;PMID: 2788364 ;source_file_1005.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..35] = [t:0..35] ;1)sentence:[e:41..147] = [t:41..147] ;2)section:[e:151..213] = [t:151..213] ;3)section:[e:217..315] = [t:217..315] ;4)sentence:[e:319..454] = [t:319..454] ;5)sentence:[e:455..617] = [t:455..617] ;6)sentence:[e:618..795] = [t:618..795] ;7)sentence:[e:796..984] = [t:796..984] ;8)sentence:[e:985..1112] = [t:985..1112] ;9)sentence:[e:1113..1316] = [t:1113..1316] ;10)sentence:[e:1317..1364] = [t:1317..1364] ;11)sentence:[e:1365..1507] = [t:1365..1507] ;12)sentence:[e:1508..1649] = [t:1508..1649] ;13)section:[e:1653..1697] = [t:1653..1697] ;section 0 Span:0..35 ;Am J Med Sci. 1989 Aug;298(2):83-8. (SEC (FRAG (NNP:[0..2] Am) (NNP:[3..4] J) (NNP:[5..8] Med) (NNP:[9..12] Sci) (.:[12..13] .) (CD:[14..18] 1989) (CC:[19..27] Aug;298-LRB-) (CD:[27..28] 2) (-RRB-:[28..29] -RRB-) (CD:[29..32] :83) (::[32..33] -) (CD:[33..35] 8.))) ;sentence 1 Span:41..147 ;19-Hydroxylase inhibition of adrenal mitochondrial P450 11 ;beta/18/19-hydroxylase by a suicide inhibitor. ;[41..55]:substance:"19-Hydroxylase" ;[92..105]...[111..123]:substance:"P450 11 beta"..."-hydroxylase" ;[92..96]...[106..108]...[111..123]:substance:"P450"..."18"..."-hydroxylase" ;[92..96]...[109..123]:substance:"P450"..."19-hydroxylase" ;[137..146]:substance:"inhibitor" (SENT (NP-HLN (NP (NN:[41..55] 19-Hydroxylase) (NN:[56..66] inhibition)) (PP (IN:[67..69] of) (NP (JJ:[70..77] adrenal) (JJ:[78..91] mitochondrial) (NN:[92..96] P450) (NML (NML (CD:[97..99] 11) (SYM:[101..105] beta)) (SYM:[105..106] /) (NML (CD:[106..108] 18)) (SYM:[108..109] /) (NML (CD:[109..111] 19))) (HYPH:[111..112] -) (NN:[112..123] hydroxylase))) (PP (IN:[124..126] by) (NP (DT:[127..128] a) (NN:[129..136] suicide) (NN:[137..146] inhibitor))) (.:[146..147] .))) ;section 2 Span:151..213 ;Griffing GT, Holbrook M, Melby JC, Alberta J, Orme-Johnson NR. (SEC (FRAG (NNP:[151..159] Griffing) (NNP:[160..162] GT) (,:[162..163] ,) (NNP:[164..172] Holbrook) (NNP:[173..175] M,) (NNP:[176..181] Melby) (NNP:[182..184] JC) (,:[184..185] ,) (NNP:[186..193] Alberta) (NNP:[194..196] J,) (NNP:[197..201] Orme) (::[201..202] -) (NNP:[202..209] Johnson) (NNP:[210..212] NR) (.:[212..213] .))) ;section 3 Span:217..315 ;Evans Memorial Department of Clinical Research, University Hospital, Boston, ;Massachusetts 02118. (SEC (FRAG (NNP:[217..222] Evans) (NNP:[223..231] Memorial) (NNP:[232..242] Department) (IN:[243..245] of) (NNP:[246..254] Clinical) (NNP:[255..263] Research) (NNP:[263..264] ,) (NNP:[265..275] University) (NNP:[276..284] Hospital) (,:[284..285] ,) (NNP:[286..292] Boston) (,:[292..293] ,) (NNP:[295..308] Massachusetts) (VBD:[309..314] 02118) (.:[314..315] .))) ;sentence 4 Span:319..454 ;19-Nor-deoxycorticosterone (19-nor-DOC) is a mineralocorticoid that is ;increased in some forms of experimental and human hypertension. ;[319..345]:substance:"19-Nor-deoxycorticosterone" ;[347..357]:substance:"19-nor-DOC" ;[364..381]:substance:"mineralocorticoid" (SENT (S (NP-SBJ (NP (NN:[319..345] 19-Nor-deoxycorticosterone)) (NP (-LRB-:[346..347] -LRB-) (NN:[347..357] 19-nor-DOC) (-RRB-:[357..358] -RRB-))) (VP (VBZ:[359..361] is) (NP-PRD (NP (DT:[362..363] a) (NN:[364..381] mineralocorticoid)) (SBAR (WHNP-2 (WDT:[382..386] that)) (S (NP-SBJ-2 (-NONE-:[386..386] *T*)) (VP (VBZ:[387..389] is) (VP (VBN:[390..399] increased) (NP-2 (-NONE-:[399..399] *)) (PP (IN:[401..403] in) (NP (NP (DT:[404..408] some) (NNS:[409..414] forms)) (PP (IN:[415..417] of) (NP (NP (JJ:[418..430] experimental) (NML-1 (-NONE-:[430..430] *P*))) (CC:[431..434] and) (NP (JJ:[435..440] human) (NML-1 (NN:[441..453] hypertension))))))))))))) (.:[453..454] .))) ;sentence 5 Span:455..617 ;The pivotal step in 19-nor-DOC biosynthesis is adrenal P450 19-hydroxylase, ;but this enzyme has not been clearly distinguished from P450 11 ;beta/18-hydroxylase. ;[476..486]:substance:"19-nor-DOC" ;[511..530]:substance:"P450 19-hydroxylase" ;[541..547]:substance:"enzyme" ;[589..601]...[604..616]:substance:"P450 11 beta"..."-hydroxylase" ;[589..593]...[602..616]:substance:"P450"..."18-hydroxylase" (SENT (S (S (NP-SBJ (NP (DT:[455..458] The) (JJ:[459..466] pivotal) (NN:[467..471] step)) (PP (IN:[472..474] in) (NP (NN:[476..486] 19-nor-DOC) (NN:[487..499] biosynthesis)))) (VP (VBZ:[500..502] is) (NP-PRD (JJ:[503..510] adrenal) (NN:[511..515] P450) (NN:[516..530] 19-hydroxylase)))) (,:[530..531] ,) (CC:[532..535] but) (S (NP-SBJ-1 (DT:[536..540] this) (NN:[541..547] enzyme)) (VP (VBZ:[548..551] has) (RB:[552..555] not) (VP (VBN:[557..561] been) (ADVP (RB:[562..569] clearly)) (VP (VBN:[570..583] distinguished) (NP-1 (-NONE-:[583..583] *)) (PP (IN:[584..588] from) (NP (NN:[589..593] P450) (NML (NML (CD:[594..596] 11) (SYM:[597..601] beta)) (SYM:[601..602] /) (NML (CD:[602..604] 18))) (HYPH:[604..605] -) (NN:[605..616] hydroxylase))))))) (.:[616..617] .))) ;sentence 6 Span:618..795 ;This study attempted to specifically inhibit adrenal 19-hydroxylation of ;deoxycorticosterone (DOC) using a suicide aromatase inhibitor, 19-acetylenic ;androstenedione (19-AA). ;[693..712]:substance:"deoxycorticosterone" ;[714..717]:substance:"DOC" ;[735..744]:substance:"aromatase" ;[745..754]:substance:"inhibitor" ;[756..786]:substance:"19-acetylenic androstenedione" ;[788..793]:substance:"19-AA" (SENT (S (NP-SBJ-1 (DT:[618..622] This) (NN:[623..628] study)) (VP (VBD:[630..639] attempted) (S (NP-SBJ-1 (-NONE-:[639..639] *)) (VP (TO:[640..642] to) (ADVP (RB:[643..655] specifically)) (VP (VB:[656..663] inhibit) (NP (NP (JJ:[664..671] adrenal) (NN:[672..688] 19-hydroxylation)) (PP (NN:[689..691] of) (NP (NP (NN:[693..712] deoxycorticosterone)) (NP (-LRB-:[713..714] -LRB-) (NN:[714..717] DOC) (-RRB-:[717..718] -RRB-))))) (S-MNR (NP-SBJ (-NONE-:[718..718] *)) (VP (VBG:[719..724] using) (NP (NP (DT:[725..726] a) (NN:[727..734] suicide) (NN:[735..744] aromatase) (NN:[745..754] inhibitor)) (,:[754..755] ,) (NP (NP (JJ:[756..769] 19-acetylenic) (NN:[771..786] androstenedione)) (NP (-LRB-:[787..788] -LRB-) (NN:[788..793] 19-AA) (-RRB-:[793..794] -RRB-)))))))))) (.:[794..795] .))) ;sentence 7 Span:796..984 ;Purified bovine P450 11 beta/18/19-hydroxylase was incubated with excess ;substrate DOC, adrenodoxin, and adrenodoxin reductase in the presence of ;increasing doses of the inhibitor, 19AA. ;[812..824]...[830..842]:substance:"P450 11 beta"..."-hydroxylase" ;[812..816]...