;PMID: 1763524 ;source_file_1008.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..36] = [t:0..36] ;1)sentence:[e:42..126] = [t:42..126] ;2)section:[e:130..175] = [t:130..175] ;3)section:[e:179..268] = [t:179..268] ;4)sentence:[e:272..409] = [t:272..409] ;5)sentence:[e:410..530] = [t:410..530] ;6)sentence:[e:531..702] = [t:531..702] ;7)sentence:[e:703..906] = [t:703..906] ;8)sentence:[e:907..1075] = [t:907..1075] ;9)sentence:[e:1076..1162] = [t:1076..1162] ;10)sentence:[e:1163..1362] = [t:1163..1362] ;11)section:[e:1366..1410] = [t:1366..1409] ;Sentence Matching Errors ;ERROR_Section end mismatch[e:1366..1410][t:1366..1409] ;Token/POS Errors ;ERROR_Token in entity file but not tree[1409..1410] ] ;ERROR_POS mismatch [1137..1140] t:token e:CD 6.7 ;section 0 Span:0..36 ;Xenobiotica. 1991 Nov;21(11):1501-9. (SEC (FRAG (RB:[0..11] Xenobiotica) (IN:[11..12] .) (CD:[13..17] 1991) (CC:[18..25] Nov;21-LRB-) (CD:[25..27] 11) (-RRB-:[27..28] -RRB-) (CD:[28..33] :1501) (::[33..34] -) (CD:[34..36] 9.))) ;sentence 1 Span:42..126 ;Thebaine O-demethylation to oripavine: genetic differences between two rat ;strains. ;[42..50]:substance:"Thebaine" ;[70..79]:substance:"oripavine" (SENT (NP-HLN (NP (NP (NN:[42..50] Thebaine) (NN:[51..66] O-demethylation)) (PP (TO:[67..69] to) (NP (NN:[70..79] oripavine)))) (::[79..80] :) (NP (NP (JJ:[81..88] genetic) (NNS:[89..100] differences)) (PP (IN:[101..108] between) (NP (CD:[109..112] two) (NN:[113..116] rat) (NNS:[118..125] strains)))) (.:[125..126] .))) ;section 2 Span:130..175 ;Mikus G, Somogyi AA, Bochner F, Eichelbaum M. (SEC (FRAG (NNP:[130..135] Mikus) (NNP:[136..137] G) (,:[137..138] ,) (NNP:[139..146] Somogyi) (NNP:[147..149] AA) (,:[149..150] ,) (NNP:[151..158] Bochner) (NNP:[159..160] F) (,:[160..161] ,) (NNP:[162..172] Eichelbaum) (NNP:[173..175] M.))) ;section 3 Span:179..268 ;Department of Clinical and Experimental Pharmacology, University of Adelaide, ; Australia. (SEC (FRAG (NNP:[179..189] Department) (IN:[190..192] of) (NNP:[193..201] Clinical) (CC:[202..205] and) (NNP:[206..218] Experimental) (NNP:[219..231] Pharmacology) (,:[231..232] ,) (NNP:[233..243] University) (IN:[244..246] of) (NNP:[247..255] Adelaide) (,:[255..256] ,) (NNP:[258..267] Australia) (.:[267..268] .))) ;sentence 4 Span:272..409 ;1. Codeine O-demethylation to morphine is mediated by cytochrome P450 IID1 ;(rat), or P450 IID6 (man), and exhibits genetic polymorphism. ;[275..282]:substance:"Codeine" ;[302..310]:substance:"morphine" ;[326..346]:cyp450:"cytochrome P450 IID1" ;[326..336]...