
"type": "Chemical",
"text": [
"MCA"
],
"offsets": [
[
77,
80
]
],
"normalized": []
},
{
"id": "51_T4",
"type": "Chemical",
"text": [
"benzo[a]pyrene"
],
"offsets": [
[
83,
97
]
],
"normalized": []
},
{
"id": "51_T5",
"type": "Chemical",
"text": [
"BP"
],
"offsets": [
[
99,
101
]
],
"normalized": []
},
{
"id": "51_T6",
"type": "Chemical",
"text": [
"7,12-dimethylbenz[a]anthracene"
],
"offsets": [
[
108,
138
]
],
"normalized": []
},
{
"id": "51_T7",
"type": "Chemical",
"text": [
"DMBA"
],
"offsets": [
[
140,
144
]
],
"normalized": []
},
{
"id": "51_T8",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
245,
249
]
],
"normalized": []
},
{
"id": "51_T9",
"type": "Chemical",
"text": [
"trioctanoin"
],
"offsets": [
[
346,
357
]
],
"normalized": []
},
{
"id": "51_T10",
"type": "Biological_Activity",
"text": [
"carcinogen"
],
"offsets": [
[
316,
326
]
],
"normalized": []
},
{
"id": "51_T11",
"type": "Biological_Activity",
"text": [
"carcinogen"
],
"offsets": [
[
425,
435
]
],
"normalized": []
},
{
"id": "51_T12",
"type": "Chemical",
"text": [
"beeswax"
],
"offsets": [
[
364,
371
]
],
"normalized": []
},
{
"id": "51_T13",
"type": "Chemical",
"text": [
"trioctanoin"
],
"offsets": [
[
373,
384
]
],
"normalized": []
},
{
"id": "51_T14",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
536,
540
]
],
"normalized": []
},
{
"id": "51_T15",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
568,
572
]
],
"normalized": []
},
{
"id": "51_T16",
"type": "Chemical",
"text": [
"BP"
],
"offsets": [
[
574,
576
]
],
"normalized": []
},
{
"id": "51_T17",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
619,
623
]
],
"normalized": []
},
{
"id": "51_T18",
"type": "Chemical",
"text": [
"MCA"
],
"offsets": [
[
652,
655
]
],
"normalized": []
},
{
"id": "51_T19",
"type": "Chemical",
"text": [
"BP"
],
"offsets": [
[
657,
659
]
],
"normalized": []
},
{
"id": "51_T20",
"type": "Chemical",
"text": [
"DMBA"
],
"offsets": [
[
664,
668
]
],
"normalized": []
},
{
"id": "51_T21",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
688,
692
]
],
"normalized": []
},
{
"id": "51_T22",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
753,
757
]
],
"normalized": []
},
{
"id": "51_T23",
"type": "Chemical",
"text": [
"DMBA"
],
"offsets": [
[
724,
728
]
],
"normalized": []
},
{
"id": "51_T24",
"type": "Chemical",
"text": [
"MCA"
],
"offsets": [
[
732,
735
]
],
"normalized": []
},
{
"id": "51_T25",
"type": "Chemical",
"text": [
"BP"
],
"offsets": [
[
786,
788
]
],
"normalized": []
},
{
"id": "51_T26",
"type": "Chemical",
"text": [
"MCA"
],
"offsets": [
[
792,
795
]
],
"normalized": []
},
{
"id": "51_T27",
"type": "Biological_Activity",
"text": [
"carcinogen"
],
"offsets": [
[
969,
979
]
],
"normalized": []
},
{
"id": "51_T28",
"type": "Biological_Activity",
"text": [
"tumor induction"
],
"offsets": [
[
855,
870
]
],
"normalized": []
},
{
"id": "51_T29",
"type": "Chemical",
"text": [
"B:T"
],
"offsets": [
[
386,
389
]
],
"normalized": []
},
{
"id": "51_T30",
"type": "Chemical",
"text": [
"B:T"
],
"offsets": [
[
672,
675
]
],
"normalized": []
},
{
"id": "51_T31",
"type": "Chemical",
"text": [
"B:T"
],
"offsets": [
[
739,
742
]
],
"normalized": []
},
{
"id": "51_T32",
"type": "Chemical",
"text": [
"B:T"
],
"offsets": [
[
799,
802
]
],
"normalized": []
},
{
"id": "51_T33",
"type": "Chemical",
"text": [
"B:T"
],
"offsets": [
[
893,
896
]
],
"normalized": []
},
{
"id": "51_T1",
"type": "Biological_Activity",
"text": [
"tumor induction"
],
"offsets": [
[
13,
28
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "51_R1",
"type": "Associated_With",
"arg1_id": "51_T2",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R2",
"type": "Associated_With",
"arg1_id": "51_T3",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R3",
"type": "Associated_With",
"arg1_id": "51_T4",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R4",
"type": "Associated_With",
"arg1_id": "51_T5",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R5",
"type": "Associated_With",
"arg1_id": "51_T6",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R6",
"type": "Associated_With",
"arg1_id": "51_T7",
"arg2_id": "51_T10",
"normalized": []
}
] |
52 | 10064158 | [
{
"id": "53",
"type": "",
"text": [
"Exposure of Clone 9 cells, a nontransformed rat liver cell line expressing only the Glutl glucose transporter isoform, to the guanylyl cyclase inhibitor LY-83583 was found to stimulate the rate of glucose transport (approximately 7- to 8-fold in 1 h). A similar response to LY-83583 was found in NIH 3T3 fibroblasts, 3T3-L1 pre-adipocytes, and C2C12 myoblasts. Neither the rate of glucose transport in cells under control conditions nor the effect of LY-83583 on glucose transport was altered by 10, 50, or 100 microM 8-bromo-cGMP or by addition of cGMP phosphodiesterase inhibitors, zaprinast, or dipyridamole suggesting that glucose transport and the response to LY-83583 is independent of cGMP levels. In addition, the effect of LY-83583 on glucose transport was not mediated by inhibition of oxidative phosphorylation, since exposure to the agent resulted in no increase in lactate production. Incubation of Clone 9 cells in the presence of the phospholipase C inhibitor U73122, however, attenuated the glucose transport response to LY-83583. Moreover, exposure to LY-83583 resulted in a rise in cell diacylglycerol content, and preincubation with U73122 significantly diminished this rise as well as the glucose transport response to LY-83583. The stimulatory effect of LY-83583 on glucose transport was significantly blocked by thapsigargin. Down-regulation of protein kinase C activity, resulting from 24 h pre-incubation in the presence of 160 nM phorbol-12-myristate 13-acetate, did not attenuate the glucose transport response to LY-83583. It is concluded that the stimulation of glucose transport in response to LY-83583 is independent of changes in cGMP levels, is not mediated by inhibition of oxidative phosphorylation, and is mediated, at least in part, through stimulation of the phospholipase C pathway. \n"
],
"offsets": [
[
0,
1827
]
]
}
] | [
{
"id": "53_T1",
"type": "Protein",
"text": [
"Glutl glucose transporter"
],
"offsets": [
[
84,
109
]
],
"normalized": []
},
{
"id": "53_T2",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
143,
152
]
],
"normalized": []
},
{
"id": "53_T3",
"type": "Protein",
"text": [
"guanylyl cyclase"
],
"offsets": [
[
126,
142
]
],
"normalized": []
},
{
"id": "53_T5",
"type": "Chemical",
"text": [
"LY-83583"
],
"offsets": [
[
153,
161
]
],
"normalized": []
},
{
"id": "53_T6",
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520,
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551,
573
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574,
584
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586,
595
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600,
612
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629,
636
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735,
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747,
754
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755,
764
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785,
795
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"id": "53_T29",
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882,
889
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953,
968
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969,
978
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1011,
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1019,
1028
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1041,
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1081
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1109,
1123
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1109,
1123
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1156,
1162
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1213,
1220
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1221,
1230
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1243,
1251
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1280,
1288
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1292,
1299
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1292,
1309
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1339,
1351
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1372,
1388
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1380,
1386
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1460,
1491
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1515,
1522
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1523,
1532
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1595,
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1698,
1708
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1801,
1816
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"rat"
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[
44,
47
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] | [] | [] | [
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"id": "53_R1",
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] |
54 | 10064560 | [
{
"id": "55",
"type": "",
"text": [
"Retinaldehyde (RAL), a key intermediate in retinoid metabolism, acts as a retinoic acid (RA) precursor, but is also reduced to retinol (ROH), which can subsequently be esterified to retinyl esters, the storage form of vitamin A. Limited information is available on the metabolism of geometric isomers of RAL as well as on the transplacental distribution of their metabolites, including RA isomers. Such information would be very helpful for the assessment of the teratogenic potency of RAL isomers, as teratogenesis represents a major side effect of retinoid use in pharmacotherapy. In the present study we examined concentrations of retinoids in plasma, maternal tissues, and embryos of pregnant rats 2 h after a single oral dose (100 mg/kg body weight) of all-trans-, 13-cis-, or 9-cis-RAL on gestational day 13. The main findings of this study were the very similar patterns of retinoid metabolites (consisting of retinoids with mainly the all-trans-configuration) after administration of all-trans- and 13-cis-RAL, and the high concentrations of 9-cis-RA, 9,13-dicis-RA, and 9-cis-retinoyl-beta-D-glucuronide after dosing with 9-cis-RAL. In addition, all-trans-RA as a RAL metabolite reached the embryos to a much greater extent than any of its cis-isomers. The results are discussed in view of in vitro data on enzymes involved in the biotransformation of RAL isomers. \n"
],
"offsets": [
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0,
1376
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0,
13
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0,
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43,
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89,
91
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127,
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127,
134
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182,
196
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182,
196
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218,
227
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218,
227
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304,
307
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304,
307
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386,
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386,
396
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"id": "55_T20",
"type": "Biological_Activity",
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"teratogenic"
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[
463,
474
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"RAL isomers"
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486,
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"RAL isomers"
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486,
497
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{
"id": "55_T23",
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[
502,
515
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{
"id": "55_T24",
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"retinoid"
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550,
558
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{
"id": "55_T25",
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"retinoids"
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[
634,
643
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{
"id": "55_T26",
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"retinoid"
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[
43,
51
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"id": "55_T27",
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[
698,
702
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{
"id": "55_T28",
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"all-trans",
"RAL"
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759,
768
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[
789,
792
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{
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"-RAL"
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771,
778
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788,
792
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{
"id": "55_T30",
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"RA"
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[
789,
791
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"id": "55_T31",
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"all-trans-",
"RAL"
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759,
769
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789,
792
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{
"id": "55_T32",
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"13-cis-",
"RAL"
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771,
778
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[
789,
792
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{
"id": "55_T34",
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"text": [
"9-cis-RAL"
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[
783,
792
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{
"id": "55_T33",
"type": "Chemical",
"text": [
"9-cis-RAL"
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[
783,
792
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"normalized": []
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{
"id": "55_T35",
"type": "Metabolite",
"text": [
"9-cis-RAL"
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"offsets": [
[
783,
792
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"normalized": []
},
{
"id": "55_T36",
"type": "Chemical",
"text": [
"retinoid metabolites"
],
"offsets": [
[
882,
902
]
],
"normalized": []
},
{
"id": "55_T37",
"type": "Metabolite",
"text": [
"retinoid metabolites"
],
"offsets": [
[
882,
902
]
],
"normalized": []
},
{
"id": "55_T38",
"type": "Chemical",
"text": [
"retinoid"
],
"offsets": [
[
918,
926
]
],
"normalized": []
},
{
"id": "55_T39",
"type": "Metabolite",
"text": [
"retinoids"
],
"offsets": [
[
918,
927
]
],
"normalized": []
},
{
"id": "55_T40",
"type": "Chemical",
"text": [
"RAL",
"all-trans-"
],
"offsets": [
[
1015,
1018
],
[
993,
1003
]
],
"normalized": []
},
{
"id": "55_T41",
"type": "Chemical",
"text": [
"13-cis-RAL"
],
"offsets": [
[
1008,
1018
]
],
"normalized": []
},
{
"id": "55_T42",
"type": "Chemical",
"text": [
"9-cis-RA"
],
"offsets": [
[
1051,
1059
]
],
"normalized": []
},
{
"id": "55_T43",
"type": "Metabolite",
"text": [
"9-cis-RA"
],
"offsets": [
[
1051,
1059
]
],
"normalized": []
},
{
"id": "55_T44",
"type": "Metabolite",
"text": [
"9,13-dicis-RA"
],
"offsets": [
[
1061,
1074
]
],
"normalized": []
},
{
"id": "55_T45",
"type": "Chemical",
"text": [
"9,13-dicis-RA"
],
"offsets": [
[
1061,
1074
]
],
"normalized": []
},
{
"id": "55_T46",
"type": "Chemical",
"text": [
"9-cis-retinoyl-beta-D-glucuronide"
],
"offsets": [
[
1080,
1113
]
],
"normalized": []
},
{
"id": "55_T47",
"type": "Metabolite",
"text": [
"9-cis-retinoyl-beta-D-glucuronide"
],
"offsets": [
[
1080,
1113
]
],
"normalized": []
},
{
"id": "55_T48",
"type": "Chemical",
"text": [
"9-cis-RAL"
],
"offsets": [
[
1132,
1141
]
],
"normalized": []
},
{
"id": "55_T49",
"type": "Chemical",
"text": [
"all-trans-RA"
],
"offsets": [
[
1156,
1168
]
],
"normalized": []
},
{
"id": "55_T50",
"type": "Metabolite",
"text": [
"all-trans-RA"
],
"offsets": [
[
1156,
1168
]
],
"normalized": []
},
{
"id": "55_T51",
"type": "Chemical",
"text": [
"RAL"
],
"offsets": [
[
1174,
1177
]
],
"normalized": []
},
{
"id": "55_T52",
"type": "Metabolite",
"text": [
"RAL"
],
"offsets": [
[
1174,
1177
]
],
"normalized": []
},
{
"id": "55_T53",
"type": "Chemical",
"text": [
"RAL isomers"
],
"offsets": [
[
1362,
1373
]
],
"normalized": []
},
{
"id": "55_T54",
"type": "Protein",
"text": [
"enzymes"
],
"offsets": [
[
1317,
1324
]
],
"normalized": []
},
{
"id": "55_T55",
"type": "Biological_Activity",
"text": [
"metabolism"
],
"offsets": [
[
52,
62
]
],
"normalized": []
},
{
"id": "55_T56",
"type": "Biological_Activity",
"text": [
"metabolism"
],
"offsets": [
[
269,
279
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "55_R1",
"type": "Metabolite_Of",
"arg1_id": "55_T7",
"arg2_id": "55_T2",
"normalized": []
},
{
"id": "55_R2",
"type": "Metabolite_Of",
"arg1_id": "55_T11",
"arg2_id": "55_T2",
"normalized": []
},
{
"id": "55_R3",
"type": "Metabolite_Of",
"arg1_id": "55_T13",
"arg2_id": "55_T10",
"normalized": []
},
{
"id": "55_R4",
"type": "Metabolite_Of",
"arg1_id": "55_T50",
"arg2_id": "55_T51",
"normalized": []
},
{
"id": "55_R5",
"type": "Associated_With",
"arg1_id": "55_T21",
"arg2_id": "55_T20",
"normalized": []
},
{
"id": "55_R6",
"type": "Associated_With",
"arg1_id": "55_T21",
"arg2_id": "55_T23",
"normalized": []
},
{
"id": "55_R7",
"type": "Associated_With",
"arg1_id": "55_T24",
"arg2_id": "55_T23",
"normalized": []
},
{
"id": "55_R8",
"type": "Isolated_From",
"arg1_id": "55_T25",
"arg2_id": "55_T27",
"normalized": []
}
] |
56 | 10066805 | [
{
"id": "57",
"type": "",
"text": [
"UDP-glucose: anthocyanin 5-O-glucosyltransferase (5-GT) is responsible for the modification of anthocyanins to more stable molecules in complexes for co-pigmentation, supposedly resulting in a purple hue. The cDNA encoding 5-GT was isolated by a differential display applied to two different forms of anthocyanin production in Perilla frutescens var. crispa. Differential display was carried out for mRNA from the leaves of reddish-purple and green forms of P. frutescens, resulting in the isolation of five cDNA clones predominantly expressed in the red form. The cDNA encoded a polypeptide of 460 amino acids, exhibiting a low homology with the sequences of several glucosyltransferases including UDP-glucose: anthocyanidin 3-O-glucosyltransferase. By using this cDNA as the probe, we also isolated a homologous cDNA clone from a petal cDNA library of Verbena hybrida. To identify the biochemical function of the encoded proteins, these cDNAs were expressed in Saccharomyces cerevisiae cells. The recombinant proteins in the yeast extracts catalyzed the conversion of anthocyanidin 3-O-glucosides into the corresponding anthocyanidin 3,5-di-O-glucosides using UDP-glucose as a cofactor, indicating the identity of the cDNAs encoding 5-GT. Several biochemical properties (optimum pH, Km values, and sensitivity to inhibitors) were similar to those reported previously for 5-GTs. Southern blot analysis indicated the presence of two copies of 5-GT genes in the genome of both red and green forms of P. frutescens. The mRNA accumulation of the 5-GT gene was detected in the leaves of the red form but not in those of the green form and was induced by illumination of light, as observed for other structural genes for anthocyanin biosynthesis in P. frutescens. \n"
],
"offsets": [
[
0,
1763
]
]
}
] | [
{
"id": "57_T1",
"type": "Protein",
"text": [
"UDP-glucose: anthocyanin 5-O-glucosyltransferase"
],
"offsets": [
[
0,
48
]
],
"normalized": []
},
{
"id": "57_T4",
"type": "Protein",
"text": [
"5-GT"
],
"offsets": [
[
50,
54
]
],
"normalized": []
},
{
"id": "57_T5",
"type": "Metabolite",
"text": [
"anthocyanins"
],
"offsets": [
[
95,
107
]
],
"normalized": []
},
{
"id": "57_T6",
"type": "Chemical",
"text": [
"anthocyanins"
],
"offsets": [
[
95,
107
]
],
"normalized": []
},
{
"id": "57_T7",
"type": "Chemical",
"text": [
"molecules"
],
"offsets": [
[
123,
132
]
],
"normalized": []
},
{
"id": "57_T8",
"type": "Protein",
"text": [
"5-GT"
],
"offsets": [
[
223,
227
]
],
"normalized": []
},
{
"id": "57_T10",
"type": "Metabolite",
"text": [
"anthocyanin"
],
"offsets": [
[
301,
312
]
],
"normalized": []
},
{
"id": "57_T11",
"type": "Species",
"text": [
"Perilla frutescens var. crispa"
],
"offsets": [
[
328,
358
]
],
"normalized": []
},
{
"id": "57_T12",
"type": "Species",
"text": [
"Perilla frutescens"
],
"offsets": [
[
328,
346
]
],
"normalized": []
},
{
"id": "57_T13",
"type": "Species",
"text": [
"P. frutescens"
],
"offsets": [
[
459,
472
]
],
"normalized": []
},
{
"id": "57_T14",
"type": "Protein",
"text": [
"polypeptide"
],
"offsets": [
[
582,
593
]
],
"normalized": []
},
{
"id": "57_T15",
"type": "Protein",
"text": [
"glucosyltransferases"
],
"offsets": [
[
670,
690
]
],
"normalized": []
},
{
"id": "57_T16",
"type": "Protein",
"text": [
"UDP-glucose: anthocyanidin 3-O-glucosyltransferase"
],
"offsets": [
[
701,
751
]
],
"normalized": []
},
{
"id": "57_T17",
"type": "Species",
"text": [
"Verbena hybrida"
],
"offsets": [
[
856,
871
]
],
"normalized": []
},
{
"id": "57_T18",
"type": "Species",
"text": [
"Saccharomyces cerevisiae"
],
"offsets": [
[
965,
989
]
],
"normalized": []
},
{
"id": "57_T19",
"type": "Protein",
"text": [
"recombinant proteins"
],
"offsets": [
[
1001,
1021
]
],
"normalized": []
},
{
"id": "57_T20",
"type": "Species",
"text": [
"yeast"
],
"offsets": [
[
1029,
1034
]
],
"normalized": []
},
{
"id": "57_T21",
"type": "Chemical",
"text": [
"anthocyanidin 3-O-glucosides"
],
"offsets": [
[
1072,
1100
]
],
"normalized": []
},
{
"id": "57_T22",
"type": "Chemical",
"text": [
"anthocyanidin 3,5-di-O-glucosides"
],
"offsets": [
[
1124,
1157
]
],
"normalized": []
},
{
"id": "57_T23",
"type": "Metabolite",
"text": [
"anthocyanidin 3,5-di-O-glucosides"
],
"offsets": [
[
1124,
1157
]
],
"normalized": []
},
{
"id": "57_T24",
"type": "Chemical",
"text": [
"UDP-glucose"
],
"offsets": [
[
1164,
1175
]
],
"normalized": []
},
{
"id": "57_T25",
"type": "Protein",
"text": [
"5-GT"
],
"offsets": [
[
1237,
1241
]
],
"normalized": []
},
{
"id": "57_T9",
"type": "Protein",
"text": [
"5-GT"
],
"offsets": [
[
1375,
1379
]
],
"normalized": []
},
{
"id": "57_T26",
"type": "Species",
"text": [
"P. frutescens"
],
"offsets": [
[
1501,
1514
]
],
"normalized": []
},
{
"id": "57_T27",
"type": "Protein",
"text": [
"5-GT"
],
"offsets": [
[
1545,
1549
]
],
"normalized": []
},
{
"id": "57_T28",
"type": "Metabolite",
"text": [
"anthocyanin"
],
"offsets": [
[
1719,
1730
]
],
"normalized": []
},
{
"id": "57_T29",
"type": "Species",
"text": [
"P. frutescens"
],
"offsets": [
[
1747,
1760
]
],
"normalized": []
},
{
"id": "57_T30",
"type": "Chemical",
"text": [
"anthocyanin"
],
"offsets": [
[
1719,
1730
]
],
"normalized": []
},
{
"id": "57_T35",
"type": "Biological_Activity",
"text": [
"cofactor"
],
"offsets": [
[
1181,
1189
]
],
"normalized": []
},
{
"id": "57_T2",
"type": "Chemical",
"text": [
"anthocyanin"
],
"offsets": [
[
301,
314
]
],
"normalized": []
},
{
"id": "57_T3",
"type": "Chemical",
"text": [
"amino acids"
],
"offsets": [
[
601,
612
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "57_R1",
"type": "Associated_With",
"arg1_id": "57_T24",
"arg2_id": "57_T35",
"normalized": []
},
{
"id": "57_R2",
"type": "Metabolite_Of",
"arg1_id": "57_T23",
"arg2_id": "57_T21",
"normalized": []
},
{
"id": "57_R3",
"type": "Isolated_From",
"arg1_id": "57_T10",
"arg2_id": "57_T11",
"normalized": []
}
] |
58 | 10069359 | [
{
"id": "59",
"type": "",
"text": [
"The cephalosporins are a large group of related beta-lactam antimicrobial agents. Favorable attributes of the cephalosporins include low rates of toxicity, relatively broad spectrum of activity, and ease of administration. Various cephalosporins are effective for treatment of many conditions, including pneumonia, skin and soft tissue infections, bacteremia, and meningitis. Differences among the numerous cephalosporin antimicrobial agents are sometimes subtle; however, an understanding of these differences is essential for optimal use of these agents. As a result of widespread use of cephalosporins, bacterial resistance to these drugs is increasingly common. New, fourth-generation agents (such as cefepime) offer an alternative for the treatment of infections caused by some drug-resistant microorganisms. \n"
],
"offsets": [
[
0,
815
]
]
}
] | [
{
"id": "59_T1",
"type": "Chemical",
"text": [
"cephalosporins"
],
"offsets": [
[
4,
18
]
],
"normalized": []
},
{
"id": "59_T2",
"type": "Chemical",
"text": [
"beta-lactam"
],
"offsets": [
[
48,
59
]
],
"normalized": []
},
{
"id": "59_T3",
"type": "Biological_Activity",
"text": [
"antimicrobial"
],
"offsets": [
[
60,
73
]
],
"normalized": []
},
{
"id": "59_T4",
"type": "Chemical",
"text": [
"cephalosporins"
],
"offsets": [
[
110,
124
]
],
"normalized": []
},
{
"id": "59_T5",
"type": "Biological_Activity",
"text": [
"toxicity"
],
"offsets": [
[
146,
154
]
],
"normalized": []
},
{
"id": "59_T7",
"type": "Chemical",
"text": [
"cephalosporins"
],
"offsets": [
[
231,
245
]
],
"normalized": []
},
{
"id": "59_T8",
"type": "Chemical",
"text": [
"cephalosporin"
],
"offsets": [
[
407,
420
]
],
"normalized": []
},
{
"id": "59_T9",
"type": "Biological_Activity",
"text": [
"antimicrobial"
],
"offsets": [
[
421,
434
]
],
"normalized": []
},
{
"id": "59_T10",
"type": "Chemical",
"text": [
"cephalosporins"
],
"offsets": [
[
590,
604
]
],
"normalized": []
},
{
"id": "59_T11",
"type": "Chemical",
"text": [
"cefepime"
],
"offsets": [
[
705,
713
]
],
"normalized": []
},
{
"id": "59_T13",
"type": "Chemical",
"text": [
"drugs"
],
"offsets": [
[
636,
641
]
],
"normalized": []
},
{
"id": "59_T12",
"type": "Chemical",
"text": [
"drug"
],
"offsets": [
[
783,
787
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "59_R1",
"type": "Associated_With",
"arg1_id": "59_T1",
"arg2_id": "59_T3",
"normalized": []
},
{
"id": "59_R3",
"type": "Associated_With",
"arg1_id": "59_T8",
"arg2_id": "59_T9",
"normalized": []
},
{
"id": "59_R4",
"type": "Associated_With",
"arg1_id": "59_T11",
"arg2_id": "59_T9",
"normalized": []
}
] |
60 | 10069454 | [
{
"id": "61",
"type": "",
"text": [
"DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP) are activated by DNA strand breaks and participate in DNA repair. We investigated the interactive effects of inhibitors of these enzymes [wortmannin (WM), which inhibits DNA-PK, and 8-hydroxy-2-methylquinazolin-4-one (NU1025), a PARP inhibitor] on cell survival and DNA double-strand break (DSB) and single-strand break (SSB) rejoining in Chinese hamster ovary-K1 cells following exposure to ionizing radiation (IR) or temozolomide. WM (20 microM) or NU1025 (300 microM) potentiated the cytotoxicity of IR with dose enhancement factors at 10% survival (DEF10) values of 4.5 +/- 0.6 and 1.7 +/- 0.2, respectively. When used in combination, a DEF10 of 7.8 +/- 1.5 was obtained. WM or NU1025 potentiated the cytotoxicity of temozolomide, and an additive effect on the DEF10 value was obtained with the combined inhibitors. Using the same inhibitor concentrations, their single and combined effects on DSB and SSB levels following IR were assessed by neutral and alkaline elution. Cells exposed to IR were post-incubated for 30 min to allow repair to occur. WM or NU1025 increased net DSB levels relative to IR alone (DSB levels of 1.29 +/- 0.04 and 1.20 +/- 0.05, respectively, compared with 1.01 +/- 0.03 for IR alone) and the combination had an additive effect. WM had no effect on SSB levels, either alone or in combination with NU1025. SSB levels were increased to 1.27 +/- 0.05 with NU1025 compared with IR alone, 1.02 +/- 0.04. The dose-dependent effects of the inhibitors on DSB levels showed that they were near maximal by 20 microM WM and 300 microM NU1025. DSB repair kinetics were studied. Both inhibitors increased net DSB levels over a 3 h time period; when they were combined, net DSB levels at 3 h were identical to DSB levels immediately post-IR. The combined use of DNA repair inhibitors may have therapeutic potential. \n"
],
"offsets": [
[
0,
1914
]
]
}
] | [
{
"id": "61_T1",
"type": "Protein",
"text": [
"DNA-dependent protein kinase"
],
"offsets": [
[
0,
28
]
],
"normalized": []
},
{
"id": "61_T2",
"type": "Protein",
"text": [
"DNA-PK"
],
"offsets": [
[
30,
36
]
],
"normalized": []
},
{
"id": "61_T3",
"type": "Protein",
"text": [
"poly(ADP-ribose) polymerase"
],
"offsets": [
[
42,
69
]
],
"normalized": []
},
{
"id": "61_T5",
"type": "Protein",
"text": [
"PARP"
],
"offsets": [
[
71,
75
]
],
"normalized": []
},
{
"id": "61_T4",
"type": "Biological_Activity",
"text": [
"DNA repair"
],
"offsets": [
[
132,
142
]
],
"normalized": []
},
{
"id": "61_T11",
"type": "Chemical",
"text": [
"wortmannin"
],
"offsets": [
[
216,
226
]
],
"normalized": []
},
{
"id": "61_T12",
"type": "Chemical",
"text": [
"WM"
],
"offsets": [
[
228,
230
]
],
"normalized": []
},
{
"id": "61_T13",
"type": "Biological_Activity",
"text": [
"inhibits"
],
"offsets": [
[
239,
247
]
],
"normalized": []
},
{
"id": "61_T14",
"type": "Chemical",
"text": [
"8-hydroxy-2-methylquinazolin-4-one"
],
"offsets": [
[
260,
294
]
],
"normalized": []
},
{
"id": "61_T15",
"type": "Chemical",
"text": [
"NU1025"
],
"offsets": [
[
296,
302
]
],
"normalized": []
},
{
"id": "61_T16",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
312,
321
]
],
"normalized": []
},
{
"id": "61_T17",
"type": "Species",
"text": [
"Chinese hamster"
],
"offsets": [
[
417,
432
]
],
"normalized": []
},
{
"id": "61_T18",
"type": "Chemical",
"text": [
"temozolomide"
],
"offsets": [
[
497,
509
]
],
"normalized": []
},
{
"id": "61_T21",
"type": "Chemical",
"text": [
"WM"
],
"offsets": [
[
511,
513
]
],
"normalized": []
},
{
"id": "61_T22",
"type": "Chemical",
"text": [
"NU1025"
],
"offsets": [
[
529,
535
]
],
"normalized": []
},
{
"id": "61_T23",
"type": "Biological_Activity",
"text": [
"cytotoxicity"
],
"offsets": [
[
565,
577
]
],
"normalized": []
},
{
"id": "61_T24",
"type": "Chemical",
"text": [
"WM"
],
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755,
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"id": "61_T25",
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761,
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"id": "61_T26",
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"cytotoxicity"
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784,
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{
"id": "61_T27",
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800,
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1133,
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"id": "61_T29",
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1870,
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"id": "61_T36",
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1682,
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914,
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"id": "61_T38",
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187,
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},
{
"id": "61_T39",
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{
"id": "61_T42",
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"DNA-PK"
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248,
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]
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"id": "61_T43",
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"PARP"
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307,
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},
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"id": "61_T6",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
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[
887,
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]
],
"normalized": []
}
] | [] | [] | [
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"id": "61_R1",
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"arg2_id": "61_T13",
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},
{
"id": "61_R2",
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},
{
"id": "61_R3",
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},
{
"id": "61_R4",
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"arg2_id": "61_T16",
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},
{
"id": "61_R7",
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},
{
"id": "61_R10",
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},
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"id": "61_R14",
"type": "Binds_With",
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},
{
"id": "61_R15",
"type": "Binds_With",
"arg1_id": "61_T11",
"arg2_id": "61_T1",
"normalized": []
},
{
"id": "61_R16",
"type": "Binds_With",
"arg1_id": "61_T12",
"arg2_id": "61_T1",
"normalized": []
},
{
"id": "61_R18",
"type": "Binds_With",
"arg1_id": "61_T14",
"arg2_id": "61_T3",
"normalized": []
},
{
"id": "61_R11",
"type": "Binds_With",
"arg1_id": "61_T15",
"arg2_id": "61_T3",
"normalized": []
},
{
"id": "61_R17",
"type": "Binds_With",
"arg1_id": "61_T14",
"arg2_id": "61_T43",
"normalized": []
},
{
"id": "61_R19",
"type": "Binds_With",
"arg1_id": "61_T15",
"arg2_id": "61_T43",
"normalized": []
},
{
"id": "61_R5",
"type": "Associated_With",
"arg1_id": "61_T24",
"arg2_id": "61_T6",
"normalized": []
},
{
"id": "61_R6",
"type": "Associated_With",
"arg1_id": "61_T25",
"arg2_id": "61_T6",
"normalized": []
}
] |
62 | 10070780 | [
{
"id": "63",
"type": "",
"text": [
"The FM4-64, a member of the family of fluorescent dyes, has been applied to the cerebellar cortex to evaluate its properties as an intracellular stain and intracortical tracer. Slabs of hamster cerebellum, 1-2 mm thick, were incubated in 10, 30, and 100 microns solutions of FM4-64 in sodium phosphate buffer and observed in a slow scan confocal laser scanning microscope. Mossy and climbing fibers were traced in the cerebellar white and gray substances. They exhibited a high fluorescence signal at the level of the myelin sheath. Mossy fibers were identified in the granular layer by their typical rosette formation and dichotomous bifurcation pattern. Climbing fiber bundles were observed crossing the granular layer and giving collateral branches around Golgi cell bodies. They ascend to the Purkinje cell layer on their way to the molecular layer. Cerebellar macroneurons (Golgi and Purkinje cells) and microneurons (granule, basket, and stellate cells) showed optimal intracellular staining of cell soma, axonal, and dendritic processes. The z-series of stacks of optodigital sections allowed us to explore in depth the cytoarchitectonic arrangement, nerve and glial cell morphology, and the topographic relationship with the afferent fibers. \n"
],
"offsets": [
[
0,
1253
]
]
}
] | [
{
"id": "63_T1",
"type": "Chemical",
"text": [
"FM4-64"
],
"offsets": [
[
4,
10
]
],
"normalized": []
},
{
"id": "63_T4",
"type": "Species",
"text": [
"hamster"
],
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186,
193
]
],
"normalized": []
},
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"id": "63_T5",
"type": "Chemical",
"text": [
"sodium phosphate buffer"
],
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[
285,
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]
],
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},
{
"id": "63_T6",
"type": "Chemical",
"text": [
"FM4-64"
],
"offsets": [
[
275,
281
]
],
"normalized": []
}
] | [] | [] | [] |
64 | 10071923 | [
{
"id": "65",
"type": "",
"text": [
"A comparative study of various procedures for tryptophanyl peptide bond cleavage by BNPS-skatole [2-(2-nitrophenyl)-3-methyl-3-bromoindolenine] was carried out on native and on reduced and alkylated bovine beta-lactoglobulin (BLG). The reaction yield and the composition of the derived products were studied in acetic acid, trifluoroacetic acid (TFA), and ethanol/TFA. For BNPS-skatole removal, extraction by water or ethyl ether was compared with dialysis and gel filtration. The three expected peptides (1-19, 20-61, 62-162) and incomplete cleaved fragments (1-61, 20-162) were separated and characterized by electrophoresis, reverse-phase high-performance liquid chromatography, and mass spectrometry. The highest hydrolysis yield (67.4%) occurred with native BLG cleaved in 88% acetic acid at 47 degrees C for 60 min. Subsequent water extraction and gel filtration led to total recovery of the material, but reagent elimination was only quantitative after gel filtration. Cleavage specificity was ensured by mass spectrometry and the amino acid composition of peptides 1-19 and 62-162. The chemical side reactions identified are discussed. \n"
],
"offsets": [
[
0,
1147
]
]
}
] | [
{
"id": "65_T1",
"type": "Chemical",
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"BNPS-skatole"
],
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85,
97
]
],
"normalized": []
},
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"id": "65_T2",
"type": "Chemical",
"text": [
"2-(2-nitrophenyl)-3-methyl-3-bromoindolenine"
],
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99,
143
]
],
"normalized": []
},
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"id": "65_T4",
"type": "Protein",
"text": [
"beta-lactoglobulin"
],
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[
207,
225
]
],
"normalized": []
},
{
"id": "65_T5",
"type": "Species",
"text": [
"bovine"
],
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[
200,
206
]
],
"normalized": []
},
{
"id": "65_T6",
"type": "Chemical",
"text": [
"acetic acid"
],
"offsets": [
[
312,
323
]
],
"normalized": []
},
{
"id": "65_T7",
"type": "Chemical",
"text": [
"trifluoroacetic acid"
],
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[
325,
345
]
],
"normalized": []
},
{
"id": "65_T8",
"type": "Chemical",
"text": [
"TFA"
],
"offsets": [
[
347,
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]
],
"normalized": []
},
{
"id": "65_T9",
"type": "Chemical",
"text": [
"ethanol"
],
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357,
364
]
],
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},
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"id": "65_T10",
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"text": [
"TFA"
],
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365,
368
]
],
"normalized": []
},
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"id": "65_T11",
"type": "Chemical",
"text": [
"BNPS-skatole"
],
"offsets": [
[
374,
386
]
],
"normalized": []
},
{
"id": "65_T12",
"type": "Chemical",
"text": [
"water"
],
"offsets": [
[
410,
415
]
],
"normalized": []
},
{
"id": "65_T13",
"type": "Chemical",
"text": [
"ethyl ether"
],
"offsets": [
[
419,
430
]
],
"normalized": []
},
{
"id": "65_T14",
"type": "Protein",
"text": [
"BLG"
],
"offsets": [
[
227,
230
]
],
"normalized": []
},
{
"id": "65_T15",
"type": "Protein",
"text": [
"BLG"
],
"offsets": [
[
765,
768
]
],
"normalized": []
},
{
"id": "65_T16",
"type": "Chemical",
"text": [
"acetic acid"
],
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784,
795
]
],
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},
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"id": "65_T17",
"type": "Chemical",
"text": [
"water"
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835,
840
]
],
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},
{
"id": "65_T18",
"type": "Chemical",
"text": [
"amino acid"
],
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1040,
1050
]
],
"normalized": []
},
{
"id": "65_T19",
"type": "Spectral_Data",
"text": [
"mass spectrometry"
],
"offsets": [
[
688,
705
]
],
"normalized": []
},
{
"id": "65_T20",
"type": "Chemical",
"text": [
"peptides",
"1-19"
],
"offsets": [
[
498,
506
],
[
508,
512
]
],
"normalized": []
},
{
"id": "65_T21",
"type": "Spectral_Data",
"text": [
"mass spectrometry"
],
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[
1014,
1031
]
],
"normalized": []
},
{
"id": "65_T22",
"type": "Chemical",
"text": [
"peptides 1-19"
],
"offsets": [
[
1066,
1079
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "65_R3",
"type": "Associated_With",
"arg1_id": "65_T20",
"arg2_id": "65_T19",
"normalized": []
},
{
"id": "65_R4",
"type": "Associated_With",
"arg1_id": "65_T22",
"arg2_id": "65_T21",
"normalized": []
}
] |
66 | 10072406 | [
{
"id": "67",
"type": "",
"text": [