[828..842]:substance:"P450"..."19-hydroxylase" ;[812..816]...[825..827]...[830..842]:substance:"P450"..."18"..."-hydroxylase" ;[870..879]:substance:"substrate" ;[880..883]:substance:"DOC" ;[885..896]:substance:"adrenodoxin" ;[902..923]:substance:"adrenodoxin reductase" ;[968..977]:substance:"inhibitor" ;[979..983]:substance:"19AA" (SENT (S (NP-SBJ-1 (VBN:[796..804] Purified) (JJ:[805..811] bovine) (NN:[812..816] P450) (NML (NML (CD:[817..819] 11) (SYM:[820..824] beta)) (SYM:[824..825] /) (NML (CD:[825..827] 18)) (SYM:[827..828] /) (NML (CD:[828..830] 19))) (HYPH:[830..831] -) (NN:[831..842] hydroxylase)) (VP (VBD:[843..846] was) (VP (VBN:[848..857] incubated) (NP-1 (-NONE-:[857..857] *)) (PP-MNR (IN:[858..862] with) (NP (NP (NN:[863..869] excess) (NN:[870..879] substrate) (NN:[880..883] DOC)) (,:[883..884] ,) (NP (NN:[885..896] adrenodoxin)) (,:[896..897] ,) (CC:[898..901] and) (NP (NN:[902..913] adrenodoxin) (NN:[914..923] reductase)))) (PP (IN:[924..926] in) (NP (NP (DT:[928..931] the) (NN:[932..940] presence)) (PP (IN:[941..943] of) (NP (NP (VBG:[944..954] increasing) (NN:[955..960] doses)) (PP (IN:[961..963] of) (NP (NP (DT:[964..967] the) (NN:[968..977] inhibitor)) (,:[977..978] ,) (NP (NN:[979..983] 19AA)))))))))) (.:[983..984] .))) ;sentence 8 Span:985..1112 ;11 beta-, 18-, and 19-hydroxylation were measured by quantification of ;corticosterone, 18-OH-DOC, and 19-OH-DOC respectively. ;[1057..1071]:substance:"corticosterone" ;[1073..1082]:substance:"18-OH-DOC" ;[1089..1098]:substance:"19-OH-DOC" (SENT (S (NP-SBJ-1 (NP (NML (CD:[985..987] 11) (SYM:[988..992] beta)) (HYPH:[992..993] -) (NML-2 (-NONE-:[993..993] *P*))) (,:[993..994] ,) (NP (CD:[995..997] 18) (HYPH:[997..998] -) (NML-2 (-NONE-:[998..998] *P*))) (,:[998..999] ,) (CC:[1000..1003] and) (NP (CD:[1005..1007] 19) (HYPH:[1007..1008] -) (NML-2 (NN:[1008..1021] hydroxylation)))) (VP (VBD:[1022..1026] were) (VP (VBN:[1027..1035] measured) (NP-1 (-NONE-:[1035..1035] *)) (PP-MNR (IN:[1036..1038] by) (NP (NP (NN:[1039..1053] quantification)) (PP (IN:[1054..1056] of) (NP (NN:[1057..1071] corticosterone) (,:[1071..1072] ,) (NN:[1073..1082] 18-OH-DOC) (,:[1082..1083] ,) (CC:[1085..1088] and) (NN:[1089..1098] 19-OH-DOC))))) (ADVP (RB:[1099..1111] respectively)))) (.:[1111..1112] .))) ;sentence 9 Span:1113..1316 ;Measurements of these products demonstrated that 11 beta- and ;18-hydroxylation was not inhibited whereas 19-hydroxylation was inhibited as ;manifested by decreased 19-OH-DOC formation (p less than .05). ;[1278..1287]:substance:"19-OH-DOC" (SENT (S (NP-SBJ (NP (NNS:[1113..1125] Measurements)) (PP (IN:[1126..1128] of) (NP (DT:[1129..1134] these) (NNS:[1135..1143] products)))) (VP (VBD:[1144..1156] demonstrated) (SBAR (IN:[1157..1161] that) (S (NP-SBJ-3 (NP (NML (CD:[1162..1164] 11) (SYM:[1166..1170] beta)) (HYPH:[1170..1171] -) (NML-2 (-NONE-:[1171..1171] *P*))) (CC:[1172..1175] and) (NP (CD:[1176..1178] 18) (HYPH:[1178..1179] -) (NML-2 (NN:[1179..1192] hydroxylation)))) (VP (VBD:[1193..1196] was) (RB:[1197..1200] not) (VP (VBN:[1201..1210] inhibited) (NP-3 (-NONE-:[1210..1210] *)) (SBAR-ADV (IN:[1211..1218] whereas) (S (NP-SBJ-1 (NN:[1219..1235] 19-hydroxylation)) (VP (VBD:[1236..1239] was) (VP (VBN:[1241..1250] inhibited) (NP-1 (-NONE-:[1250..1250] *)) (SBAR-ADV (IN:[1251..1253] as) (S (NP-SBJ (-NONE-:[1253..1253] *)) (VP (VBN:[1254..1264] manifested) (PP (IN:[1265..1267] by) (NP-LGS (VBN:[1268..1277] decreased) (NN:[1278..1287] 19-OH-DOC) (NN:[1288..1297] formation)))))))))) (PRN (-LRB-:[1298..1299] -LRB-) (S (NP-SBJ (NN:[1299..1300] p)) (ADJP-PRD (ADJP (JJR:[1301..1305] less)) (PP (IN:[1306..1310] than) (NP (CD:[1311..1314] .05))))) (-RRB-:[1314..1315] -RRB-))))))) (.:[1315..1316] .))) ;sentence 10 Span:1317..1364 ;The IC50 of 19-AA was approximately 10(-12) M. ;[1322..1326]:quantitative-name:"IC50" ;[1330..1335]:substance:"19-AA" ;[1354..1361]:quantitative-value:"10(-12)" ;[1362..1363]:quantitative-units:"M" (SENT (S (NP-SBJ (NP (DT:[1317..1320] The) (NN:[1322..1326] IC50)) (PP (IN:[1327..1329] of) (NP (NN:[1330..1335] 19-AA)))) (VP (VBD:[1336..1339] was) (NP-PRD (QP (RB:[1340..1353] approximately) (CD:[1354..1361] 10-LRB--12-RRB-)) (NN:[1362..1363] M))) (.:[1363..1364] .))) ;sentence 11 Span:1365..1507 ;The specific inhibition of 19-hydroxylation suggests that the 19-hydroxylase ;may be an enzyme distinct from the P450 11 beta/18-hydroxylase. ;[1428..1442]:substance:"19-hydroxylase" ;[1453..1459]:substance:"enzyme" ;[1479..1491]...[1494..1506]:substance:"P450 11 beta"..."-hydroxylase" ;[1479..1483]...[1492..1506]:substance:"P450"..."18-hydroxylase" (SENT (S (NP-SBJ (NP (DT:[1365..1368] The) (JJ:[1369..1377] specific) (NN:[1378..1388] inhibition)) (PP (IN:[1389..1391] of) (NP (NN:[1393..1409] 19-hydroxylation)))) (VP (VBZ:[1410..1418] suggests) (SBAR (IN:[1419..1423] that) (S (NP-SBJ (DT:[1424..1427] the) (NN:[1428..1442] 19-hydroxylase)) (VP (MD:[1443..1446] may) (VP (VB:[1447..1449] be) (NP-PRD (NP (DT:[1450..1452] an) (NN:[1453..1459] enzyme)) (ADJP (JJ:[1460..1468] distinct) (PP (IN:[1469..1473] from) (NP (DT:[1475..1478] the) (NN:[1479..1483] P450) (NML (NML (CD:[1484..1486] 11) (SYM:[1487..1491] beta)) (SYM:[1491..1492] /) (NML (CD:[1492..1494] 18))) (HYPH:[1494..1495] -) (NN:[1495..1506] hydroxylase)))))))))) (.:[1506..1507] .))) ;sentence 12 Span:1508..1649 ;This further suggests that 19-nor-DOC biosynthesis may be under independent ;regulation and may be amendable to specific in vivo inhibition. ;[1535..1545]:substance:"19-nor-DOC" (SENT (S (NP-SBJ (DT:[1508..1512] This) (RBR:[1513..1520] further)) (VP (VBZ:[1521..1529] suggests) (SBAR (IN:[1530..1534] that) (S (NP-SBJ (NN:[1535..1545] 19-nor-DOC) (NN:[1547..1559] biosynthesis)) (VP (MD:[1560..1563] may) (VP (VB:[1564..1566] be) (PP-PRD (IN:[1567..1572] under) (NP (JJ:[1573..1584] independent) (NN:[1585..1595] regulation)))) (CC:[1596..1599] and) (VP (MD:[1600..1603] may) (VP (VB:[1604..1606] be) (ADJP-PRD (JJ:[1607..1616] amendable) (PP (TO:[1617..1619] to) (NP (JJ:[1621..1629] specific) (ADJP (FW:[1630..1632] in) (FW:[1633..1637] vivo)) (NN:[1638..1648] inhibition)))))))))) (.:[1648..1649] .))) ;section 13 Span:1653..1697 ;PMID: 2788364 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1653..1657] PMID) (::[1657..1658] :) (CD:[1659..1666] 2788364) (NN:[1667..1668] -LSB-) (NNP:[1668..1674] PubMed) (::[1675..1676] -) (NN:[1677..1684] indexed) (IN:[1685..1688] for) (NNP:[1689..1697] MEDLINE-RSB-)))