[358..367]:cyp450:"cytochrome"..."P450 IID6" (SENT (LST (LS:[272..274] 1.)) (S (NP-SBJ-2 (NP (NN:[275..282] Codeine) (NN:[283..298] O-demethylation)) (PP (TO:[299..301] to) (NP (NN:[302..310] morphine)))) (VP (VP (VBZ:[311..313] is) (VP (VBN:[314..322] mediated) (NP-2 (-NONE-:[322..322] *)) (PP (IN:[323..325] by) (NP-LGS (NP (NML (NML-1 (NN:[326..336] cytochrome)) (NN:[337..341] P450)) (NN:[342..346] IID1) (PRN (-LRB-:[348..349] -LRB-) (NP (NN:[349..352] rat)) (-RRB-:[352..353] -RRB-))) (,:[353..354] ,) (CC:[355..357] or) (NP (NML (NML-1 (-NONE-:[357..357] *P*)) (NN:[358..362] P450)) (NN:[363..367] IID6) (PRN (-LRB-:[368..369] -LRB-) (NP (NN:[369..372] man)) (-RRB-:[372..373] -RRB-))))))) (,:[373..374] ,) (CC:[375..378] and) (VP (VBZ:[379..387] exhibits) (NP (JJ:[388..395] genetic) (NN:[396..408] polymorphism)))) (.:[408..409] .))) ;ERROR_Sentence has multiple Children (Sentence Error)[272..409]::LST:S: ;sentence 5 Span:410..530 ;Thebaine is a precursor in the formation of endogenous morphine and codeine ;in man, being O-demethylated to oripavine. ;[410..418]:substance:"Thebaine" ;[425..434]:substance:"precursor" ;[466..474]:substance:"morphine" ;[479..486]:substance:"codeine" ;[520..529]:substance:"oripavine" (SENT (S (NP-SBJ (NN:[410..418] Thebaine)) (VP (VBZ:[419..421] is) (NP-PRD (NP (DT:[422..423] a) (NN:[425..434] precursor)) (PP (IN:[435..437] in) (NP (NP (DT:[438..441] the) (NN:[442..451] formation)) (PP (IN:[452..454] of) (NP (NP (ADJP-2 (JJ:[455..465] endogenous)) (NN:[466..474] morphine)) (CC:[475..478] and) (NP (ADJP-2 (-NONE-:[478..478] *P*)) (NN:[479..486] codeine)))) (PP (IN:[487..489] in) (NP (NN:[490..493] man)))))) (,:[493..494] ,) (S-ADV (NP-SBJ-1 (-NONE-:[494..494] *)) (VP (VBG:[495..500] being) (VP (VBN:[502..516] O-demethylated) (NP-1 (-NONE-:[516..516] *)) (PP (TO:[517..519] to) (NP (NN:[520..529] oripavine))))))) (.:[529..530] .))) ;sentence 6 Span:531..702 ;2. The objective of the present study was to ascertain whether the ;O-demethylation of thebaine to oripavine was mediated by cytochrome P450 ;IID1 in rat liver microsomes. ;[618..626]:substance:"thebaine" ;[630..639]:substance:"oripavine" ;[657..677]:cyp450:"cytochrome P450 IID1" (SENT (LST (LS:[531..533] 2.)) (S (NP-SBJ (NP (DT:[534..537] The) (NN:[538..547] objective)) (PP (IN:[548..550] of) (NP (DT:[551..554] the) (JJ:[555..562] present) (NN:[563..568] study)))) (VP (VBD:[569..572] was) (S-NOM-PRP-PRD (NP-SBJ (-NONE-:[572..572] *)) (VP (TO:[573..575] to) (VP (VB:[577..586] ascertain) (SBAR (IN:[587..594] whether) (S (NP-SBJ-1 (NP (DT:[595..598] the) (NN:[599..614] O-demethylation)) (PP (IN:[615..617] of) (NP (NN:[618..626] thebaine))) (PP (TO:[627..629] to) (NP (NN:[630..639] oripavine)))) (VP (VBD:[640..643] was) (VP (VBN:[644..652] mediated) (NP-1 (-NONE-:[652..652] *)) (PP (IN:[653..655] by) (NP-LGS (NML (NN:[657..667] cytochrome) (NN:[668..672] P450)) (NN:[673..677] IID1))) (PP-LOC (IN:[678..680] in) (NP (NN:[681..684] rat) (NN:[685..690] liver) (NNS:[691..701] microsomes))))))))))) (.:[701..702] .))) ;ERROR_Sentence has multiple Children (Sentence Error)[531..702]::LST:S: ;sentence 7 Span:703..906 ;3. Thebaine O-demethylation showed strain differences in female ;Sprague-Dawley (SD) and female Dark-Agouti (DA) rats, which serve as a model ;for the human debrisoquine/sparteine metabolism phenotypes. ;[706..714]:substance:"Thebaine" ;[860..872]:substance:"debrisoquine" ;[873..882]:substance:"sparteine" (SENT (LST (LS:[703..705] 3.)) (S (NP-SBJ (NN:[706..714] Thebaine) (NN:[715..730] O-demethylation)) (VP (VBD:[731..737] showed) (NP (NN:[739..745] strain) (NNS:[746..757] differences)) (PP-LOC (IN:[758..760] in) (NP (NP (NP (JJ:[761..767] female) (NML (NML (NNP:[768..775] Sprague) (HYPH:[775..776] -) (NNP:[776..782] Dawley)) (NML (-LRB-:[783..784] -LRB-) (NNP:[784..786] SD) (-RRB-:[786..787] -RRB-))) (NML-2 (-NONE-:[787..787] *P*))) (CC:[788..791] and) (NP (JJ:[792..798] female) (NML (NML (NNP:[799..803] Dark) (HYPH:[803..804] -) (NNP:[804..810] Agouti)) (NML (-LRB-:[811..812] -LRB-) (NNP:[812..814] DA) (-RRB-:[814..815] -RRB-))) (NML-2 (NNS:[817..821] rats)))) (,:[821..822] ,) (SBAR (WHNP-1 (WDT:[823..828] which)) (S (NP-SBJ-1 (-NONE-:[828..828] *T*)) (VP (VBP:[829..834] serve) (PP-CLR (IN:[835..837] as) (NP (NP (DT:[838..839] a) (NN:[840..845] model)) (PP (IN:[846..849] for) (NP (DT:[850..853] the) (JJ:[854..859] human) (NML (NN:[860..872] debrisoquine) (SYM:[872..873] /) (NN:[873..882] sparteine)) (NN:[883..893] metabolism) (NNS:[895..905] phenotypes))))))))))) (.:[905..906] .))) ;ERROR_Sentence has multiple Children (Sentence Error)[703..906]::LST:S: ;sentence 8 Span:907..1075 ;4. The total intrinsic clearance of thebaine to oripavine was high (19.7 ;ml/h per mg protein) in SD rats, indicating that oripavine is a major ;metabolite of thebaine. ;[943..951]:substance:"thebaine" ;[955..964]:substance:"oripavine" ;[976..980]:quantitative-value:"19.7" ;[981..1000]:quantitative-units:"ml/h per mg protein" ;[1030..1039]:substance:"oripavine" ;[1052..1062]:substance:"metabolite" ;[1066..1074]:substance:"thebaine" (SENT (LST (LS:[907..909] 4.)) (S (NP-SBJ (NP (DT:[910..913] The) (JJ:[914..919] total) (JJ:[920..929] intrinsic) (NN:[930..939] clearance)) (PP (IN:[940..942] of) (NP (NN:[943..951] thebaine))) (PP (TO:[952..954] to) (NP (NN:[955..964] oripavine)))) (VP (VBD:[965..968] was) (ADJP-PRD (JJ:[969..973] high) (PRN (-LRB-:[975..976] -LRB-) (NP (NP (CD:[976..980] 19.7) (NN:[981..983] ml)) (PP (SYM:[983..984] /) (NP (NN:[984..985] h))) (PP (IN:[986..989] per) (NP (NN:[990..992] mg) (NN:[993..1000] protein)))) (-RRB-:[1000..1001] -RRB-))) (PP-LOC (IN:[1002..1004] in) (NP (NNP:[1005..1007] SD) (NNS:[1008..1012] rats))) (,:[1012..1013] ,) (S-ADV (NP-SBJ (-NONE-:[1013..1013] *)) (VP (VBG:[1014..1024] indicating) (SBAR (IN:[1025..1029] that) (S (NP-SBJ (NN:[1030..1039] oripavine)) (VP (VBZ:[1040..1042] is) (NP-PRD (NP (DT:[1043..1044] a) (JJ:[1045..1050] major) (NN:[1052..1062] metabolite)) (PP (IN:[1063..1065] of) (NP (NN:[1066..1074] thebaine)))))))))) (.:[1074..1075] .))) ;ERROR_Sentence has multiple Children (Sentence Error)[907..1075]::LST:S: ;sentence 