"We conducted a study of the patterns and dynamics of oxidized fatty acid derivatives (oxylipins) in potato leaves infected with the late-blight pathogen Phytophthora infestans. Two 18-carbon divinyl ether fatty acids, colneleic acid and colnelenic acid, accumulated during disease development. To date, there are no reports that such compounds have been detected in higher plants. The divinyl ether fatty acids accumulate more rapidly in potato cultivar Matilda (a cultivar with increased resistance to late blight) than in cultivar Bintje, a susceptible cultivar. Colnelenic acid reached levels of up to approximately 24 nmol (7 microgram) per g fresh weight of tissue in infected leaves. By contrast, levels of members of the jasmonic acid family did not change significantly during pathogenesis. The divinyl ethers also accumulated during the incompatible interaction of tobacco with tobacco mosaic virus. Colneleic and colnelenic acids were found to be inhibitory to P. infestans, suggesting a function in plant defense for divinyl ethers, which are unstable compounds rarely encountered in biological systems. \n"
],
"offsets": [
[
0,
1119
]
]
}
] | [
{
"id": "67_T1",
"type": "Chemical",
"text": [
"oxidized fatty acid derivatives"
],
"offsets": [
[
53,
84
]
],
"normalized": []
},
{
"id": "67_T2",
"type": "Chemical",
"text": [
"oxylipins"
],
"offsets": [
[
86,
95
]
],
"normalized": []
},
{
"id": "67_T3",
"type": "Metabolite",
"text": [
"oxidized fatty acid derivatives"
],
"offsets": [
[
53,
84
]
],
"normalized": []
},
{
"id": "67_T4",
"type": "Metabolite",
"text": [
"oxylipins"
],
"offsets": [
[
86,
95
]
],
"normalized": []
},
{
"id": "67_T5",
"type": "Species",
"text": [
"potato"
],
"offsets": [
[
100,
106
]
],
"normalized": []
},
{
"id": "67_T6",
"type": "Species",
"text": [
"Phytophthora infestans"
],
"offsets": [
[
153,
175
]
],
"normalized": []
},
{
"id": "67_T7",
"type": "Chemical",
"text": [
"18-carbon divinyl ether fatty acids"
],
"offsets": [
[
181,
216
]
],
"normalized": []
},
{
"id": "67_T8",
"type": "Chemical",
"text": [
"colneleic acid"
],
"offsets": [
[
218,
232
]
],
"normalized": []
},
{
"id": "67_T9",
"type": "Metabolite",
"text": [
"colneleic acid"
],
"offsets": [
[
218,
232
]
],
"normalized": []
},
{
"id": "67_T10",
"type": "Chemical",
"text": [
"colnelenic acid"
],
"offsets": [
[
237,
252
]
],
"normalized": []
},
{
"id": "67_T11",
"type": "Metabolite",
"text": [
"colnelenic acid"
],
"offsets": [
[
237,
252
]
],
"normalized": []
},
{
"id": "67_T12",
"type": "Chemical",
"text": [
"divinyl ether fatty acids"
],
"offsets": [
[
385,
410
]
],
"normalized": []
},
{
"id": "67_T13",
"type": "Species",
"text": [
"potato",
"cultivar Bintje"
],
"offsets": [
[
438,
444
],
[
525,
540
]
],
"normalized": []
},
{
"id": "67_T14",
"type": "Chemical",
"text": [
"Colnelenic acid"
],
"offsets": [
[
567,
582
]
],
"normalized": []
},
{
"id": "67_T15",
"type": "Metabolite",
"text": [
"Colnelenic acid"
],
"offsets": [
[
567,
582
]
],
"normalized": []
},
{
"id": "67_T16",
"type": "Chemical",
"text": [
"jasmonic acid family"
],
"offsets": [
[
730,
750
]
],
"normalized": []
},
{
"id": "67_T17",
"type": "Chemical",
"text": [
"divinyl ethers"
],
"offsets": [
[
805,
819
]
],
"normalized": []
},
{
"id": "67_T18",
"type": "Species",
"text": [
"tobacco"
],
"offsets": [
[
876,
883
]
],
"normalized": []
},
{
"id": "67_T19",
"type": "Species",
"text": [
"tobacco mosaic virus"
],
"offsets": [
[
889,
909
]
],
"normalized": []
},
{
"id": "67_T20",
"type": "Metabolite",
"text": [
"divinyl ethers"
],
"offsets": [
[
805,
819
]
],
"normalized": []
},
{
"id": "67_T21",
"type": "Chemical",
"text": [
"Colneleic",
"acid"
],
"offsets": [
[
911,
920
],
[
936,
940
]
],
"normalized": []
},
{
"id": "67_T22",
"type": "Chemical",
"text": [
"colnelenic acid"
],
"offsets": [
[
925,
940
]
],
"normalized": []
},
{
"id": "67_T23",
"type": "Metabolite",
"text": [
"colnelenic acid"
],
"offsets": [
[
925,
940
]
],
"normalized": []
},
{
"id": "67_T24",
"type": "Metabolite",
"text": [
"Colneleic",
"acid"
],
"offsets": [
[
911,
920
],
[
936,
940
]
],
"normalized": []
},
{
"id": "67_T25",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
960,
969
]
],
"normalized": []
},
{
"id": "67_T26",
"type": "Species",
"text": [
"P. infestans"
],
"offsets": [
[
974,
986
]
],
"normalized": []
},
{
"id": "67_T27",
"type": "Chemical",
"text": [
"divinyl ethers"
],
"offsets": [
[
1031,
1045
]
],
"normalized": []
},
{
"id": "67_T29",
"type": "Species",
"text": [
"potato cultivar Matilda"
],
"offsets": [
[
438,
461
]
],
"normalized": []
},
{
"id": "67_T30",
"type": "Metabolite",
"text": [
"jasmonic acid family"
],
"offsets": [
[
730,
750
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "67_R1",
"type": "Associated_With",
"arg1_id": "67_T24",
"arg2_id": "67_T25",
"normalized": []
},
{
"id": "67_R2",
"type": "Associated_With",
"arg1_id": "67_T23",
"arg2_id": "67_T25",
"normalized": []
},
{
"id": "67_R4",
"type": "Isolated_From",
"arg1_id": "67_T9",
"arg2_id": "67_T5",
"normalized": []
},
{
"id": "67_R5",
"type": "Isolated_From",
"arg1_id": "67_T11",
"arg2_id": "67_T5",
"normalized": []
},
{
"id": "67_R6",
"type": "Isolated_From",
"arg1_id": "67_T30",
"arg2_id": "67_T5",
"normalized": []
},
{
"id": "67_R7",
"type": "Isolated_From",
"arg1_id": "67_T9",
"arg2_id": "67_T18",
"normalized": []
},
{
"id": "67_R8",
"type": "Isolated_From",
"arg1_id": "67_T11",
"arg2_id": "67_T18",
"normalized": []
}
] |
68 | 10073739 | [
{
"id": "69",
"type": "",
"text": [
"AIMS: Cysteamine, the only drug available for the treatment of cystinosis in paediatric patients, is available as the hydrochloride, the bitartrate and as sodium phosphocysteamine salts. It has been suggested that cysteamine bitartrate and phosphocysteamine are better tolerated and may have a better bioavailability than cysteamine hydrochloride. This has, however, never been demonstrated. METHODS: We compared the pharmacokinetics and tolerance of these three formulations of cysteamine in 18 healthy adult male volunteers in a double-blind, latin-square, three-period, single oral dose cross-over relative bioavailability study. RESULTS: No statistical difference was found between relative bioavailabilities, AUC (0, infinity) (geometric mean and s.d. in micromol l(-1) h: 169+/-51, 158+/-46, 173+/-49 with cysteamine hydrochloride, phosphocysteamine and cysteamine bitartrate respectively), Cmax (geometric mean and s.d. in micromol l(-1); 66+/-25.5, 59+/-12, 63+/-20) and tmax (median and range in h: 0.88 (0.25-2), 1.25 (0.25-2), 0.88 (0.25-2)) with each of the three forms of cysteamine tested. Bioequivalence statistics (90% confidence intervals) showed non equivalence of Cmax of cysteamine base as the only non equivalence of pharmacokinetics between the three formulations: 90% CI for Cmax relative ratios to cysteamine hydrochloride were [75.6-105.81 for phosphocysteamine and [74.2-124.2] for cysteamine bitartrate. The only significant adverse event was vomiting whose frequency was inversely correlated with body weight (Spearman's r=-0.76, P<0.001). The nature of the salt tested did not influence vomiting. CONCLUSIONS: While none of the three forms of cysteamine tested has a clear advantage over the others in terms of pharmacokinetics and tolerance profile, this should now however be addressed in patients treated for cystinosis during repeat administrations. \n"
],
"offsets": [
[
0,
1889
]
]
}
] | [
{
"id": "69_T1",
"type": "Chemical",
"text": [
"hydrochloride",
"bitartrate",
"Cysteamine"
],
"offsets": [
[
118,
131
],
[
137,
147
],
[
6,
16
]
],
"normalized": []
},
{
"id": "69_T2",
"type": "Chemical",
"text": [
"hydrochloride"
],
"offsets": [
[
118,
131
]
],
"normalized": []
},
{
"id": "69_T4",
"type": "Chemical",
"text": [
"sodium phosphocysteamine"
],
"offsets": [
[
155,
179
]
],
"normalized": []
},
{
"id": "69_T5",
"type": "Chemical",
"text": [
"Cysteamine"
],
"offsets": [
[
6,
16
]
],
"normalized": []
},
{
"id": "69_T3",
"type": "Chemical",
"text": [
"cysteamine bitartrate"
],
"offsets": [
[
214,
235
]
],
"normalized": []
},
{
"id": "69_T6",
"type": "Chemical",
"text": [
"phosphocysteamine"
],
"offsets": [
[
241,
258
]
],
"normalized": []
},
{
"id": "69_T9",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
88,
96
]
],
"normalized": []
},
{
"id": "69_T10",
"type": "Chemical",
"text": [
"cysteamine"
],
"offsets": [
[
324,
334
]
],
"normalized": []
},
{
"id": "69_T11",
"type": "Chemical",
"text": [
"cysteamine hydrochloride"
],
"offsets": [
[
324,
348
]
],
"normalized": []
},
{
"id": "69_T12",
"type": "Chemical",
"text": [
"cysteamine"
],
"offsets": [
[
481,
491
]
],
"normalized": []
},
{
"id": "69_T13",
"type": "Species",
"text": [
"adult male volunteers"
],
"offsets": [
[
506,
527
]
],
"normalized": []
},
{
"id": "69_T14",
"type": "Chemical",
"text": [
"cysteamine hydrochloride"
],
"offsets": [
[
815,
839
]
],
"normalized": []
},
{
"id": "69_T15",
"type": "Chemical",
"text": [
"phosphocysteamine"
],
"offsets": [
[
841,
858
]
],
"normalized": []
},
{
"id": "69_T16",
"type": "Chemical",
"text": [
"cysteamine bitartrate"
],
"offsets": [
[
864,
885
]
],
"normalized": []
},
{
"id": "69_T17",
"type": "Chemical",
"text": [
"cysteamine"
],
"offsets": [
[
1089,
1099
]
],
"normalized": []
},
{
"id": "69_T18",
"type": "Chemical",
"text": [
"cysteamine"
],
"offsets": [
[
1195,
1205
]
],
"normalized": []
},
{
"id": "69_T19",
"type": "Chemical",
"text": [
"cysteamine base"
],
"offsets": [
[
1195,
1210
]
],
"normalized": []
},
{
"id": "69_T20",
"type": "Chemical",
"text": [
"cysteamine hydrochloride"
],
"offsets": [
[
1327,
1351
]
],
"normalized": []
},
{
"id": "69_T21",
"type": "Chemical",
"text": [
"phosphocysteamine"
],
"offsets": [
[
1374,
1391
]
],
"normalized": []
},
{
"id": "69_T22",
"type": "Chemical",
"text": [
"cysteamine bitartrate"
],
"offsets": [
[
1413,
1434
]
],
"normalized": []
},
{
"id": "69_T23",
"type": "Chemical",
"text": [
"cysteamine"
],
"offsets": [
[
1677,
1687
]
],
"normalized": []
},
{
"id": "69_T24",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
1825,
1833
]
],
"normalized": []
},
{
"id": "69_T7",
"type": "Chemical",
"text": [
"drug"
],
"offsets": [
[
27,
31
]
],
"normalized": []
},
{
"id": "69_T8",
"type": "Biological_Activity",
"text": [
"adverse event"
],
"offsets": [
[
1457,
1470
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "69_R1",
"type": "Associated_With",
"arg1_id": "69_T20",
"arg2_id": "69_T8",
"normalized": []
},
{
"id": "69_R2",
"type": "Associated_With",
"arg1_id": "69_T21",
"arg2_id": "69_T8",
"normalized": []
},
{
"id": "69_R3",
"type": "Associated_With",
"arg1_id": "69_T22",
"arg2_id": "69_T8",
"normalized": []
}
] |
70 | 10073910 | [
{
"id": "71",
"type": "",
"text": [
"Tyrosinaemia type I is caused by a deficiency of fumarylacetoacetate hydrolase and mainly affects the liver. This disease is characterized by the presence of a high level of succinylacetone. This metabolite has been used for prenatal diagnosis from amniotic fluid samples. One case with a normal level of succinylacetone in amniotic fluid has recently been described (Grenier et al., 1996). Here, we report that this patient is a compound heterozygote for two known mutations: E364X and IVS6-1g-->t. The low level of succinylacetone cannot be explained by these mutations. \n"
],
"offsets": [
[
0,
575
]
]
}
] | [
{
"id": "71_T2",
"type": "Protein",
"text": [
"fumarylacetoacetate hydrolase"
],
"offsets": [
[
49,
78
]
],
"normalized": []
},
{
"id": "71_T4",
"type": "Chemical",
"text": [
"succinylacetone"
],
"offsets": [
[
175,
190
]
],
"normalized": []
},
{
"id": "71_T5",
"type": "Metabolite",
"text": [
"succinylacetone"
],
"offsets": [
[
175,
190
]
],
"normalized": []
},
{
"id": "71_T6",
"type": "Metabolite",
"text": [
"succinylacetone"
],
"offsets": [
[
306,
321
]
],
"normalized": []
},
{
"id": "71_T7",
"type": "Chemical",
"text": [
"succinylacetone"
],
"offsets": [
[
306,
321
]
],
"normalized": []
},
{
"id": "71_T8",
"type": "Chemical",
"text": [
"succinylacetone"
],
"offsets": [
[
518,
533
]
],
"normalized": []
},
{
"id": "71_T1",
"type": "Metabolite",
"text": [
"succinylacetone"
],
"offsets": [
[
518,
533
]
],
"normalized": []
}
] | [] | [] | [] |
72 | 10074065 | [
{
"id": "73",
"type": "",
"text": [
"An aminotransferase which catalyzes the final step in methionine recycling from methylthioadenosine, the conversion of alpha-ketomethiobutyrate to methionine, has been purified from Klebsiella pneumoniae and characterized. The enzyme was found to be a homodimer of 45-kDa subunits, and it catalyzed methionine formation primarily using aromatic amino acids and glutamate as the amino donors. Histidine, leucine, asparagine, and arginine were also functional amino donors but to a lesser extent. The N-terminal amino acid sequence of the enzyme was determined and found to be almost identical to the N-terminal sequence of both the Escherichia coli and Salmonella typhimurium tyrosine aminotransferases (tyrB gene products). The structural gene for the tyrosine aminotransferase was cloned from K. pneumoniae and expressed in E. coli. The deduced amino acid sequence displayed 83, 80, 38, and 34% identity to the tyrosine aminotransferases from E. coli, S. typhimurium, Paracoccus denitrificans, and Rhizobium meliloti, respectively, but it showed less than 13% identity to any characterized eukaryotic tyrosine aminotransferase. Structural motifs around key invariant residues placed the K. pneumoniae enzyme within the Ia subfamily of aminotransferases. Kinetic analysis of the aminotransferase showed that reactions of an aromatic amino acid with alpha-ketomethiobutyrate and of glutamate with alpha-ketomethiobutyrate proceed as favorably as the well-known reactions of tyrosine with alpha-ketoglutarate and tyrosine with oxaloacetate normally associated with tyrosine aminotransferases. The aminotransferase was inhibited by the aminooxy compounds canaline and carboxymethoxylamine but not by substrate analogues, such as nitrotyrosine or nitrophenylalanine. \n"
],
"offsets": [
[
0,
1767
]
]
}
] | [
{
"id": "73_T1",
"type": "Protein",
"text": [
"aminotransferase"
],
"offsets": [
[
3,
19
]
],
"normalized": []
},
{
"id": "73_T2",
"type": "Chemical",
"text": [
"methionine"
],
"offsets": [
[
54,
64
]
],
"normalized": []
},
{
"id": "73_T3",
"type": "Chemical",
"text": [
"methylthioadenosine"
],
"offsets": [
[
80,
99
]
],
"normalized": []
},
{
"id": "73_T4",
"type": "Chemical",
"text": [
"alpha-ketomethiobutyrate"
],
"offsets": [
[
119,
143
]
],
"normalized": []
},
{
"id": "73_T5",
"type": "Metabolite",
"text": [
"methionine"
],
"offsets": [
[
54,
64
]
],
"normalized": []
},
{
"id": "73_T6",
"type": "Metabolite",
"text": [
"methylthioadenosine"
],
"offsets": [
[
80,
99
]
],
"normalized": []
},
{
"id": "73_T7",
"type": "Metabolite",
"text": [
"alpha-ketomethiobutyrate"
],
"offsets": [
[
119,
143
]
],
"normalized": []
},
{
"id": "73_T8",
"type": "Chemical",
"text": [
"methionine"
],
"offsets": [
[
147,
157
]
],
"normalized": []
},
{
"id": "73_T9",
"type": "Metabolite",
"text": [
"methionine"
],
"offsets": [
[
147,
157
]
],
"normalized": []
},
{
"id": "73_T10",
"type": "Species",
"text": [
"Klebsiella pneumoniae"
],
"offsets": [
[
182,
203
]
],
"normalized": []
},
{
"id": "73_T11",
"type": "Protein",
"text": [
"enzyme"
],
"offsets": [
[
227,
233
]
],
"normalized": []
},
{
"id": "73_T12",
"type": "Chemical",
"text": [
"aromatic amino acids"
],
"offsets": [
[
336,
356
]
],
"normalized": []
},
{
"id": "73_T13",
"type": "Chemical",
"text": [
"glutamate"
],
"offsets": [
[
361,
370
]
],
"normalized": []
},
{
"id": "73_T14",
"type": "Chemical",
"text": [
"methionine"
],
"offsets": [
[
299,
309
]
],
"normalized": []
},
{
"id": "73_T15",
"type": "Metabolite",
"text": [
"methionine"
],
"offsets": [
[
299,
309
]
],
"normalized": []
},
{
"id": "73_T16",
"type": "Chemical",
"text": [
"Histidine"
],
"offsets": [
[
392,
401
]
],
"normalized": []
},
{
"id": "73_T17",
"type": "Chemical",
"text": [
"leucine"
],
"offsets": [
[
403,
410
]
],
"normalized": []
},
{
"id": "73_T18",
"type": "Chemical",
"text": [
"asparagine"
],
"offsets": [
[
412,
422
]
],
"normalized": []
},
{
"id": "73_T19",
"type": "Chemical",
"text": [
"arginine"
],
"offsets": [
[
428,
436
]
],
"normalized": []
},
{
"id": "73_T20",
"type": "Species",
"text": [
"Escherichia coli"
],
"offsets": [
[
631,
647
]
],
"normalized": []
},
{
"id": "73_T21",
"type": "Species",
"text": [
"Salmonella typhimurium"
],
"offsets": [
[
652,
674
]
],
"normalized": []
},
{
"id": "73_T22",
"type": "Protein",
"text": [
"tyrosine aminotransferases"
],
"offsets": [
[
675,
701
]
],
"normalized": []
},
{
"id": "73_T23",
"type": "Protein",
"text": [
"tyrosine aminotransferase"
],
"offsets": [
[
753,
778
]
],
"normalized": []
},
{
"id": "73_T24",
"type": "Species",
"text": [
"K. pneumoniae"
],
"offsets": [
[
796,
809
]
],
"normalized": []
},
{
"id": "73_T25",
"type": "Species",
"text": [
"E. coli"
],
"offsets": [
[
827,
834
]
],
"normalized": []
},
{
"id": "73_T26",
"type": "Protein",
"text": [
"tyrosine aminotransferase"
],
"offsets": [
[
914,
939
]
],
"normalized": []
},
{
"id": "73_T27",
"type": "Species",
"text": [
"E. coli"
],
"offsets": [
[
946,
954
]
],
"normalized": []
},
{
"id": "73_T28",
"type": "Species",
"text": [
"S. typhimurium"
],
"offsets": [
[
956,
970
]
],
"normalized": []
},
{
"id": "73_T29",
"type": "Species",
"text": [
"Paracoccus denitrificans"
],
"offsets": [
[
972,
996
]
],
"normalized": []
},
{
"id": "73_T30",
"type": "Species",
"text": [
"Rhizobium meliloti"
],
"offsets": [
[
1002,
1020
]
],
"normalized": []
},
{
"id": "73_T31",
"type": "Protein",
"text": [
"tyrosine aminotransferase"
],
"offsets": [
[
1105,
1130
]
],
"normalized": []
},
{
"id": "73_T32",
"type": "Species",
"text": [
"K. pneumoniae"
],
"offsets": [
[
1191,
1204
]
],
"normalized": []
},
{
"id": "73_T33",
"type": "Protein",
"text": [
"enzyme"
],
"offsets": [
[
1205,
1211
]
],
"normalized": []
},
{
"id": "73_T34",
"type": "Protein",
"text": [
"aminotransferases"
],
"offsets": [
[
1239,
1256
]
],
"normalized": []
},
{
"id": "73_T35",
"type": "Protein",
"text": [
"aminotransferase"
],
"offsets": [
[
1282,
1298
]
],
"normalized": []
},
{
"id": "73_T36",
"type": "Chemical",
"text": [
"aromatic amino acid"
],
"offsets": [
[
1327,
1346
]
],
"normalized": []
},
{
"id": "73_T37",
"type": "Chemical",
"text": [
"alpha-ketomethiobutyrate"
],
"offsets": [
[
1352,
1376
]
],
"normalized": []
},
{
"id": "73_T38",
"type": "Chemical",
"text": [
"glutamate"
],
"offsets": [
[
1384,
1393
]
],
"normalized": []
},
{
"id": "73_T39",
"type": "Chemical",
"text": [
"alpha-ketomethiobutyrate"
],
"offsets": [
[
1399,
1423
]
],
"normalized": []
},
{
"id": "73_T40",
"type": "Chemical",
"text": [
"tyrosine"
],
"offsets": [
[
1476,
1484
]
],
"normalized": []
},
{
"id": "73_T41",
"type": "Chemical",
"text": [
"alpha-ketoglutarate"
],
"offsets": [
[
1490,
1509
]
],
"normalized": []
},
{
"id": "73_T42",
"type": "Chemical",
"text": [
"tyrosine"
],
"offsets": [
[
1514,
1522
]
],
"normalized": []
},
{
"id": "73_T43",
"type": "Chemical",
"text": [
"oxaloacetate"
],
"offsets": [
[
1528,
1540
]
],
"normalized": []
},
{
"id": "73_T44",
"type": "Protein",
"text": [
"tyrosine aminotransferase"
],
"offsets": [
[
1566,
1591
]
],
"normalized": []
},
{
"id": "73_T45",
"type": "Protein",
"text": [
"aminotransferase"
],
"offsets": [
[
1598,
1614
]
],
"normalized": []
},
{
"id": "73_T46",
"type": "Chemical",
"text": [
"canaline"
],
"offsets": [
[
1655,
1663
]
],
"normalized": []
},
{
"id": "73_T47",
"type": "Chemical",
"text": [
"carboxymethoxylamine"
],
"offsets": [
[
1668,
1688
]
],
"normalized": []
},
{
"id": "73_T48",
"type": "Chemical",
"text": [
"nitrotyrosine"
],
"offsets": [
[
1729,
1742
]
],
"normalized": []
},
{
"id": "73_T49",
"type": "Chemical",
"text": [
"nitrophenylalanine"
],
"offsets": [
[
1746,
1764
]
],
"normalized": []
},
{
"id": "73_T51",
"type": "Chemical",
"text": [
"aminooxy compound"
],
"offsets": [
[
1636,
1653
]
],
"normalized": []
},
{
"id": "73_T52",
"type": "Biological_Activity",
"text": [
"inhibited"
],
"offsets": [
[
1619,
1628
]
],
"normalized": []
},
{
"id": "73_T50",
"type": "Chemical",
"text": [
"N-terminal amino acid"
],
"offsets": [
[
499,
520
]
],
"normalized": []
},
{
"id": "73_T55",
"type": "Protein",
"text": [
"enzyme"
],
"offsets": [
[
537,
543
]
],
"normalized": []
},
{
"id": "73_T54",
"type": "Chemical",
"text": [
"amino acid"
],
"offsets": [
[
848,
858
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "73_R1",
"type": "Associated_With",
"arg1_id": "73_T46",
"arg2_id": "73_T52",
"normalized": []
},
{
"id": "73_R2",
"type": "Associated_With",
"arg1_id": "73_T47",
"arg2_id": "73_T52",
"normalized": []
},
{
"id": "73_R3",
"type": "Metabolite_Of",
"arg1_id": "73_T9",
"arg2_id": "73_T4",
"normalized": []
},
{
"id": "73_R4",
"type": "Metabolite_Of",
"arg1_id": "73_T7",
"arg2_id": "73_T3",
"normalized": []
},
{
"id": "73_R7",
"type": "Binds_With",
"arg1_id": "73_T46",
"arg2_id": "73_T45",
"normalized": []
},
{
"id": "73_R8",
"type": "Binds_With",
"arg1_id": "73_T47",
"arg2_id": "73_T45",
"normalized": []
}
] |
74 | 10075107 | [
{
"id": "75",
"type": "",
"text": [
"Both alpha- and beta-D-glucose pentaacetate (1.7 mM each) augmented, to almost the same extent, insulin release caused by succinic acid dimethyl ester (10.0 mM) in rat pancreatic islets. The secretory response to these hexose esters largely exceeded that evoked by unesterified D-glucose tested at the same concentration (1.7 mM). The release of insulin provoked by succinic acid dimethyl ester was inhibited, however, by alpha-D-galactose pentaacetate, whilst being unaffected by beta-D-galactose pentaacetate (each also 1.7 mM). It appears, therefore, that the insulinotropic action of hexose esters is not attributable solely to the catabolism of their carbohydrate moiety, but may also involve a receptor system that displays anomeric specificity and can be directly activated or inhibited by the esters themselves. Hence, it is proposed that selected esters of non-nutrient monosaccharides may represent new tools to either stimulate insulin release in diabetes or prevent excessive hormonal secretion in situations of hyperinsulinemia. \n"
],
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0,
1044
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5,
10
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16,
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122,
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"id": "75_T5",
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164,
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"id": "75_T6",
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219,
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"id": "75_T7",
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278,
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"id": "75_T9",
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366,
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"id": "75_T10",
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"id": "75_T11",
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481,
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"id": "75_T12",
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563,
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"id": "75_T13",
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"id": "75_T14",
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656,
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"id": "75_T15",
"type": "Chemical",
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880,
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"id": "75_T16",
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940,
955
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"id": "75_T18",
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96,
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"id": "75_T20",
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588,
601
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"id": "75_T21",
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857,
895
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{
"id": "75_T3",
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802,
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"id": "75_T8",
"type": "Biological_Activity",
"text": [
"inhibited"
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399,
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}
] | [] | [] | [
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"id": "75_R1",
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"id": "75_R3",
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"id": "75_R7",
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"id": "75_R9",
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}
] |
76 | 10075120 | [
{
"id": "77",
"type": "",
"text": [
"Bioassay-directed fractionation of the methanolic extract of seeds of Casimiroa edulis led to the isolation of seven constituents with cardiovascular activity, namely the new compound synephrine acetonide and the known compounds N-monomethylhistamine, N,N-dimethylhistamine, proline, N-methylproline, gamma-aminobutyric acid and casimiroedine. In anesthetized rats, both histamine derivatives produced transient hypotension mediated via H1-histaminergic receptors and in the case of N,N-dimethylhistamine, via nitric oxide release. Synephrine acetonide produced transient hypertension and tachycardia, mediated via alpha- and alpha- and beta-adrenergic receptores, respectively. The chromatographic zone containing N-methyproline, proline and gamma-aminobutyric acid elicited marked and prolonged hypotension. Finally, casimiroedine did not modify the blood pressure of anesthetized rats, but lowered it persistently in anesthetized guinea pigs. It was concluded that hypotension produced by C. edulis is due to several active components. The immediate effect can be attributed to the histamine derivatives acting on H1-receptors. More prolonged hypotension would be produced by the mixture of amino acids through an unknown mechanism, as well as by casimiroedine, possibly by activation of H3-receptors. Hypotension is partially offset by synephrine acetonide through adrenergic mechanisms. \n"
],
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0,
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229,
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275,
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284,
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301,
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329,
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371,
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"id": "77_T25",
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"N,N-dimethylhistamine"
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483,
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743,
766
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{
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[
819,
832
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],
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{
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"casimiroedine"
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819,
832
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883,
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933,
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] |
78 | 10075742 | [
{
"id": "79",
"type": "",
"text": [
"Fractionation of cube resin from Lonchocarpus utilus and L. urucu roots led to the isolation and identification of 11 minor flavonoids and stilbenes containing the gem-dimethylpyran moiety or a dihydrodiol derivative thereof. The eight new compounds were as follows: the isoflavonoid cis-4'',5''-dihydro-4'',5' '-dihydroxylonchocarpusone (2); four (2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanones with substituents of 5-hydroxy-3',4'-dimethoxy (3), 5, 3'-dihydroxy-4'-methoxy (4), 5,4'-dihydroxy-3'-methoxy (5), and 3', 4'-dimethoxy (6); and three 6'',6''-dimethylpyran[2'',3'':3', 4']stilbenes with 4-hydroxy-5'-methoxy (9), 3,5'-dimethoxy-4-hydroxy (10) and 3,4,5-trimethoxy (11) substitution patterns. Structure-activity relationships for inhibition of NADH:ubiquinone oxidoreductase activity (bovine heart electron transport particles) and phorbol ester-induced ornithine decarboxylase activity (cultured MCF-7 cells) generally parallel those for cytotoxicity (MCF-7 and Hepa 1clc7 cells). \n"
],
"offsets": [
[
0,
1030
]
]
}
] | [
{
"id": "79_T1",
"type": "Species",
"text": [
"Lonchocarpus utilus"
],
"offsets": [
[
33,
52
]
],
"normalized": []
},
{
"id": "79_T2",
"type": "Species",
"text": [
"L. urucu"
],
"offsets": [
[
57,
65
]
],
"normalized": []
},
{
"id": "79_T3",
"type": "Chemical",
"text": [
"flavonoids"
],
"offsets": [
[
124,
134
]
],
"normalized": []
},
{
"id": "79_T4",
"type": "Chemical",
"text": [
"stilbenes"
],
"offsets": [
[
139,
148
]
],
"normalized": []
},
{
"id": "79_T5",
"type": "Chemical",
"text": [
"gem-dimethylpyran"
],
"offsets": [
[
165,
182
]
],
"normalized": []
},
{
"id": "79_T6",
"type": "Chemical",
"text": [
"gem-dimethylpyran moiety or a dihydrodiol derivative"
],
"offsets": [
[
165,
217
]
],
"normalized": []
},
{
"id": "79_T7",
"type": "Chemical",
"text": [
"isoflavonoid"
],
"offsets": [
[
272,
284
]
],
"normalized": []
},
{
"id": "79_T8",
"type": "Chemical",
"text": [
"cis-4'',5''-dihydro-4'',5' '-dihydroxylonchocarpusone"
],
"offsets": [
[
285,
338
]
],
"normalized": []
},
{
"id": "79_T9",
"type": "Metabolite",
"text": [
"cis-4'',5''-dihydro-4'',5' '-dihydroxylonchocarpusone"
],
"offsets": [
[
285,
338
]
],
"normalized": []
},
{
"id": "79_T11",
"type": "Metabolite",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"5-hydroxy-3',4'-dimethoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
452,
477
]
],
"normalized": []
},
{
"id": "79_T14",
"type": "Chemical",
"text": [
"NADH"
],
"offsets": [
[
790,
794
]
],
"normalized": []
},
{
"id": "79_T15",
"type": "Chemical",
"text": [
"ubiquinone"
],
"offsets": [
[
795,
805
]
],
"normalized": []
},
{
"id": "79_T16",
"type": "Protein",
"text": [
"NADH:ubiquinone oxidoreductase"
],
"offsets": [
[
790,
820
]
],
"normalized": []
},
{
"id": "79_T17",
"type": "Biological_Activity",
"text": [
"oxidoreductase"
],
"offsets": [
[
806,
820
]
],
"normalized": []
},
{
"id": "79_T19",
"type": "Chemical",
"text": [
"phorbol ester"
],
"offsets": [
[
878,
891
]
],
"normalized": []
},
{
"id": "79_T20",
"type": "Chemical",
"text": [
"ornithine"
],
"offsets": [
[
900,
909
]
],
"normalized": []
},
{
"id": "79_T21",
"type": "Protein",
"text": [
"ornithine decarboxylase"
],
"offsets": [
[
900,
923
]
],
"normalized": []
},
{
"id": "79_T23",
"type": "Biological_Activity",
"text": [
"inhibition"
],
"offsets": [
[
776,
786
]
],
"normalized": []
},
{
"id": "79_T24",
"type": "Biological_Activity",
"text": [
"cytotoxicity"
],
"offsets": [
[
986,
998
]
],
"normalized": []
},
{
"id": "79_T25",
"type": "Species",
"text": [
"bovine"
],
"offsets": [
[
831,
837
]
],
"normalized": []
},
{
"id": "79_T26",
"type": "Species",
"text": [
"MCF-7 cells"
],
"offsets": [
[
943,
954
]
],
"normalized": []
},
{
"id": "79_T27",
"type": "Species",
"text": [
"Hepa 1clc7"
],
"offsets": [
[
1010,
1020
]
],
"normalized": []
},
{
"id": "79_T28",
"type": "Species",
"text": [
"MCF-7"
],
"offsets": [
[
1000,
1005
]
],
"normalized": []
},
{
"id": "79_T29",
"type": "Metabolite",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"5, 3'-dihydroxy-4'-methoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
483,
509
]
],
"normalized": []
},
{
"id": "79_T30",
"type": "Metabolite",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"5,4'-dihydroxy-3'-methoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
515,
540
]
],
"normalized": []
},
{
"id": "79_T31",
"type": "Metabolite",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"3', 4'-dimethoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
550,
566
]
],
"normalized": []
},
{
"id": "79_T32",
"type": "Chemical",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"5-hydroxy-3',4'-dimethoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
452,
477
]
],
"normalized": []
},
{
"id": "79_T33",
"type": "Chemical",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"5, 3'-dihydroxy-4'-methoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
483,
509
]
],
"normalized": []
},
{
"id": "79_T34",
"type": "Chemical",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"5,4'-dihydroxy-3'-methoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
515,
540
]
],
"normalized": []
},
{
"id": "79_T35",
"type": "Chemical",
"text": [
"(2S)-6-(gamma, gamma-dimethylallyl)-6'',6''-dimethylpyran[2'',3'':7, 8]flavanone",
"with substituents of",
"3', 4'-dimethoxy"
],
"offsets": [
[
349,
429
],
[
431,
451
],
[
550,
566
]
],
"normalized": []
},
{
"id": "79_T10",
"type": "Metabolite",
"text": [
"6'',6''-dimethylpyran[2'',3'':3', 4']stilbene",
"with 4-hydroxy-5'-methoxy",
"substitution"
],
"offsets": [
[
582,
627
],
[
629,
654
],
[
716,
728
]
],
"normalized": []
},
{
"id": "79_T12",
"type": "Metabolite",
"text": [
"6'',6''-dimethylpyran[2'',3'':3', 4']stilbene",
"with",
"3,5'-dimethoxy-4-hydroxy",
"substitution"
],
"offsets": [
[
582,
627
],
[
629,
633
],
[
660,
684
],
[
716,
728
]
],
"normalized": []
},
{
"id": "79_T13",
"type": "Metabolite",
"text": [
"6'',6''-dimethylpyran[2'',3'':3', 4']stilbene",
"with",
"3,4,5-trimethoxy",
"substitution"
],
"offsets": [
[
582,
627
],
[
629,
633
],
[
694,
710
],
[
716,
728
]
],
"normalized": []
},
{
"id": "79_T36",
"type": "Chemical",
"text": [
"6'',6''-dimethylpyran[2'',3'':3', 4']stilbene",
"with 4-hydroxy-5'-methoxy",
"substitution"
],
"offsets": [
[
582,
627
],
[
629,
654
],
[
716,
728
]
],
"normalized": []
},
{
"id": "79_T37",
"type": "Chemical",
"text": [
"6'',6''-dimethylpyran[2'',3'':3', 4']stilbene",
"with",
"3,5'-dimethoxy-4-hydroxy",
"substitution"
],
"offsets": [
[
582,
627
],
[
629,
633
],
[
660,
684
],
[
716,
728
]
],
"normalized": []
},
{
"id": "79_T38",
"type": "Chemical",
"text": [
"6'',6''-dimethylpyran[2'',3'':3', 4']stilbene",
"with",
"3,4,5-trimethoxy",
"substitution"
],
"offsets": [
[
582,
627
],
[
629,
633
],
[
694,
710
],
[
716,
728
]
],
"normalized": []
},
{
"id": "79_T18",
"type": "Biological_Activity",
"text": [
"decarboxylase"
],
"offsets": [
[
910,
923
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "79_R1",
"type": "Isolated_From",
"arg1_id": "79_T9",
"arg2_id": "79_T1",
"normalized": []
},
{
"id": "79_R2",
"type": "Isolated_From",
"arg1_id": "79_T11",
"arg2_id": "79_T1",
"normalized": []
},
{
"id": "79_R3",
"type": "Isolated_From",
"arg1_id": "79_T29",
"arg2_id": "79_T1",
"normalized": []
},
{
"id": "79_R4",
"type": "Isolated_From",
"arg1_id": "79_T30",
"arg2_id": "79_T1",
"normalized": []
},
{
"id": "79_R5",
"type": "Isolated_From",
"arg1_id": "79_T31",
"arg2_id": "79_T1",
"normalized": []
},
{
"id": "79_R6",
"type": "Isolated_From",
"arg1_id": "79_T10",
"arg2_id": "79_T1",
"normalized": []
},
{
"id": "79_R7",
"type": "Isolated_From",
"arg1_id": "79_T13",
"arg2_id": "79_T1",
"normalized": []
},
{
"id": "79_R8",
"type": "Isolated_From",
"arg1_id": "79_T12",
"arg2_id": "79_T1",
"normalized": []
}
] |
80 | 10075756 | [
{
"id": "81",
"type": "",
"text": [
"Three novel triterpene alcohols, camelliols A (1), B (3), and C (5), possessing a mono-, bi-, and tricyclic ring system, respectively, have been isolated, along with achilleol A, a known monocyclic triterpene alcohol, from the nonsaponifiable lipids of sasanqua oil (Camellia sasanqua). The structures of these new alcohols were determined on the basis of spectroscopic methods. \n"
],
"offsets": [
[
0,
381
]
]
}
] | [
{
"id": "81_T1",
"type": "Chemical",
"text": [
"triterpene"
],
"offsets": [
[
12,
22
]
],
"normalized": []
},
{
"id": "81_T2",
"type": "Chemical",
"text": [
"alcohols"
],
"offsets": [
[
23,
31
]
],
"normalized": []
},
{
"id": "81_T4",
"type": "Metabolite",
"text": [
"camelliol",
"A"
],
"offsets": [
[
33,
42
],
[
44,
45
]
],
"normalized": []
},
{
"id": "81_T9",
"type": "Metabolite",
"text": [
"achilleol A"
],
"offsets": [
[
166,
177
]
],
"normalized": []
},
{
"id": "81_T10",
"type": "Chemical",
"text": [
"achilleol A"
],
"offsets": [
[
166,
177
]
],
"normalized": []
},
{
"id": "81_T11",
"type": "Chemical",
"text": [
"monocyclic triterpene alcohol"
],
"offsets": [
[
187,
216
]
],
"normalized": []
},
{
"id": "81_T12",
"type": "Chemical",
"text": [
"triterpene alcohol"
],
"offsets": [
[
198,
216
]
],
"normalized": []
},
{
"id": "81_T13",
"type": "Chemical",
"text": [
"nonsaponifiable lipid"
],
"offsets": [
[
227,
248
]
],
"normalized": []
},
{
"id": "81_T14",
"type": "Chemical",
"text": [
"sasanqua oil"
],
"offsets": [
[
253,
265
]
],
"normalized": []
},
{
"id": "81_T15",
"type": "Species",
"text": [
"Camellia sasanqua"
],
"offsets": [
[
267,
284
]
],
"normalized": []
},
{
"id": "81_T16",
"type": "Spectral_Data",
"text": [
"spectroscopic methods"
],
"offsets": [
[
357,
378
]
],
"normalized": []
},
{
"id": "81_T17",
"type": "Chemical",
"text": [
"triterpene alcohols"
],
"offsets": [
[
12,
31
]
],
"normalized": []
},
{
"id": "81_T18",
"type": "Chemical",
"text": [
"camelliol",
"B"
],
"offsets": [
[
33,
42
],
[
51,
52
]
],
"normalized": []
},
{
"id": "81_T19",
"type": "Chemical",
"text": [
"camelliol",
"C"
],
"offsets": [
[
33,
42
],
[
62,
63
]
],
"normalized": []
},
{
"id": "81_T20",
"type": "Chemical",
"text": [
"camelliol",
"A"
],
"offsets": [
[
33,
42
],
[
44,
45
]
],
"normalized": []
},
{
"id": "81_T3",
"type": "Metabolite",
"text": [
"camelliol",
"B"
],
"offsets": [
[
33,
42
],
[
51,
52
]
],
"normalized": []
},
{
"id": "81_T21",
"type": "Metabolite",
"text": [
"camelliol",
"C"
],
"offsets": [
[
33,
42
],
[
62,
63
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "81_R2",
"type": "Isolated_From",
"arg1_id": "81_T9",
"arg2_id": "81_T15",
"normalized": []
},
{
"id": "81_R1",
"type": "Isolated_From",
"arg1_id": "81_T21",
"arg2_id": "81_T15",
"normalized": []
},
{
"id": "81_R3",
"type": "Isolated_From",
"arg1_id": "81_T3",
"arg2_id": "81_T15",
"normalized": []
},
{
"id": "81_R4",
"type": "Isolated_From",
"arg1_id": "81_T4",
"arg2_id": "81_T15",
"normalized": []
},
{
"id": "81_R5",
"type": "Associated_With",
"arg1_id": "81_T4",
"arg2_id": "81_T16",
"normalized": []
},
{
"id": "81_R6",
"type": "Associated_With",
"arg1_id": "81_T3",
"arg2_id": "81_T16",
"normalized": []
},
{
"id": "81_R7",
"type": "Associated_With",
"arg1_id": "81_T21",
"arg2_id": "81_T16",
"normalized": []
},
{
"id": "81_R8",
"type": "Associated_With",
"arg1_id": "81_T18",
"arg2_id": "81_T16",
"normalized": []
},
{
"id": "81_R9",
"type": "Associated_With",
"arg1_id": "81_T19",
"arg2_id": "81_T16",
"normalized": []
},
{
"id": "81_R10",
"type": "Associated_With",
"arg1_id": "81_T20",
"arg2_id": "81_T16",
"normalized": []
}
] |
82 | 10075761 | [
{
"id": "83",
"type": "",
"text": [
"Chemical investigation of the sponge Spongia matamata collected in Yap, Micronesia, has resulted in the isolation of six new spongian diterpenoids, 2-7, along with the known compound, spongia-13(16), 14-dien-19-oic acid (1). The structures were determined by spectroscopic methods. \n"
],
"offsets": [
[
0,
284
]
]
}
] | [
{
"id": "83_T1",
"type": "Species",
"text": [
"Spongia matamata"
],
"offsets": [
[
37,
53
]
],
"normalized": []
},
{
"id": "83_T2",
"type": "Metabolite",
"text": [
"spongian diterpenoids"
],
"offsets": [
[
125,
146
]
],
"normalized": []
},
{
"id": "83_T4",
"type": "Chemical",
"text": [
"spongia-13(16), 14-dien-19-oic acid"
],
"offsets": [
[
185,
220
]
],
"normalized": []
},
{
"id": "83_T5",
"type": "Metabolite",
"text": [
"spongia-13(16), 14-dien-19-oic acid"
],
"offsets": [
[
185,
220
]
],
"normalized": []
},
{
"id": "83_T6",
"type": "Spectral_Data",
"text": [
"spectroscopic methods"
],
"offsets": [
[
260,
281
]
],
"normalized": []
},
{
"id": "83_T7",
"type": "Chemical",
"text": [
"spongian diterpenoids"
],
"offsets": [
[
125,
146
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "83_R1",
"type": "Isolated_From",
"arg1_id": "83_T2",
"arg2_id": "83_T1",
"normalized": []
},
{
"id": "83_R2",
"type": "Isolated_From",
"arg1_id": "83_T5",
"arg2_id": "83_T1",
"normalized": []
},
{
"id": "83_R3",
"type": "Associated_With",
"arg1_id": "83_T2",
"arg2_id": "83_T6",
"normalized": []
},
{
"id": "83_R4",
"type": "Associated_With",
"arg1_id": "83_T5",
"arg2_id": "83_T6",
"normalized": []
},
{
"id": "83_R6",
"type": "Associated_With",
"arg1_id": "83_T4",
"arg2_id": "83_T6",
"normalized": []
},
{
"id": "83_R7",
"type": "Associated_With",
"arg1_id": "83_T7",
"arg2_id": "83_T6",
"normalized": []
}
] |
84 | 10075776 | [
{
"id": "85",
"type": "",
"text": [
"A new natural product, 4-epifriedelin (1), and 12 known terpenoids have been isolated from the leaves of Syzygium formosanum. The known compounds include caryophyllene oxide, friedelin, canophyllal, glutinol, alpha-terpineol, phytol, betulinic acid, uvaol, lupeol, betulin, ursolic acid, and oleanolic acid. All of these compounds are reported for the first time from S. formosanum. \n"
],
"offsets": [
[
0,
385
]
]
}
] | [
{
"id": "85_T1",
"type": "Chemical",
"text": [
"4-epifriedelin"
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23,
37
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"id": "85_T2",
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"4-epifriedelin"
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23,
37
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"id": "85_T3",
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"terpenoids"
],
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56,
66
]
],
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},
{
"id": "85_T4",
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"terpenoids"
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56,
66
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{
"id": "85_T5",
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"Syzygium formosanum"
],
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105,
124
]
],
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},
{
"id": "85_T6",
"type": "Chemical",
"text": [
"caryophyllene oxide"
],
"offsets": [
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154,
173
]
],
"normalized": []
},
{
"id": "85_T7",
"type": "Metabolite",
"text": [
"caryophyllene oxide"
],
"offsets": [
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154,
173
]
],
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},
{
"id": "85_T8",
"type": "Metabolite",
"text": [
"friedelin"
],
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175,
184
]
],
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},
{
"id": "85_T9",
"type": "Chemical",
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"friedelin"
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175,
184
]
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{
"id": "85_T10",
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"canophyllal"
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186,
197
]
],
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},
{
"id": "85_T11",
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"canophyllal"
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186,
197
]
],
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},
{
"id": "85_T12",
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"glutinol"
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199,
207
]
],
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},
{
"id": "85_T13",
"type": "Chemical",
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"alpha-terpineol"
],
"offsets": [
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209,
224
]
],
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},
{
"id": "85_T14",
"type": "Metabolite",
"text": [
"alpha-terpineol"
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209,
224
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"id": "85_T15",
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"glutinol"
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199,
207
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"id": "85_T16",
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"phytol"
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226,
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"phytol"
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226,
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"id": "85_T18",
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"betulinic acid"
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"id": "85_T19",
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"uvaol"
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255
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"id": "85_T21",
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"uvaol"
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250,
255
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"id": "85_T22",
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"lupeol"
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257,
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"id": "85_T23",
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"lupeol"
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257,
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"id": "85_T24",
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265,
272
]
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{
"id": "85_T25",
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"betulin"
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265,
272
]
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},
{
"id": "85_T26",
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274,
286
]
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{
"id": "85_T27",
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"ursolic acid"
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274,
286
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},
{
"id": "85_T28",
"type": "Metabolite",
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"oleanolic acid"
],
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292,
306
]
],
"normalized": []
},
{
"id": "85_T29",
"type": "Chemical",
"text": [
"oleanolic acid"
],
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292,
306
]
],
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},
{
"id": "85_T30",
"type": "Species",
"text": [
"S. formosanum"
],
"offsets": [
[
369,
382
]
],
"normalized": []
}
] | [] | [] | [
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},
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"id": "85_R7",
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},
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"id": "85_R8",
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},
{
"id": "85_R9",
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},
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"id": "85_R10",
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},
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"id": "85_R11",
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"id": "85_R12",
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},
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"id": "85_R13",
"type": "Isolated_From",
"arg1_id": "85_T28",
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"normalized": []
}
] |
86 | 10075778 | [
{
"id": "87",
"type": "",
"text": [
"Two new jaspamide derivatives (1 and 2) along with jaspamide have been isolated from the marine sponge Jaspis splendans collected in Vanuatu. Their chemical structures were determined from 1D and 2D NMR studies and MS data. These two compounds inhibited the in vitro growth of the NSCLC-N6 human tumor cell lines with IC50 values in the microg/mL range. \n"
],
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0,
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]
}
] | [
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8,
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31,
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8,
28
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],
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"jaspamide"
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51,
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"id": "87_T4",
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51,
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"id": "87_T5",
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"id": "87_T6",
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]
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"id": "87_T7",
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"MS data"
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215,
222
]
],
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},
{
"id": "87_T8",
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"inhibited"
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244,
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]
],
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37,
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8,
28
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],
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"id": "87_T10",
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"1",
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31,
32
],
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8,
28
]
],
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}
] | [] | [] | [
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},
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},
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"id": "87_R6",
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},
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"id": "87_R7",
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"arg2_id": "87_T6",
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},
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"id": "87_R8",
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},
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"id": "87_R2",
"type": "Associated_With",
"arg1_id": "87_T10",
"arg2_id": "87_T8",
"normalized": []
}
] |
88 | 10075788 | [
{
"id": "89",
"type": "",
"text": [
"Reinvestigation of fractions derived from large-scale fractionation of Maytenus buchananii led to the isolation of two new maytansinoids. The structures of these principles were determined using electrospray MS, 1H NMR, 13C NMR, and 2D NMR techniques. One principle was found to be 2'-N-demethylmaytanbutine (2), while the other was found to be maytanbicyclinol (3), the first maytansinoid with two macrocyclic rings to be isolated from a Maytenus species. \n"
],
"offsets": [
[
0,
458
]
]
}
] | [
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],
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],
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],
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},
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345,
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],
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],
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},
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"id": "89_T9",
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"text": [
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439,
447
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],
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"type": "Spectral_Data",
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],
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"id": "89_T13",
"type": "Spectral_Data",
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"13C NMR"
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220,
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],
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},
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"id": "89_T14",
"type": "Spectral_Data",
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"2D NMR"
],
"offsets": [
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233,
239
]
],
"normalized": []
},
{
"id": "89_T15",
"type": "Chemical",
"text": [
"macrocyclic"
],
"offsets": [
[
399,
410
]
],
"normalized": []
}
] | [] | [] | [
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},
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},
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},
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"arg2_id": "89_T3",
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},
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"id": "89_R11",
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"arg2_id": "89_T12",
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},
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"arg2_id": "89_T13",
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},
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},
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"id": "89_R9",
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"arg1_id": "89_T7",
"arg2_id": "89_T14",
"normalized": []
},
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"id": "89_R10",
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"arg1_id": "89_T6",
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"normalized": []
},
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"id": "89_R13",
"type": "Associated_With",
"arg1_id": "89_T4",
"arg2_id": "89_T3",
"normalized": []
},
{
"id": "89_R14",
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"arg2_id": "89_T3",
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},
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"id": "89_R15",
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"arg1_id": "89_T4",
"arg2_id": "89_T12",
"normalized": []
},
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"id": "89_R16",
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"arg2_id": "89_T12",
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},
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"id": "89_R17",
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"arg2_id": "89_T13",
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},
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},
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"id": "89_R19",
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"arg1_id": "89_T4",
"arg2_id": "89_T14",
"normalized": []
},
{
"id": "89_R20",
"type": "Associated_With",
"arg1_id": "89_T5",
"arg2_id": "89_T14",
"normalized": []
}
] |
90 | 10075791 | [
{
"id": "91",
"type": "",
"text": [
"7-Epiclusianone, isolated from Rheedia gardneriana, was tested in several biological assays. It was active in vitro against trypomastigotes of Trypanosoma cruzi but inactive in vivo in experimentally infected mice. It was also active against Artemia salina, but inactive against the fungus Cladosporium sphaerospermum and the snail Biomphalaria glabrata. \n"
],
"offsets": [
[
0,
357
]
]
}
] | [
{
"id": "91_T1",
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"text": [
"7-Epiclusianone"
],
"offsets": [
[
0,
15
]
],
"normalized": []
},
{
"id": "91_T2",
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"text": [
"7-Epiclusianone"
],
"offsets": [
[
0,
15
]
],
"normalized": []
},
{
"id": "91_T3",
"type": "Species",
"text": [
"Rheedia gardneriana"
],
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31,
50
]
],
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},
{
"id": "91_T4",
"type": "Species",
"text": [
"Trypanosoma cruzi"
],
"offsets": [
[
143,
161
]
],
"normalized": []
},
{
"id": "91_T5",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
210,
214
]
],
"normalized": []
},
{
"id": "91_T6",
"type": "Species",
"text": [
"Artemia salina"
],
"offsets": [
[
243,
257
]
],
"normalized": []
},
{
"id": "91_T7",
"type": "Species",
"text": [
"Cladosporium sphaerospermum"
],
"offsets": [
[
291,
318
]
],
"normalized": []
},
{
"id": "91_T8",
"type": "Species",
"text": [
"Biomphalaria glabrata"
],
"offsets": [
[
333,
354
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "91_R1",
"type": "Isolated_From",
"arg1_id": "91_T1",
"arg2_id": "91_T3",
"normalized": []
}
] |
92 | 10077434 | [
{
"id": "93",
"type": "",
"text": [
"Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme which plays a role in the metabolism of proline-containing neuropeptides, e.g., vasopressin, substance P and thyrotropin-releasing hormone (TRH), which have been suggested to be involved in learning and memory processes. In our systematic screening for PEP inhibitors from traditional Chinese medicines, we found that MeOH extract from the underground part of Rhodiola sacra S. H. Fu shows significant inhibitory activity against PEP from Flavobacterium meningosepticum. Examination of the constituents of the extract resulted in the isolation of nineteen known compounds, identified as hydroquinone (1), 4-hydroxybenzoic acid (2), caffeic acid (3), 4-hydroxycinnamic acid (4), suberic acid (5), protocatechuic acid (6), gallic acid (7), (-)-epigallocatechin 3-O-gallate (8), 2-phenylethyl beta-D-glucopyranoside (9), 3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate (10), 2-phenylethyl alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside (11), sacranoside A (12), beta-D-glucopyranosyl 4-hydroxybenzoate (13), rhodiocyanoside A (14), rhodiooctanoside (15), sarmentosin (16), heterodendrin (17), arbutin (18) and 4-O-(beta-D-glucopyranosyl)-gallic acid (19). Among these, 1, 2, 5, 8-10, 13, 16, 18 and 19 have been isolated for the first time from R. sacra, among which 5, 9, 10, 13, 16, 18 and 19 have been isolated from Rhodiola plants for the first time. On the PEP inhibition, seven compounds (6-8, 10, 12, 18, 19) showed inhibition with an 1C50 of 27.8, 487, 1.47, 0.437, 348, 391 and 215 microM, respectively. The kinetic study of these inhibitors indicated that they are noncompetitive inhibitors, except for 6 which is a competitive inhibitor. \n"
],
"offsets": [
[
0,
1738
]
]
}
] | [
{
"id": "93_T2",
"type": "Protein",
"text": [
"Prolyl endopeptidase"
],
"offsets": [
[
0,
20
]
],
"normalized": []
},
{
"id": "93_T3",
"type": "Protein",
"text": [
"PEP"
],
"offsets": [
[
22,
25
]
],
"normalized": []
},
{
"id": "93_T4",
"type": "Protein",
"text": [
"EC 3.4.21.26"
],
"offsets": [
[
27,
39
]
],
"normalized": []
},
{
"id": "93_T6",
"type": "Protein",
"text": [
"enzyme"
],
"offsets": [
[
47,
53
]
],
"normalized": []
},
{
"id": "93_T8",
"type": "Chemical",
"text": [
"proline"
],
"offsets": [
[
94,
101
]
],
"normalized": []
},
{
"id": "93_T9",
"type": "Chemical",
"text": [
"neuropeptides"
],
"offsets": [
[
113,
126
]
],
"normalized": []
},
{
"id": "93_T10",
"type": "Chemical",
"text": [
"vasopressin"
],
"offsets": [
[
134,
145
]
],
"normalized": []
},
{
"id": "93_T11",
"type": "Metabolite",
"text": [
"vasopressin"
],
"offsets": [
[
134,
145
]
],
"normalized": []
},
{
"id": "93_T12",
"type": "Chemical",
"text": [
"substance P"
],
"offsets": [
[
147,
158
]
],
"normalized": []
},
{
"id": "93_T13",
"type": "Metabolite",
"text": [
"substance P"
],
"offsets": [
[
147,
158
]
],
"normalized": []
},
{
"id": "93_T14",
"type": "Chemical",
"text": [
"thyrotropin-releasing hormone"
],
"offsets": [
[
163,
192
]
],
"normalized": []
},
{
"id": "93_T15",
"type": "Metabolite",
"text": [
"thyrotropin-releasing hormone"
],
"offsets": [
[
163,
192
]
],
"normalized": []
},
{
"id": "93_T16",
"type": "Chemical",
"text": [
"TRH"
],
"offsets": [
[
194,
197
]
],
"normalized": []
},
{
"id": "93_T17",
"type": "Metabolite",
"text": [
"TRH"
],
"offsets": [
[
194,
197
]
],
"normalized": []
},
{
"id": "93_T18",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
311,
320
]
],
"normalized": []
},
{
"id": "93_T19",
"type": "Chemical",
"text": [
"MeOH"
],
"offsets": [
[
373,
377
]
],
"normalized": []
},
{
"id": "93_T20",
"type": "Species",
"text": [
"Rhodiola sacra"
],
"offsets": [
[
415,
429
]
],
"normalized": []
},
{
"id": "93_T21",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
457,
466
]
],
"normalized": []
},
{
"id": "93_T22",
"type": "Species",
"text": [
"Flavobacterium meningosepticum"
],
"offsets": [
[
494,
524
]
],
"normalized": []
},
{
"id": "93_T23",
"type": "Chemical",
"text": [
"hydroquinone"
],
"offsets": [
[
644,
656
]
],
"normalized": []
},
{
"id": "93_T24",
"type": "Metabolite",
"text": [
"hydroquinone"
],
"offsets": [
[
644,
656
]
],
"normalized": []
},
{
"id": "93_T25",
"type": "Metabolite",
"text": [
"4-hydroxybenzoic acid"
],
"offsets": [
[
662,
683
]
],
"normalized": []
},
{
"id": "93_T26",
"type": "Chemical",
"text": [
"4-hydroxybenzoic acid"
],
"offsets": [
[
662,
683
]
],
"normalized": []
},
{
"id": "93_T27",
"type": "Chemical",
"text": [
"caffeic acid"
],
"offsets": [
[
689,
701
]
],
"normalized": []
},
{
"id": "93_T28",
"type": "Metabolite",
"text": [
"caffeic acid"
],
"offsets": [
[
689,
701
]
],
"normalized": []
},
{
"id": "93_T29",
"type": "Metabolite",
"text": [
"4-hydroxycinnamic acid"
],
"offsets": [
[
707,
729
]
],
"normalized": []
},
{
"id": "93_T30",
"type": "Chemical",
"text": [
"4-hydroxycinnamic acid"
],
"offsets": [
[
707,
729
]
],
"normalized": []
},
{
"id": "93_T31",
"type": "Chemical",
"text": [
"suberic acid"
],
"offsets": [
[
735,
747
]
],
"normalized": []
},
{
"id": "93_T32",
"type": "Metabolite",
"text": [
"suberic acid"
],
"offsets": [
[
735,
747
]
],
"normalized": []
},
{
"id": "93_T33",
"type": "Chemical",
"text": [
"protocatechuic acid"
],
"offsets": [
[
753,
772
]
],
"normalized": []
},
{
"id": "93_T34",
"type": "Metabolite",
"text": [
"protocatechuic acid"
],
"offsets": [
[
753,
772
]
],
"normalized": []
},
{
"id": "93_T35",
"type": "Metabolite",
"text": [
"gallic acid"
],
"offsets": [
[
778,
789
]
],
"normalized": []
},
{
"id": "93_T36",
"type": "Chemical",
"text": [
"gallic acid"
],
"offsets": [
[
778,
789
]
],
"normalized": []
},
{
"id": "93_T37",
"type": "Chemical",
"text": [
"(-)-epigallocatechin 3-O-gallate"
],
"offsets": [
[
795,
827
]
],
"normalized": []
},
{
"id": "93_T38",
"type": "Metabolite",
"text": [
"(-)-epigallocatechin 3-O-gallate"
],
"offsets": [
[
795,
827
]
],
"normalized": []
},
{
"id": "93_T39",
"type": "Chemical",
"text": [
"2-phenylethyl beta-D-glucopyranoside"
],
"offsets": [
[
833,
869
]
],
"normalized": []
},
{
"id": "93_T40",
"type": "Metabolite",
"text": [
"2-phenylethyl beta-D-glucopyranoside"
],
"offsets": [
[
833,
869
]
],
"normalized": []
},
{
"id": "93_T41",
"type": "Metabolite",
"text": [
"3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate"
],
"offsets": [
[
875,
947
]
],
"normalized": []
},
{
"id": "93_T42",
"type": "Chemical",
"text": [
"3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate"
],
"offsets": [
[
875,
947
]
],
"normalized": []
},
{
"id": "93_T43",
"type": "Chemical",
"text": [
"2-phenylethyl alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside"
],
"offsets": [
[
954,
1023
]
],
"normalized": []
},
{
"id": "93_T44",
"type": "Metabolite",
"text": [
"2-phenylethyl alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside"
],
"offsets": [
[
954,
1023
]
],
"normalized": []
},
{
"id": "93_T45",
"type": "Chemical",
"text": [
"sacranoside A"
],
"offsets": [
[
1030,
1043
]
],
"normalized": []
},
{
"id": "93_T46",
"type": "Metabolite",
"text": [
"sacranoside A"
],
"offsets": [
[
1030,
1043
]
],
"normalized": []
},
{
"id": "93_T47",
"type": "Chemical",
"text": [
"beta-D-glucopyranosyl 4-hydroxybenzoate"
],
"offsets": [
[
1050,
1089
]
],
"normalized": []
},
{
"id": "93_T48",
"type": "Metabolite",
"text": [
"beta-D-glucopyranosyl 4-hydroxybenzoate"
],
"offsets": [
[
1050,
1089
]
],
"normalized": []
},
{
"id": "93_T49",
"type": "Metabolite",
"text": [
"rhodiocyanoside A"
],
"offsets": [
[
1096,
1113
]
],
"normalized": []
},
{
"id": "93_T50",
"type": "Chemical",
"text": [
"rhodiocyanoside A"
],
"offsets": [
[
1096,
1113
]
],
"normalized": []
},
{
"id": "93_T51",
"type": "Chemical",
"text": [
"rhodiooctanoside"
],
"offsets": [
[
1120,
1136
]
],
"normalized": []
},
{
"id": "93_T52",
"type": "Metabolite",
"text": [
"rhodiooctanoside"
],
"offsets": [
[
1120,
1136
]
],
"normalized": []
},
{
"id": "93_T53",
"type": "Chemical",
"text": [
"sarmentosin"
],
"offsets": [
[
1143,
1154
]
],
"normalized": []
},
{
"id": "93_T54",
"type": "Metabolite",
"text": [
"sarmentosin"
],
"offsets": [
[
1143,
1154
]
],
"normalized": []
},
{
"id": "93_T55",
"type": "Chemical",
"text": [
"heterodendrin"
],
"offsets": [
[
1161,
1174
]
],
"normalized": []
},
{
"id": "93_T56",
"type": "Metabolite",
"text": [
"heterodendrin"
],
"offsets": [
[
1161,
1174
]
],
"normalized": []
},
{
"id": "93_T57",
"type": "Metabolite",
"text": [
"arbutin"
],
"offsets": [
[
1181,
1188
]
],
"normalized": []
},
{
"id": "93_T58",
"type": "Chemical",
"text": [
"arbutin"
],
"offsets": [
[
1181,
1188
]
],
"normalized": []
},
{
"id": "93_T59",
"type": "Metabolite",
"text": [
"4-O-(beta-D-glucopyranosyl)-gallic acid"
],
"offsets": [
[
1198,
1237
]
],
"normalized": []
},
{
"id": "93_T60",
"type": "Species",
"text": [
"R. sacra"
],
"offsets": [
[
1333,
1341
]
],
"normalized": []
},
{
"id": "93_T61",
"type": "Biological_Activity",
"text": [
"inhibition"
],
"offsets": [
[
1454,
1464
]
],
"normalized": []
},
{
"id": "93_T63",
"type": "Chemical",
"text": [
"4-O-(beta-D-glucopyranosyl)-gallic acid"
],
"offsets": [
[
1198,
1237
]
],
"normalized": []
},
{
"id": "93_T1",
"type": "Species",
"text": [
"Rhodiola"
],
"offsets": [
[
1407,
1415
]
],
"normalized": []
},
{
"id": "93_T5",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
1678,
1687
]
],
"normalized": []
},
{
"id": "93_T62",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
1726,
1735
]
],
"normalized": []
},
{
"id": "93_T7",
"type": "Protein",
"text": [
"PEP"
],
"offsets": [
[
1450,
1453
]
],
"normalized": []
},
{
"id": "93_T64",
"type": "Biological_Activity",
"text": [
"inhibitors"
],
"offsets": [
[
1628,
1638
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "93_R1",
"type": "Isolated_From",
"arg1_id": "93_T24",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R2",
"type": "Isolated_From",
"arg1_id": "93_T25",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R3",
"type": "Isolated_From",
"arg1_id": "93_T28",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R4",
"type": "Isolated_From",
"arg1_id": "93_T29",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R5",
"type": "Isolated_From",
"arg1_id": "93_T32",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R6",
"type": "Isolated_From",
"arg1_id": "93_T34",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R7",
"type": "Isolated_From",
"arg1_id": "93_T35",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R8",
"type": "Isolated_From",
"arg1_id": "93_T38",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R9",
"type": "Isolated_From",
"arg1_id": "93_T40",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R10",
"type": "Isolated_From",
"arg1_id": "93_T41",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R11",
"type": "Isolated_From",
"arg1_id": "93_T44",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R12",
"type": "Isolated_From",
"arg1_id": "93_T46",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R13",
"type": "Isolated_From",
"arg1_id": "93_T48",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R14",
"type": "Isolated_From",
"arg1_id": "93_T49",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R15",
"type": "Isolated_From",
"arg1_id": "93_T52",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R16",
"type": "Isolated_From",
"arg1_id": "93_T54",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R17",
"type": "Isolated_From",
"arg1_id": "93_T56",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R18",
"type": "Isolated_From",
"arg1_id": "93_T57",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R19",
"type": "Isolated_From",
"arg1_id": "93_T59",
"arg2_id": "93_T20",
"normalized": []
},
{
"id": "93_R20",
"type": "Associated_With",
"arg1_id": "93_T34",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R21",
"type": "Associated_With",
"arg1_id": "93_T35",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R22",
"type": "Associated_With",
"arg1_id": "93_T37",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R23",
"type": "Associated_With",
"arg1_id": "93_T41",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R24",
"type": "Associated_With",
"arg1_id": "93_T46",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R25",
"type": "Associated_With",
"arg1_id": "93_T57",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R26",
"type": "Associated_With",
"arg1_id": "93_T59",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R28",
"type": "Associated_With",
"arg1_id": "93_T36",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R27",
"type": "Associated_With",
"arg1_id": "93_T33",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R29",
"type": "Associated_With",
"arg1_id": "93_T38",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R30",
"type": "Associated_With",
"arg1_id": "93_T42",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R31",
"type": "Associated_With",
"arg1_id": "93_T45",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R32",
"type": "Associated_With",
"arg1_id": "93_T58",
"arg2_id": "93_T61",
"normalized": []
},
{
"id": "93_R33",
"type": "Associated_With",
"arg1_id": "93_T63",
"arg2_id": "93_T61",
"normalized": []
}
] |
94 | 10077490 | [
{
"id": "95",
"type": "",
"text": [
"The growth-promoting effects of estrogens in hormone-dependent tumor tissues involve receptor-mediated pathways that are well-recognized; however, the role of estrogens in tumor initiation remains controversial. Estrogen metabolites, primarily the catechol estrogens (CE's), have been implicated in tumor initiation via a redox cycling mechanism. We have developed metabolically stable CE analogues for the study of receptor versus redox cycling effects on DNA damage. Comparisons between hydroxy estradiols (HE2's), methoxy estradiols (ME2's), and hydroxymethyl estradiols (HME2) in potentiometric and DNA damaging studies were made. DNA damage was assessed in calf thymus DNA using 8-oxo-2'-deoxyguanosine (8-oxo-dG) as a genotoxic marker for oxidative stress. Increases in the number of 8-oxo-dG/10(5) dG were significant for each 2-HE2 and 4-HE2. Cu(II)SO4, a transition metal known to catalyze the redox cycling of o-quinones, substantially increased the amount of DNA damage caused by both CE's. However, DNA damage was only observed at concentrations of 10 microM or higher, much greater than what is found under physiologic conditions. Furthermore, the presence of endogenous antioxidants such as glutathione, SOD, and catalase drastically reduced the amount of DNA damage induced by high concentrations of 2-HE2. There was no DNA damage observed for the non-redox cycling HME2's, making these compounds useful probes in the study of receptor-mediated carcinogenesis. Thus, both 2-HE2 and 4-HE2 are capable of producing oxidative DNA damage at micromolar concentrations in vitro. However, since the amount of CE's has not been shown to surpass nanomolar levels in vivo, it is unlikely that free radical production via redox cycling of CE's is a causative factor in human tumorigenesis. \n"
],
"offsets": [
[
0,
1796
]
]
}
] | [
{
"id": "95_T1",
"type": "Chemical",
"text": [
"estrogens"
],
"offsets": [
[
32,
41
]
],
"normalized": []
},
{
"id": "95_T2",
"type": "Biological_Activity",
"text": [
"estrogens"
],
"offsets": [
[
32,
41
]
],
"normalized": []
},
{
"id": "95_T3",
"type": "Metabolite",
"text": [
"catechol estrogens"
],
"offsets": [
[
248,
266
]
],
"normalized": []
},
{
"id": "95_T4",
"type": "Chemical",
"text": [
"catechol estrogens"
],
"offsets": [
[
248,
266
]
],
"normalized": []
},
{
"id": "95_T5",
"type": "Biological_Activity",
"text": [
"tumor initiation"
],
"offsets": [
[
299,
315
]
],
"normalized": []
},
{
"id": "95_T6",
"type": "Chemical",
"text": [
"Estrogen"
],
"offsets": [
[
212,
220
]
],
"normalized": []
},
{
"id": "95_T7",
"type": "Chemical",
"text": [
"hydroxy estradiols"
],
"offsets": [
[
489,
507
]
],
"normalized": []
},
{
"id": "95_T8",
"type": "Chemical",
"text": [
"HE2's"
],
"offsets": [
[
509,
514
]
],
"normalized": []
},
{
"id": "95_T9",
"type": "Chemical",
"text": [
"methoxy estradiols"
],
"offsets": [
[
517,
535
]
],
"normalized": []
},
{
"id": "95_T10",
"type": "Chemical",
"text": [
"ME2's"
],
"offsets": [
[
537,
542
]
],
"normalized": []
},
{
"id": "95_T11",
"type": "Chemical",
"text": [
"hydroxymethyl estradiols"
],
"offsets": [
[
549,
573
]
],
"normalized": []
},
{
"id": "95_T12",
"type": "Chemical",
"text": [
"HME2"
],
"offsets": [
[
575,
579
]
],
"normalized": []
},
{
"id": "95_T13",
"type": "Chemical",
"text": [
"8-oxo-2'-deoxyguanosine"
],
"offsets": [
[
684,
707
]
],
"normalized": []
},
{
"id": "95_T14",
"type": "Chemical",
"text": [
"8-oxo-dG"
],
"offsets": [
[
709,
717
]
],
"normalized": []
},
{
"id": "95_T16",
"type": "Chemical",
"text": [
"8-oxo-dG"
],
"offsets": [
[
790,
798
]
],
"normalized": []
},
{
"id": "95_T17",
"type": "Chemical",
"text": [
"10(5) dG"
],
"offsets": [
[
799,
807
]
],
"normalized": []
},
{
"id": "95_T18",
"type": "Chemical",
"text": [
"2-HE2"
],
"offsets": [
[
834,
839
]
],
"normalized": []
},
{
"id": "95_T19",
"type": "Chemical",
"text": [
"4-HE2"
],
"offsets": [
[
844,
849
]
],
"normalized": []
},
{
"id": "95_T20",
"type": "Chemical",
"text": [
"Cu(II)SO4"
],
"offsets": [
[
851,
860
]
],
"normalized": []
},
{
"id": "95_T21",
"type": "Chemical",
"text": [
"transition metal"
],
"offsets": [
[
864,
880
]
],
"normalized": []
},
{
"id": "95_T22",
"type": "Chemical",
"text": [
"o-quinones"
],
"offsets": [
[
920,
930
]
],
"normalized": []
},
{
"id": "95_T23",
"type": "Chemical",
"text": [
"CE's"
],
"offsets": [
[
996,
1000
]
],
"normalized": []
},
{
"id": "95_T24",
"type": "Metabolite",
"text": [
"CE's"
],
"offsets": [
[
996,
1000
]
],
"normalized": []
},
{
"id": "95_T26",
"type": "Biological_Activity",
"text": [
"antioxidants"
],
"offsets": [
[
1184,
1196
]
],
"normalized": []
},
{
"id": "95_T27",
"type": "Chemical",
"text": [
"glutathione"
],
"offsets": [
[
1205,
1216
]
],
"normalized": []
},
{
"id": "95_T28",
"type": "Metabolite",
"text": [
"glutathione"
],
"offsets": [
[
1205,
1216
]
],
"normalized": []
},
{
"id": "95_T29",
"type": "Protein",
"text": [
"SOD"
],
"offsets": [
[
1218,
1221
]
],
"normalized": []
},
{
"id": "95_T30",
"type": "Protein",
"text": [
"catalase"
],
"offsets": [
[
1227,
1235
]
],
"normalized": []
},
{
"id": "95_T31",
"type": "Chemical",
"text": [
"2-HE2"
],
"offsets": [
[
1315,
1320
]
],
"normalized": []
},
{
"id": "95_T32",
"type": "Chemical",
"text": [
"HME2"
],
"offsets": [
[
1381,
1385
]
],
"normalized": []
},
{
"id": "95_T33",
"type": "Chemical",
"text": [
"2-HE2"
],
"offsets": [
[
1487,
1492
]
],
"normalized": []
},
{
"id": "95_T34",
"type": "Chemical",
"text": [
"4-HE2"
],
"offsets": [
[
1497,
1502
]
],
"normalized": []
},
{
"id": "95_T36",
"type": "Metabolite",
"text": [
"CE"
],
"offsets": [
[
1618,
1620
]
],
"normalized": []
},
{
"id": "95_T37",
"type": "Chemical",
"text": [
"CE's"
],
"offsets": [
[
1618,
1622
]
],
"normalized": []
},
{
"id": "95_T38",
"type": "Chemical",
"text": [
"free radical"
],
"offsets": [
[
1699,
1711
]
],
"normalized": []
},
{
"id": "95_T39",
"type": "Chemical",
"text": [
"CE"
],
"offsets": [
[
1744,
1746
]
],
"normalized": []
},
{
"id": "95_T40",
"type": "Metabolite",
"text": [
"CE"
],
"offsets": [
[
1744,
1746
]
],
"normalized": []
},
{
"id": "95_T41",
"type": "Biological_Activity",
"text": [
"tumorigenesis"
],
"offsets": [
[
1780,
1793
]
],
"normalized": []
},
{
"id": "95_T42",
"type": "Chemical",
"text": [
"Estrogen metabolites"
],
"offsets": [
[
212,
232
]
],
"normalized": []
},
{
"id": "95_T43",
"type": "Chemical",
"text": [
"CE"
],
"offsets": [
[
268,
270
]
],
"normalized": []
},
{
"id": "95_T44",
"type": "Metabolite",
"text": [
"CE"
],
"offsets": [
[
268,
270
]
],
"normalized": []
},
{
"id": "95_T45",
"type": "Chemical",
"text": [
"CE analogue"
],
"offsets": [
[
386,
397
]
],
"normalized": []
},
{
"id": "95_T46",
"type": "Species",
"text": [
"calf"
],
"offsets": [
[
662,
666
]
],
"normalized": []
},
{
"id": "95_T47",
"type": "Chemical",
"text": [
"estrogens"
],
"offsets": [
[
159,
168
]
],
"normalized": []
},
{
"id": "95_T48",
"type": "Biological_Activity",
"text": [
"tumor initiation"
],
"offsets": [
[
172,
188
]
],
"normalized": []
},
{
"id": "95_T49",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
1774,
1779
]
],
"normalized": []
},
{
"id": "95_T52",
"type": "Metabolite",
"text": [
"Estrogen metabolites"
],
"offsets": [
[
212,
232
]
],
"normalized": []
},
{
"id": "95_T15",
"type": "Biological_Activity",
"text": [
"carcinogenesis"
],
"offsets": [
[
1460,
1474
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "95_R1",
"type": "Associated_With",
"arg1_id": "95_T4",
"arg2_id": "95_T5",
"normalized": []
},
{
"id": "95_R2",
"type": "Associated_With",
"arg1_id": "95_T42",
"arg2_id": "95_T5",
"normalized": []
},
{
"id": "95_R5",
"type": "Associated_With",
"arg1_id": "95_T28",
"arg2_id": "95_T26",
"normalized": []
},
{
"id": "95_R6",
"type": "Associated_With",
"arg1_id": "95_T27",
"arg2_id": "95_T26",
"normalized": []
}
] |
96 | 10077738 | [
{
"id": "97",
"type": "",
"text": [
"In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10 days with lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms. \n"
],
"offsets": [
[
0,
1070
]
]
}
] | [
{
"id": "97_T1",
"type": "Biological_Activity",
"text": [
"inhibition"
],
"offsets": [
[
48,
58
]
],
"normalized": []
},
{
"id": "97_T2",
"type": "Chemical",
"text": [
"nonsteroidal anti-inflammatory drugs"
],
"offsets": [
[
126,
163
]
],
"normalized": []
},
{
"id": "97_T3",
"type": "Biological_Activity",
"text": [
"anti-inflammatory"
],
"offsets": [
[
139,
156
]
],
"normalized": []
},
{
"id": "97_T4",
"type": "Chemical",
"text": [
"NSAID"
],
"offsets": [
[
165,
170
]
],
"normalized": []
},
{
"id": "97_T5",
"type": "Chemical",
"text": [
"NSAID"
],
"offsets": [
[
251,
256
]
],
"normalized": []
},
{
"id": "97_T7",
"type": "Protein",
"text": [
"opioid receptors"
],
"offsets": [
[
281,
297
]
],
"normalized": []
},
{
"id": "97_T9",
"type": "Protein",
"text": [
"mu receptors"
],
"offsets": [
[
431,
443
]
],
"normalized": []
},
{
"id": "97_T10",
"type": "Species",
"text": [
"rats"
],
"offsets": [
[
529,
533
]
],
"normalized": []
},
{
"id": "97_T11",
"type": "Chemical",
"text": [
"lysine clonixinate"
],
"offsets": [
[
559,
577
]
],
"normalized": []
},
{
"id": "97_T12",
"type": "Protein",
"text": [
"delta receptors"
],
"offsets": [
[
591,
606
]
],
"normalized": []
},
{
"id": "97_T14",
"type": "Protein",
"text": [
"opioid-binding sites"
],
"offsets": [
[
751,
771
]
],
"normalized": []
},
{
"id": "97_T16",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
809,
812
]
],
"normalized": []
},
{
"id": "97_T17",
"type": "Chemical",
"text": [
"clonixinate"
],
"offsets": [
[
844,
855
]
],
"normalized": []
},
{
"id": "97_T19",
"type": "Chemical",
"text": [
"NSAIDs"
],
"offsets": [
[
963,
969
]
],
"normalized": []
},
{
"id": "97_T20",
"type": "Chemical",
"text": [
"opioid"
],
"offsets": [
[
281,
287
]
],
"normalized": []
},
{
"id": "97_T22",
"type": "Protein",
"text": [
"opioid receptor"
],
"offsets": [
[
1017,
1032
]
],
"normalized": []
},
{
"id": "97_T21",
"type": "Protein",
"text": [
"mu",
"receptor"
],
"offsets": [
[
896,
898
],
[
917,
925
]
],
"normalized": []
},
{
"id": "97_T25",
"type": "Protein",
"text": [
"delta",
"receptor"
],
"offsets": [
[
900,
905
],
[
917,
925
]
],
"normalized": []
},
{
"id": "97_T26",
"type": "Protein",
"text": [
"kappa receptor"
],
"offsets": [
[
911,
925
]
],
"normalized": []
},
{
"id": "97_T34",
"type": "Metabolite",
"text": [
"prostaglandin"
],
"offsets": [
[
62,
75
]
],
"normalized": []
},
{
"id": "97_T35",
"type": "Chemical",
"text": [
"prostaglandin"
],
"offsets": [
[
62,
75
]
],
"normalized": []
},
{
"id": "97_T6",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
935,
942
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "97_R1",
"type": "Associated_With",
"arg1_id": "97_T2",
"arg2_id": "97_T1",
"normalized": []
},
{
"id": "97_R2",
"type": "Associated_With",
"arg1_id": "97_T4",
"arg2_id": "97_T1",
"normalized": []
}
] |
98 | 10078838 | [
{
"id": "99",
"type": "",
"text": [
"1. Quantitative relationships between molecular physico-chemical properties of 22 substituted benzoic acids and the extent of excretion of their metabolites in rat urine have been investigated using computational chemistry and multivariate statistics. 2. A data set of 34 theoretically derived physico-chemical descriptors calculated was used to classify the benzoic acids according to their predominant urinary metabolic fate. 3. Quantitative structure-metabolism relationships were obtained by linear regression using combinations of physico-chemical descriptors allowing the prediction of % urinary excretion of glycine (r = 0.73) and glucuronide conjugates (r = 0.82) and % urinary excretion of the parent compound (r = 0.91). \n"
],
"offsets": [
[
0,
734
]
]
}
] | [
{
"id": "99_T1",
"type": "Chemical",
"text": [
"substituted benzoic acids"
],
"offsets": [
[
82,
107
]
],
"normalized": []
},
{
"id": "99_T2",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
160,
163
]
],
"normalized": []
},
{
"id": "99_T3",
"type": "Chemical",
"text": [
"benzoic acids"
],
"offsets": [
[
359,
372
]
],
"normalized": []
},
{
"id": "99_T4",
"type": "Chemical",
"text": [
"glycine",
"conjugates"
],
"offsets": [
[
616,
623
],
[
651,
661
]
],
"normalized": []
},
{
"id": "99_T5",
"type": "Metabolite",
"text": [
"glycine",
"conjugates"
],
"offsets": [
[
616,
623
],
[
651,
661
]
],
"normalized": []
},
{
"id": "99_T6",
"type": "Chemical",
"text": [
"glucuronide conjugates"
],
"offsets": [
[
639,
661
]
],
"normalized": []
},
{
"id": "99_T7",
"type": "Metabolite",
"text": [
"glucuronide conjugates"
],
"offsets": [
[
639,
661
]
],
"normalized": []
},
{
"id": "99_T8",
"type": "Metabolite",
"text": [
"metabolites",
"substituted benzoic acid"