9 Span:1076..1162 ;A 3-fold lower intrinsic clearance was observed in DA rats (6.7 ml/h per mg ;protein). ;[1078..1084]:quantitative-value:"3-fold" ;[1137..1140]:quantitative-value:"6.7" ;[1141..1160]:quantitative-units:"ml/h per mg protein" (SENT (S (NP-SBJ-1 (DT:[1076..1077] A) (ADJP (QP (CD:[1078..1079] 3) (HYPH:[1079..1080] -) (RB:[1080..1084] fold)) (JJR:[1085..1090] lower)) (JJ:[1091..1100] intrinsic) (NN:[1101..1110] clearance)) (VP (VBD:[1111..1114] was) (VP (VBN:[1115..1123] observed) (NP-1 (-NONE-:[1123..1123] *)) (PP-LOC (IN:[1124..1126] in) (NP (NNP:[1127..1129] DA) (NNS:[1131..1135] rats))) (PRN (-LRB-:[1136..1137] -LRB-) (NP (NP (token:[1137..1140] 6.7) (NN:[1141..1143] ml)) (PP (SYM:[1143..1144] /) (NP (NN:[1144..1145] h))) (PP (IN:[1146..1149] per) (NP (NN:[1150..1152] mg) (NN:[1153..1160] protein)))) (-RRB-:[1160..1161] -RRB-)))) (.:[1161..1162] .))) ;sentence 10 Span:1163..1362 ;5. Thebaine O-demethylation was inhibited by quinine and known substrates of ;cytochrome P450 IID1/P450 IID6, supporting the major involvement of ;cytochrome P450 IID1 in oripavine formation in rats. ;[1166..1174]:substance:"Thebaine" ;[1209..1216]:substance:"quinine" ;[1227..1237]:substance:"substrates" ;[1241..1261]:cyp450:"cytochrome P450 IID1" ;[1241..1251]...[1262..1271]:cyp450:"cytochrome"..."P450 IID6" ;[1310..1330]:cyp450:"cytochrome P450 IID1" ;[1334..1343]:substance:"oripavine" (SENT (LST (LS:[1163..1165] 5.)) (S (NP-SBJ-1 (NN:[1166..1174] Thebaine) (NN:[1175..1190] O-demethylation)) (VP (VBD:[1191..1194] was) (VP (VBN:[1195..1204] inhibited) (NP-1 (-NONE-:[1204..1204] *)) (PP (IN:[1205..1207] by) (NP-LGS (NP (NN:[1209..1216] quinine)) (CC:[1217..1220] and) (NP (NP (VBN:[1221..1226] known) (NNS:[1227..1237] substrates)) (PP (IN:[1238..1240] of) (NP (NP (NML (NML-2 (NN:[1241..1251] cytochrome)) (NN:[1252..1256] P450)) (NN:[1257..1261] IID1)) (SYM:[1261..1262] /) (NP (NML (NML-2 (-NONE-:[1262..1262] *P*)) (NN:[1262..1266] P450)) (NN:[1267..1271] IID6))))))) (,:[1271..1272] ,) (S-ADV (NP-SBJ (-NONE-:[1272..1272] *)) (VP (VBG:[1273..1283] supporting) (NP (NP (DT:[1284..1287] the) (JJ:[1289..1294] major) (NN:[1295..1306] involvement)) (PP (IN:[1307..1309] of) (NP (NN:[1310..1320] cytochrome) (NN:[1321..1325] P450) (NN:[1326..1330] IID1))) (PP (IN:[1331..1333] in) (NP (NP (NN:[1334..1343] oripavine) (NN:[1344..1353] formation)) (PP-LOC (IN:[1354..1356] in) (NP (NNS:[1357..1361] rats)))))))))) (.:[1361..1362] .))) ;ERROR_Sentence has multiple Children (Sentence Error)[1163..1362]::LST:S: ;section 11 Span:1366..1409 ;PMID: 1763524 [PubMed - indexed for MEDLINE (SEC (FRAG (NNP:[1366..1370] PMID) (::[1370..1371] :) (CD:[1372..1379] 1763524) (-LRB-:[1380..1381] -LSB-) (NNP:[1381..1387] PubMed) (::[1388..1389] -) (VBN:[1390..1397] indexed) (IN:[1398..1401] for) (NNP:[1402..1409] MEDLINE))) ;ERROR_Orphan Text from EOF Tree File[1409..EOF] ] (ORPH -RSB-)