],
"offsets": [
[
145,
156
],
[
82,
106
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "99_R1",
"type": "Isolated_From",
"arg1_id": "99_T5",
"arg2_id": "99_T2",
"normalized": []
},
{
"id": "99_R2",
"type": "Isolated_From",
"arg1_id": "99_T7",
"arg2_id": "99_T2",
"normalized": []
}
] |
100 | 10080387 | [
{
"id": "101",
"type": "",
"text": [
"A novel phospholipid has been purified from strain Dm 28c of Trypanosoma cruzi, and characterized by fast atom bombardment mass spectrometry and nuclear magnetic resonance spectroscopy as a plasmenylethanolamine with a hexadec-l-enyl group in the sn-1 position and an approximately equimolar mixture of octadecenoate and octadecadienoate esterified to the sn-2 hydroxyl. The purified plasmenylethanolamine reacted positively when probed with sera from patients with chronic Chagas' disease. Since plasmenylethanolamines of similar structure are abundant in mammalian cardiac and neuronal tissues, cross reactions between these epitopes may be a factor in the mechanism of autoimmune pathology in the chronic phase of Chagas' disease. \n"
],
"offsets": [
[
0,
737
]
]
}
] | [
{
"id": "101_T1",
"type": "Chemical",
"text": [
"phospholipid"
],
"offsets": [
[
8,
20
]
],
"normalized": []
},
{
"id": "101_T2",
"type": "Metabolite",
"text": [
"phospholipid"
],
"offsets": [
[
8,
20
]
],
"normalized": []
},
{
"id": "101_T3",
"type": "Species",
"text": [
"Trypanosoma cruzi"
],
"offsets": [
[
61,
78
]
],
"normalized": []
},
{
"id": "101_T4",
"type": "Spectral_Data",
"text": [
"fast atom bombardment mass spectrometry"
],
"offsets": [
[
101,
140
]
],
"normalized": []
},
{
"id": "101_T5",
"type": "Chemical",
"text": [
"plasmenylethanolamine"
],
"offsets": [
[
190,
211
]
],
"normalized": []
},
{
"id": "101_T6",
"type": "Chemical",
"text": [
"hexadec-l-enyl group"
],
"offsets": [
[
219,
239
]
],
"normalized": []
},
{
"id": "101_T7",
"type": "Chemical",
"text": [
"octadecenoate",
"esterified to the sn-2 hydroxyl"
],
"offsets": [
[
304,
317
],
[
339,
370
]
],
"normalized": []
},
{
"id": "101_T8",
"type": "Chemical",
"text": [
"octadecadienoate esterified to the sn-2 hydroxyl"
],
"offsets": [
[
322,
370
]
],
"normalized": []
},
{
"id": "101_T9",
"type": "Chemical",
"text": [
"plasmenylethanolamine"
],
"offsets": [
[
385,
406
]
],
"normalized": []
},
{
"id": "101_T10",
"type": "Metabolite",
"text": [
"plasmenylethanolamine"
],
"offsets": [
[
385,
406
]
],
"normalized": []
},
{
"id": "101_T11",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
453,
461
]
],
"normalized": []
},
{
"id": "101_T12",
"type": "Chemical",
"text": [
"plasmenylethanolamines"
],
"offsets": [
[
498,
520
]
],
"normalized": []
},
{
"id": "101_T13",
"type": "Metabolite",
"text": [
"plasmenylethanolamines"
],
"offsets": [
[
498,
520
]
],
"normalized": []
},
{
"id": "101_T14",
"type": "Spectral_Data",
"text": [
"nuclear magnetic resonance spectroscopy"
],
"offsets": [
[
145,
184
]
],
"normalized": []
},
{
"id": "101_T15",
"type": "Species",
"text": [
"mammalian"
],
"offsets": [
[
558,
567
]
],
"normalized": []
},
{
"id": "101_T18",
"type": "Biological_Activity",
"text": [
"epitopes"
],
"offsets": [
[
628,
636
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "101_R1",
"type": "Associated_With",
"arg1_id": "101_T2",
"arg2_id": "101_T4",
"normalized": []
},
{
"id": "101_R2",
"type": "Associated_With",
"arg1_id": "101_T1",
"arg2_id": "101_T4",
"normalized": []
},
{
"id": "101_R3",
"type": "Associated_With",
"arg1_id": "101_T2",
"arg2_id": "101_T14",
"normalized": []
},
{
"id": "101_R4",
"type": "Associated_With",
"arg1_id": "101_T1",
"arg2_id": "101_T14",
"normalized": []
}
] |
102 | 10082215 | [
{
"id": "103",
"type": "",
"text": [
"Previous studies have indicated that part of the binding of [3H] [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride] ([3H]GBR 12935) to human platelets is to a piperazine acceptor site, which might be associated with cytochrome P-450IID6 (CYP4502D6, debrisoquine-4-hydroxylase). Due to mutant CYP4502D6 alleles, 5-10% of Caucasians are poor metabolizers of CYP4502D6 substrates such as debrisoquine and dextromethorphan. In the present study, possible differences in binding characteristics of [3H]GBR 12935 in platelets from CYP4502D6 poor and extensive metabolizers were investigated. The most prominent finding was a gender difference, with males having significantly higher Kd values than females. There were no differences in Bmax. After correction for gender, there was a tendency towards higher Kd values in poor metabolizers than in extensive metabolizers, although the difference was not statistically significant. Whether this finding corresponds to reduced CYP4502D6 activity is a matter of further investigation. \n"
],
"offsets": [
[
0,
1054
]
]
}
] | [
{
"id": "103_T1",
"type": "Chemical",
"text": [
"[3H] [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride]"
],
"offsets": [
[
60,
141
]
],
"normalized": []
},
{
"id": "103_T2",
"type": "Chemical",
"text": [
"3H]GBR 12935"
],
"offsets": [
[
144,
156
]
],
"normalized": []
},
{
"id": "103_T3",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
161,
166
]
],
"normalized": []
},
{
"id": "103_T4",
"type": "Chemical",
"text": [
"piperazine"
],
"offsets": [
[
185,
195
]
],
"normalized": []
},
{
"id": "103_T5",
"type": "Protein",
"text": [
"cytochrome P-450IID6"
],
"offsets": [
[
243,
263
]
],
"normalized": []
},
{
"id": "103_T6",
"type": "Protein",
"text": [
"CYP4502D6"
],
"offsets": [
[
265,
274
]
],
"normalized": []
},
{
"id": "103_T7",
"type": "Protein",
"text": [
"debrisoquine-4-hydroxylase"
],
"offsets": [
[
276,
302
]
],
"normalized": []
},
{
"id": "103_T8",
"type": "Protein",
"text": [
"CYP4502D6"
],
"offsets": [
[
320,
329
]
],
"normalized": []
},
{
"id": "103_T9",
"type": "Protein",
"text": [
"CYP4502D6"
],
"offsets": [
[
384,
393
]
],
"normalized": []
},
{
"id": "103_T10",
"type": "Chemical",
"text": [
"debrisoquine"
],
"offsets": [
[
413,
425
]
],
"normalized": []
},
{
"id": "103_T11",
"type": "Chemical",
"text": [
"dextromethorphan"
],
"offsets": [
[
430,
446
]
],
"normalized": []
},
{
"id": "103_T12",
"type": "Chemical",
"text": [
"[3H]GBR 12935"
],
"offsets": [
[
521,
534
]
],
"normalized": []
},
{
"id": "103_T13",
"type": "Protein",
"text": [
"CYP4502D6"
],
"offsets": [
[
553,
562
]
],
"normalized": []
},
{
"id": "103_T14",
"type": "Protein",
"text": [
"CYP4502D6"
],
"offsets": [
[
995,
1004
]
],
"normalized": []
},
{
"id": "103_T16",
"type": "Protein",
"text": [
"piperazine acceptor site"
],
"offsets": [
[
185,
209
]
],
"normalized": []
},
{
"id": "103_T17",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
49,
56
]
],
"normalized": []
},
{
"id": "103_T18",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
494,
501
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "103_R5",
"type": "Binds_With",
"arg1_id": "103_T1",
"arg2_id": "103_T16",
"normalized": []
},
{
"id": "103_R6",
"type": "Binds_With",
"arg1_id": "103_T2",
"arg2_id": "103_T16",
"normalized": []
},
{
"id": "103_R1",
"type": "Associated_With",
"arg1_id": "103_T1",
"arg2_id": "103_T17",
"normalized": []
},
{
"id": "103_R2",
"type": "Associated_With",
"arg1_id": "103_T2",
"arg2_id": "103_T17",
"normalized": []
}
] |
104 | 10085103 | [
{
"id": "105",
"type": "",
"text": [
"We have previously identified two enzyme activities that transfer the acetyl group from platelet-activating factor (PAF) in a CoA-independent manner to lysoplasmalogen or sphingosine in HL-60 cells, endothelial cells, and a variety of rat tissues. These were termed as PAF:lysoplasmalogen (lysophospholipid) transacetylase and PAF:sphingosine transacetylase, respectively. In the present study, we have solubilized and purified this PAF-dependent transacetylase 13,700-fold from rat kidney membranes (mitochondrial plus microsomal membranes) based on the PAF:lysoplasmalogen transacetylase activity. The mitochondria and microsomes were prepared and washed three times, then solubilized with 0.04% Tween 20 at a detergent/protein (w/w) ratio of 0.1. The solubilized fractions from mitochondria and microsomes were combined and subjected to sequential column chromatographies on DEAE-Sepharose, hydroxyapatite, phenyl-Sepharose, and chromatofocusing. The enzyme was further purified by native-polyacrylamide gel electrophoresis (PAGE) and affinity gel matrix in which the competitive inhibitor of the enzyme, 1-O-hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphoethanolamine was covalently attached to the CH-Sepharose. On SDS-PAGE, the purified enzyme showed a single homogeneous band with an apparent molecular mass of 40 kDa. The purified enzyme catalyzed transacetylation of the acetyl group not only from PAF to lysoplasmalogen forming plasmalogen analogs of PAF, but also to sphingosine producing N-acetylsphingosine (C2-ceramide). In addition, this enzyme acted as a PAF-acetylhydrolase in the absence of lipid acceptor molecules. These results suggest that PAF-dependent transacetylase is an enzyme that modifies the cellular functions of PAF through generation of other diverse lipid mediators. \n"
],
"offsets": [
[
0,
1807
]
]
}
] | [
{
"id": "105_T1",
"type": "Chemical",
"text": [
"acetyl group"
],
"offsets": [
[
70,
82
]
],
"normalized": []
},
{
"id": "105_T2",
"type": "Chemical",
"text": [
"platelet-activating factor"
],
"offsets": [
[
88,
114
]
],
"normalized": []
},
{
"id": "105_T3",
"type": "Chemical",
"text": [
"PAF"
],
"offsets": [
[
116,
119
]
],
"normalized": []
},
{
"id": "105_T4",
"type": "Chemical",
"text": [
"CoA"
],
"offsets": [
[
126,
129
]
],
"normalized": []
},
{
"id": "105_T5",
"type": "Chemical",
"text": [
"lysoplasmalogen"
],
"offsets": [
[
152,
167
]
],
"normalized": []
},
{
"id": "105_T6",
"type": "Chemical",
"text": [
"sphingosine"
],
"offsets": [
[
171,
182
]
],
"normalized": []
},
{
"id": "105_T7",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
235,
238
]
],
"normalized": []
},
{
"id": "105_T8",
"type": "Protein",
"text": [
"PAF:lysoplasmalogen (lysophospholipid) transacetylase"
],
"offsets": [
[
269,
322
]
],
"normalized": []
},
{
"id": "105_T9",
"type": "Protein",
"text": [
"PAF:sphingosine transacetylase"
],
"offsets": [
[
327,
357
]
],
"normalized": []
},
{
"id": "105_T10",
"type": "Protein",
"text": [
"PAF-dependent transacetylase"
],
"offsets": [
[
433,
461
]
],
"normalized": []
},
{
"id": "105_T11",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
479,
482
]
],
"normalized": []
},
{
"id": "105_T14",
"type": "Protein",
"text": [
"PAF:lysoplasmalogen transacetylase"
],
"offsets": [
[
555,
589
]
],
"normalized": []
},
{
"id": "105_T15",
"type": "Biological_Activity",
"text": [
"transacetylase"
],
"offsets": [
[
575,
589
]
],
"normalized": []
},
{
"id": "105_T21",
"type": "Chemical",
"text": [
"Tween 20"
],
"offsets": [
[
698,
706
]
],
"normalized": []
},
{
"id": "105_T22",
"type": "Chemical",
"text": [
"DEAE"
],
"offsets": [
[
878,
882
]
],
"normalized": []
},
{
"id": "105_T23",
"type": "Chemical",
"text": [
"Sepharose"
],
"offsets": [
[
883,
892
]
],
"normalized": []
},
{
"id": "105_T24",
"type": "Chemical",
"text": [
"hydroxyapatite"
],
"offsets": [
[
894,
908
]
],
"normalized": []
},
{
"id": "105_T25",
"type": "Chemical",
"text": [
"phenyl-Sepharose"
],
"offsets": [
[
910,
926
]
],
"normalized": []
},
{
"id": "105_T26",
"type": "Chemical",
"text": [
"polyacrylamide"
],
"offsets": [
[
992,
1006
]
],
"normalized": []
},
{
"id": "105_T27",
"type": "Chemical",
"text": [
"1-O-hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphoethanolamine"
],
"offsets": [
[
1108,
1173
]
],
"normalized": []
},
{
"id": "105_T28",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
1083,
1092
]
],
"normalized": []
},
{
"id": "105_T29",
"type": "Chemical",
"text": [
"CH-Sepharose"
],
"offsets": [
[
1206,
1218
]
],
"normalized": []
},
{
"id": "105_T30",
"type": "Chemical",
"text": [
"acetyl group"
],
"offsets": [
[
1383,
1395
]
],
"normalized": []
},
{
"id": "105_T31",
"type": "Chemical",
"text": [
"PAF"
],
"offsets": [
[
1410,
1413
]
],
"normalized": []
},
{
"id": "105_T32",
"type": "Chemical",
"text": [
"lysoplasmalogen"
],
"offsets": [
[
1418,
1433
]
],
"normalized": []
},
{
"id": "105_T33",
"type": "Chemical",
"text": [
"plasmalogen analogs of PAF"
],
"offsets": [
[
1442,
1468
]
],
"normalized": []
},
{
"id": "105_T34",
"type": "Chemical",
"text": [
"plasmalogen"
],
"offsets": [
[
1442,
1453
]
],
"normalized": []
},
{
"id": "105_T35",
"type": "Chemical",
"text": [
"PAF"
],
"offsets": [
[
1465,
1468
]
],
"normalized": []
},
{
"id": "105_T36",
"type": "Chemical",
"text": [
"sphingosine"
],
"offsets": [
[
1482,
1493
]
],
"normalized": []
},
{
"id": "105_T37",
"type": "Chemical",
"text": [
"N-acetylsphingosine"
],
"offsets": [
[
1504,
1523
]
],
"normalized": []
},
{
"id": "105_T38",
"type": "Chemical",
"text": [
"C2-ceramide"
],
"offsets": [
[
1525,
1536
]
],
"normalized": []
},
{
"id": "105_T39",
"type": "Protein",
"text": [
"PAF-acetylhydrolase"
],
"offsets": [
[
1576,
1595
]
],
"normalized": []
},
{
"id": "105_T40",
"type": "Chemical",
"text": [
"lipid"
],
"offsets": [
[
1614,
1619
]
],
"normalized": []
},
{
"id": "105_T41",
"type": "Protein",
"text": [
"PAF-dependent transacetylase"
],
"offsets": [
[
1667,
1695
]
],
"normalized": []
},
{
"id": "105_T42",
"type": "Chemical",
"text": [
"PAF"
],
"offsets": [
[
1749,
1752
]
],
"normalized": []
},
{
"id": "105_T43",
"type": "Chemical",
"text": [
"lipid"
],
"offsets": [
[
1789,
1794
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "105_R1",
"type": "Associated_With",
"arg1_id": "105_T27",
"arg2_id": "105_T28",
"normalized": []
}
] |
106 | 10085152 | [
{
"id": "107",
"type": "",
"text": [
"It has been proposed that cells sense hypoxia by a heme protein, which transmits a signal that activates the heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1), thereby inducing a number of physiologically relevant genes such as erythropoietin (Epo). We have investigated the mechanism by which two heme-binding ligands, carbon monoxide and nitric oxide, affect oxygen sensing and signaling. Two concentrations of CO (10 and 80%) suppressed the activation of HIF-1 and induction of Epo mRNA by hypoxia in a dose-dependent manner. In contrast, CO had no effect on the induction of HIF-1 activity and Epo expression by either cobalt chloride or the iron chelator desferrioxamine. The affinity of CO for the putative sensor was much lower than that of oxygen (Haldane coefficient, approximately 0.5). Parallel experiments were done with 100 microM sodium nitroprusside, a nitric oxide donor. Both NO and CO inhibited HIF-1 DNA binding by abrogating hypoxia-induced accumulation of HIF-1alpha protein. Moreover, both NO and CO specifically targeted the internal oxygen-dependent degradation domain of HIF-1alpha, and also repressed the C-terminal transactivation domain of HIF-1alpha. Thus, NO and CO act proximally, presumably as heme ligands binding to the oxygen sensor, whereas desferrioxamine and perhaps cobalt appear to act at a site downstream. \n"
],
"offsets": [
[
0,
1373
]
]
}
] | [
{
"id": "107_T3",
"type": "Protein",
"text": [
"heme protein"
],
"offsets": [
[
51,
63
]
],
"normalized": []
},
{
"id": "107_T4",
"type": "Protein",
"text": [
"hypoxia-inducible factor 1"
],
"offsets": [
[
145,
172
]
],
"normalized": []
},
{
"id": "107_T5",
"type": "Protein",
"text": [
"HIF-1"
],
"offsets": [
[
174,
179
]
],
"normalized": []
},
{
"id": "107_T6",
"type": "Protein",
"text": [
"erythropoietin"
],
"offsets": [
[
250,
264
]
],
"normalized": []
},
{
"id": "107_T7",
"type": "Protein",
"text": [
"Epo"
],
"offsets": [
[
266,
269
]
],
"normalized": []
},
{
"id": "107_T9",
"type": "Chemical",
"text": [
"carbon monoxide"
],
"offsets": [
[
342,
357
]
],
"normalized": []
},
{
"id": "107_T10",
"type": "Chemical",
"text": [
"nitric oxide"
],
"offsets": [
[
362,
374
]
],
"normalized": []
},
{
"id": "107_T8",
"type": "Chemical",
"text": [
"heme"
],
"offsets": [
[
320,
324
]
],
"normalized": []
},
{
"id": "107_T11",
"type": "Biological_Activity",
"text": [
"sensing"
],
"offsets": [
[
390,
397
]
],
"normalized": []
},
{
"id": "107_T12",
"type": "Biological_Activity",
"text": [
"signaling"
],
"offsets": [
[
402,
411
]
],
"normalized": []
},
{
"id": "107_T13",
"type": "Chemical",
"text": [
"CO"
],
"offsets": [
[
435,
437
]
],
"normalized": []
},
{
"id": "107_T16",
"type": "Chemical",
"text": [
"CO"
],
"offsets": [
[
564,
566
]
],
"normalized": []
},
{
"id": "107_T17",
"type": "Protein",
"text": [
"HIF-1"
],
"offsets": [
[
480,
485
]
],
"normalized": []
},
{
"id": "107_T18",
"type": "Protein",
"text": [
"Epo"
],
"offsets": [
[
503,
506
]
],
"normalized": []
},
{
"id": "107_T19",
"type": "Protein",
"text": [
"HIF-1"
],
"offsets": [
[
601,
606
]
],
"normalized": []
},
{
"id": "107_T21",
"type": "Protein",
"text": [
"Epo"
],
"offsets": [
[
620,
623
]
],
"normalized": []
},
{
"id": "107_T22",
"type": "Chemical",
"text": [
"cobalt chloride"
],
"offsets": [
[
646,
661
]
],
"normalized": []
},
{
"id": "107_T24",
"type": "Chemical",
"text": [
"desferrioxamine"
],
"offsets": [
[
683,
698
]
],
"normalized": []
},
{
"id": "107_T25",
"type": "Biological_Activity",
"text": [
"chelator"
],
"offsets": [
[
674,
682
]
],
"normalized": []
},
{
"id": "107_T26",
"type": "Chemical",
"text": [
"CO"
],
"offsets": [
[
716,
718
]
],
"normalized": []
},
{
"id": "107_T27",
"type": "Chemical",
"text": [
"oxygen"
],
"offsets": [
[
771,
777
]
],
"normalized": []
},
{
"id": "107_T28",
"type": "Chemical",
"text": [
"sodium nitroprusside"
],
"offsets": [
[
867,
887
]
],
"normalized": []
},
{
"id": "107_T29",
"type": "Chemical",
"text": [
"nitric oxide"
],
"offsets": [
[
891,
903
]
],
"normalized": []
},
{
"id": "107_T31",
"type": "Chemical",
"text": [
"NO"
],
"offsets": [
[
916,
918
]
],
"normalized": []
},
{
"id": "107_T32",
"type": "Chemical",
"text": [
"CO"
],
"offsets": [
[
923,
925
]
],
"normalized": []
},
{
"id": "107_T33",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
946,
953
]
],
"normalized": []
},
{
"id": "107_T34",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
1000,
1010
]
],
"normalized": []
},
{
"id": "107_T35",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
1119,
1129
]
],
"normalized": []
},
{
"id": "107_T36",
"type": "Protein",
"text": [
"HIF-1alpha"
],
"offsets": [
[
1191,
1201
]
],
"normalized": []
},
{
"id": "107_T37",
"type": "Chemical",
"text": [
"NO"
],
"offsets": [
[
1035,
1037
]
],
"normalized": []
},
{
"id": "107_T38",
"type": "Chemical",
"text": [
"CO"
],
"offsets": [
[
1042,
1044
]
],
"normalized": []
},
{
"id": "107_T39",
"type": "Chemical",
"text": [
"NO"
],
"offsets": [
[
1209,
1211
]
],
"normalized": []
},
{
"id": "107_T40",
"type": "Chemical",
"text": [
"CO"
],
"offsets": [
[
1216,
1218
]
],
"normalized": []
},
{
"id": "107_T41",
"type": "Chemical",
"text": [
"oxygen"
],
"offsets": [
[
1080,
1086
]
],
"normalized": []
},
{
"id": "107_T42",
"type": "Chemical",
"text": [
"heme"
],
"offsets": [
[
1250,
1254
]
],
"normalized": []
},
{
"id": "107_T43",
"type": "Chemical",
"text": [
"oxygen"
],
"offsets": [
[
1278,
1284
]
],
"normalized": []
},
{
"id": "107_T44",
"type": "Chemical",
"text": [
"desferrioxamine"
],
"offsets": [
[
1301,
1316
]
],
"normalized": []
},
{
"id": "107_T45",
"type": "Species",
"text": [
"cobalt"
],
"offsets": [
[
1329,
1335
]
],
"normalized": []
},
{
"id": "107_T1",
"type": "Chemical",
"text": [
"oxygen"
],
"offsets": [
[
383,
389
]
],
"normalized": []
},
{
"id": "107_T2",
"type": "Chemical",
"text": [
"iron"
],
"offsets": [
[
669,
673
]
],
"normalized": []
},
{
"id": "107_T20",
"type": "Biological_Activity",
"text": [
"suppressed"
],
"offsets": [
[
451,
461
]
],
"normalized": []
},
{
"id": "107_T14",
"type": "Biological_Activity",
"text": [
"inhibited"
],
"offsets": [
[
926,
935
]
],
"normalized": []
},
{
"id": "107_T15",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
1263,
1270
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "107_R1",
"type": "Associated_With",
"arg1_id": "107_T9",
"arg2_id": "107_T11",
"normalized": []
},
{
"id": "107_R2",
"type": "Associated_With",
"arg1_id": "107_T10",
"arg2_id": "107_T11",
"normalized": []
},
{
"id": "107_R3",
"type": "Associated_With",
"arg1_id": "107_T9",
"arg2_id": "107_T12",
"normalized": []
},
{
"id": "107_R4",
"type": "Associated_With",
"arg1_id": "107_T10",
"arg2_id": "107_T12",
"normalized": []
},
{
"id": "107_R6",
"type": "Associated_With",
"arg1_id": "107_T24",
"arg2_id": "107_T25",
"normalized": []
},
{
"id": "107_R5",
"type": "Associated_With",
"arg1_id": "107_T13",
"arg2_id": "107_T20",
"normalized": []
},
{
"id": "107_R7",
"type": "Associated_With",
"arg1_id": "107_T31",
"arg2_id": "107_T14",
"normalized": []
},
{
"id": "107_R8",
"type": "Associated_With",
"arg1_id": "107_T32",
"arg2_id": "107_T14",
"normalized": []
}
] |
108 | 10085244 | [
{
"id": "109",
"type": "",
"text": [
"Binding of fluorescent fatty acids to bovine liver non-specific lipid-transfer protein (nsL-TP) was assessed by measuring fluorescence resonance energy transfer (FRET) between the single tryptophan residue of nsL-TP and the fluorophore. Upon addition of pyrene dodecanoic acid (Pyr-C12) and cis-parinaric acid to nsL-TP, FRET was observed indicating that these fatty acids were accommodated in the lipid binding site closely positioned to the tryptophan residue. Substantial binding was observed only when these fatty acids were presented in the monomeric form complexed to beta-cyclodextrin. As shown by time-resolved fluorescence measurements, translocation of Pyr-C12 from the Pyr-C12-beta-cyclodextrin complex to nsL-TP changed dramatically the direct molecular environment of the pyrene moiety: i.e. the fluorescence lifetime of the directly excited pyrene increased at least by 25% and a distinct rotational correlation time of 7 ns was observed. In order to evaluate the affinity of nsL-TP for intermediates of the beta-oxidation pathway, a binding assay was developed based on the ability of fatty acyl derivatives to displace Pyr-C12 from the lipid binding site as reflected by the reduction of FRET. Hexadecanoyl-CoA and 2-hexadecenoyl-CoA were found to bind readily to nsL-TP, whereas 3-hydroxyhexadecanoyl-CoA and 3-ketohexadecanoyl-CoA bound poorly. The highest affinities were observed for the very-long-chain fatty acyl-CoA esters (24:0-CoA, 26:0-CoA) and their enoyl derivatives (24:1-CoA, 26:1-CoA). Binding of non-esterified hexadecanoic acid and tetracosanoic acid (24:0) was negligible. \n"
],
"offsets": [
[
0,
1612
]
]
}
] | [
{
"id": "109_T1",
"type": "Chemical",
"text": [
"fatty acids"
],
"offsets": [
[
23,
34
]
],
"normalized": []
},
{
"id": "109_T2",
"type": "Species",
"text": [
"bovine"
],
"offsets": [
[
38,
44
]
],
"normalized": []
},
{
"id": "109_T3",
"type": "Protein",
"text": [
"non-specific lipid-transfer protein"
],
"offsets": [
[
51,
86
]
],
"normalized": []
},
{
"id": "109_T4",
"type": "Protein",
"text": [
"nsL-TP"
],
"offsets": [
[
88,
94
]
],
"normalized": []
},
{
"id": "109_T7",
"type": "Chemical",
"text": [
"tryptophan residue"
],
"offsets": [
[
187,
205
]
],
"normalized": []
},
{
"id": "109_T9",
"type": "Chemical",
"text": [
"pyrene dodecanoic acid"
],
"offsets": [
[
255,
277
]
],
"normalized": []
},
{
"id": "109_T10",
"type": "Chemical",
"text": [
"Pyr-C12"
],
"offsets": [
[
279,
286
]
],
"normalized": []
},
{
"id": "109_T11",
"type": "Chemical",
"text": [
"cis-parinaric acid"
],
"offsets": [
[
292,
310
]
],
"normalized": []
},
{
"id": "109_T12",
"type": "Protein",
"text": [
"nsL-TP"
],
"offsets": [
[
314,
320
]
],
"normalized": []
},
{
"id": "109_T14",
"type": "Chemical",
"text": [
"fatty acids"
],
"offsets": [
[
362,
373
]
],
"normalized": []
},
{
"id": "109_T16",
"type": "Chemical",
"text": [
"tryptophan residue"
],
"offsets": [
[
444,
462
]
],
"normalized": []
},
{
"id": "109_T17",
"type": "Chemical",
"text": [
"fatty acids"
],
"offsets": [
[
513,
524
]
],
"normalized": []
},
{
"id": "109_T18",
"type": "Chemical",
"text": [
"beta-cyclodextrin"
],
"offsets": [
[
576,
593
]
],
"normalized": []
},
{
"id": "109_T19",
"type": "Chemical",
"text": [
"Pyr-C12"
],
"offsets": [
[
665,
672
]
],
"normalized": []
},
{
"id": "109_T20",
"type": "Chemical",
"text": [
"Pyr-C12-beta-cyclodextrin complex"
],
"offsets": [
[
682,
715
]
],
"normalized": []
},
{
"id": "109_T21",
"type": "Protein",
"text": [
"nsL-TP"
],
"offsets": [
[
719,
725
]
],
"normalized": []
},
{
"id": "109_T23",
"type": "Chemical",
"text": [
"pyrene"
],
"offsets": [
[
787,
793
]
],
"normalized": []
},
{
"id": "109_T24",
"type": "Chemical",
"text": [
"pyrene"
],
"offsets": [
[
857,
863
]
],
"normalized": []
},
{
"id": "109_T25",
"type": "Protein",
"text": [
"nsL-TP"
],
"offsets": [
[
993,
999
]
],
"normalized": []
},
{
"id": "109_T27",
"type": "Chemical",
"text": [
"fatty acyl derivatives"
],
"offsets": [
[
1103,
1125
]
],
"normalized": []
},
{
"id": "109_T28",
"type": "Chemical",
"text": [
"Pyr-C12"
],
"offsets": [
[
1138,
1145
]
],
"normalized": []
},
{
"id": "109_T29",
"type": "Chemical",
"text": [
"lipid"
],
"offsets": [
[
1155,
1160
]
],
"normalized": []
},
{
"id": "109_T31",
"type": "Chemical",
"text": [
"Hexadecanoyl-CoA"
],
"offsets": [
[
1213,
1229
]
],
"normalized": []
},
{
"id": "109_T32",
"type": "Chemical",
"text": [
"2-hexadecenoyl-CoA"
],
"offsets": [
[
1234,
1252
]
],
"normalized": []
},
{
"id": "109_T34",
"type": "Protein",
"text": [
"nsL-TP"
],
"offsets": [
[
1284,
1290
]
],
"normalized": []
},
{
"id": "109_T35",
"type": "Chemical",
"text": [
"3-hydroxyhexadecanoyl-CoA"
],
"offsets": [
[
1300,
1325
]
],
"normalized": []
},
{
"id": "109_T36",
"type": "Chemical",
"text": [
"3-ketohexadecanoyl-CoA"
],
"offsets": [
[
1330,
1352
]
],
"normalized": []
},
{
"id": "109_T37",
"type": "Chemical",
"text": [
"very-long-chain fatty acyl-CoA esters"
],
"offsets": [
[
1412,
1449
]
],
"normalized": []
},
{
"id": "109_T38",
"type": "Chemical",
"text": [
"24:0-CoA"
],
"offsets": [
[
1451,
1459
]
],
"normalized": []
},
{
"id": "109_T39",
"type": "Chemical",
"text": [
"26:0-CoA"
],
"offsets": [
[
1461,
1469
]
],
"normalized": []
},
{
"id": "109_T40",
"type": "Chemical",
"text": [
"24:1-CoA"
],
"offsets": [
[
1500,
1508
]
],
"normalized": []
},
{
"id": "109_T41",
"type": "Chemical",
"text": [
"26:1-CoA"
],
"offsets": [
[
1510,
1518
]
],
"normalized": []
},
{
"id": "109_T42",
"type": "Chemical",
"text": [
"hexadecanoic acid"
],
"offsets": [
[
1547,
1564
]
],
"normalized": []
},
{
"id": "109_T43",
"type": "Chemical",
"text": [
"tetracosanoic acid"
],
"offsets": [
[
1569,
1587
]
],
"normalized": []
},
{
"id": "109_T44",
"type": "Chemical",
"text": [
"24:0"
],
"offsets": [
[
1589,
1593
]
],
"normalized": []
},
{
"id": "109_T45",
"type": "Biological_Activity",
"text": [
"Binding"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "109_T46",
"type": "Biological_Activity",
"text": [
"binding"
],
"offsets": [
[
476,
483
]
],
"normalized": []
},
{
"id": "109_T47",
"type": "Biological_Activity",
"text": [
"bind"
],
"offsets": [
[
1268,
1272
]
],
"normalized": []
},
{
"id": "109_T48",
"type": "Protein",
"text": [
"nsL-TP"
],
"offsets": [
[
209,
215
]
],
"normalized": []
},
{
"id": "109_T5",
"type": "Biological_Activity",
"text": [
"Binding"
],
"offsets": [
[
1521,
1528
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "109_R1",
"type": "Associated_With",
"arg1_id": "109_T31",
"arg2_id": "109_T47",
"normalized": []
},
{
"id": "109_R2",
"type": "Associated_With",
"arg1_id": "109_T32",
"arg2_id": "109_T47",
"normalized": []
},
{
"id": "109_R3",
"type": "Associated_With",
"arg1_id": "109_T37",
"arg2_id": "109_T47",
"normalized": []
},
{
"id": "109_R4",
"type": "Associated_With",
"arg1_id": "109_T38",
"arg2_id": "109_T47",
"normalized": []
},
{
"id": "109_R5",
"type": "Associated_With",
"arg1_id": "109_T39",
"arg2_id": "109_T47",
"normalized": []
},
{
"id": "109_R6",
"type": "Associated_With",
"arg1_id": "109_T40",
"arg2_id": "109_T47",
"normalized": []
},
{
"id": "109_R7",
"type": "Associated_With",
"arg1_id": "109_T41",
"arg2_id": "109_T47",
"normalized": []
},
{
"id": "109_R9",
"type": "Binds_With",
"arg1_id": "109_T1",
"arg2_id": "109_T3",
"normalized": []
},
{
"id": "109_R8",
"type": "Binds_With",
"arg1_id": "109_T1",
"arg2_id": "109_T4",
"normalized": []
},
{
"id": "109_R10",
"type": "Binds_With",
"arg1_id": "109_T31",
"arg2_id": "109_T34",
"normalized": []
},
{
"id": "109_R11",
"type": "Binds_With",
"arg1_id": "109_T32",
"arg2_id": "109_T34",
"normalized": []
},
{
"id": "109_R12",
"type": "Binds_With",
"arg1_id": "109_T37",
"arg2_id": "109_T34",
"normalized": []
},
{
"id": "109_R13",
"type": "Binds_With",
"arg1_id": "109_T38",
"arg2_id": "109_T34",
"normalized": []
},
{
"id": "109_R14",
"type": "Binds_With",
"arg1_id": "109_T39",
"arg2_id": "109_T34",
"normalized": []
},
{
"id": "109_R15",
"type": "Binds_With",
"arg1_id": "109_T40",
"arg2_id": "109_T34",
"normalized": []
},
{
"id": "109_R16",
"type": "Binds_With",
"arg1_id": "109_T41",
"arg2_id": "109_T34",
"normalized": []
}
] |
110 | 10086325 | [
{
"id": "111",
"type": "",
"text": [
"Isatin is an endogenous indole and an inhibitor of atrial natriuretic peptide (ANP) receptors coupled with particulate guanylyl cyclase (GC). In this study, several isatin analogues were tested as inhibitors of ANP-stimulated GC in rat brain and heart membranes. None of these analogues affected activity in the absence of ANP, or stimulated ANP-induced activity. In both tissues, some 5-substituted isatins (5-hydroxyisatin, 5-methylisatin, and 5-aminoisatin) exhibited more effective inhibitory activity than isatin itself, with IC50 values in the range 1.3-20 microM. The efficacy of other analogues varied and was not consistent between the two tissues, raising the possibility of receptor heterogeneity and relative selectivity of inhibition. Some substituted isatins may have a role as pharmacological tools for investigating the physiological roles of natriuretic peptides and their receptors. \n"
],
"offsets": [
[
0,
902
]
]
}
] | [
{
"id": "111_T1",
"type": "Chemical",
"text": [
"Isatin"
],
"offsets": [
[
0,
6
]
],
"normalized": []
},
{
"id": "111_T2",
"type": "Metabolite",
"text": [
"Isatin"
],
"offsets": [
[
0,
6
]
],
"normalized": []
},
{
"id": "111_T3",
"type": "Chemical",
"text": [
"indole"
],
"offsets": [
[
24,
30
]
],
"normalized": []
},
{
"id": "111_T4",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
38,
47
]
],
"normalized": []
},
{
"id": "111_T5",
"type": "Protein",
"text": [
"atrial natriuretic peptide (ANP) receptor"
],
"offsets": [
[
51,
92
]
],
"normalized": []
},
{
"id": "111_T6",
"type": "Protein",
"text": [
"particulate guanylyl cyclase"
],
"offsets": [
[
107,
135
]
],
"normalized": []
},
{
"id": "111_T7",
"type": "Protein",
"text": [
"GC"
],
"offsets": [
[
137,
139
]
],
"normalized": []
},
{
"id": "111_T9",
"type": "Chemical",
"text": [
"isatin"
],
"offsets": [
[
165,
171
]
],
"normalized": []
},
{
"id": "111_T10",
"type": "Chemical",
"text": [
"isatin analogues"
],
"offsets": [
[
165,
181
]
],
"normalized": []
},
{
"id": "111_T11",
"type": "Biological_Activity",
"text": [
"inhibitors"
],
"offsets": [
[
197,
207
]
],
"normalized": []
},
{
"id": "111_T12",
"type": "Protein",
"text": [
"atrial natriuretic peptide"
],
"offsets": [
[
51,
77
]
],
"normalized": []
},
{
"id": "111_T13",
"type": "Protein",
"text": [
"ANP"
],
"offsets": [
[
79,
82
]
],
"normalized": []
},
{
"id": "111_T14",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
232,
235
]
],
"normalized": []
},
{
"id": "111_T15",
"type": "Protein",
"text": [
"ANP"
],
"offsets": [
[
211,
214
]
],
"normalized": []
},
{
"id": "111_T16",
"type": "Protein",
"text": [
"ANP-stimulated GC"
],
"offsets": [
[
211,
228
]
],
"normalized": []
},
{
"id": "111_T18",
"type": "Protein",
"text": [
"ANP"
],
"offsets": [
[
323,
326
]
],
"normalized": []
},
{
"id": "111_T19",
"type": "Chemical",
"text": [
"5-substituted isatins"
],
"offsets": [
[
386,
407
]
],
"normalized": []
},
{
"id": "111_T20",
"type": "Chemical",
"text": [
"5-hydroxyisatin"
],
"offsets": [
[
409,
424
]
],
"normalized": []
},
{
"id": "111_T21",
"type": "Chemical",
"text": [
"5-methylisatin"
],
"offsets": [
[
426,
440
]
],
"normalized": []
},
{
"id": "111_T22",
"type": "Chemical",
"text": [
"5-aminoisatin"
],
"offsets": [
[
446,
459
]
],
"normalized": []
},
{
"id": "111_T23",
"type": "Chemical",
"text": [
"substituted isatins"
],
"offsets": [
[
753,
772
]
],
"normalized": []
},
{
"id": "111_T24",
"type": "Protein",
"text": [
"natriuretic peptides",
"receptors"
],
"offsets": [
[
859,
879
],
[
890,
899
]
],
"normalized": []
},
{
"id": "111_T25",
"type": "Chemical",
"text": [
"isatin"
],
"offsets": [
[
511,
517
]
],
"normalized": []
},
{
"id": "111_T26",
"type": "Metabolite",
"text": [
"isatin"
],
"offsets": [
[
511,
517
]
],
"normalized": []
},
{
"id": "111_T8",
"type": "Protein",
"text": [
"ANP"
],
"offsets": [
[
342,
345
]
],
"normalized": []
},
{
"id": "111_T17",
"type": "Biological_Activity",
"text": [
"inhibitory"
],
"offsets": [
[
486,
496
]
],
"normalized": []
},
{
"id": "111_T27",
"type": "Biological_Activity",
"text": [
"inhibition"
],
"offsets": [
[
736,
746
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "111_R1",
"type": "Associated_With",
"arg1_id": "111_T2",
"arg2_id": "111_T4",
"normalized": []
},
{
"id": "111_R2",
"type": "Associated_With",
"arg1_id": "111_T1",
"arg2_id": "111_T4",
"normalized": []
},
{
"id": "111_R3",
"type": "Associated_With",
"arg1_id": "111_T19",
"arg2_id": "111_T17",
"normalized": []
},
{
"id": "111_R4",
"type": "Associated_With",
"arg1_id": "111_T20",
"arg2_id": "111_T17",
"normalized": []
},
{
"id": "111_R5",
"type": "Associated_With",
"arg1_id": "111_T21",
"arg2_id": "111_T17",
"normalized": []
},
{
"id": "111_R6",
"type": "Associated_With",
"arg1_id": "111_T22",
"arg2_id": "111_T17",
"normalized": []
}
] |
112 | 10086326 | [
{
"id": "113",
"type": "",
"text": [
"It has been shown previously that 4-anilino quinazolines compete with the ability of ATP to bind the epidermal growth factor receptor (EGF-R), inhibit EGF-stimulated autophosphorylation of tyrosine residues in EGF-R, and block EGF-mediated growth. Since millimolar concentrations of ATP in cells could reduce the efficacy of 4-anilino quinazolines in cells and the activity of these compounds would not be sustained once they were removed from the body, we reasoned that irreversible inhibitors of EGF-R might improve the activity of this series of compounds in animals. Molecular modeling of the EGF-R kinase domain was used to design irreversible inhibitors. We herein describe one such inhibitor: N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]2-butynamide, known as CL-387,785. This compound covalently bound to EGF-R. It also specifically inhibited kinase activity of the protein (IC50 = 370+/-120 pM), blocked EGF-stimulated autophosphorylation of the receptor in cells (ic50 approximately 5 nM), inhibited cell proliferation (IC50 = 31-125 nM) primarily in a cytostatic manner in cell lines that overexpress EGF-R or c-erbB-2, and profoundly blocked the growth of a tumor that overexpresses EGF-R in nude mice (when given orally at 80 mg/kg/day for 10 days, daily). We conclude that CL-387,785 is useful for studying the interaction of small molecules with EGF-R and may have clinical utility. \n"
],
"offsets": [
[
0,
1399
]
]
}
] | [
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"id": "113_T1",
"type": "Chemical",
"text": [
"4-anilino quinazolines"
],
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34,
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]
],
"normalized": []
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"id": "113_T2",
"type": "Chemical",
"text": [
"ATP"
],
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85,
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]
],
"normalized": []
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"id": "113_T3",
"type": "Protein",
"text": [
"epidermal growth factor receptor"
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101,
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"type": "Protein",
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"EGF-R"
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"id": "113_T5",
"type": "Biological_Activity",
"text": [
"bind"
],
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[
92,
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]
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"id": "113_T6",
"type": "Chemical",
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"EGF"
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[
151,
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]
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"id": "113_T9",
"type": "Protein",
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"EGF-R"
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[
210,
215
]
],
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},
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"id": "113_T11",
"type": "Biological_Activity",
"text": [
"inhibit"
],
"offsets": [
[
143,
150
]
],
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},
{
"id": "113_T13",
"type": "Chemical",
"text": [
"ATP"
],
"offsets": [
[
283,
286
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"normalized": []
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{
"id": "113_T14",
"type": "Chemical",
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"4-anilino quinazolines"
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325,
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]
],
"normalized": []
},
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"id": "113_T15",
"type": "Protein",
"text": [
"EGF-R"
],
"offsets": [
[
498,
503
]
],
"normalized": []
},
{
"id": "113_T18",
"type": "Biological_Activity",
"text": [
"inhibitors"
],
"offsets": [
[
484,
494
]
],
"normalized": []
},
{
"id": "113_T20",
"type": "Protein",
"text": [
"EGF-R"
],
"offsets": [
[
597,
602
]
],
"normalized": []
},
{
"id": "113_T21",
"type": "Protein",
"text": [
"EGF-R kinase"
],
"offsets": [
[
597,
609
]
],
"normalized": []
},
{
"id": "113_T23",
"type": "Chemical",
"text": [
"N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]2-butynamide"
],
"offsets": [
[
700,
755
]
],
"normalized": []
},
{
"id": "113_T24",
"type": "Chemical",
"text": [
"CL-387,785"
],
"offsets": [
[
766,
776
]
],
"normalized": []
},
{
"id": "113_T25",
"type": "Protein",
"text": [
"EGF-R"
],
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[
812,
817
]
],
"normalized": []
},
{
"id": "113_T27",
"type": "Biological_Activity",
"text": [
"inhibited"
],
"offsets": [
[
840,
849
]
],
"normalized": []
},
{
"id": "113_T28",
"type": "Protein",
"text": [
"EGF"
],
"offsets": [
[
912,
915
]
],
"normalized": []
},
{
"id": "113_T29",
"type": "Biological_Activity",
"text": [
"phosphorylation"
],
"offsets": [
[
931,
946
]
],
"normalized": []
},
{
"id": "113_T30",
"type": "Biological_Activity",
"text": [
"inhibited"
],
"offsets": [
[
999,
1008
]
],
"normalized": []
},
{
"id": "113_T32",
"type": "Protein",
"text": [
"EGF-R"
],
"offsets": [
[
1111,
1116
]
],
"normalized": []
},
{
"id": "113_T33",
"type": "Protein",
"text": [
"c-erbB-2"
],
"offsets": [
[
1120,
1128
]
],
"normalized": []
},
{
"id": "113_T34",
"type": "Biological_Activity",
"text": [
"blocked"
],
"offsets": [
[
1145,
1152
]
],
"normalized": []
},
{
"id": "113_T36",
"type": "Protein",
"text": [
"EGF-R"
],
"offsets": [
[
1195,
1200
]
],
"normalized": []
},
{
"id": "113_T39",
"type": "Species",
"text": [
"nude mice"
],
"offsets": [
[
1204,
1213
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],
"normalized": []
},
{
"id": "113_T40",
"type": "Chemical",
"text": [
"CL-387,785"
],
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[
1287,
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},
{
"id": "113_T43",
"type": "Protein",
"text": [
"EGF-R"
],
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[
1361,
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],
"normalized": []
},
{
"id": "113_T16",
"type": "Chemical",
"text": [
"tyrosine residues"
],
"offsets": [
[
189,
206
]
],
"normalized": []
},
{
"id": "113_T44",
"type": "Biological_Activity",
"text": [
"phosphorylation"
],
"offsets": [
[
170,
185
]
],
"normalized": []
},
{
"id": "113_T12",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
689,
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]
],
"normalized": []
},
{
"id": "113_T17",
"type": "Biological_Activity",
"text": [
"kinase"
],
"offsets": [
[
850,
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]
],
"normalized": []
},
{
"id": "113_T19",
"type": "Protein",
"text": [
"protein"
],
"offsets": [
[
873,
880
]
],
"normalized": []
},
{
"id": "113_T22",
"type": "Biological_Activity",
"text": [
"blocked"
],
"offsets": [
[
904,
911
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "113_R1",
"type": "Associated_With",
"arg1_id": "113_T1",
"arg2_id": "113_T5",
"normalized": []
},
{
"id": "113_R2",
"type": "Associated_With",
"arg1_id": "113_T2",
"arg2_id": "113_T5",
"normalized": []
},
{
"id": "113_R3",
"type": "Associated_With",
"arg1_id": "113_T1",
"arg2_id": "113_T11",
"normalized": []
},
{
"id": "113_R7",
"type": "Associated_With",
"arg1_id": "113_T23",
"arg2_id": "113_T27",
"normalized": []
},
{
"id": "113_R11",
"type": "Associated_With",
"arg1_id": "113_T23",
"arg2_id": "113_T30",
"normalized": []
},
{
"id": "113_R13",
"type": "Associated_With",
"arg1_id": "113_T23",
"arg2_id": "113_T34",
"normalized": []
},
{
"id": "113_R19",
"type": "Binds_With",
"arg1_id": "113_T1",
"arg2_id": "113_T3",
"normalized": []
},
{
"id": "113_R20",
"type": "Binds_With",
"arg1_id": "113_T1",
"arg2_id": "113_T4",
"normalized": []
},
{
"id": "113_R15",
"type": "Binds_With",
"arg1_id": "113_T2",
"arg2_id": "113_T3",
"normalized": []
},
{
"id": "113_R16",
"type": "Associated_With",
"arg1_id": "113_T1",
"arg2_id": "113_T5",
"normalized": []
},
{
"id": "113_R4",
"type": "Associated_With",
"arg1_id": "113_T23",
"arg2_id": "113_T12",
"normalized": []
},
{
"id": "113_R21",
"type": "Associated_With",
"arg1_id": "113_T24",
"arg2_id": "113_T12",
"normalized": []
},
{
"id": "113_R5",
"type": "Binds_With",
"arg1_id": "113_T23",
"arg2_id": "113_T25",
"normalized": []
},
{
"id": "113_R6",
"type": "Binds_With",
"arg1_id": "113_T24",
"arg2_id": "113_T25",
"normalized": []
},
{
"id": "113_R9",
"type": "Associated_With",
"arg1_id": "113_T23",
"arg2_id": "113_T22",
"normalized": []
},
{
"id": "113_R14",
"type": "Associated_With",
"arg1_id": "113_T40",
"arg2_id": "113_T34",
"normalized": []
},
{
"id": "113_R12",
"type": "Associated_With",
"arg1_id": "113_T40",
"arg2_id": "113_T30",
"normalized": []
},
{
"id": "113_R10",
"type": "Associated_With",
"arg1_id": "113_T40",
"arg2_id": "113_T22",
"normalized": []
},
{
"id": "113_R8",
"type": "Associated_With",
"arg1_id": "113_T40",
"arg2_id": "113_T27",
"normalized": []
}
] |
114 | 10086989 | [
{
"id": "115",
"type": "",
"text": [
"Rhus javanica, a medicinal herb, has been shown to exhibit oral therapeutic anti-herpes simplex virus (HSV) activity in mice. We purified two major anti-HSV compounds, moronic acid and betulonic acid, from the herbal extract by extraction with ethyl acetate at pH 10 followed by chromatographic separations and examined their anti-HSV activity in vitro and in vivo. Moronic acid was quantitatively a major anti-HSV compound in the ethyl acetate-soluble fraction. The effective concentrations for 50% plaque reduction of moronic acid and betulonic acid for wild-type HSV type 1 (HSV-1) were 3.9 and 2.6 microgram/ml, respectively. The therapeutic index of moronic acid (10.3-16.3) was larger than that of betulonic acid (6.2). Susceptibility of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1, and wild-type HSV type 2 to moronic acid was similar to that of the wild-type HSV-1. When this compound was administered orally to mice infected cutaneously with HSV-1 three times daily, it significantly retarded the development of skin lesions and/or prolonged the mean survival times of infected mice without toxicity compared with the control. Moronic acid suppressed virus yields in the brain more efficiently than those in the skin. This was consistent with the prolongation of mean survival times. Thus, moronic acid was purified as a major anti-HSV compound from the herbal extract of Rhus javanica. Mode of the anti-HSV activity was different from that of ACV. Moronic acid showed oral therapeutic efficacy in HSV-infected mice and possessed novel anti-HSV activity that was consistent with that of the extract. \n"
],
"offsets": [
[
0,
1652
]
]
}
] | [
{
"id": "115_T1",
"type": "Species",
"text": [
"Rhus javanica"
],
"offsets": [
[
0,
13
]
],
"normalized": []
},
{
"id": "115_T2",
"type": "Biological_Activity",
"text": [
"anti-herpes simplex virus"
],
"offsets": [
[
76,
101
]
],
"normalized": []
},
{
"id": "115_T3",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
120,
124
]
],
"normalized": []
},
{
"id": "115_T4",
"type": "Metabolite",
"text": [
"moronic acid"
],
"offsets": [
[
169,
181
]
],
"normalized": []
},
{
"id": "115_T5",
"type": "Chemical",
"text": [
"betulonic acid"
],
"offsets": [
[
186,
200
]
],
"normalized": []
},
{
"id": "115_T6",
"type": "Chemical",
"text": [
"moronic acid"
],
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[
169,
181
]
],
"normalized": []
},
{
"id": "115_T7",
"type": "Metabolite",
"text": [
"betulonic acid"
],
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[
186,
200
]
],
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},
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"id": "115_T8",
"type": "Chemical",
"text": [
"ethyl acetate"
],
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245,
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]
],
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},
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"id": "115_T9",
"type": "Biological_Activity",
"text": [
"anti-HSV"
],
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[
328,
336
]
],
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},
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"id": "115_T10",
"type": "Biological_Activity",
"text": [
"anti-HSV"
],
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[
148,
156
]
],
"normalized": []
},
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"id": "115_T11",
"type": "Metabolite",
"text": [
"Moronic acid"
],
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[
368,
380
]
],
"normalized": []
},
{
"id": "115_T12",
"type": "Chemical",
"text": [
"Moronic acid"
],
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[
368,
380
]
],
"normalized": []
},
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"id": "115_T13",
"type": "Biological_Activity",
"text": [
"anti-HSV"
],
"offsets": [
[
408,
416
]
],
"normalized": []
},
{
"id": "115_T14",
"type": "Chemical",
"text": [
"ethyl acetate"
],
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[
433,
446
]
],
"normalized": []
},
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"id": "115_T15",
"type": "Chemical",
"text": [
"moronic acid"
],
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522,
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],
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},
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"text": [
"betulonic acid"
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539,
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],
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"id": "115_T17",
"type": "Metabolite",
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"moronic acid"
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522,
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]
],
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},
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"id": "115_T18",
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[
539,
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],
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"text": [
"moronic acid"
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657,
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],
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"text": [
"moronic acid"
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657,
669
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},
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"id": "115_T21",
"type": "Chemical",
"text": [
"betulonic acid"
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706,
720
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],
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},
{
"id": "115_T22",
"type": "Metabolite",
"text": [
"betulonic acid"
],
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[
706,
720
]
],
"normalized": []
},
{
"id": "115_T23",
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"text": [
"moronic acid"
],
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856,
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},
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"id": "115_T24",
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"text": [
"moronic acid"
],
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[
856,
868
]
],
"normalized": []
},
{
"id": "115_T25",
"type": "Chemical",
"text": [
"acyclovir"
],
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[
746,
755
]
],
"normalized": []
},
{
"id": "115_T26",
"type": "Chemical",
"text": [
"phosphonoacetic acid"
],
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[
756,
776
]
],
"normalized": []
},
{
"id": "115_T27",
"type": "Chemical",
"text": [
"thymidine"
],
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[
794,
803
]
],
"normalized": []
},
{
"id": "115_T28",
"type": "Protein",
"text": [
"thymidine kinase"
],
"offsets": [
[
794,
810
]
],
"normalized": []
},
{
"id": "115_T29",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
959,
963
]
],
"normalized": []
},
{
"id": "115_T31",
"type": "Species",
"text": [
"mice"
],
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[
1127,
1131
]
],
"normalized": []
},
{
"id": "115_T32",
"type": "Chemical",
"text": [
"Moronic acid"
],
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1176,
1188
]
],
"normalized": []
},
{
"id": "115_T33",
"type": "Metabolite",
"text": [
"Moronic acid"
],
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[
1176,
1188
]
],
"normalized": []
},
{
"id": "115_T34",
"type": "Chemical",
"text": [
"moronic acid"
],
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[
1340,
1352
]
],
"normalized": []
},
{
"id": "115_T35",
"type": "Metabolite",
"text": [
"moronic acid"
],
"offsets": [
[
1340,
1352
]
],
"normalized": []
},
{
"id": "115_T36",
"type": "Biological_Activity",
"text": [
"anti-HSV"
],
"offsets": [
[
1377,
1385
]
],
"normalized": []
},
{
"id": "115_T37",
"type": "Species",
"text": [
"Rhus javanica"
],
"offsets": [
[
1422,
1435
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],
"normalized": []
},
{
"id": "115_T38",
"type": "Biological_Activity",
"text": [
"anti-HSV"
],
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[
1449,
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]
],
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},
{
"id": "115_T39",
"type": "Chemical",
"text": [
"ACV"
],
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[
1494,
1497
]
],
"normalized": []
},
{
"id": "115_T40",
"type": "Species",
"text": [
"mice"
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1561,
1565
]
],
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},
{
"id": "115_T41",
"type": "Chemical",
"text": [
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],
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1499,
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]
],
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},
{
"id": "115_T42",
"type": "Metabolite",
"text": [
"Moronic acid"
],
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[
1499,
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]
],
"normalized": []
},
{
"id": "115_T43",
"type": "Biological_Activity",
"text": [
"anti-HSV"
],
"offsets": [
[
1587,
1595
]
],
"normalized": []
},
{
"id": "115_T44",
"type": "Biological_Activity",
"text": [
"HSV",
"anti-"
],
"offsets": [
[
103,
106
],
[
76,
81
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "115_R1",
"type": "Isolated_From",
"arg1_id": "115_T4",
"arg2_id": "115_T1",
"normalized": []
},
{
"id": "115_R2",
"type": "Isolated_From",
"arg1_id": "115_T7",
"arg2_id": "115_T1",
"normalized": []
},
{
"id": "115_R3",
"type": "Associated_With",
"arg1_id": "115_T11",
"arg2_id": "115_T13",
"normalized": []
},
{
"id": "115_R4",
"type": "Associated_With",
"arg1_id": "115_T12",
"arg2_id": "115_T13",
"normalized": []
},
{
"id": "115_R7",
"type": "Associated_With",
"arg1_id": "115_T35",
"arg2_id": "115_T36",
"normalized": []
},
{
"id": "115_R8",
"type": "Associated_With",
"arg1_id": "115_T34",
"arg2_id": "115_T36",
"normalized": []
},
{
"id": "115_R9",
"type": "Isolated_From",
"arg1_id": "115_T35",
"arg2_id": "115_T37",
"normalized": []
},
{
"id": "115_R10",
"type": "Associated_With",
"arg1_id": "115_T42",
"arg2_id": "115_T43",
"normalized": []
},
{
"id": "115_R11",
"type": "Associated_With",
"arg1_id": "115_T41",
"arg2_id": "115_T43",
"normalized": []
},
{
"id": "115_R12",
"type": "Associated_With",
"arg1_id": "115_T4",
"arg2_id": "115_T10",
"normalized": []
},
{
"id": "115_R13",
"type": "Associated_With",
"arg1_id": "115_T6",
"arg2_id": "115_T10",
"normalized": []
},
{
"id": "115_R14",
"type": "Associated_With",
"arg1_id": "115_T7",
"arg2_id": "115_T10",
"normalized": []
},
{
"id": "115_R15",
"type": "Associated_With",
"arg1_id": "115_T5",
"arg2_id": "115_T10",
"normalized": []
}
] |
116 | 10088182 | [
{
"id": "117",
"type": "",
"text": [
"Ethylene-di-bromide is a popular fumigant. Delayed long-term effects of this chemical include carcinogenicity and genotoxicity in animals. Only a few cases of acute ethylene-di-bromide toxicity have been reported and all of them have resulted in a fatal outcome. We report the first case of ethylene-di-bromide poisoning presenting with acute renal failure and toxic hepatitis that was managed successfully. \n"
],
"offsets": [
[
0,
409
]
]
}
] | [
{
"id": "117_T1",
"type": "Chemical",
"text": [
"Ethylene-di-bromide"
],
"offsets": [
[
0,
19
]
],
"normalized": []
},
{
"id": "117_T3",
"type": "Biological_Activity",
"text": [
"carcinogenicity"
],
"offsets": [
[
94,
109
]
],
"normalized": []
},
{
"id": "117_T4",
"type": "Biological_Activity",
"text": [
"genotoxicity"
],
"offsets": [
[
114,
126
]
],
"normalized": []
},
{
"id": "117_T5",
"type": "Biological_Activity",
"text": [
"toxicity"
],
"offsets": [
[
185,
193
]
],
"normalized": []
},
{
"id": "117_T6",
"type": "Chemical",
"text": [
"ethylene-di-bromide"
],
"offsets": [
[
165,
184
]
],
"normalized": []
},
{
"id": "117_T7",
"type": "Chemical",
"text": [
"ethylene-di-bromide"
],
"offsets": [
[
291,
310
]
],
"normalized": []
},
{
"id": "117_T2",
"type": "Biological_Activity",
"text": [
"poisoning"
],
"offsets": [
[
311,
320
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "117_R2",
"type": "Associated_With",
"arg1_id": "117_T1",
"arg2_id": "117_T3",
"normalized": []
},
{
"id": "117_R3",
"type": "Associated_With",
"arg1_id": "117_T1",
"arg2_id": "117_T4",
"normalized": []
},
{
"id": "117_R4",
"type": "Associated_With",
"arg1_id": "117_T6",
"arg2_id": "117_T5",
"normalized": []
},
{
"id": "117_R1",
"type": "Associated_With",
"arg1_id": "117_T7",
"arg2_id": "117_T2",
"normalized": []
}
] |
118 | 1008820 | [
{
"id": "119",
"type": "",
"text": [
"By using wild-type and deoxystreptamine-negative mutants of Streptomyces fradiae grown in media containing [6(-3)H]glucose or [U-14C]glucose, and by subsequent hydrolysis of the labelled neomycin produced, neamines labelled with 3H in both rings I and II, but with 14C in ring I only, were prepared. A mixture of these two forms of neamine was converted by deoxystreptamine-negative Streptomyces rimosus forma paromomycinus into neomycin (not paromomycin) with a 30% yield. The3H: 14C ratio in this neomycin was the same as the measured in neamine produced by hydrolysis of the neomycin, and in unused neamine reisolated from the incubation medium. The 3H:14C ratio in the neomycin was not affected by the presence of unlabelled deoxystreptamine during the incubation. The radioactivity in the neomycin was associated with rings I and II only. It is concluded that the added neamine is incorporated into antibiotic intact, without initial hydrolysis, and that the probable first step in the subunit assembly of neomycin is the formation of neamine. \n"
],
"offsets": [
[
0,
1052
]
]
}
] | [
{
"id": "119_T1",
"type": "Species",
"text": [
"Streptomyces fradiae"
],
"offsets": [
[
60,
80
]
],
"normalized": []
},
{
"id": "119_T2",
"type": "Chemical",
"text": [
"deoxystreptamine"
],
"offsets": [
[
23,
39
]
],
"normalized": []
},
{
"id": "119_T3",
"type": "Chemical",
"text": [
"[6(-3)H]glucose"
],
"offsets": [
[
108,
123
]
],
"normalized": []
},
{
"id": "119_T4",
"type": "Chemical",
"text": [
"neomycin"
],
"offsets": [
[
188,
196
]
],
"normalized": []
},
{
"id": "119_T5",
"type": "Chemical",
"text": [
"neamines"
],
"offsets": [
[
207,
215
]
],
"normalized": []
},
{
"id": "119_T6",
"type": "Chemical",
"text": [
"3H"
],
"offsets": [
[
230,
232
]
],
"normalized": []
},
{
"id": "119_T7",
"type": "Chemical",
"text": [
"14C"
],
"offsets": [
[
266,
269
]
],
"normalized": []
},
{
"id": "119_T8",
"type": "Chemical",
"text": [
"neamine"
],
"offsets": [
[
333,
340
]
],
"normalized": []
},
{
"id": "119_T9",
"type": "Chemical",
"text": [
"deoxystreptamine"
],
"offsets": [
[
358,
374
]
],
"normalized": []
},
{
"id": "119_T10",
"type": "Species",
"text": [
"Streptomyces rimosus forma paromomycinus"
],
"offsets": [
[
384,
424
]
],
"normalized": []
},
{
"id": "119_T11",
"type": "Chemical",
"text": [
"neomycin"
],
"offsets": [
[
430,
438
]
],
"normalized": []
},
{
"id": "119_T12",
"type": "Chemical",
"text": [
"paromomycin"
],
"offsets": [
[
444,
455
]
],
"normalized": []
},
{
"id": "119_T13",
"type": "Chemical",
"text": [
"labelled neomycin"
],
"offsets": [
[
179,
196
]
],
"normalized": []
},
{
"id": "119_T14",
"type": "Metabolite",
"text": [
"neomycin"
],
"offsets": [
[
188,
196
]
],
"normalized": []
},
{
"id": "119_T15",
"type": "Metabolite",
"text": [
"neomycin"
],
"offsets": [
[
500,
508
]
],
"normalized": []
},
{
"id": "119_T16",
"type": "Chemical",
"text": [
"3H"
],
"offsets": [
[
478,
480
]
],
"normalized": []
},
{
"id": "119_T17",
"type": "Chemical",
"text": [
"14C"
],
"offsets": [
[
482,
485
]
],
"normalized": []
},
{
"id": "119_T18",
"type": "Chemical",
"text": [
"3H"
],
"offsets": [
[
654,
656
]
],
"normalized": []
},
{
"id": "119_T19",
"type": "Chemical",
"text": [
"14C"
],
"offsets": [
[
657,
660
]
],
"normalized": []
},
{
"id": "119_T20",
"type": "Chemical",
"text": [
"neomycin"
],
"offsets": [
[
674,
682
]
],
"normalized": []
},
{
"id": "119_T21",
"type": "Chemical",
"text": [
"neomycin"
],
"offsets": [
[
500,
508
]
],
"normalized": []
},
{
"id": "119_T22",
"type": "Metabolite",
"text": [
"neomycin"
],
"offsets": [
[
674,
682
]
],
"normalized": []
},
{
"id": "119_T23",
"type": "Chemical",
"text": [
"neamine"
],
"offsets": [
[
541,
548
]
],
"normalized": []
},
{
"id": "119_T24",
"type": "Chemical",
"text": [
"neomycin"
],
"offsets": [
[
579,
587
]
],
"normalized": []
},
{
"id": "119_T25",
"type": "Metabolite",
"text": [
"neomycin"
],
"offsets": [
[
579,
587
]
],
"normalized": []
},
{
"id": "119_T26",
"type": "Chemical",
"text": [
"neamine"
],
"offsets": [
[
603,
610
]
],
"normalized": []
},
{
"id": "119_T27",
"type": "Chemical",
"text": [
"deoxystreptamine"
],
"offsets": [
[
730,
746
]
],
"normalized": []
},
{
"id": "119_T28",
"type": "Chemical",
"text": [
"neomycin"
],
"offsets": [
[
796,
804
]
],
"normalized": []
},
{
"id": "119_T29",
"type": "Metabolite",
"text": [
"neomycin"
],
"offsets": [
[
796,
804
]
],
"normalized": []
},
{
"id": "119_T30",
"type": "Chemical",
"text": [
"neamine"
],
"offsets": [
[
877,
884
]
],
"normalized": []
},
{
"id": "119_T32",
"type": "Chemical",
"text": [
"neomycin"
],
"offsets": [
[
1013,
1021
]
],
"normalized": []
},
{
"id": "119_T33",
"type": "Metabolite",
"text": [
"neomycin"
],
"offsets": [
[
1013,
1021
]
],
"normalized": []
},
{
"id": "119_T34",
"type": "Chemical",
"text": [
"neamine"
],
"offsets": [
[
1042,
1049
]
],
"normalized": []
},
{
"id": "119_T35",
"type": "Metabolite",
"text": [
"neamine"
],
"offsets": [
[
1042,
1049
]
],
"normalized": []
},
{
"id": "119_T31",
"type": "Chemical",
"text": [
"[U-14C]glucose"
],
"offsets": [
[
127,
141
]
],
"normalized": []
},
{
"id": "119_T36",
"type": "Metabolite",
"text": [
"neomycin"
],
"offsets": [
[
430,
438
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "119_R1",
"type": "Isolated_From",
"arg1_id": "119_T14",
"arg2_id": "119_T1",
"normalized": []
},
{
"id": "119_R2",
"type": "Metabolite_Of",
"arg1_id": "119_T36",
"arg2_id": "119_T8",
"normalized": []
},
{
"id": "119_R3",
"type": "Isolated_From",
"arg1_id": "119_T36",
"arg2_id": "119_T10",
"normalized": []
},
{
"id": "119_R4",
"type": "Metabolite_Of",
"arg1_id": "119_T33",
"arg2_id": "119_T34",
"normalized": []
}
] |
120 | 1008863 | [
{
"id": "121",
"type": "",
"text": [
"Extraction with butan-1-ol of freeze-dried microsomal fractions from livers of 3-methyl-cholarthrene-pre-treated hamsters removed about 90% of the total lipid content, but the lipid remaining proved sufficient for the cytochrome P-450 enzyme system to retain about 15-40% of its original catalytic activity for dimethylnitrosamine demethylation. Addition of butan-1-ol-extracted total phospholipid or phosphatidylcholine could not restore any activity, whereas the addition of the synthetic phospholipid dilauroyl phosphatidylcholine was able to restore almost complete activity. Synthetic dipalmitoyl or distearoyl phosphatidylcholine was ineffective in restoring the activity in this reconstituted system. \n"
],
"offsets": [
[
0,
710
]
]
}
] | [
{
"id": "121_T1",
"type": "Chemical",
"text": [
"butan-1-ol"
],
"offsets": [
[
16,
26
]
],
"normalized": []
},
{
"id": "121_T2",
"type": "Chemical",
"text": [
"3-methyl-cholarthrene"
],
"offsets": [
[
79,
100
]
],
"normalized": []
},
{
"id": "121_T3",
"type": "Species",
"text": [
"hamsters"
],
"offsets": [
[
113,
121
]
],
"normalized": []
},
{
"id": "121_T4",
"type": "Chemical",
"text": [
"lipid"
],
"offsets": [
[
153,
158
]
],
"normalized": []
},
{
"id": "121_T5",
"type": "Chemical",
"text": [
"lipid"
],
"offsets": [
[
176,
181
]
],
"normalized": []
},
{
"id": "121_T7",
"type": "Protein",
"text": [
"cytochrome P-450"
],
"offsets": [
[
218,
234
]
],
"normalized": []
},
{
"id": "121_T8",
"type": "Chemical",
"text": [
"dimethylnitrosamine"
],
"offsets": [
[
311,
330
]
],
"normalized": []
},
{
"id": "121_T10",
"type": "Chemical",
"text": [
"butan-1-ol"
],
"offsets": [
[
358,
368
]
],
"normalized": []
},
{
"id": "121_T11",
"type": "Chemical",
"text": [
"phospholipid"
],
"offsets": [
[
385,
397
]
],
"normalized": []
},
{
"id": "121_T12",
"type": "Chemical",
"text": [
"phosphatidylcholine"
],
"offsets": [
[
401,
420
]
],
"normalized": []
},
{
"id": "121_T13",
"type": "Chemical",
"text": [
"phospholipid"
],
"offsets": [
[
491,
503
]
],
"normalized": []
},
{
"id": "121_T14",
"type": "Chemical",
"text": [
"dilauroyl phosphatidylcholine"
],
"offsets": [
[
504,
533
]
],
"normalized": []
},
{
"id": "121_T15",
"type": "Chemical",
"text": [
"dipalmitoyl",
"phosphatidylcholine"
],
"offsets": [
[
591,
602
],
[
617,
636
]
],
"normalized": []
},
{
"id": "121_T16",
"type": "Chemical",
"text": [
"distearoyl phosphatidylcholine"
],
"offsets": [
[
606,
636
]
],
"normalized": []
}
] | [] | [] | [] |
122 | 10088651 | [
{
"id": "123",
"type": "",
"text": [
"The prevention of cerebral palsy and neuroprotection of the immature brain continue to be health care priorities. The pathophysiology of perinatal brain lesions associated with cerebral palsy seems to be multifactorial and includes pre- and perinatal factors such as preconceptional events, hormone and growth factors deficiencies, maternal infections with production of cytokines, and hypoxic/ischemic perfusion failures. Excitotoxic cascade could represent a common pathway that leads to neural cell death and subsequent brain damage. Brain injuries induced by ibotenate, a glutamatergic analog, which are essentially mediated through the N-methyl-D-aspartate receptor, mimic some aspects of the white matter cysts and transcortical necrosis observed in human perinatal brain damage. The purpose of the present study was to assess the protective role of several pharmacological agents, administered in conjunction with ibotenate, against induced excitotoxic lesions. We injected ibotenate in the developing mouse brain 5 d postnatally, after the full settlement of neuronal layers. Co-treatment with kynurenic acid, an antagonist of the facilitating glycine site of the N-methyl-D-aspartate receptor, or with N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, induced a dose-dependent neuroprotective effect. Conversely, zinc gluconate, a blocking agent of the channel linked to the N-methyl-D-aspartate receptor, and a free radical scavenger (U74389F), were unable to protect the developing brain against excitotoxic attack. These data help to clarify some molecular mechanisms involved in excitotoxic lesions of the developing mouse brain and permit us to envision new strategies in the prevention of cerebral palsy. \n"
],
"offsets": [
[
0,
1736
]
]
}
] | [
{
"id": "123_T1",
"type": "Biological_Activity",
"text": [
"neuroprotection"
],
"offsets": [
[
37,
52
]
],
"normalized": []
},
{
"id": "123_T5",
"type": "Chemical",
"text": [
"ibotenate"
],
"offsets": [
[
563,
572
]
],
"normalized": []
},
{
"id": "123_T7",
"type": "Protein",
"text": [
"N-methyl-D-aspartate receptor"
],
"offsets": [
[
641,
670
]
],
"normalized": []
},
{
"id": "123_T10",
"type": "Chemical",
"text": [
"ibotenate"
],
"offsets": [
[
921,
930
]
],
"normalized": []
},
{
"id": "123_T11",
"type": "Chemical",
"text": [
"ibotenate"
],
"offsets": [
[
981,
990
]
],
"normalized": []
},
{
"id": "123_T12",
"type": "Species",
"text": [
"mouse"
],
"offsets": [
[
1009,
1014
]
],
"normalized": []
},
{
"id": "123_T13",
"type": "Chemical",
"text": [
"kynurenic acid"
],
"offsets": [
[
1102,
1116
]
],
"normalized": []
},
{
"id": "123_T14",
"type": "Chemical",
"text": [
"N-methyl-D-aspartate"
],
"offsets": [
[
1173,
1193
]
],
"normalized": []
},
{
"id": "123_T15",
"type": "Protein",
"text": [
"N-methyl-D-aspartate receptor"
],
"offsets": [
[
1173,
1202
]
],
"normalized": []
},
{
"id": "123_T17",
"type": "Biological_Activity",
"text": [
"antagonist"
],
"offsets": [
[
1121,
1131
]
],
"normalized": []
},
{
"id": "123_T18",
"type": "Chemical",
"text": [
"N(G)-nitro-L-arginine"
],
"offsets": [
[
1212,
1233
]
],
"normalized": []
},
{
"id": "123_T19",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
1238,
1247
]
],
"normalized": []
},
{
"id": "123_T20",
"type": "Biological_Activity",
"text": [
"neuroprotective"
],
"offsets": [
[
1300,
1315
]
],
"normalized": []
},
{
"id": "123_T21",
"type": "Chemical",
"text": [
"inc gluconate"
],
"offsets": [
[
1337,
1350
]
],
"normalized": []
},
{
"id": "123_T22",
"type": "Chemical",
"text": [
"N-methyl-D-aspartate"
],
"offsets": [
[
1398,
1418
]
],
"normalized": []
},
{
"id": "123_T23",
"type": "Protein",
"text": [
"N-methyl-D-aspartate receptor"
],
"offsets": [
[
1398,
1427
]
],
"normalized": []
},
{
"id": "123_T25",
"type": "Biological_Activity",
"text": [
"scavenger"
],
"offsets": [
[
1448,
1457
]
],
"normalized": []
},
{
"id": "123_T26",
"type": "Chemical",
"text": [
"U74389F"
],
"offsets": [
[
1459,
1466
]
],
"normalized": []
},
{
"id": "123_T27",
"type": "Biological_Activity",
"text": [
"blocking agent"
],
"offsets": [
[
1354,
1368
]
],
"normalized": []
},
{
"id": "123_T28",
"type": "Species",
"text": [
"mouse"
],
"offsets": [
[
1645,
1650
]
],
"normalized": []
},
{
"id": "123_T6",
"type": "Biological_Activity",
"text": [
"necrosis"
],
"offsets": [
[
735,
743
]
],
"normalized": []
},
{
"id": "123_T31",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
756,
761
]
],
"normalized": []
},
{
"id": "123_T34",
"type": "Protein",
"text": [
"cytokines"
],
"offsets": [
[
371,
380
]
],
"normalized": []
},
{
"id": "123_T2",
"type": "Chemical",
"text": [
"glycine"
],
"offsets": [
[
1152,
1159
]
],
"normalized": []
},
{
"id": "123_T3",
"type": "Chemical",
"text": [
"nitric oxide"
],
"offsets": [
[
1251,
1263
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "123_R2",
"type": "Associated_With",
"arg1_id": "123_T13",
"arg2_id": "123_T17",
"normalized": []
},
{
"id": "123_R3",
"type": "Associated_With",
"arg1_id": "123_T18",
"arg2_id": "123_T19",
"normalized": []
},
{
"id": "123_R4",
"type": "Associated_With",
"arg1_id": "123_T13",
"arg2_id": "123_T20",
"normalized": []
},
{
"id": "123_R5",
"type": "Associated_With",
"arg1_id": "123_T18",
"arg2_id": "123_T20",
"normalized": []
},
{
"id": "123_R6",
"type": "Associated_With",
"arg1_id": "123_T26",
"arg2_id": "123_T25",
"normalized": []
},
{
"id": "123_R7",
"type": "Associated_With",
"arg1_id": "123_T21",
"arg2_id": "123_T27",
"normalized": []
},
{
"id": "123_R1",
"type": "Binds_With",
"arg1_id": "123_T13",
"arg2_id": "123_T15",
"normalized": []
},
{
"id": "123_R8",
"type": "Binds_With",
"arg1_id": "123_T21",
"arg2_id": "123_T23",
"normalized": []
}
] |
124 | 10092191 | [
{
"id": "125",
"type": "",
"text": [
"A novel tricyclic diterpenoid antibiotic, brasilicardin A, was isolated from the culture broth of Nocardia brasiliensis IFM 0406. The antibiotic exhibited immunosuppressive activity in a mouse mixed lymphocyte reaction (MLR) assay system and its IC50 value was 0.057 microg/ml. Although the inhibitory activity of cyclosporin A (CyA) against IL-2 production was confirmed in the MLR assay system, brasilicardin A did not have the activity. The results of in vitro toxicity testing of brasilicardin A against various human cell lines were compared with those of CyA. \n"
],
"offsets": [
[
0,
568
]
]
}
] | [
{
"id": "125_T1",
"type": "Chemical",
"text": [
"tricyclic diterpenoid"
],
"offsets": [
[
8,
29
]
],
"normalized": []
},
{
"id": "125_T2",
"type": "Biological_Activity",
"text": [
"antibiotic"
],
"offsets": [
[
30,
40
]
],
"normalized": []
},
{
"id": "125_T3",
"type": "Chemical",
"text": [
"brasilicardin A"
],
"offsets": [
[
42,
57
]
],
"normalized": []
},
{
"id": "125_T4",
"type": "Metabolite",
"text": [
"brasilicardin A"
],
"offsets": [
[
42,
57
]
],
"normalized": []
},
{
"id": "125_T5",
"type": "Species",
"text": [
"Nocardia brasiliensis IFM 0406"
],
"offsets": [
[
99,
129
]
],
"normalized": []
},
{
"id": "125_T6",
"type": "Biological_Activity",
"text": [
"antibiotic"
],
"offsets": [
[
135,
145
]
],
"normalized": []
},
{
"id": "125_T7",
"type": "Biological_Activity",
"text": [
"immunosuppressive"
],
"offsets": [
[
156,
173
]
],
"normalized": []
},
{
"id": "125_T8",
"type": "Species",
"text": [
"mouse"
],
"offsets": [
[
188,
193
]
],
"normalized": []
},
{
"id": "125_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
343,
347
]
],
"normalized": []
},
{
"id": "125_T10",
"type": "Chemical",
"text": [
"cyclosporin A"
],
"offsets": [
[
315,
328
]
],
"normalized": []
},
{
"id": "125_T11",
"type": "Chemical",
"text": [
"CyA"
],
"offsets": [
[
330,
333
]
],
"normalized": []
},
{
"id": "125_T12",
"type": "Chemical",
"text": [
"brasilicardin A"
],
"offsets": [
[
398,
413
]
],
"normalized": []
},
{
"id": "125_T13",
"type": "Metabolite",
"text": [
"brasilicardin A"
],
"offsets": [
[
398,
413
]
],
"normalized": []
},
{
"id": "125_T14",
"type": "Chemical",
"text": [
"brasilicardin A"
],
"offsets": [
[
485,
500
]
],
"normalized": []
},
{
"id": "125_T15",
"type": "Metabolite",
"text": [
"brasilicardin A"
],
"offsets": [
[
485,
500
]
],
"normalized": []
},
{
"id": "125_T16",
"type": "Biological_Activity",
"text": [
"toxicity"
],
"offsets": [
[
465,
473
]
],
"normalized": []
},
{
"id": "125_T17",
"type": "Biological_Activity",
"text": [
"inhibitor"
],
"offsets": [
[
292,
301
]
],
"normalized": []
},
{
"id": "125_T18",
"type": "Chemical",
"text": [
"CyA"
],
"offsets": [
[
562,
565
]
],
"normalized": []
},
{
"id": "125_T19",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
517,
522
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "125_R1",
"type": "Associated_With",
"arg1_id": "125_T4",
"arg2_id": "125_T2",
"normalized": []
},
{
"id": "125_R2",
"type": "Associated_With",
"arg1_id": "125_T3",
"arg2_id": "125_T2",
"normalized": []
},
{
"id": "125_R3",
"type": "Isolated_From",
"arg1_id": "125_T4",
"arg2_id": "125_T5",
"normalized": []
},
{
"id": "125_R4",
"type": "Associated_With",
"arg1_id": "125_T3",
"arg2_id": "125_T7",
"normalized": []
},
{
"id": "125_R5",
"type": "Associated_With",
"arg1_id": "125_T3",
"arg2_id": "125_T7",
"normalized": []
},
{
"id": "125_R6",
"type": "Associated_With",
"arg1_id": "125_T10",
"arg2_id": "125_T17",
"normalized": []
},
{
"id": "125_R7",
"type": "Associated_With",
"arg1_id": "125_T11",
"arg2_id": "125_T17",
"normalized": []
}
] |
126 | 10092192 | [
{
"id": "127",
"type": "",
"text": [
"IC202A, a new immunosuppressive compound, was isolated from the culture filtrate of Streptoalloteichus sp. 1454-19. It showed a suppressive effect on mixed lymphocyte culture reaction with an IC50 value of 3.6 microg/ml and mitogen induced lymphocyte blastogenesis in vitro. \n"
],
"offsets": [
[
0,
277
]
]
}
] | [
{
"id": "127_T1",
"type": "Chemical",
"text": [
"IC202A"
],
"offsets": [
[
0,
6
]
],
"normalized": []
},
{
"id": "127_T2",
"type": "Biological_Activity",
"text": [
"immunosuppressive"
],
"offsets": [
[
14,
31
]
],
"normalized": []
},
{
"id": "127_T3",
"type": "Metabolite",
"text": [
"IC202A"
],
"offsets": [
[
0,
6
]
],
"normalized": []
},
{
"id": "127_T4",
"type": "Species",
"text": [
"Streptoalloteichus sp. 1454-19"
],
"offsets": [
[
85,
115
]
],
"normalized": []
},
{
"id": "127_T5",
"type": "Protein",
"text": [
"mitogen"
],
"offsets": [
[
225,
232
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "127_R1",
"type": "Associated_With",
"arg1_id": "127_T1",
"arg2_id": "127_T2",
"normalized": []
},
{
"id": "127_R2",
"type": "Isolated_From",
"arg1_id": "127_T3",
"arg2_id": "127_T4",
"normalized": []
},
{
"id": "127_R5",
"type": "Associated_With",
"arg1_id": "127_T3",
"arg2_id": "127_T2",
"normalized": []
}
] |
128 | 10092193 | [
{
"id": "129",
"type": "",
"text": [
"IC202A (1) was isolated from the culture filtrate of Streptoalloteichus sp. 1454-19. The structure of 1 was determined by spectral analysis including a variety of two-dimentional NMR and FAB-MS experiments. IC202A is a ferrioxamine-related compound containing a butylidene N-oxide function. \n"
],
"offsets": [
[
0,
292
]
]
}
] | [
{
"id": "129_T1",
"type": "Chemical",
"text": [
"IC202A"
],
"offsets": [
[
0,
6
]
],
"normalized": []
},
{
"id": "129_T2",
"type": "Metabolite",
"text": [
"IC202A"
],
"offsets": [
[
0,
6
]
],
"normalized": []
},
{
"id": "129_T3",
"type": "Species",
"text": [
"Streptoalloteichus sp. 1454-19"
],
"offsets": [
[
53,
83
]
],
"normalized": []
},
{
"id": "129_T4",
"type": "Spectral_Data",
"text": [
"spectral analysis"
],
"offsets": [
[
122,
139
]
],
"normalized": []
},
{
"id": "129_T5",
"type": "Spectral_Data",
"text": [
"two-dimentional NMR"
],
"offsets": [
[
163,
182
]
],
"normalized": []
},
{
"id": "129_T6",
"type": "Chemical",
"text": [
"IC202A"
],
"offsets": [
[
207,
213
]
],
"normalized": []
},
{
"id": "129_T7",
"type": "Metabolite",
"text": [
"IC202A"
],
"offsets": [
[
207,
213
]
],
"normalized": []
},
{
"id": "129_T8",
"type": "Chemical",
"text": [
"ferrioxamine"
],
"offsets": [
[
219,
231
]
],
"normalized": []
},
{
"id": "129_T9",
"type": "Chemical",
"text": [
"butylidene N-oxide"
],
"offsets": [
[
262,
280
]
],
"normalized": []
},
{
"id": "129_T10",
"type": "Spectral_Data",
"text": [
"FAB-MS experiments"
],
"offsets": [
[
187,
205
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "129_R1",
"type": "Associated_With",
"arg1_id": "129_T2",
"arg2_id": "129_T4",
"normalized": []
},
{
"id": "129_R2",
"type": "Associated_With",
"arg1_id": "129_T1",
"arg2_id": "129_T4",
"normalized": []
},
{
"id": "129_R3",
"type": "Associated_With",
"arg1_id": "129_T1",
"arg2_id": "129_T5",
"normalized": []
},
{
"id": "129_R4",
"type": "Associated_With",
"arg1_id": "129_T1",
"arg2_id": "129_T5",
"normalized": []
},
{
"id": "129_R5",
"type": "Isolated_From",
"arg1_id": "129_T2",
"arg2_id": "129_T3",
"normalized": []
},
{
"id": "129_R6",
"type": "Associated_With",
"arg1_id": "129_T1",
"arg2_id": "129_T10",
"normalized": []
},
{
"id": "129_R7",
"type": "Associated_With",
"arg1_id": "129_T2",
"arg2_id": "129_T10",
"normalized": []
}
] |
130 | 10092958 | [
{
"id": "131",
"type": "",
"text": [
"Meloxicam [4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine -3-carboxamide-1, 1-dioxide] is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class which shows preferential inhibition of cyclo-oxygenase-2. Meloxicam has a plasma half-life of approximately 20 hours, making it convenient for once-daily administration. Meloxicam is eliminated after biotransformation to 4 pharmacologically inactive metabolites, which are excreted in urine and faeces. Meloxicam and its metabolites bind extensively to plasma albumin. Substantial concentrations of meloxicam are attained in synovial fluid, the proposed site of action in chronic inflammatory arthropathies. Neither moderate renal nor hepatic insufficiency significantly alter the pharmacokinetics of meloxicam. Dosage adjustment is not required in the elderly. Drug-drug interaction studies are available for some commonly co-prescribed medications. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for this NSAID. \n"
],
"offsets": [
[
0,
1046
]
]
}
] | [
{
"id": "131_T1",
"type": "Chemical",
"text": [
"Meloxicam"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "131_T2",
"type": "Chemical",
"text": [
"4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine -3-carboxamide-1, 1-dioxide"
],
"offsets": [
[
11,
103
]
],
"normalized": []
},
{
"id": "131_T3",
"type": "Biological_Activity",
"text": [
"anti-inflammatory"
],
"offsets": [
[
123,
140
]
],
"normalized": []
},
{
"id": "131_T5",
"type": "Chemical",
"text": [
"oxicam"
],
"offsets": [
[
162,
168
]
],
"normalized": []
},
{
"id": "131_T6",
"type": "Biological_Activity",
"text": [
"inhibition"
],
"offsets": [
[
200,
210
]
],
"normalized": []
},
{
"id": "131_T7",
"type": "Chemical",
"text": [
"Meloxicam"
],
"offsets": [
[
233,
242
]
],
"normalized": []
},
{
"id": "131_T8",
"type": "Chemical",
"text": [
"Meloxicam"
],
"offsets": [
[
346,
355
]
],
"normalized": []
},
{
"id": "131_T9",
"type": "Chemical",
"text": [
"Meloxicam"
],
"offsets": [
[
479,
488
]
],
"normalized": []
},
{
"id": "131_T10",
"type": "Biological_Activity",
"text": [
"bind"
],
"offsets": [
[
509,
513
]
],
"normalized": []
},
{
"id": "131_T11",
"type": "Chemical",
"text": [
"meloxicam"
],
"offsets": [
[
575,
584
]
],
"normalized": []
},
{
"id": "131_T12",
"type": "Chemical",
"text": [
"meloxicam"
],
"offsets": [
[
779,
788
]
],
"normalized": []
},
{
"id": "131_T13",
"type": "Chemical",
"text": [
"nonsteroidal anti-inflammatory drug"
],
"offsets": [
[
110,
145
]
],
"normalized": []
},
{
"id": "131_T14",
"type": "Protein",
"text": [
"cyclo-oxygenase-2"
],
"offsets": [
[
214,
231
]
],
"normalized": []
},
{
"id": "131_T16",
"type": "Chemical",
"text": [
"Meloxicam",
"metabolites"
],
"offsets": [
[
479,
488
],
[
497,
508
]
],
"normalized": []
},
{
"id": "131_T17",
"type": "Metabolite",
"text": [
"Meloxicam",
"metabolites"
],
"offsets": [
[
479,
488
],
[
497,
508
]
],
"normalized": []
},
{
"id": "131_T19",
"type": "Chemical",
"text": [
"NSAID"
],
"offsets": [
[
147,
152
]
],
"normalized": []
},
{
"id": "131_T20",
"type": "Chemical",
"text": [
"NSAID"
],
"offsets": [
[
1038,
1043
]
],
"normalized": []
},
{
"id": "131_T21",
"type": "Biological_Activity",
"text": [
"toxicological"
],
"offsets": [
[
969,
982
]
],
"normalized": []
},
{
"id": "131_T15",
"type": "Biological_Activity",
"text": [
"biotransformation"
],
"offsets": [
[
376,
393
]
],
"normalized": []
},
{
"id": "131_T22",
"type": "Metabolite",
"text": [
"Meloxicam",
"metabolites"
],
"offsets": [
[
346,
355
],
[
426,
437
]
],
"normalized": []
},
{
"id": "131_T23",
"type": "Chemical",
"text": [
"Meloxicam",
"metabolites"
],
"offsets": [
[
346,
355
],
[
426,
437
]
],
"normalized": []
},
{
"id": "131_T24",
"type": "Chemical",
"text": [
"Drug"
],
"offsets": [
[
840,
844
]
],
"normalized": []
},
{
"id": "131_T25",
"type": "Chemical",
"text": [
"drug"
],
"offsets": [
[
845,
849
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "131_R1",
"type": "Associated_With",
"arg1_id": "131_T1",
"arg2_id": "131_T6",
"normalized": []
},
{
"id": "131_R2",
"type": "Associated_With",
"arg1_id": "131_T2",
"arg2_id": "131_T6",
"normalized": []
},
{
"id": "131_R3",
"type": "Associated_With",
"arg1_id": "131_T2",
"arg2_id": "131_T3",
"normalized": []
},
{
"id": "131_R4",
"type": "Associated_With",
"arg1_id": "131_T1",
"arg2_id": "131_T3",
"normalized": []
},
{
"id": "131_R5",
"type": "Associated_With",
"arg1_id": "131_T9",
"arg2_id": "131_T10",
"normalized": []
},
{
"id": "131_R9",
"type": "Associated_With",
"arg1_id": "131_T16",
"arg2_id": "131_T10",
"normalized": []
},
{
"id": "131_R10",
"type": "Associated_With",
"arg1_id": "131_T17",
"arg2_id": "131_T10",
"normalized": []
},
{
"id": "131_R11",
"type": "Binds_With",
"arg1_id": "131_T1",
"arg2_id": "131_T14",
"normalized": []
},
{
"id": "131_R12",
"type": "Binds_With",
"arg1_id": "131_T2",
"arg2_id": "131_T14",
"normalized": []
},
{
"id": "131_R7",
"type": "Metabolite_Of",
"arg1_id": "131_T22",
"arg2_id": "131_T8",
"normalized": []
}
] |
132 | 10093966 | [
{
"id": "133",
"type": "",
"text": [
"It is suspected that not only fibrinogen concentration but also the quality of fibrin networks may contribute to cardiovascular risk. Evidence is accumulating that a \"prudent\" diet may protect against diseases associated with raised clotting factors. The effect of diet on fibrinogen is, however, still controversial. In a previous study performed in our laboratory, it was shown that dietary pectin influences fibrin network architecture in hypercholesterolaemic men without causing any changes in fibrinogen concentration. To elucidate the possible mechanisms, it was necessary to study the possibility that pectin may itself have indirect effects on fibrin network architecture. Pectin is fermented in the gastrointestinal tract to acetate, propionate, and butyrate. In humans, only acetate reaches the circulation beyond the liver. This investigation primarily examined the possibility that pectin may, through acetate, influence fibrin network architecture in vivo. The effects of pectin and acetate supplementation in hypercholesterolaemic subjects were compared. Furthermore, this study also aimed at describing the possible in vitro effects of acetate on fibrin network architecture. Two groups of 10 male hyperlipidaemic volunteers each received a pectin (15 g/day) or acetate (6.8 g/day) supplement for 4 weeks. Acetate supplementation did not cause a significant change in plasma fibrinogen levels. As in the pectin group, significant differences were found in the characteristics of fibrin networks developed in plasma after 4 weeks of acetate supplementation. Fibrin networks were more permeable (from 213+/-76 to 307+/-81 x 10(11) cm2), had lower tensile strength (from 23+/-3 to 32+/-9% compaction), and were more lyseable (from 252+/-11 to 130+/-15 minutes). These results strongly suggest that the effect of pectin on network architecture could partially be mediated by acetate. Progressive amounts of acetate were used in vitro to investigate the possibility that acetate may be directly responsible for changes that occurred in fibrin network architecture in the plasma medium. Results indicated that acetate influenced fibrin network architecture directly. From the results, it seems highly possible that acetate may be responsible in part for the beneficial effects of pectin supplementation in vivo. It is evident that pectin or acetate supplementation can be useful during the treatment or prevention of some clinical manifestations, especially those associated with raised total cholesterol and possibly also plasma fibrinogen. \n"
],
"offsets": [
[
0,
2558
]
]
}
] | [
{
"id": "133_T1",
"type": "Protein",
"text": [
"fibrinogen"
],
"offsets": [
[
30,
40
]
],
"normalized": []
},
{
"id": "133_T2",
"type": "Protein",
"text": [
"fibrin"
],
"offsets": [
[
79,
85
]
],
"normalized": []
},
{
"id": "133_T3",
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}
] |
134 | 10094686 | [
{
"id": "135",
"type": "",
"text": [
"A glutathione S-transferase (GST) with activity toward 1, 2-epoxy-2-methyl-3-butene (isoprene monoxide) and cis-1, 2-dichloroepoxyethane was purified from the isoprene-utilizing bacterium Rhodococcus sp. strain AD45. The homodimeric enzyme (two subunits of 27 kDa each) catalyzed the glutathione (GSH)-dependent ring opening of various epoxides. At 5 mM GSH, the enzyme followed Michaelis-Menten kinetics for isoprene monoxide and cis-1, 2-dichloroepoxyethane, with Vmax values of 66 and 2.4 micromol min-1 mg of protein-1 and Km values of 0.3 and 0.1 mM for isoprene monoxide and cis-1,2-dichloroepoxyethane, respectively. Activities increased linearly with the GSH concentration up to 25 mM. 1H nuclear magnetic resonance spectroscopy showed that the product of GSH conjugation to isoprene monoxide was 1-hydroxy-2-glutathionyl-2-methyl-3-butene (HGMB). Thus, nucleophilic attack of GSH occurred on the tertiary carbon atom of the epoxide ring. HGMB was further converted by an NAD+-dependent dehydrogenase, and this enzyme was also purified from isoprene-grown cells. The homodimeric enzyme (two subunits of 25 kDa each) showed a high activity for HGMB, whereas simple primary and secondary alcohols were not oxidized. The enzyme catalyzed the sequential oxidation of the alcohol function to the corresponding aldehyde and carboxylic acid and followed Michaelis-Menten kinetics with respect to NAD+ and HGMB. The results suggest that the initial steps in isoprene metabolism are a monooxygenase-catalyzed conversion to isoprene monoxide, a GST-catalyzed conjugation to HGMB, and a dehydrogenase-catalyzed two-step oxidation to 2-glutathionyl-2-methyl-3-butenoic acid. \n"
],
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}
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284,
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297,
300
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336,
344
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354,
357
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426
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559,
576
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608
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"id": "135_T19",
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694,
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801
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850,
854
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886,
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934,
946
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948,
952
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"id": "135_T27",
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981,
985
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1009
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1020,
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1152,
1156
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1185,
1203
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"simple primary",
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1166,
1180
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1195,
1203
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"glutathione S-transferase"
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[
2,
27
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1227,
1233
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"id": "135_T37",
"type": "Chemical",
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"alcohol function"
],
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[
1276,
1292
]
],
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{
"id": "135_T38",
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"aldehyde"
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[
1314,
1322
]
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},
{
"id": "135_T39",
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"carboxylic acid"
],
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[
1327,
1342
]
],
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},
{
"id": "135_T40",
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"GST"
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1544,
1547
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"HGMB"
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1573,
1577
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"id": "135_T42",
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"dehydrogenase"
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1585,
1598
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"id": "135_T43",
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1631,
1671
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1459,
1467
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1485,
1498
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1523,
1540
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"type": "Metabolite",
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1523,
1540
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"HGMB"
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1573,
1577
]
],
"normalized": []
},
{
"id": "135_T50",
"type": "Metabolite",
"text": [
"2-glutathionyl-2-methyl-3-butenoic acid"
],
"offsets": [
[
1631,
1671
]
],
"normalized": []
},
{
"id": "135_T1",
"type": "Biological_Activity",
"text": [
"metabolism"
],
"offsets": [
[
1468,
1478
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "135_R1",
"type": "Associated_With",
"arg1_id": "135_T22",
"arg2_id": "135_T19",
"normalized": []
},
{
"id": "135_R2",
"type": "Associated_With",
"arg1_id": "135_T23",
"arg2_id": "135_T19",
"normalized": []
},
{
"id": "135_R3",
"type": "Metabolite_Of",
"arg1_id": "135_T47",
"arg2_id": "135_T44",
"normalized": []
},
{
"id": "135_R4",
"type": "Metabolite_Of",
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},
{
"id": "135_R5",
"type": "Metabolite_Of",
"arg1_id": "135_T50",
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},
{
"id": "135_R6",
"type": "Metabolite_Of",
"arg1_id": "135_T50",
"arg2_id": "135_T22",
"normalized": []
}
] |
136 | 10095931 | [
{
"id": "137",
"type": "",
"text": [
"This paper reports the preparation and identification of two monoclonal antibodies against FTB, and the establishment of an indirect competitive ELISA methods for FTB determination in buckwheat, rice, and corn. Two of the hybridoma cell lines (1C9 and 2D10), which could produce specific antibodies against fumitremorgin B(FTB), were selected and developed. The affinity Kaff constants of the monoclonal antibodies with the coating antigen, FTBS-IgG, were found to be 6 x 10(8) M-1 and 9.8 x 10 M-1, respectively. The isotypes of the monoclonal antibodies are of two isotypes, IgG1 and IgM, respectively. The antibody titers were found around 1 x 10(6) and 1.5 x 10(6). The standard curves showed that as little as 5 pg of FTB in 50 mL could be detected, and the linear range of standard curve was from 10 pg to 1000 pg of standard FTB. There were no cross-reaction for McAbs in the assay system with some mycotoxins tested. The mean recovery rate from buckwheat spiked with 10-60 ng/g of FTB was 78-88.7%. \n"
],
"offsets": [
[
0,
1010
]
]
}
] | [
{
"id": "137_T1",
"type": "Protein",
"text": [
"monoclonal antibodies"
],
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[
61,
82
]
],
"normalized": []
},
{
"id": "137_T2",
"type": "Chemical",
"text": [
"FTB"
],
"offsets": [
[
91,
94
]
],
"normalized": []
},
{
"id": "137_T3",
"type": "Chemical",
"text": [
"FTB"
],
"offsets": [
[
163,
166
]
],
"normalized": []
},
{
"id": "137_T4",
"type": "Species",
"text": [
"buckwheat"
],
"offsets": [
[
184,
193
]
],
"normalized": []
},
{
"id": "137_T5",
"type": "Species",
"text": [
"rice"
],
"offsets": [
[
195,
199
]
],
"normalized": []
},
{
"id": "137_T6",
"type": "Species",
"text": [
"corn"
],
"offsets": [
[
205,
209
]
],
"normalized": []
},
{
"id": "137_T7",
"type": "Protein",
"text": [
"antibodies"
],
"offsets": [
[
289,
299
]
],
"normalized": []
},
{
"id": "137_T8",
"type": "Chemical",
"text": [
"fumitremorgin B"
],
"offsets": [
[
308,
323
]
],
"normalized": []
},
{
"id": "137_T9",
"type": "Chemical",
"text": [
"FTB"
],
"offsets": [
[
324,
327
]
],
"normalized": []
},
{
"id": "137_T10",
"type": "Protein",
"text": [
"monoclonal antibodies"
],
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[
394,
415
]
],
"normalized": []
},
{
"id": "137_T11",
"type": "Chemical",
"text": [
"antigen"
],
"offsets": [
[
433,
440
]
],
"normalized": []
},
{
"id": "137_T12",
"type": "Protein",
"text": [
"monoclonal antibodies"
],
"offsets": [
[
536,
557
]
],
"normalized": []
},
{
"id": "137_T13",
"type": "Protein",
"text": [
"antibody"
],
"offsets": [
[
611,
619
]
],
"normalized": []
},
{
"id": "137_T14",
"type": "Chemical",
"text": [
"FTB"
],
"offsets": [
[
725,
728
]
],
"normalized": []
},
{
"id": "137_T15",
"type": "Chemical",
"text": [
"FTB"
],
"offsets": [
[
834,
837
]
],
"normalized": []
},
{
"id": "137_T16",
"type": "Species",
"text": [
"buckwheat"
],
"offsets": [
[
955,
964
]
],
"normalized": []
},
{
"id": "137_T17",
"type": "Chemical",
"text": [
"FTB"
],
"offsets": [
[
991,
994
]
],
"normalized": []
},
{
"id": "137_T18",
"type": "Biological_Activity",
"text": [
"mycotoxins"
],
"offsets": [
[
908,
918
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "137_R3",
"type": "Binds_With",
"arg1_id": "137_T2",
"arg2_id": "137_T1",
"normalized": []
}
] |
138 | 1009629 | [
{
"id": "139",
"type": "",
"text": [
"The reaction of [3H]p-nitrophenyl acetate (NPA) or [14C]methyl acetimidate (MAI) with amino groups of ribosomal pade between the reactivity of the proteins in situ in the ribosomal subunit with that of isolated protein mixtures. In the small subunit reactivity compared with the protein mixture was only 10-65% in the case of NPA but 45 to more than 100% in the case of MAI. In the large subunit reactivity to MAI was 10-60% that of the isas a denser structure than the small one. In agreement with earlier experiments with iodoacetamide the proteins S2, 5, 7, 8, 10 and 13 of the small subunit and L15, 17, 20, 24, 25, 27, 29, 33, 34, 35 and 38 in the large subunit are quite accessible while proteins S9, 14, 19, 20, 24, 25, 27, 29 and 30 of the small subunit and L1, 7, 8, 10, 11, 19, 28, 31, and 32 of the large one are relatively inaccessible. \n"
],
"offsets": [
[
0,
853
]
]
}
] | [
{
"id": "139_T1",
"type": "Chemical",
"text": [
"[3H]p-nitrophenyl acetate"
],
"offsets": [
[
16,
41
]
],
"normalized": []
},
{
"id": "139_T2",
"type": "Chemical",
"text": [
"p-nitrophenyl acetate"
],
"offsets": [
[
20,
41
]
],
"normalized": []
},
{
"id": "139_T3",
"type": "Chemical",
"text": [
"NPA"
],
"offsets": [
[
43,
46
]
],
"normalized": []
},
{
"id": "139_T4",
"type": "Chemical",
"text": [
"[14C]methyl acetimidate"
],
"offsets": [
[
51,
74
]
],
"normalized": []
},
{
"id": "139_T5",
"type": "Chemical",
"text": [
"methyl acetimidate"
],
"offsets": [
[
56,
74
]
],
"normalized": []
},
{
"id": "139_T6",
"type": "Chemical",
"text": [
"MAI"
],
"offsets": [
[
76,
79
]
],
"normalized": []
},
{
"id": "139_T7",
"type": "Chemical",
"text": [
"amino groups"
],
"offsets": [
[
87,
99
]
],
"normalized": []
},
{
"id": "139_T8",
"type": "Protein",
"text": [
"proteins"
],
"offsets": [
[
148,
156
]
],
"normalized": []
},
{
"id": "139_T9",
"type": "Protein",
"text": [
"protein"
],
"offsets": [
[
212,
219
]
],
"normalized": []
},
{
"id": "139_T10",
"type": "Protein",
"text": [
"protein"
],
"offsets": [
[
280,
287
]
],
"normalized": []
},
{
"id": "139_T11",
"type": "Chemical",
"text": [
"NPA"
],
"offsets": [
[
327,
330
]
],
"normalized": []
},
{
"id": "139_T12",
"type": "Chemical",
"text": [
"MAI"
],
"offsets": [
[
371,
374
]
],
"normalized": []
},
{
"id": "139_T13",
"type": "Chemical",
"text": [
"MAI"
],
"offsets": [
[
411,
414
]
],
"normalized": []
},
{
"id": "139_T14",
"type": "Chemical",
"text": [
"iodoacetamide"
],
"offsets": [
[
525,
538
]
],
"normalized": []
},
{
"id": "139_T15",
"type": "Protein",
"text": [
"proteins"
],
"offsets": [
[
543,
551
]
],
"normalized": []
},
{
"id": "139_T16",
"type": "Protein",
"text": [
"proteins"
],
"offsets": [
[
696,
704
]
],
"normalized": []
}
] | [] | [] | [] |
140 | 10096519 | [
{
"id": "141",
"type": "",
"text": [
"BACKGROUND: Removal and/or \"neutralization\" of anti-Gal alpha1-3Gal (alphaGal) antibodies can prevent or delay the hyperacute rejection of pig organs transplanted into primates. AIM: To determine variations in (1) cytotoxicity to pig kidney (PK15) cells, (2) anti-alphaGal antibody level, and (3) specificity in adult human (n=46) and baboon (n=38) sera. METHODS: Cytotoxicity to PK15 cells was determined by adding rabbit complement to heat-inactivated serum, using a two-color fluorescent dye to distinguish live and dead cells. Anti-alphaGal antibody level was determined by ELISA using alphaGal trisaccharide type 2-BSA glycoconjugate as antigen target. Specificity determined by ELISA using four different alphaGal-BSA glycoconjugates: (disaccharide, trisaccharides type 2 and 6, and pentasaccharide). RESULTS: Cytotoxicity of human AB sera varied from 30-100% PK15 relative cell damage (%RCD), although that of baboon sera of all blood groups varied from 35-100% RCD. In human AB sera, anti-alphaGal antibody level (at a dilution of 1:80) varied from undetectable to 0.75 (OD at 405 nm), although in baboon sera of all blood groups, anti-alphaGal antibody level varied from undetectable to >2.0. There was no correlation between anti-alphaGal antibody level and serum cytotoxicity in either species. Specificity varied among individuals in both human and baboon sera. CONCLUSIONS: These studies have demonstrated (1) considerable variation in cytotoxicity and anti-alphaGal antibody level in human and baboon sera, but a lack of correlation between these two parameters; (2) considerable variation in the specificity of anti-alphaGal antibodies; (3) blood group B human and baboon sera have lower levels of anti-alphaGal antibodies; (4) no relation between blood group and specificity of anti-alphaGal antibodies. Although there are minor differences in the parameters measured, baboons would appear to be suitable surrogates for humans in the pig-to-primate xenograft model. \n"
],
"offsets": [
[
0,
1988
]
]
}
] | [
{
"id": "141_T2",
"type": "Protein",
"text": [
"anti-Gal alpha1-3Gal",
"antibodies"
],
"offsets": [
[
47,
67
],
[
79,
89
]
],
"normalized": []
},
{
"id": "141_T1",
"type": "Species",
"text": [
"primates"
],
"offsets": [
[
168,
176
]
],
"normalized": []
},
{
"id": "141_T4",
"type": "Species",
"text": [
"pig"
],
"offsets": [
[
139,
142
]
],
"normalized": []
},
{
"id": "141_T5",
"type": "Biological_Activity",
"text": [
"cytotoxicity"
],
"offsets": [
[
214,
226
]
],
"normalized": []
},
{
"id": "141_T6",
"type": "Species",
"text": [
"pig"
],
"offsets": [
[
230,
233
]
],
"normalized": []
},
{
"id": "141_T7",
"type": "Protein",
"text": [
"anti-alphaGal antibody"
],
"offsets": [
[
259,
281
]
],
"normalized": []
},
{
"id": "141_T8",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
318,
323
]
],
"normalized": []
},
{
"id": "141_T9",
"type": "Species",
"text": [
"baboon"
],
"offsets": [
[
335,
341
]
],
"normalized": []
},
{
"id": "141_T10",
"type": "Biological_Activity",
"text": [
"Cytotoxicity"
],
"offsets": [
[
364,
376
]
],
"normalized": []
},
{
"id": "141_T11",
"type": "Chemical",
"text": [
"fluorescent dye"
],
"offsets": [
[
479,
494
]
],
"normalized": []
},
{
"id": "141_T12",
"type": "Species",
"text": [
"rabbit"
],
"offsets": [
[
416,
422
]
],
"normalized": []
},
{
"id": "141_T13",
"type": "Protein",
"text": [
"Anti-alphaGal antibody"
],
"offsets": [
[
531,
553
]
],
"normalized": []
},
{
"id": "141_T14",
"type": "Protein",
"text": [
"alphaGal trisaccharide type 2-BSA"
],
"offsets": [
[
590,
623
]
],
"normalized": []
},
{
"id": "141_T15",
"type": "Chemical",
"text": [
"antigen"
],
"offsets": [
[
642,
649
]
],
"normalized": []
},
{
"id": "141_T16",
"type": "Protein",
"text": [
"alphaGal-BSA"
],
"offsets": [
[
711,
723
]
],
"normalized": []
},
{
"id": "141_T17",
"type": "Chemical",
"text": [
"disaccharide"
],
"offsets": [
[
742,
754
]
],
"normalized": []
},
{
"id": "141_T18",
"type": "Chemical",
"text": [
"trisaccharides"
],
"offsets": [
[
756,
770
]
],
"normalized": []
},
{
"id": "141_T19",
"type": "Chemical",
"text": [
"pentasaccharide"
],
"offsets": [
[
790,
805
]
],
"normalized": []
},
{
"id": "141_T20",
"type": "Biological_Activity",
"text": [
"Cytotoxicity"
],
"offsets": [
[
817,
829
]
],
"normalized": []
},
{
"id": "141_T21",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
833,
838
]
],
"normalized": []
},
{
"id": "141_T22",
"type": "Species",
"text": [
"baboon"
],
"offsets": [
[
918,
924
]
],
"normalized": []
},
{
"id": "141_T23",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
978,
983
]
],
"normalized": []
},
{
"id": "141_T24",
"type": "Protein",
"text": [
"anti-alphaGal antibody"
],
"offsets": [
[
993,
1015
]
],
"normalized": []
},
{
"id": "141_T25",
"type": "Species",
"text": [
"baboon"
],
"offsets": [
[
1107,
1113
]
],
"normalized": []
},
{
"id": "141_T26",
"type": "Protein",
"text": [
"anti-alphaGal antibody"
],
"offsets": [
[
1140,
1162
]
],
"normalized": []
},
{
"id": "141_T27",
"type": "Protein",
"text": [
"anti-alphaGal antibody"
],
"offsets": [
[
1237,
1259
]
],
"normalized": []
},
{
"id": "141_T28",
"type": "Biological_Activity",
"text": [
"cytotoxicity"
],
"offsets": [
[
1276,
1288
]
],
"normalized": []
},
{
"id": "141_T29",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
1353,
1358
]
],
"normalized": []
},
{
"id": "141_T30",
"type": "Species",
"text": [
"baboon"
],
"offsets": [
[
1363,
1369
]
],
"normalized": []
},
{
"id": "141_T31",
"type": "Biological_Activity",
"text": [
"cytotoxicity"
],
"offsets": [
[
1451,
1463
]
],
"normalized": []
},
{
"id": "141_T32",
"type": "Protein",
"text": [
"anti-alphaGal antibody"
],
"offsets": [
[
1468,
1490
]
],
"normalized": []
},
{
"id": "141_T33",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
1500,
1505
]
],
"normalized": []
},
{
"id": "141_T34",
"type": "Species",
"text": [
"o"
],
"offsets": [
[
1513,
1514
]
],
"normalized": []
},
{
"id": "141_T35",
"type": "Protein",
"text": [
"anti-alphaGal antibodies"
],
"offsets": [
[
1629,
1653
]
],
"normalized": []
},
{
"id": "141_T36",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
1673,
1678
]
],
"normalized": []
},
{
"id": "141_T37",
"type": "Species",
"text": [
"baboon"
],
"offsets": [
[
1683,
1689
]
],
"normalized": []
},
{
"id": "141_T38",
"type": "Protein",
"text": [
"anti-alphaGal antibodies"
],
"offsets": [
[
1716,
1740
]
],
"normalized": []
},
{
"id": "141_T39",
"type": "Protein",
"text": [
"anti-alphaGal antibodies"
],
"offsets": [
[
1798,
1822
]
],
"normalized": []
},
{
"id": "141_T40",
"type": "Species",
"text": [
"baboons"
],
"offsets": [
[
1890,
1897
]
],
"normalized": []
},
{
"id": "141_T41",
"type": "Species",
"text": [
"humans"
],
"offsets": [
[
1941,
1947
]
],
"normalized": []
},
{
"id": "141_T42",
"type": "Species",
"text": [
"pig"
],
"offsets": [
[
1955,
1958
]
],
"normalized": []
},
{
"id": "141_T43",
"type": "Species",
"text": [
"primate"
],
"offsets": [
[
1962,
1969
]
],
"normalized": []
},
{
"id": "141_T3",
"type": "Protein",
"text": [
"anti-",
"alphaGal",
"antibodies"
],
"offsets": [
[
47,
52
],
[
69,
77
],
[
79,
89
]
],
"normalized": []
}
] | [] | [] | [] |
142 | 10096848 | [
{
"id": "143",
"type": "",
"text": [
"Three novel sesquiterpene esters of aristolochic acid, aristoloterpenate-II (2), -III (3), and-IV (4), together with known aristoloterpenate-I (1), were isolated and characterized from the root and stem of Aristolochia heterophylla. Their structures were elucidated by spectroscopic methods. The absolute configuration of these compounds at C-4' was determined as R by circular dichroic studies. These compounds showed cytotoxicity against hepatoma G2, 2, 2, 15 cells. \n"
],
"offsets": [
[
0,
472
]
]
}
] | [
{
"id": "143_T1",
"type": "Chemical",
"text": [
"sesquiterpene"
],
"offsets": [
[
12,
25
]
],
"normalized": []
},
{
"id": "143_T2",
"type": "Chemical",
"text": [
"esters of aristolochic acid"
],
"offsets": [
[
26,
53
]
],
"normalized": []
},
{
"id": "143_T6",
"type": "Chemical",
"text": [
"aristoloterpenate-I"
],
"offsets": [
[
124,
143
]
],
"normalized": []
},
{
"id": "143_T11",
"type": "Species",
"text": [
"Aristolochia heterophylla"
],
"offsets": [
[
208,
233
]
],
"normalized": []
},
{
"id": "143_T12",
"type": "Metabolite",
"text": [
"aristoloterpenate-II"
],
"offsets": [
[
55,
75
]
],
"normalized": []
},
{
"id": "143_T16",
"type": "Metabolite",
"text": [
"4"
],
"offsets": [
[
100,
101
]
],
"normalized": []
},
{
"id": "143_T17",
"type": "Metabolite",
"text": [
"aristoloterpenate-I"
],
"offsets": [
[
124,
143
]
],
"normalized": []
},
{
"id": "143_T19",
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"id": "143_T20",
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"cytotoxicity"
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421,
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"id": "143_T3",
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"id": "143_T9",
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"id": "143_R17",
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"id": "143_R18",
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}
] |
144 | 10098223 | [
{
"id": "145",
"type": "",
"text": [
"Raloxifene hydrochloride (HCl) is a selective estrogen receptor modulator with estrogen agonist effects on bone and lipid metabolism and estrogen antagonist effects on reproductive tissues. Animal studies suggest that raloxifene may affect brain function as well, although the effects of raloxifene on the human brain remain to be established. This paper presents an early safety assessment of raloxifene effects on cognition and mood in postmenopausal women participating in a randomized, double-blind osteoporosis treatment trial. Psychometric test batteries were administered to postmenopausal women at baseline and 1, 6, and 12 months after initiating treatment with raloxifene (60 and 120 mg/day). The Memory Assessment Clinics (MAC) battery and Walter Reed Performance Assessment Battery (PAB) were used to assess multiple and independent aspects of cognitive function, while mood was assessed with the Geriatric Depression Scale (GDS). After 12 months of treatment, there were no significant differences between the raloxifene groups and placebo on performance in either the MAC battery or the PAB. The only significant difference observed was a slight increase in performance favoring the raloxifene 120 mg/day group in an assessment of verbal memory on the MAC battery after 1 month of treatment. Scores on the GDS and the self-reported incidence of mood-related events were not different between treatment groups at any of the assessment periods. These data do not suggest that raloxifene impairs cognition or affects mood in postmenopausal women treated for 1 year. Studies to further assess the safety and potential efficacy of raloxifene with respect to cognitive function are ongoing. \n"
],
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0,
1705
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]
}
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"id": "145_T4",
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672,
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"id": "145_T14",
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"id": "145_T24",
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"id": "145_T25",
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"estrogen"
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],
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},
{
"id": "145_T26",
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"lipid"
],
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116,
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]
],
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},
{
"id": "145_T27",
"type": "Biological_Activity",
"text": [
"metabolism"
],
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122,
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]
],
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},
{
"id": "145_T28",
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"text": [
"estrogen"
],
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137,
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]
],
"normalized": []
}
] | [] | [] | [
{
"id": "145_R1",
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"id": "145_R2",
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"id": "145_R3",
"type": "Associated_With",
"arg1_id": "145_T1",
"arg2_id": "145_T4",
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}
] |
146 | 10098663 | [
{
"id": "147",
"type": "",
"text": [
"A novel series of nonpeptide small-molecular dipeptidyl peptidase IV (DPP-IV) inhibitors with an N-phenylphthalimide skeleton has been developed. Some of the compounds, including 4-amino-(2,6-dimethylphenyl)phthalimides (7), 4- and 5-hydroxy-(2,6-diethylphenyl)phthalimide (11 and 14), 4-hydroxy-(2,6-diisopropylphenyl)phthalimide (12), and thiocarbonyl analogs of (2,6-diisopropylphenyl)phthalimide and their 4,5,6,7-tetrafluorinated derivative (18, 19 and 20), were more potent than the well-known DPP-IV-specific inhibitor, Pro-boroPro (PBP). Among them, 18 was revealed to be a DPP-IV-specific inhibitor, while the others also showed inhibitory activity toward another peptidase, aminopeptidase N (APN). \n"
],
"offsets": [
[
0,
711
]
]
}
] | [
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"id": "147_T1",
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]
],
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},
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"id": "147_T2",
"type": "Protein",
"text": [
"DPP-IV"
],
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70,
76
]
],
"normalized": []
},
{
"id": "147_T5",
"type": "Biological_Activity",
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"inhibitor"
],
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],
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{
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"N-phenylphthalimide skeleton"
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],
"normalized": []
},
{
"id": "147_T7",
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179,
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]
],
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"5-hydroxy-(2,6-diethylphenyl)phthalimide"
],
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232,
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]
],
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},
{
"id": "147_T12",
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"4-hydroxy-(2,6-diisopropylphenyl)phthalimide"
],
"offsets": [
[
286,
330
]
],
"normalized": []
},
{
"id": "147_T14",
"type": "Chemical",
"text": [
"thiocarbonyl analogs of (2,6-diisopropylphenyl)phthalimide",
"their 4,5,6,7-tetrafluorinated derivative"
],
"offsets": [
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341,
399
],
[
404,
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]
],
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},
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"id": "147_T15",
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"text": [
"18"
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"offsets": [
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"id": "147_T16",
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"19"
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452,
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]
],
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"offsets": [
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459,
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]
],
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},
{
"id": "147_T18",
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"text": [
"inhibitor"
],
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517,
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]
],
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},
{
"id": "147_T19",
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],
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},
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542,
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]
],
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},
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560,
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],
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},
{
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],
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600,
609
]
],
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},
{
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],
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675,
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],
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},
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"id": "147_T25",
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],
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},
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],
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704,
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]
],
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},
{
"id": "147_T28",
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640,
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],
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{
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"4-",
"hydroxy-(2,6-diethylphenyl)phthalimide"
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225,
227
],
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234,
272
]
],
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},
{
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"DPP-IV"
],
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501,
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],
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},
{
"id": "147_T3",
"type": "Protein",
"text": [
"DPP-IV"
],
"offsets": [
[
584,
590
]
],
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}
] | [] | [] | [
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},
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},
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},
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"id": "147_R25",
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"arg2_id": "147_T1",
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},
{
"id": "147_R26",
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},
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"id": "147_R27",
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"arg1_id": "147_T29",
"arg2_id": "147_T1",
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},
{
"id": "147_R28",
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"arg2_id": "147_T2",
"normalized": []
},
{
"id": "147_R29",
"type": "Binds_With",
"arg1_id": "147_T9",
"arg2_id": "147_T1",
"normalized": []
},
{
"id": "147_R30",
"type": "Binds_With",
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"arg2_id": "147_T2",
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},
{
"id": "147_R5",
"type": "Binds_With",
"arg1_id": "147_T12",
"arg2_id": "147_T2",
"normalized": []
},
{
"id": "147_R7",
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},
{
"id": "147_R8",
"type": "Associated_With",
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"arg2_id": "147_T5",
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},
{
"id": "147_R9",
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"arg1_id": "147_T15",
"arg2_id": "147_T1",
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},
{
"id": "147_R10",
"type": "Binds_With",
"arg1_id": "147_T16",
"arg2_id": "147_T1",
"normalized": []
},
{
"id": "147_R17",
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"arg1_id": "147_T17",
"arg2_id": "147_T1",
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},
{
"id": "147_R18",
"type": "Binds_With",
"arg1_id": "147_T15",
"arg2_id": "147_T27",
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},
{
"id": "147_R19",
"type": "Binds_With",
"arg1_id": "147_T16",
"arg2_id": "147_T27",
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},
{
"id": "147_R20",
"type": "Binds_With",
"arg1_id": "147_T17",
"arg2_id": "147_T27",
"normalized": []
},
{
"id": "147_R21",
"type": "Binds_With",
"arg1_id": "147_T21",
"arg2_id": "147_T3",
"normalized": []
}
] |
148 | 10098675 | [
{
"id": "149",
"type": "",
"text": [
"Methyl- and hydroxymethyl derivatives of the highly potent glycosidase inhibitor isofagomine are accessible via aldolase-catalyzed C-C bond formation and competitively inhibit beta-glucosidase at low micromolar concentrations. \n"
],
"offsets": [
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0,
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"hydroxymethyl derivatives of",
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12,
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"glycosidase"
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"inhibitor"
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"beta-glucosidase"
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169,
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"text": [
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82,
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}
] | [] | [] | [
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"id": "149_R1",
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"arg2_id": "149_T11",
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},
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"id": "149_R2",
"type": "Associated_With",
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"id": "149_R7",
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"type": "Binds_With",
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}
] |
150 | 10098958 | [
{
"id": "151",
"type": "",
"text": [
"Glutamate contributes to secondary brain damage, resulting in cell swelling and brain edema. Under in vitro conditions, increased extracellular levels of the amino acid taurine reflect glutamate-induced osmotic cell swelling. In vivo, increases in cerebrospinal fluid (CSF) taurine could, therefore, unmask glutamate-mediated cytotoxic edema formation and possibly differentiate it from vasogenic edema. To test this hypothesis, ventricular CSF glutamate and taurine levels were measured in 28 severely brain-injured patients on days 1, 5, and 14 after trauma. Posttraumatic changes in CSF amino acids were investigated in regard to extent of tissue damage and alterations in brain edema as estimated by computerized tomography. On day 1, CSF glutamate and taurine levels were significantly increased in patients with subdural or epidural hematomas (8+/-0.8/71+/-12 microM), contusions (21+/-4.1/122+/-18 microM), and generalized brain edema (13+/-3.2/80+/-15 microM) compared to lumbar control CSF (1.3+/-0.1/12+/-1 microM; p < 0.001). CSF amino acids, however, did not reflect edema formation and resolution as estimated by computerized tomography. CSF taurine correlated positively with glutamate, eventually depicting glutamate-induced cell swelling. However, parallel neuronal release of taurine with its inhibitory function cannot be excluded. Thus, the sensitivity of taurine in unmasking cytotoxic edema formation is weakened by the inability in defining its origin and function under the conditions chosen in the present study. Overall, persisting pathologic ventricular CSF glutamate and taurine levels are highly suggestive of ongoing glial and neuronal impairment in humans following severe traumatic brain injury. \n"
],
"offsets": [
[
0,
1730
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]
}
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"taurine"
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"id": "151_T7",
"type": "Chemical",
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"glutamate"
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"id": "151_T9",
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"taurine"
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274,
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"id": "151_T10",
"type": "Biological_Activity",
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"cytotoxic"
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"id": "151_T11",
"type": "Chemical",
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"glutamate"
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"id": "151_T13",
"type": "Chemical",
"text": [
"glutamate"
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"type": "Chemical",
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"taurine"
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"id": "151_T15",
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"patients"
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"type": "Chemical",
"text": [
"amino acids"
],
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590,
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]
],
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},
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"id": "151_T17",
"type": "Chemical",
"text": [
"glutamate"
],
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]
],
"normalized": []
},
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"id": "151_T18",
"type": "Chemical",
"text": [
"taurine"
],
"offsets": [
[
758,
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]
],
"normalized": []
},
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"id": "151_T22",
"type": "Chemical",
"text": [
"amino acids"
],
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[
1043,
1054
]
],
"normalized": []
},
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"id": "151_T24",
"type": "Chemical",
"text": [
"taurine"
],
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[
1157,
1164
]
],
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"id": "151_T25",
"type": "Chemical",
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"glutamate"
],
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]
],
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"id": "151_T27",
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"taurine"
],
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]
],
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"id": "151_T28",
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"taurine"
],
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[
1377,
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]
],
"normalized": []
},
{
"id": "151_T30",
"type": "Chemical",
"text": [
"glutamate"
],
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1586,
1595
]
],
"normalized": []
},
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"id": "151_T31",
"type": "Chemical",
"text": [
"taurine"
],
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[
1600,
1607
]
],
"normalized": []
},
{
"id": "151_T33",
"type": "Species",
"text": [
"humans"
],
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[
1681,
1687
]
],
"normalized": []
},
{
"id": "151_T2",
"type": "Chemical",
"text": [
"glutamate"
],
"offsets": [
[
1224,
1233
]
],
"normalized": []
},
{
"id": "151_T3",
"type": "Biological_Activity",
"text": [
"cytotoxic"
],
"offsets": [
[
1398,
1407
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "151_R1",
"type": "Associated_With",
"arg1_id": "151_T11",
"arg2_id": "151_T10",
"normalized": []
}
] |
152 | 10099036 | [
{
"id": "153",
"type": "",
"text": [
"Dopamine is a biogenic amine synthesized in the hypothalamus, in the arcuate nucleus, the caudad, and various areas of the central and peripheral nervous system. It has been widely established that dopamine and its agonists play an important role in cardiovascular, renal, hormonal, and central nervous system regulation through stimulation of alpha and beta adrenergic and dopaminergic receptors. There are several agonists of dopamine-2 (DA 2 ) dopaminergic receptors, such as bromocriptine, pergolide, lisuride, quinpirole, and carmoxirole, which inhibit norepinephrine release and produce a decrease in arterial blood pressure; in some cases, bromocriptine and pergolide also reduce heart rate. From a therapeutic point of view, the above-mentioned agonists are used for treating Parkinson's disease, acting over DA 2 dopaminergic receptors of the nigrostriatal system. Bromocriptine and the other dopaminergic agonists mentioned act over DA 2 receptors of the tuberoinfundibular system, inhibiting prolactin release and decreasing hyperprolactinemia and tumor size. Among DA 1 receptor agonists, we can mention fenoldopam, piribedil, ibopamine, SKF 3893, and apomorphine (nonspecific). Activation of these receptors decreases peripheral resistance, inducing lowering of arterial blood pressure and increases in heart rate, sympathetic tone, and activity of the renin aldosterone system. Among DA 2 receptor antagonists, we can mention metoclopramide, domperidone, sulpiride, and haloperidol. From a therapeutic point of view, metoclopramide and domperidone are used in gastric motility disorders, and haloperidol is used in psychotic alterations. Antagonists of DA 1 receptors are SCH23390 and clozapine. Clozapine is used for treating schizophrenia. \n"
],
"offsets": [
[
0,
1760
]
]
}
] | [
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"text": [
"Dopamine"
],
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0,
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]
],
"normalized": []
},
{
"id": "153_T2",
"type": "Metabolite",
"text": [
"Dopamine"
],
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0,
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],
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},
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"id": "153_T3",
"type": "Metabolite",
"text": [
"dopamine"
],
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198,
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]
],
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},
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"id": "153_T4",
"type": "Chemical",
"text": [
"dopamine"
],
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198,
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]
],
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},
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"id": "153_T5",
"type": "Chemical",
"text": [
"amine"
],
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[
23,
28
]
],
"normalized": []
},
{
"id": "153_T6",
"type": "Biological_Activity",
"text": [
"agonist"
],
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[
215,
222
]
],
"normalized": []
},
{
"id": "153_T7",
"type": "Biological_Activity",
"text": [
"stimulation"
],
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[
329,
340
]
],
"normalized": []
},
{
"id": "153_T8",
"type": "Protein",
"text": [
"alpha and beta adrenergic and dopaminergic receptors"
],
"offsets": [
[
344,
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]
],
"normalized": []
},
{
"id": "153_T10",
"type": "Protein",
"text": [
"dopamine-2 (DA 2 ) dopaminergic receptors"
],
"offsets": [
[
428,
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],
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"id": "153_T12",
"type": "Biological_Activity",
"text": [
"agonists"
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[
416,
424
]
],
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},
{
"id": "153_T13",
"type": "Chemical",
"text": [
"bromocriptine"
],
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[
479,
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],
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{
"id": "153_T14",
"type": "Chemical",
"text": [
"pergolide"
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494,
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]
],
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},
{
"id": "153_T15",
"type": "Chemical",
"text": [
"lisuride"
],
"offsets": [
[
505,
513
]
],
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},
{
"id": "153_T16",
"type": "Chemical",
"text": [
"quinpirole"
],
"offsets": [
[
515,
525
]
],
"normalized": []
},
{
"id": "153_T17",
"type": "Chemical",
"text": [
"carmoxirole"
],
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[
531,
542
]
],
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},
{
"id": "153_T18",
"type": "Chemical",
"text": [
"norepinephrine"
],
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558,
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],
"normalized": []
},
{
"id": "153_T19",
"type": "Metabolite",
"text": [
"norepinephrine"
],
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[
558,
572
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],
"normalized": []
},
{
"id": "153_T20",
"type": "Biological_Activity",
"text": [
"inhibit"
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[
550,
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],
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"id": "153_T23",
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647,
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665,
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"id": "153_T26",
"type": "Protein",
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"DA 2 dopaminergic receptors"
],
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[
817,
844
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"id": "153_T28",
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"text": [
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874,
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"type": "Biological_Activity",
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"agonists"
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"type": "Protein",
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{
"id": "153_T32",
"type": "Protein",
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{
"id": "153_T33",
"type": "Protein",
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],
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"id": "153_T35",
"type": "Biological_Activity",
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"agonists"
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1091,
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{
"id": "153_T36",
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],
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1116,
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],
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},
{
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],
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1128,
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],
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{
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1139,
1148
]
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{
"id": "153_T39",
"type": "Chemical",
"text": [
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1150,
1158
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],
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{
"id": "153_T40",
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],
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{
"id": "153_T44",
"type": "Protein",
"text": [
"DA 2 receptor"
],
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1398,
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},
{
"id": "153_T45",
"type": "Biological_Activity",
"text": [
"antagonists"
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1413,
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]
],
"normalized": []
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{
"id": "153_T46",
"type": "Chemical",
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"metoclopramide"
],
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1441,
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]
],
"normalized": []
},
{
"id": "153_T47",
"type": "Chemical",
"text": [
"domperidone"
],
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[
1457,
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]
],
"normalized": []
},
{
"id": "153_T48",
"type": "Chemical",
"text": [
"sulpiride"
],
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[
1470,
1479
]
],
"normalized": []
},
{
"id": "153_T49",
"type": "Chemical",
"text": [
"haloperidol"
],
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[
1486,
1497
]
],
"normalized": []
},
{
"id": "153_T50",
"type": "Chemical",
"text": [
"metoclopramide"
],
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1533,
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]
],
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},
{
"id": "153_T51",
"type": "Chemical",
"text": [
"domperidone"
],
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]
],
"normalized": []
},
{
"id": "153_T53",
"type": "Chemical",
"text": [
"haloperidol"
],
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1608,
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]
],
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},
{
"id": "153_T55",
"type": "Biological_Activity",
"text": [
"cardiovascular",
"regulation"
],
"offsets": [
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250,
264
],
[
310,
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]
],
"normalized": []
},
{
"id": "153_T56",
"type": "Biological_Activity",
"text": [
"renal",
"regulation"
],
"offsets": [
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266,
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],
[
310,
320
]
],
"normalized": []
},
{
"id": "153_T57",
"type": "Biological_Activity",
"text": [
"hormonal",
"regulation"
],
"offsets": [
[
273,
281
],
[
310,
320
]
],
"normalized": []
},
{
"id": "153_T58",
"type": "Biological_Activity",
"text": [
"central nervous system regulation"
],
"offsets": [
[
287,
320
]
],
"normalized": []
},
{
"id": "153_T59",
"type": "Chemical",
"text": [
"dopamine",
"agonists"
],
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[
198,
206
],
[
215,
223
]
],
"normalized": []
},
{
"id": "153_T60",
"type": "Biological_Activity",
"text": [
"inhibiting"
],
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[
992,
1002
]
],
"normalized": []
},
{
"id": "153_T62",
"type": "Biological_Activity",
"text": [
"Antagonists"
],
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[
1654,
1665
]
],
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},
{
"id": "153_T63",
"type": "Chemical",
"text": [
"SCH23390"
],
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[
1688,
1696
]
],
"normalized": []
},
{
"id": "153_T64",
"type": "Chemical",
"text": [
"clozapine"
],
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1701,
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]
],
"normalized": []
},
{
"id": "153_T66",
"type": "Chemical",
"text": [
"Clozapine"
],
"offsets": [
[
1712,
1723
]
],
"normalized": []
},
{
"id": "153_T67",
"type": "Protein",
"text": [
"DA 1 receptors"
],
"offsets": [
[
1669,
1683
]
],
"normalized": []
},
{
"id": "153_T9",
"type": "Protein",
"text": [
"receptors"
],
"offsets": [
[
1211,
1220
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "153_R1",
"type": "Associated_With",
"arg1_id": "153_T13",
"arg2_id": "153_T12",
"normalized": []
},
{
"id": "153_R2",
"type": "Associated_With",
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},
{
"id": "153_R3",
"type": "Associated_With",
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},
{
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},
{
"id": "153_R5",
"type": "Associated_With",
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"arg2_id": "153_T12",
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},
{
"id": "153_R6",
"type": "Associated_With",
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"arg2_id": "153_T20",
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},
{
"id": "153_R7",
"type": "Associated_With",
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},
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154 | 10099363 | [
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"A kilogram-scale synthesis of (Z)-3-hexen-1-yl acetate, in hexane, on direct esterification of (Z)-3-hexen-1-ol with acetic acid in the presence of 2% (w/w reactants) of an immobilized lipase from Candida antarctica (Novozym 435) is reported. Conversion yields ranging from 92 to 96% were obtained after optimization of various parameters. In that respect, elimination of the water proved crucial. Using at both the laboratory large scale (preparation of 200-400 g of ester) and the pilot scale (1-5 kg) a \"reflux\" rotary evaporator equipped with a graduated decantation flask, we were able to trap the water evolved during esterification while at the same time monitor the time course of the reaction. As a consequence of both an efficient water trapping and of a gentle dispersion of the immobilized lipase into the reaction medium, the lifetime of the enzyme was significantly prolonged. At the laboratory large scale (LLS), the yield was still >/=90% after seven consecutive utilizations whereas at the pilot scale (PS), it reached 93% after reusing the enzyme four times. In those conditions, the amount of immobilized enzyme necessary to produce 1 kg of (Z)-3-hexen-1-yl acetate was 18 g (1. 8%) and 60 g (6%) at the LLS and the PS, respectively. Copyright 1998 John Wiley & Sons, Inc. \n"
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] | [] | [] | [] |
156 | 1009998 | [
{
"id": "157",
"type": "",
"text": [
"Administered to rats by stomach tubing oxythioquinox (Morestan) toxicity is very strongly increased after solubilisation in olive oil. The oxythioquinox DL50, in this case, is 500 mg/kg although we can reach 2.8 g/kg in aqueous suspensions. When it is administered (1 g/kg) in aqueous suspension, the decrease in body weight is the same as these observed with a 5 fold lower dose in oil. Conversion rate feed and weight of differents organs decrease when animals are daily submitted to oxythioquinox in oil, during 16 days, compared with animals treated with an equivalent dose in aqueous suspension. Potentiation, in oil solutions, of the decrease of oxythioquinox intestinal transit, promoting its absorption, could explain the increase of oxythioquinox toxicity in oil solution. \n"
],
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125,
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}
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158 | 10100801 | [
{
"id": "159",
"type": "",
"text": [
"BACKGROUND: Phenylephrine is an alpha1-adrenergic agonist which causes contraction of human internal anal sphincter muscle in vitro. Its intra-arterial administration in animals has been shown to increase resting sphincter pressure in vivo. In this study the effect of topical application of phenylephrine on resting anal pressure in healthy human volunteers was investigated. METHODS: Twelve healthy volunteers had measurements of maximum resting sphincter pressure (MRP) and anodermal blood flow taken before and after topical application of increasing concentrations of phenylephrine gel to the anus. To determine the duration of effect of the agent, readings were taken throughout the day after a single application. RESULTS: There was a dose-dependent rise in the resting anal sphincter pressure, with a small 8 per cent rise after 5 per cent phenylephrine (P = 0.012) and a larger 33 per cent rise with 10 per cent phenylephrine (mean(s.d.) MRP 85(12) cmH2O before versus 127(12) cmH2O after treatment, P < 0.0001). Thereafter no additional response was noted with higher concentrations of phenylephrine. The median duration of action of a single application of 10 per cent phenylephrine was 7 (range from 6 to more than 8) h. CONCLUSION: Topical application of 10 per cent phenylephrine gel to the anus produces a significant rise in the resting anal sphincter pressure in healthy human volunteers. This represents a potential novel therapeutic approach to the treatment of passive faecal incontinence associated with a low resting anal sphincter pressure. \n"
],
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32,
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] | [] | [] | [
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"id": "159_R1",
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}
] |
160 | 10100848 | [
{
"id": "161",
"type": "",
"text": [
"We have previously shown that the methyl ester of hepoxilin A3 causes a receptor-induced rise in intracellular calcium through the release from intracellular stores in suspended human neutrophils. The corresponding free acid was devoid of activity. We now report that the action of the free acid form of hepoxilin A3 is dependent on the type of vehicle used, i.e. it is active in releasing calcium when used in an ethanol vehicle but not in DMSO. The methyl ester is equally active in either vehicle. The pattern of calcium release between the free acid and the methyl ester is qualitatively different. Both compounds show a biphasic pattern, i.e. an initial rapid phase followed by a slow decline in calcium levels but never reaching pre-hepoxilin A3 baseline levels. The methyl ester appears slightly more potent in the initial phase of calcium release than the free acid (methyl = 188+/-14 S.D., free acid = 135+/-11 S.D. nM, P < 0.0005). Both compounds appear to reach the same calcium levels at the plateau of the second prolonged phase (methyl = 88+/-8 S.D., free acid = 107+/-15 S.D. nM, not significant). Lanthanum chloride (an inhibitor of calcium influx) interfered with the second phase of the curve causing calcium levels to return to normal pre-hepoxilin levels for both compounds. Addition of lanthanum chloride prior to the hepoxilin addition or carrying out the experiments in calcium-free medium, eliminated the second phase completely, with the calcium peak returning rapidly to normal baseline levels, suggesting that the second phase is due to calcium influx. Again the methyl ester is more active than the free acid (methyl, 189+/-12; free acid, 145+/-6 S.D. nM, P<0.005). Additional experiments with tritium-labelled methyl ester of hepoxilin A3 demonstrated that the compound is hydrolyzed into the free acid intracellularly. These experiments demonstrate that DMSO interacts with hepoxilin free acid, interfering with its entry into the cell while ethanol does not. Once inside the cell, hepoxilin interacts with its own receptor to release calcium rapidly from stores, but it also causes a more prolonged influx of calcium from the extracellular milieu. \n"
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1724,
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2014,
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1150,
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] | [] | [] | [
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}
] |
162 | 10101144 | [
{
"id": "163",
"type": "",
"text": [
"Curcumin, the yellow pigment in turmeric and curry, has antioxidative and anticarcinogenic activities. In this study, we investigated the pharmacokinetic properties of curcumin in mice. After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25 microg/ml of curcumin appeared in the plasma in the first 15 min. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 microg/g, respectively. Only traces (0.41 microg/g) were observed in the brain at 1 h. To clarify the nature of the metabolites of curcumin, the plasma was analyzed by reversed-phase HPLC, and two putative conjugates were observed. Treatment of the plasma with beta-glucuronidase resulted in a decrease in the concentrations of these two putative conjugates and the concomitant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To investigate the nature of these glucuronide conjugates in vivo, the plasma was analyzed by electrospray. The chemical structures of these metabolites, determined by mass spectrometry/mass spectrometry analysis, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates. Because THC is one of the major metabolites of curcumin, we studied its stability at different pH values. THC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, THC was more stable than curcumin in 0.1 M phosphate buffer, pH 7.2 (37 degrees C). These results, together with previous findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronoside, THC-glucuronoside, and THC are major metabolites of curcumin in vivo. \n"
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0,
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1191,
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872,
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]
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872,
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],
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1251,
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"THC"
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1287,
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"curcumin"
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1464,
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"THC"
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1464,
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1489,
1497
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"curcumin"
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] |
164 | 10101221 | [
{
"id": "165",
"type": "",
"text": [
"Manoalide is a potent analgesic and antiinflammatory sesterterpene isolated in 1980 from a marine sponge. The antiinflammatory activity of manoalide is due to inhibition of PLA2, through irreversible binding to several lysine residues. The binding is realized by means of the two masked aldehyde functions present in the polar part of manoalide. Of the two aldehyde groups, only that present in the g-hydroxybutenolide ring seems to be essential, since cacospongionolides, naturally occurring analogues lacking the second masked aldehyde group, were also shown to be irreversible PLA2 inhibitors. It appears that the minimum structural requirement for exhibiting manoalide-like PLA2 inhibition would be the presence in the inhibitor of functional groups able to seize the amino groups of PLA2 lysine residues with formation of stable covalent bonds. Many manoalide analogues have been isolated from marine sponges, most of them sharing PLA2 inhibitory properties. Other interesting bioactivities have also been reported for some of these compounds. \n"
],
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0,
1053
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0,
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"id": "165_T10",
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139,
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"id": "165_T11",
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"inhibition"
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159,
169
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],
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"id": "165_T12",
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"PLA2"
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173,
177
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"id": "165_T14",
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"lysine residues"
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219,
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"id": "165_T15",
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288,
296
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],
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"id": "165_T16",
"type": "Chemical",
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"aldehyde functions"
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288,
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337,
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359,
367
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359,
374
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401,
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455,
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"masked aldehyde"
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524,
539
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"PLA2"
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582,
586
]
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"id": "165_T26",
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"inhibitors"
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666,
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"id": "165_T29",
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"manoalide"
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[
666,
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]
],
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},
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"id": "165_T30",
"type": "Biological_Activity",
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"inhibition"
],
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686,
696
]
],
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"id": "165_T31",
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"functional groups"
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739,
756
]
],
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"amino groups"
],
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775,
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]
],
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"type": "Protein",
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"PLA2"
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[
791,
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]
],
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},
{
"id": "165_T35",
"type": "Chemical",
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"lysine residues"
],
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796,
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],
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"type": "Chemical",
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"manoalide"
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"id": "165_T37",
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"manoalide"
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"id": "165_T38",
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"manoalide analogues"
],
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858,
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]
],
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"id": "165_T39",
"type": "Metabolite",
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"manoalide analogues"
],
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[
858,
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],
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},
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"id": "165_T40",
"type": "Species",
"text": [
"marine sponges"
],
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[
902,
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]
],
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},
{
"id": "165_T41",
"type": "Biological_Activity",
"text": [
"inhibitory"
],
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[
944,
954
]
],
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},
{
"id": "165_T42",
"type": "Chemical",
"text": [
"lysine"
],
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[
219,
225
]
],
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},
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"id": "165_T44",
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"PLA2"
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681,
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]
],
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},
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"id": "165_T45",
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"PLA2"
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939,
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]
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"id": "165_T13",
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"binding"
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200,
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]
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"type": "Biological_Activity",
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"binding"
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]
],
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}
] | [] | [] | [
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},
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},
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},
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},
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},
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"type": "Binds_With",
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"arg2_id": "165_T45",
"normalized": []
}
] |
166 | 10101262 | [
{
"id": "167",
"type": "",
"text": [
"Recent work within our laboratory has focused on the enzymes we hypothesize are involved in the biosynthesis of bis(monoacylglycerol)phosphate from phosphatidylglycerol. Here we describe a transacylase, active at acidic pH values, isolated from a macrophage-like cell line, RAW 264.7. This enzyme acylates the head group glycerol of sn-3:sn-1' lysophosphatidylglycerol to form sn-3:sn-1' bis(monoacylglycerol)phosphate. Here we demonstrate that this enzyme uses two lysophosphatidylglycerol molecules, one as an acyl donor and another as an acyl acceptor, and that the acyl contributions from all other lipids tested are comparatively minor. This enzyme prefers saturated acyl chains to monounsaturates, 16 and 18 carbon fatty acids over 14 carbon fatty acids, and saturated acyl chains at the sn-1 position to monounsaturated acyl chains on the sn-2 carbon of lysophosphatidylglycerol. We present data which show the transacylase activity depends on the presence of a lipid-water interface and the lipid polymorphic state. \n"
],
"offsets": [
[
0,
1028
]
]
}
] | [
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"enzymes"
],
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53,
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]
],
"normalized": []
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"id": "167_T2",
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"bis(monoacylglycerol)phosphate"
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112,
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]
],
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"bis(monoacylglycerol)phosphate"
],
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112,
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]
],
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"id": "167_T4",
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"phosphatidylglycerol"
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148,
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],
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"id": "167_T5",
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"phosphatidylglycerol"
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[
148,
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]
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"id": "167_T6",
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"transacylase"
],
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[
189,
201
]
],
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"id": "167_T7",
"type": "Chemical",
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"sn-3:sn-1' lysophosphatidylglycerol"
],
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[
333,
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]
],
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"id": "167_T8",
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"sn-3:sn-1' bis(monoacylglycerol)phosphate"
],
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377,
418
]
],
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},
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"id": "167_T9",
"type": "Metabolite",
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"sn-3:sn-1' lysophosphatidylglycerol"
],
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333,
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377,
418
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"id": "167_T11",
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"enzyme"
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290,
296
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450,
456
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466,
490
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"lipids"
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604,
610
]
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"id": "167_T17",
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648,
654
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"id": "167_T18",
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"saturated acyl chain"
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663,
683
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"id": "167_T19",
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673,
683
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688,
702
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"id": "167_T20",
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"16 and 18 carbon fatty acids"
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705,
733
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"id": "167_T21",
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739,
760
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766,
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812,
839
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864,
887
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920,
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848,
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321,
329
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512,
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542,
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570,
574
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"transacylase"
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920,
932
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"id": "167_R1",
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] |
168 | 101016 | [
{
"id": "169",
"type": "",
"text": [
"The authors attempted to evaluate different reagents in order to quantify the amino groups of the platelet membrane. The study was carried out by the action of different aldehydes and acid anhydrides. The use of 2,4,6-trinitrobenzenesulfonic acid made possible an approach by electrophoresis and chemical assay. The results showed an increase in the surface charge corresponding to a mean number of amino groups varying from 1.86.10(5) groups with citraconic acid to 3.94.10(5) groups with acetaldehyde. \n"
],
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0,
506
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]
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44,
52
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78,
90
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"id": "169_T3",
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"aldehydes"
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170,
179
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"id": "169_T4",
"type": "Chemical",
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"acid anhydrides"
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184,
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"id": "169_T5",
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212,
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399,
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449,
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"id": "169_T8",
"type": "Chemical",
"text": [
"acetaldehyde"
],
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[
491,
503
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],
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}
] | [] | [] | [] |
170 | 10102460 | [
{
"id": "171",
"type": "",
"text": [
"Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT. \n"
],
"offsets": [
[
0,
1318
]
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130,
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"inhibitor"
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190,
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219,
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386,
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704,
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"id": "171_T14",
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"thrombin"
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[
181,
189
]
],
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] | [] | [] | [
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"id": "171_R1",
"type": "Associated_With",
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"arg2_id": "171_T3",
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}
] |
172 | 10103229 | [
{
"id": "173",
"type": "",
"text": [
"Bacterial strain LW1, which belongs to the family Comamonadaceae, utilizes 1-chloro-4-nitrobenzene (1C4NB) as a sole source of carbon, nitrogen, and energy. Suspensions of 1C4NB-grown cells removed 1C4NB from culture fluids, and there was a concomitant release of ammonia and chloride. Under anaerobic conditions LW1 transformed 1C4NB into a product which was identified as 2-amino-5-chlorophenol by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. This transformation indicated that there was partial reduction of the nitro group to the hydroxylamino substituent, followed by Bamberger rearrangement. In the presence of oxygen but in the absence of NAD, fast transformation of 2-amino-5-chlorophenol into a transiently stable yellow product was observed with resting cells and cell extracts. This compound exhibited an absorption maximum at 395 nm and was further converted to a dead-end product with maxima at 226 and 272 nm. The compound formed was subsequently identified by 1H and 13C NMR spectroscopy and mass spectrometry as 5-chloropicolinic acid. In contrast, when NAD was added in the presence of oxygen, only minor amounts of 5-chloropicolinic acid were formed, and a new product, which exhibited an absorption maximum at 306 nm, accumulated. \n"
],
"offsets": [
[
0,
1286
]
]
}
] | [
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],
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[
50,
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"id": "173_T2",
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0,
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"id": "173_T3",
"type": "Chemical",
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75,
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]
],
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"id": "173_T4",
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"1C4NB"
],
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[
100,
105
]
],
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"id": "173_T5",
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"carbon"
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127,
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"nitrogen"
],
"offsets": [
[
135,
143
]
],
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"id": "173_T7",
"type": "Chemical",
"text": [
"1C4NB"
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[
172,
177
]
],
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"id": "173_T8",
"type": "Chemical",
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"1C4NB"
],
"offsets": [
[
198,
203
]
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"id": "173_T9",
"type": "Chemical",
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"ammonia"
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264,
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"id": "173_T10",
"type": "Metabolite",
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264,
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"id": "173_T11",
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"chloride"
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276,
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]
],
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},
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"id": "173_T12",
"type": "Metabolite",
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"chloride"
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[
276,
284
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],
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"id": "173_T13",
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"LW1"
],
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313,
316
]
],
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"id": "173_T14",
"type": "Chemical",
"text": [
"1C4NB"
],
"offsets": [
[
329,
334
]
],
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},
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"id": "173_T15",
"type": "Chemical",
"text": [
"2-amino-5-chlorophenol"
],
"offsets": [
[
374,
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]
],
"normalized": []
},
{
"id": "173_T16",
"type": "Metabolite",
"text": [
"2-amino-5-chlorophenol"
],
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[
374,
396
]
],
"normalized": []
},
{
"id": "173_T17",
"type": "Spectral_Data",
"text": [
"13C nuclear magnetic resonance"
],
"offsets": [
[
407,
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]
],
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},
{
"id": "173_T18",
"type": "Chemical",
"text": [
"nitro group"
],
"offsets": [
[
550,
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]
],
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},
{
"id": "173_T19",
"type": "Chemical",
"text": [
"hydroxylamino"
],
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[
569,
582
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"normalized": []
},
{
"id": "173_T20",
"type": "Chemical",
"text": [
"oxygen"
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"offsets": [
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652,
658
]
],
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{
"id": "173_T21",
"type": "Chemical",
"text": [
"NAD"
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"offsets": [
[
681,
684
]
],
"normalized": []
},
{
"id": "173_T22",
"type": "Metabolite",
"text": [
"2-amino-5-chlorophenol"
],
"offsets": [
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709,
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],
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},
{
"id": "173_T23",
"type": "Chemical",
"text": [
"2-amino-5-chlorophenol"
],
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709,
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],
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},
{
"id": "173_T24",
"type": "Spectral_Data",
"text": [
"absorption maximum at 395 nm"
],
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[
851,
879
]
],
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},
{
"id": "173_T27",
"type": "Spectral_Data",
"text": [
"maxima at 226 and 272 nm"
],
"offsets": [
[
933,
957
]
],
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},
{
"id": "173_T25",
"type": "Spectral_Data",
"text": [
"13C NMR spectroscopy"
],
"offsets": [
[
1017,
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],
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},
{
"id": "173_T26",
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"text": [
"5-chloropicolinic acid"
],
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[
1063,
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],
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},
{
"id": "173_T28",
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"5-chloropicolinic acid"
],
"offsets": [
[
1063,
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],
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{
"id": "173_T29",
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"NAD"
],
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1105,
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],
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"id": "173_T30",
"type": "Chemical",
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"oxygen"
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1138,
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"text": [
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1168,
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]
],
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},
{
"id": "173_T32",
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"text": [
"5-chloropicolinic acid"
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1168,
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{
"id": "173_T33",
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"text": [
"new product"
],
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1210,
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},
{
"id": "173_T34",
"type": "Metabolite",
"text": [
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1210,
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{
"id": "173_T35",
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"text": [
"absorption maximum at 306 nm"
],
"offsets": [
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1242,
1270
]
],
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{
"id": "173_T36",
"type": "Spectral_Data",
"text": [
"1H",
"nuclear magnetic resonance"
],
"offsets": [
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400,
402
],
[
411,
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]
],
"normalized": []
},
{
"id": "173_T37",
"type": "Spectral_Data",
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"mass spectrometry"
],
"offsets": [
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461,
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],
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},
{
"id": "173_T38",
"type": "Spectral_Data",
"text": [
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"NMR spectroscopy"
],
"offsets": [
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1010,
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],
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1021,
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]
],
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"id": "173_T39",
"type": "Spectral_Data",
"text": [
"mass spectrometry"
],
"offsets": [
[
1042,
1059
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "173_R1",
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"arg2_id": "173_T27",
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"id": "173_R14",
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"arg2_id": "173_T2",
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},
{
"id": "173_R15",
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},
{
"id": "173_R16",
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},
{
"id": "173_R17",
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"arg2_id": "173_T2",
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},
{
"id": "173_R18",
"type": "Metabolite_Of",
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"arg2_id": "173_T14",
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},
{
"id": "173_R19",
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"arg2_id": "173_T26",
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},
{
"id": "173_R20",
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"arg1_id": "173_T16",
"arg2_id": "173_T36",
"normalized": []
},
{
"id": "173_R21",
"type": "Associated_With",
"arg1_id": "173_T15",
"arg2_id": "173_T36",
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},
{
"id": "173_R22",
"type": "Associated_With",
"arg1_id": "173_T16",
"arg2_id": "173_T37",
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},
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"id": "173_R23",
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"arg2_id": "173_T37",
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"id": "173_R24",
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"arg2_id": "173_T3",
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"id": "173_R25",
"type": "Associated_With",
"arg1_id": "173_T28",
"arg2_id": "173_T38",
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},
{
"id": "173_R26",
"type": "Associated_With",
"arg1_id": "173_T26",
"arg2_id": "173_T38",
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},
{
"id": "173_R27",
"type": "Associated_With",
"arg1_id": "173_T26",
"arg2_id": "173_T39",
"normalized": []
},
{
"id": "173_R28",
"type": "Associated_With",
"arg1_id": "173_T28",
"arg2_id": "173_T39",
"normalized": []
},
{
"id": "173_R29",
"type": "Metabolite_Of",
"arg1_id": "173_T10",
"arg2_id": "173_T8",
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},
{
"id": "173_R30",
"type": "Metabolite_Of",
"arg1_id": "173_T12",
"arg2_id": "173_T8",
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},
{
"id": "173_R31",
"type": "Metabolite_Of",
"arg1_id": "173_T10",
"arg2_id": "173_T3",
"normalized": []
},
{
"id": "173_R32",
"type": "Metabolite_Of",
"arg1_id": "173_T12",
"arg2_id": "173_T3",
"normalized": []
}
] |
174 | 1010599 | [
{
"id": "175",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
176 | 10109799 | [
{
"id": "177",
"type": "",
"text": [
"In this article, a cost-minimization model was used to make an economic comparison between cefmetazole and cefoxitin--two drugs with comparable in vitro spectra of activity, clinical efficacy, and safety profiles. Drug acquisition costs were estimated from published information and labor and material costs were calculated based on actual costs at Presbyterian Hospital of Dallas. Costs of the agents were calculated based on the dosage and administration schedules typically used in published clinical trials of cefmetazole and cefoxitin and on the typical dosing patterns of cefoxitin used at Presbyterian Hospital. Results of the cost analysis revealed that an annual savings of $36,015 to $59,143 could be realized at Presbyterian Hospital if cefmetazole were used in place of cefoxitin for surgical prophylaxis. Furthermore, use of cefmetazole in place of cefoxitin for wound treatment would yield annual savings of $33,242. \n"
],
"offsets": [
[
0,
934
]
]
}
] | [
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"id": "177_T1",
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"cefmetazole"
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91,
102
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{
"id": "177_T2",
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"cefoxitin"
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107,
116
]
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},
{
"id": "177_T3",
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"cefmetazole"
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515,
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{
"id": "177_T4",
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"cefoxitin"
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[
531,
540
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],
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{
"id": "177_T5",
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"cefoxitin"
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[
579,
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},
{
"id": "177_T6",
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"cefmetazole"
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[
750,
761
]
],
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},
{
"id": "177_T7",
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"cefoxitin"
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[
784,
793
]
],
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},
{
"id": "177_T8",
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"cefmetazole"
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[
840,
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],
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{
"id": "177_T9",
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"cefoxitin"
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[
864,
873
]
],
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},
{
"id": "177_T11",
"type": "Chemical",
"text": [
"drugs"
],
"offsets": [
[
122,
127
]
],
"normalized": []
}
] | [] | [] | [] |
178 | 1011375 | [
{
"id": "179",
"type": "",
"text": [
"Aspergillus candidus Link, one of the commonest constituents of cereal mycoflora, produces two kinds of mycotoxins, terphenyllin and xanthoascin, which show different chemical and toxicological properties. The latter, xanthoascin, caused severe hepatic injury with jaundice and focal or confluent necrosis of hepatocytes, when given to mice in doses of 6 mg/kg b.w. or higher by a single subcutaneous injection. With higher doses above 15 mg/kg, myocardial degeneration and necrosis was induced after a week or two in addition to the hepatic injury. Vacuolation of the nuclei of the alveolar interstitial cells of the lung and myocardial interstitial cells was another characteristic lesion caused by this mycotoxin. Other organs including the testicles and thymus were widely involved. The unique nature of lesions in the liver and heart may necessitate further investigations in the field of mycotoxicology in relation to human diseases such as nutritional hepatitis and primary myocardial degeneration. \n"
],
"offsets": [
[
0,
1010
]
]
}
] | [
{
"id": "179_T1",
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"Aspergillus candidus Link"
],
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[
0,
25
]
],
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},
{
"id": "179_T2",
"type": "Chemical",
"text": [
"terphenyllin"
],
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[
116,
128
]
],
"normalized": []
},
{
"id": "179_T3",
"type": "Chemical",
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"xanthoascin"
],
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133,
144
]
],
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},
{
"id": "179_T4",
"type": "Biological_Activity",
"text": [
"mycotoxin"
],
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[
104,
113
]
],
"normalized": []
},
{
"id": "179_T5",
"type": "Metabolite",
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"terphenyllin"
],
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[
116,
128
]
],
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},
{
"id": "179_T6",
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"text": [
"xanthoascin"
],
"offsets": [
[
133,
144
]
],
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},
{
"id": "179_T7",
"type": "Metabolite",
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"xanthoascin"
],
"offsets": [
[
218,
229
]
],
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},
{
"id": "179_T8",
"type": "Chemical",
"text": [
"xanthoascin"
],
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[
218,
229
]
],
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},
{
"id": "179_T11",
"type": "Biological_Activity",
"text": [
"necrosis"
],
"offsets": [
[
298,
306
]
],
"normalized": []
},
{
"id": "179_T12",
"type": "Species",
"text": [
"mice"
],
"offsets": [
[
337,
341
]
],
"normalized": []
},
{
"id": "179_T14",
"type": "Biological_Activity",
"text": [
"necrosis"
],
"offsets": [
[
475,
483
]
],
"normalized": []
},
{
"id": "179_T17",
"type": "Biological_Activity",
"text": [
"mycotoxin"
],
"offsets": [
[
707,
716
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "179_R1",
"type": "Associated_With",
"arg1_id": "179_T5",
"arg2_id": "179_T4",
"normalized": []
},
{
"id": "179_R2",
"type": "Associated_With",
"arg1_id": "179_T6",
"arg2_id": "179_T4",
"normalized": []
},
{
"id": "179_R3",
"type": "Associated_With",
"arg1_id": "179_T2",
"arg2_id": "179_T4",
"normalized": []
},
{
"id": "179_R4",
"type": "Associated_With",
"arg1_id": "179_T3",
"arg2_id": "179_T4",
"normalized": []
},
{
"id": "179_R7",
"type": "Associated_With",
"arg1_id": "179_T7",
"arg2_id": "179_T11",
"normalized": []
},
{
"id": "179_R10",
"type": "Associated_With",
"arg1_id": "179_T8",
"arg2_id": "179_T11",
"normalized": []
},
{
"id": "179_R12",
"type": "Associated_With",
"arg1_id": "179_T7",
"arg2_id": "179_T14",
"normalized": []
},
{
"id": "179_R14",
"type": "Associated_With",
"arg1_id": "179_T8",
"arg2_id": "179_T14",
"normalized": []
},
{
"id": "179_R19",
"type": "Isolated_From",
"arg1_id": "179_T5",
"arg2_id": "179_T1",
"normalized": []
},
{
"id": "179_R20",
"type": "Isolated_From",
"arg1_id": "179_T6",
"arg2_id": "179_T1",
"normalized": []
}
] |
180 | 10116 | [
{
"id": "181",
"type": "",
"text": [
"1. The central depressant effects of bromvaletone, carbromal and six non-bromo analogues were compared in mice. 2. The chloro analogues of bromvaletone and carbromal were slightly less potent as central depressant agents than the bromo compounds. 3. The chloro analogue of bromvaletone had the greatest margin between central depressant and lethal doses. 4. Lipophilicity (octanol-water partition coefficient) did not provide a unifying relationship for potency within this group of eight acylureas. However, within each of the two subsets of compounds, a linear relationship was found between relative potency and lipophilicity. \n"
],
"offsets": [
[
0,
631
]
]
}
] | [
{
"id": "181_T1",
"type": "Biological_Activity",
"text": [
"central depressant"
],
"offsets": [
[
7,
25
]
],
"normalized": []
},
{
"id": "181_T2",
"type": "Chemical",
"text": [
"bromvaletone"
],
"offsets": [
[
37,
49
]
],
"normalized": []
},
{
"id": "181_T3",
"type": "Chemical",
"text": [
"carbromal"
],
"offsets": [
[
51,
60
]
],
"normalized": []
},
{
"id": "181_T4",
"type": "Chemical",
"text": [
"non-bromo analogues"
],
"offsets": [
[
69,
88
]
],
"normalized": []
},
{
"id": "181_T5",
"type": "Species",
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"mice"
],
"offsets": [
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106,
110
]
],
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},
{
"id": "181_T6",
"type": "Chemical",
"text": [
"chloro analogues of bromvaletone"
],
"offsets": [
[
119,
151
]
],
"normalized": []
},
{
"id": "181_T7",
"type": "Chemical",
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"carbromal"
],
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119,
134
],
[
156,
165
]
],
"normalized": []
},
{
"id": "181_T8",
"type": "Biological_Activity",
"text": [
"central depressant"
],
"offsets": [
[
195,
213
]
],
"normalized": []
},
{
"id": "181_T9",
"type": "Chemical",
"text": [
"bromvaletone"
],
"offsets": [
[
139,
151
]
],
"normalized": []
},
{
"id": "181_T10",
"type": "Chemical",
"text": [
"carbromal"
],
"offsets": [
[
156,
165
]
],
"normalized": []
},
{
"id": "181_T11",
"type": "Chemical",
"text": [
"chloro analogue of bromvaletone"
],
"offsets": [
[
254,
285
]
],
"normalized": []
},
{
"id": "181_T12",
"type": "Chemical",
"text": [
"bromvaletone"
],
"offsets": [
[
273,
285
]
],
"normalized": []
},
{
"id": "181_T13",
"type": "Biological_Activity",
"text": [
"central depressant"
],
"offsets": [
[
318,
336
]
],
"normalized": []
},
{
"id": "181_T14",
"type": "Chemical",
"text": [
"octanol"
],
"offsets": [
[
373,
380
]
],
"normalized": []
},
{
"id": "181_T15",
"type": "Chemical",
"text": [
"water"
],
"offsets": [
[
381,
386
]
],
"normalized": []
},
{
"id": "181_T16",
"type": "Chemical",
"text": [
"acylureas"
],
"offsets": [
[
489,
498
]
],
"normalized": []
},
{
"id": "181_T17",
"type": "Chemical",
"text": [
"bromo compounds"
],
"offsets": [
[
230,
245
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "181_R1",
"type": "Associated_With",
"arg1_id": "181_T7",
"arg2_id": "181_T8",
"normalized": []
},
{
"id": "181_R2",
"type": "Associated_With",
"arg1_id": "181_T6",
"arg2_id": "181_T8",
"normalized": []
},
{
"id": "181_R3",
"type": "Associated_With",
"arg1_id": "181_T9",
"arg2_id": "181_T8",
"normalized": []
},
{
"id": "181_R4",
"type": "Associated_With",
"arg1_id": "181_T10",
"arg2_id": "181_T8",
"normalized": []
},
{
"id": "181_R5",
"type": "Associated_With",
"arg1_id": "181_T2",
"arg2_id": "181_T1",
"normalized": []
},
{
"id": "181_R6",
"type": "Associated_With",
"arg1_id": "181_T3",
"arg2_id": "181_T1",
"normalized": []
}
] |
182 | 1011939 | [
{
"id": "183",
"type": "",
"text": [
"The study on the metabolism after oral administration of chenodeoxycholic acid-24-14C was performed by analysis of radioactivity that had appeared in bile and feces of male hamsters. The radioactive bile acids were analyzed by thin layer chromatography and identified by the isotope dilution method. In the bile of the hamsters with bile fistula, radioactivity was originated from unchanged chenodeoxycholic acid for the most part, and 7-ketolithocholic acid, lithocholic acid, and beta-muricholic acid for the remainder. In the feces lithocholic acid, dehydrolithocholic acid, isolithocholic acid, and unchanged form were identified. After the multiple dosing of chenodeoxycholic acid-24-14C for 6 days, beta-muricholic acid was also identified in the feces. \n"
],
"offsets": [
[
0,
764
]
]
}
] | [
{
"id": "183_T1",
"type": "Chemical",
"text": [
"chenodeoxycholic acid-24-14C"
],
"offsets": [
[
57,
85
]
],
"normalized": []
},
{
"id": "183_T2",
"type": "Species",
"text": [
"hamsters"
],
"offsets": [
[
174,
182
]
],
"normalized": []
},
{
"id": "183_T3",
"type": "Chemical",
"text": [
"chenodeoxycholic acid"
],
"offsets": [
[
57,
78
]
],
"normalized": []
},
{
"id": "183_T4",
"type": "Metabolite",
"text": [
"chenodeoxycholic acid"
],
"offsets": [
[
57,
78
]
],
"normalized": []
},
{
"id": "183_T5",
"type": "Chemical",
"text": [
"bile acid"
],
"offsets": [
[
200,
209
]
],
"normalized": []
},
{
"id": "183_T6",
"type": "Species",
"text": [
"hamsters"
],
"offsets": [
[
320,
328
]
],
"normalized": []
},
{
"id": "183_T7",
"type": "Metabolite",
"text": [
"chenodeoxycholic acid"
],
"offsets": [
[
392,
413
]
],
"normalized": []
},
{
"id": "183_T8",
"type": "Chemical",
"text": [
"chenodeoxycholic acid"
],
"offsets": [
[
392,
413
]
],
"normalized": []
},
{
"id": "183_T9",
"type": "Chemical",
"text": [
"7-ketolithocholic acid"
],
"offsets": [
[
437,
459
]
],
"normalized": []
},
{
"id": "183_T10",
"type": "Metabolite",
"text": [
"7-ketolithocholic acid"
],
"offsets": [
[
437,
459
]
],
"normalized": []
},
{
"id": "183_T11",
"type": "Metabolite",
"text": [
"lithocholic acid"
],
"offsets": [
[
461,
478
]
],
"normalized": []
},
{
"id": "183_T12",
"type": "Chemical",
"text": [
"lithocholic acid"
],
"offsets": [
[
461,
478
]
],
"normalized": []
},
{
"id": "183_T13",
"type": "Chemical",
"text": [
"beta-muricholic acid"
],
"offsets": [
[
484,
504
]
],
"normalized": []
},
{
"id": "183_T14",
"type": "Metabolite",
"text": [
"beta-muricholic acid"
],
"offsets": [
[
484,
504
]
],
"normalized": []
},
{
"id": "183_T15",
"type": "Chemical",
"text": [
"lithocholic acid"
],
"offsets": [
[
537,
553
]
],
"normalized": []
},
{
"id": "183_T16",
"type": "Metabolite",
"text": [
"lithocholic acid"
],
"offsets": [
[
537,
553
]
],
"normalized": []
},
{
"id": "183_T17",
"type": "Chemical",
"text": [
"dehydrolithocholic acid"
],
"offsets": [
[
556,
579
]
],
"normalized": []
},
{
"id": "183_T18",
"type": "Metabolite",
"text": [
"dehydrolithocholic acid"
],
"offsets": [
[
556,
579
]
],
"normalized": []
},
{
"id": "183_T19",
"type": "Chemical",
"text": [
"isolithocholic acid"
],
"offsets": [
[
581,
600
]
],
"normalized": []
},
{
"id": "183_T20",
"type": "Metabolite",
"text": [
"isolithocholic acid"
],
"offsets": [
[
581,
600
]
],
"normalized": []
},
{
"id": "183_T21",
"type": "Chemical",
"text": [
"chenodeoxycholic acid"
],
"offsets": [
[
667,
688
]
],
"normalized": []
},
{
"id": "183_T22",
"type": "Chemical",
"text": [
"chenodeoxycholic acid-24-14C"
],
"offsets": [
[
667,
695
]
],
"normalized": []
},
{
"id": "183_T23",
"type": "Metabolite",
"text": [
"chenodeoxycholic acid"
],
"offsets": [
[
667,
688
]
],
"normalized": []
},
{
"id": "183_T24",
"type": "Metabolite",
"text": [
"beta-muricholic acid"
],
"offsets": [
[
708,
728
]
],
"normalized": []
},
{
"id": "183_T25",
"type": "Chemical",
"text": [
"beta-muricholic acid"
],
"offsets": [
[
708,
728
]
],
"normalized": []
},
{
"id": "183_T26",
"type": "Metabolite",
"text": [
"bile acids"
],
"offsets": [
[
200,
210
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "183_R1",
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},
{
"id": "183_R2",
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"normalized": []
},
{
"id": "183_R3",
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"arg2_id": "183_T6",
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},
{
"id": "183_R4",
"type": "Isolated_From",
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"arg2_id": "183_T6",
"normalized": []
},
{
"id": "183_R5",
"type": "Isolated_From",
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"arg2_id": "183_T6",
"normalized": []
},
{
"id": "183_R6",
"type": "Isolated_From",
"arg1_id": "183_T18",
"arg2_id": "183_T6",
"normalized": []
},
{
"id": "183_R7",
"type": "Isolated_From",
"arg1_id": "183_T20",
"arg2_id": "183_T6",
"normalized": []
},
{
"id": "183_R8",
"type": "Isolated_From",
"arg1_id": "183_T24",
"arg2_id": "183_T6",
"normalized": []
},
{
"id": "183_R9",
"type": "Metabolite_Of",
"arg1_id": "183_T10",
"arg2_id": "183_T8",
"normalized": []
},
{
"id": "183_R10",
"type": "Metabolite_Of",
"arg1_id": "183_T11",
"arg2_id": "183_T8",
"normalized": []
},
{
"id": "183_R11",
"type": "Metabolite_Of",
"arg1_id": "183_T14",
"arg2_id": "183_T8",
"normalized": []
},
{
"id": "183_R12",
"type": "Metabolite_Of",
"arg1_id": "183_T16",
"arg2_id": "183_T8",
"normalized": []
},
{
"id": "183_R13",
"type": "Metabolite_Of",
"arg1_id": "183_T18",
"arg2_id": "183_T8",
"normalized": []
},
{
"id": "183_R14",
"type": "Metabolite_Of",
"arg1_id": "183_T20",
"arg2_id": "183_T8",
"normalized": []
},
{
"id": "183_R15",
"type": "Metabolite_Of",
"arg1_id": "183_T24",
"arg2_id": "183_T21",
"normalized": []
}
] |
184 | 101233 | [
{
"id": "185",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
186 | 101268 | [
{
"id": "187",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
188 | 101555 | [
{
"id": "189",
"type": "",
"text": [
"Manganous chloride and Congo red incorporated into blotting paper discs have been used to differentiate gonococci from meningococci. The new technique is simple and reliable; the materials for the test are inexpensive. The method will increase the efficiency of distinguishing between the pathogenic Neisseria in any clinical bacteriology laboratory and especially in those in the tropical areas. \n"
],
"offsets": [
[
0,
398
]
]
}
] | [
{
"id": "189_T1",
"type": "Chemical",
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"Manganous chloride"
],
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[
0,
18
]
],
"normalized": []
},
{
"id": "189_T2",
"type": "Chemical",
"text": [
"Congo red"
],
"offsets": [
[
23,
32
]
],
"normalized": []
},
{
"id": "189_T4",
"type": "Species",
"text": [
"meningococci"
],
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119,
131
]
],
"normalized": []
},
{
"id": "189_T5",
"type": "Species",
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"gonococci"
],
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104,
113
]
],
"normalized": []
},
{
"id": "189_T3",
"type": "Species",
"text": [
"Neisseria"
],
"offsets": [
[
300,
309
]
],
"normalized": []
}
] | [] | [] | [] |
190 | 1016232 | [
{
"id": "191",
"type": "",
"text": [
"1. Normal human urine contains small amounts (less than 4 mg/g of creatinine) of 2-ethylhydracrylic acid, formed, we believe, by a previously undisclosed endogenous catabolic pathway for the oxidation of a newly described series of R metabolites of isoleucine. 2. Urinary excretion of 2-ethylhydracrylic acid is variably increased in defects of isoleucine oxidation at distal steps in the catabolic pathway (3-oxoacyl-CoA thiolase deficiency and methylmalonyl-CoA mutase deficiency) and is diminished when proximal steps of the oxidative pathway are blocked as in branched-chain oxo acid decarboxylase deficiency ('maple-syrup-urine' disease). 3. Precursors of R-pathway metabolites [R(-)-2-methylbutyrate and 2-ethylacrylate ] lead to increased 2-ethylhydracrylate excretion in the mammal(rat, rabbit and dog); the corresponding S metabolites [S(+)-2-methylbutyric acid and tiglic acid ], when given in equimolar amounts, have little effect on its excretion, suggesting that little or no interconversion between S and R metabolites occurs in vivo. 4. Studies with 2H-labelled precursors indicate that conversion of R 2-methylbutyrate into 2-ethylhydracrylic acid occurs by a direct pathway (apparently via 2-ethylacrylic acid). 5. The further oxidation of 2-ethylhydracrylic acid to ethylmalonic acid was demonstrated, and may be analogous to S-metabolite oxidation via methyl malonate. 6. Valine metabolites do not interact with the R=isoleucine pathway under the conditions of these experiments in vivo. \n"
],
"offsets": [
[
0,
1510
]
]
}
] | [
{
"id": "191_T1",
"type": "Species",
"text": [
"human"
],
"offsets": [
[
10,
15
]
],
"normalized": []
},
{
"id": "191_T2",
"type": "Chemical",
"text": [
"creatinine"
],
"offsets": [
[
66,
76
]
],
"normalized": []
},
{
"id": "191_T3",
"type": "Metabolite",
"text": [
"creatinine"
],
"offsets": [
[
66,
76
]
],
"normalized": []
},
{
"id": "191_T4",
"type": "Chemical",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
82,
105
]
],
"normalized": []
},
{
"id": "191_T5",
"type": "Metabolite",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
82,
105
]
],
"normalized": []
},
{
"id": "191_T6",
"type": "Chemical",
"text": [
"isoleucine"
],
"offsets": [
[
250,
260
]
],
"normalized": []
},
{
"id": "191_T7",
"type": "Chemical",
"text": [
"R metabolites of isoleucine"
],
"offsets": [
[
233,
260
]
],
"normalized": []
},
{
"id": "191_T8",
"type": "Metabolite",
"text": [
"R metabolites of isoleucine"
],
"offsets": [
[
233,
260
]
],
"normalized": []
},
{
"id": "191_T9",
"type": "Chemical",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
286,
309
]
],
"normalized": []
},
{
"id": "191_T10",
"type": "Metabolite",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
286,
309
]
],
"normalized": []
},
{
"id": "191_T11",
"type": "Chemical",
"text": [
"isoleucine"
],
"offsets": [
[
346,
356
]
],
"normalized": []
},
{
"id": "191_T12",
"type": "Metabolite",
"text": [
"isoleucine"
],
"offsets": [
[
346,
356
]
],
"normalized": []
},
{
"id": "191_T13",
"type": "Metabolite",
"text": [
"isoleucine"
],
"offsets": [
[
250,
260
]
],
"normalized": []
},
{
"id": "191_T14",
"type": "Chemical",
"text": [
"3-oxoacyl-CoA"
],
"offsets": [
[
409,
422
]
],
"normalized": []
},
{
"id": "191_T15",
"type": "Protein",
"text": [
"3-oxoacyl-CoA thiolase"
],
"offsets": [
[
409,
431
]
],
"normalized": []
},
{
"id": "191_T18",
"type": "Chemical",
"text": [
"methylmalonyl-CoA"
],
"offsets": [
[
447,
464
]
],
"normalized": []
},
{
"id": "191_T17",
"type": "Protein",
"text": [
"methylmalonyl-CoA mutase"
],
"offsets": [
[
447,
471
]
],
"normalized": []
},
{
"id": "191_T21",
"type": "Chemical",
"text": [
"branched-chain oxo acid"
],
"offsets": [
[
565,
588
]
],
"normalized": []
},
{
"id": "191_T22",
"type": "Protein",
"text": [
"branched-chain oxo acid decarboxylase"
],
"offsets": [
[
565,
602
]
],
"normalized": []
},
{
"id": "191_T27",
"type": "Chemical",
"text": [
"R(-)-2-methylbutyrate"
],
"offsets": [
[
685,
706
]
],
"normalized": []
},
{
"id": "191_T28",
"type": "Chemical",
"text": [
"R(-)-",
"2-ethylacrylate"
],
"offsets": [
[
685,
690
],
[
711,
726
]
],
"normalized": []
},
{
"id": "191_T29",
"type": "Metabolite",
"text": [
"R(-)-2-methylbutyrate"
],
"offsets": [
[
685,
706
]
],
"normalized": []
},
{
"id": "191_T30",
"type": "Metabolite",
"text": [
"R(-)-",
"2-ethylacrylate"
],
"offsets": [
[
685,
690
],
[
711,
726
]
],
"normalized": []
},
{
"id": "191_T31",
"type": "Chemical",
"text": [
"2-ethylhydracrylate"
],
"offsets": [
[
747,
766
]
],
"normalized": []
},
{
"id": "191_T32",
"type": "Metabolite",
"text": [
"2-ethylhydracrylate"
],
"offsets": [
[
747,
766
]
],
"normalized": []
},
{
"id": "191_T34",
"type": "Species",
"text": [
"mammal"
],
"offsets": [
[
784,
790
]
],
"normalized": []
},
{
"id": "191_T35",
"type": "Species",
"text": [
"rat"
],
"offsets": [
[
791,
794
]
],
"normalized": []
},
{
"id": "191_T36",
"type": "Species",
"text": [
"rabbit"
],
"offsets": [
[
796,
802
]
],
"normalized": []
},
{
"id": "191_T37",
"type": "Species",
"text": [
"dog"
],
"offsets": [
[
807,
810
]
],
"normalized": []
},
{
"id": "191_T38",
"type": "Chemical",
"text": [
"S(+)-2-methylbutyric acid"
],
"offsets": [
[
846,
871
]
],
"normalized": []
},
{
"id": "191_T39",
"type": "Metabolite",
"text": [
"S(+)-2-methylbutyric acid"
],
"offsets": [
[
846,
871
]
],
"normalized": []
},
{
"id": "191_T40",
"type": "Chemical",
"text": [
"S(+)-",
"tiglic acid"
],
"offsets": [
[
846,
851
],
[
876,
887
]
],
"normalized": []
},
{
"id": "191_T41",
"type": "Metabolite",
"text": [
"S(+)-",
"tiglic acid"
],
"offsets": [
[
846,
851
],
[
876,
887
]
],
"normalized": []
},
{
"id": "191_T42",
"type": "Chemical",
"text": [
"R 2-methylbutyrate"
],
"offsets": [
[
1118,
1136
]
],
"normalized": []
},
{
"id": "191_T43",
"type": "Metabolite",
"text": [
"R 2-methylbutyrate"
],
"offsets": [
[
1118,
1136
]
],
"normalized": []
},
{
"id": "191_T44",
"type": "Chemical",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
1142,
1165
]
],
"normalized": []
},
{
"id": "191_T45",
"type": "Metabolite",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
1142,
1165
]
],
"normalized": []
},
{
"id": "191_T46",
"type": "Chemical",
"text": [
"2-ethylacrylic acid"
],
"offsets": [
[
1209,
1228
]
],
"normalized": []
},
{
"id": "191_T47",
"type": "Metabolite",
"text": [
"2-ethylacrylic acid"
],
"offsets": [
[
1209,
1228
]
],
"normalized": []
},
{
"id": "191_T48",
"type": "Chemical",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
1259,
1282
]
],
"normalized": []
},
{
"id": "191_T49",
"type": "Metabolite",
"text": [
"2-ethylhydracrylic acid"
],
"offsets": [
[
1259,
1282
]
],
"normalized": []
},
{
"id": "191_T50",
"type": "Metabolite",
"text": [
"ethylmalonic acid"
],
"offsets": [
[
1286,
1303
]
],
"normalized": []
},
{
"id": "191_T51",
"type": "Chemical",
"text": [
"ethylmalonic acid"
],
"offsets": [
[
1286,
1303
]
],
"normalized": []
},
{
"id": "191_T52",
"type": "Chemical",
"text": [
"methyl malonate"
],
"offsets": [
[
1373,
1388
]
],
"normalized": []
},
{
"id": "191_T53",
"type": "Chemical",
"text": [
"Valine"
],
"offsets": [
[
1393,
1399
]
],
"normalized": []
},
{
"id": "191_T54",
"type": "Metabolite",
"text": [
"Valine"
],
"offsets": [
[
1393,
1399
]
],
"normalized": []
},
{
"id": "191_T55",
"type": "Metabolite",
"text": [
"Valine metabolites"
],
"offsets": [
[
1393,
1411
]
],
"normalized": []
},
{
"id": "191_T56",
"type": "Chemical",
"text": [
"R=isoleucine"
],
"offsets": [
[
1437,
1449
]
],
"normalized": []
},
{
"id": "191_T57",
"type": "Metabolite",
"text": [
"R=isoleucine"
],
"offsets": [
[
1437,
1449
]
],
"normalized": []
}
] | [] | [] | [
{
"id": "191_R1",
"type": "Isolated_From",
"arg1_id": "191_T3",
"arg2_id": "191_T1",
"normalized": []
},
{
"id": "191_R2",
"type": "Isolated_From",
"arg1_id": "191_T5",
"arg2_id": "191_T1",
"normalized": []
},
{
"id": "191_R3",
"type": "Isolated_From",
"arg1_id": "191_T10",
"arg2_id": "191_T1",
"normalized": []
},
{
"id": "191_R4",
"type": "Metabolite_Of",
"arg1_id": "191_T45",
"arg2_id": "191_T42",
"normalized": []
},
{
"id": "191_R5",
"type": "Metabolite_Of",
"arg1_id": "191_T50",
"arg2_id": "191_T48",
"normalized": []
},
{
"id": "191_R6",
"type": "Metabolite_Of",
"arg1_id": "191_T45",
"arg2_id": "191_T46",
"normalized": []
},
{
"id": "191_R7",
"type": "Metabolite_Of",
"arg1_id": "191_T47",
"arg2_id": "191_T42",
"normalized": []
}
] |
192 | 1017174 | [
{
"id": "193",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
194 | 1017184 | [
{
"id": "195",
"type": "",
"text": [
"In six persons with contact allergy to chrysanthemum of florists, patch tests were performed with 25 sequiterpene lactones. Positive responses were observed to 15 lactones. The most frequently encountered positive responses were to alantolactone (positive in all cases) and to arbusculin A, 8-deoxycumambrin, ambrosin, damsin and psilostachynin. The findings corroborate the assumption that an alpha-methylene group attached to the gamma-lactone ring is an essential prerequisite for allergenic activity of sesquiterpene lactones. Pyrethrum produced a positive reaction in one of the patients, pyrethrins gave negative reactions in all. Some of the chrysanthemum patients were also hypersensitive to turpentine and colophony and to garlic, primin and tars. \n"
],
"offsets": [
[
0,
759
]
]
}
] | [
{
"id": "195_T1",
"type": "Species",
"text": [
"persons"
],
"offsets": [
[
7,
14
]
],
"normalized": []
},
{
"id": "195_T3",
"type": "Species",
"text": [
"chrysanthemum"
],
"offsets": [
[
39,
52
]
],
"normalized": []
},
{
"id": "195_T4",
"type": "Chemical",
"text": [
"sequiterpene lactones"
],
"offsets": [
[
101,
122
]
],
"normalized": []
},
{
"id": "195_T5",
"type": "Chemical",
"text": [
"lactones"
],
"offsets": [
[
163,
171
]
],
"normalized": []
},
{
"id": "195_T6",
"type": "Chemical",
"text": [
"alantolactone"
],
"offsets": [
[
232,
245
]
],
"normalized": []
},
{
"id": "195_T8",
"type": "Chemical",
"text": [
"arbusculin A"
],
"offsets": [
[
277,
289
]
],
"normalized": []
},
{
"id": "195_T9",
"type": "Chemical",
"text": [
"8-deoxycumambrin"
],
"offsets": [
[
291,
307
]
],
"normalized": []
},
{
"id": "195_T10",
"type": "Chemical",
"text": [
"ambrosin"
],
"offsets": [
[
309,
317
]
],
"normalized": []
},
{
"id": "195_T11",
"type": "Chemical",
"text": [
"damsin"
],
"offsets": [
[
319,
325
]
],
"normalized": []
},
{
"id": "195_T12",
"type": "Chemical",
"text": [
"psilostachynin"
],
"offsets": [
[
330,
344
]
],
"normalized": []
},
{
"id": "195_T13",
"type": "Chemical",
"text": [
"alpha-methylene group"
],
"offsets": [
[
394,
415
]
],
"normalized": []
},
{
"id": "195_T14",
"type": "Chemical",
"text": [
"gamma-lactone ring"
],
"offsets": [
[
432,
450
]
],
"normalized": []
},
{
"id": "195_T15",
"type": "Chemical",
"text": [
"alpha-methylene group attached to the gamma-lactone ring"
],
"offsets": [
[
394,
450
]
],
"normalized": []
},
{
"id": "195_T16",
"type": "Biological_Activity",
"text": [
"allergenic"
],
"offsets": [
[
484,
494
]
],
"normalized": []
},
{
"id": "195_T17",
"type": "Chemical",
"text": [
"sesquiterpene lactones"
],
"offsets": [
[
507,
529
]
],
"normalized": []
},
{
"id": "195_T18",
"type": "Chemical",
"text": [
"Pyrethrum"
],
"offsets": [
[
531,
540
]
],
"normalized": []
},
{
"id": "195_T19",
"type": "Chemical",
"text": [
"pyrethrins"
],
"offsets": [
[
594,
604
]
],
"normalized": []
},
{
"id": "195_T20",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
584,
592
]
],
"normalized": []
},
{
"id": "195_T21",
"type": "Species",
"text": [
"chrysanthemum"
],
"offsets": [
[
649,
662
]
],
"normalized": []
},
{
"id": "195_T22",
"type": "Species",
"text": [
"patients"
],
"offsets": [
[
663,
671
]
],
"normalized": []
},
{
"id": "195_T23",
"type": "Species",
"text": [
"florists"
],
"offsets": [
[
56,
64
]
],
"normalized": []
},
{
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198 | 1018622 | [
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