;PMID: 2604739 ;source_file_1891.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..46] = [t:0..46] ;1)sentence:[e:52..114] = [t:52..114] ;2)sentence:[e:115..198] = [t:115..198] ;3)section:[e:202..221] = [t:202..221] ;4)section:[e:225..305] = [t:225..305] ;5)sentence:[e:309..404] = [t:309..404] ;6)sentence:[e:405..552] = [t:405..552] ;7)sentence:[e:553..705] = [t:553..705] ;8)sentence:[e:707..891] = [t:707..891] ;9)sentence:[e:892..1115] = [t:892..1115] ;10)sentence:[e:1116..1313] = [t:1116..1313] ;11)sentence:[e:1314..1447] = [t:1314..1447] ;12)sentence:[e:1448..1613] = [t:1448..1613] ;13)sentence:[e:1614..1806] = [t:1614..1806] ;14)sentence:[e:1807..1930] = [t:1807..1930] ;15)sentence:[e:1931..2099] = [t:1931..2099] ;16)sentence:[e:2100..2262] = [t:2100..2262] ;17)section:[e:2266..2310] = [t:2266..2310] ;section 0 Span:0..46 ;Biochem Pharmacol. 1989 Dec 15;38(24):4359-65. (SEC (FRAG (NNP:[0..7] Biochem) (NNP:[8..17] Pharmacol) (,:[17..18] .) (CD:[19..23] 1989) (NNP:[24..27] Dec) (CC:[28..34] 15;38-LRB-) (CD:[34..36] 24) (-RRB-:[36..37] -RRB-) (CD:[37..41] :435) (CD:[41..42] 9) (NN:[42..43] -) (CD:[43..45] 65) (.:[45..46] .))) ;sentence 1 Span:52..114 ;In vitro inhibition of hepatic drug oxidation by thioridazine. ;[83..87]:substance:"drug" ;[101..113]:substance:"thioridazine" (SENT (NP-HLN (NP (ADJP (FW:[52..54] In) (FW:[55..60] vitro)) (NN:[61..71] inhibition)) (PP (IN:[72..74] of) (NP (JJ:[75..82] hepatic) (NN:[83..87] drug) (NN:[88..97] oxidation))) (PP (IN:[98..100] by) (NP (NN:[101..113] thioridazine))) (.:[113..114] .))) ;sentence 2 Span:115..198 ;Kinetic analysis of the inhibition of cytochrome P-450 isoform-specific ;reactions. ;[154..178]:cyp450:"cytochrome P-450 isoform" (SENT (NP-HLN (NP (JJ:[115..122] Kinetic) (NN:[123..131] analysis)) (PP (IN:[133..135] of) (NP (NP (DT:[136..139] the) (NN:[140..150] inhibition)) (PP (IN:[151..153] of) (NP (ADJP (NML (NML (NN:[154..164] cytochrome) (NN:[165..170] P-450)) (NN:[171..178] isoform)) (HYPH:[178..179] -) (JJ:[179..187] specific)) (NNS:[188..197] reactions))))) (.:[197..198] .))) ;section 3 Span:202..221 ;Murray M, Reidy GF. (SEC (FRAG (NNP:[202..208] Murray) (NNP:[209..211] M,) (NNP:[212..217] Reidy) (NNP:[218..221] GF.))) ;section 4 Span:225..305 ;Department of Medicine, University of Sydney, Westmead Hospital, NSW, ;Australia. (SEC (FRAG (NNP:[225..235] Department) (IN:[236..238] of) (NNP:[239..247] Medicine) (,:[247..248] ,) (NNP:[249..259] University) (IN:[260..262] of) (NNP:[263..269] Sydney) (,:[269..270] ,) (NNP:[271..279] Westmead) (NNP:[280..288] Hospital) (,:[288..289] ,) (NNP:[290..293] NSW) (,:[293..294] ,) (NNP:[295..304] Australia) (.:[304..305] .))) ;sentence 5 Span:309..404 ;The phenothiazine tranquilizer thioridazine has been associated with drug ;interactions in man. ;[313..339]:substance:"phenothiazine tranquilizer" ;[340..352]:substance:"thioridazine" ;[378..382]:substance:"drug" (SENT (S (NP-SBJ-1 (NP (DT:[309..312] The) (NN:[313..326] phenothiazine) (NN:[327..339] tranquilizer)) (NP (NN:[340..352] thioridazine))) (VP (VBZ:[353..356] has) (VP (VBN:[357..361] been) (VP (VBN:[362..372] associated) (NP-1 (-NONE-:[372..372] *)) (PP-CLR (IN:[373..377] with) (NP (NN:[378..382] drug) (NNS:[384..396] interactions))) (PP-LOC (IN:[397..399] in) (NP (NN:[400..403] man)))))) (.:[403..404] .))) ;sentence 6 Span:405..552 ;This study investigated the capacity of the drug to inhibit hepatic drug ;oxidations mediated by cytochromes P-450 (P-450) in microsomes in vitro. ;[449..453]:substance:"drug" ;[474..478]:substance:"drug" ;[502..519]:cyp450:"cytochromes P-450" ;[521..526]:cyp450:"P-450" (SENT (S (NP-SBJ (DT:[405..409] This) (NN:[410..415] study)) (VP (VBD:[416..428] investigated) (NP (NP (DT:[429..432] the) (NN:[433..441] capacity) (S-1 (-NONE-:[441..441] *ICH*))) (PP (IN:[442..444] of) (NP (DT:[445..448] the) (NN:[449..453] drug))) (S-1 (NP-SBJ (-NONE-:[453..453] *)) (VP (TO:[454..456] to) (VP (VB:[457..464] inhibit) (NP (NP (JJ:[466..473] hepatic) (NN:[474..478] drug) (NNS:[479..489] oxidations)) (VP (VBN:[490..498] mediated) (NP (-NONE-:[498..498] *)) (PP-MNR (IN:[499..501] by) (NP (NP (NP (NNS:[502..513] cytochromes) (NN:[514..519] P-450)) (NP (-LRB-:[520..521] -LRB-) (NN:[521..526] P-450) (-RRB-:[526..527] -RRB-))) (PP-LOC (IN:[528..530] in) (NP (NNS:[531..541] microsomes))))) (ADVP (FW:[542..544] in) (FW:[546..551] vitro))))))))) (.:[551..552] .))) ;sentence 7 Span:553..705 ;Thioridazine was a potent linear mixed-type inhibitor of P-450b-dependent ;7-pentoxyresorufin O-depentylase activity in phenobarbital-induced rat ;liver. ;[553..565]:substance:"Thioridazine" ;[597..606]:substance:"inhibitor" ;[610..616]:cyp450:"P-450b" ;[628..660]:substance:"7-pentoxyresorufin O-depentylase" ;[673..686]:substance:"phenobarbital" (SENT (S (NP-SBJ (NN:[553..565] Thioridazine)) (VP (VBD:[566..569] was) (NP-PRD (NP (DT:[570..571] a) (JJ:[572..578] potent) (JJ:[579..585] linear) (NML (VBN:[586..591] mixed) (HYPH:[591..592] -) (NN:[592..596] type)) (NN:[597..606] inhibitor)) (PP (IN:[607..609] of) (NP (ADJP (NN:[610..616] P-450b) (HYPH:[616..617] -) (JJ:[617..626] dependent)) (NN:[628..646] 7-pentoxyresorufin) (NN:[647..660] O-depentylase) (NN:[661..669] activity)))) (PP-LOC (IN:[670..672] in) (NP (ADJP (NN:[673..686] phenobarbital) (HYPH:[686..687] -) (VBN:[687..694] induced)) (NN:[695..698] rat) (NN:[699..704] liver)))) (.:[704..705] .))) ;sentence 8 Span:707..891 ;The kinetic analysis revealed the enzyme-substrate dissociation constant (Ks) ;to be 1.6 microM whereas the dissociation constant of the enzyme-inhibitor ;complex (Ki) was 0.11 microM. ;[741..747]:substance:"enzyme" ;[748..757]:substance:"substrate" ;[781..783]:quantitative-name:"Ks" ;[792..795]:quantitative-value:"1.6" ;[796..802]:quantitative-units:"microM" ;[844..868]:substance:"enzyme-inhibitor complex" ;[871..873]:quantitative-name:"Ki" ;[879..883]:quantitative-value:"0.11" ;[884..890]:quantitative-units:"microM" (SENT (S (NP-SBJ (DT:[707..710] The) (JJ:[711..718] kinetic) (NN:[719..727] analysis)) (VP (VBD:[728..736] revealed) (S (NP-SBJ (DT:[737..740] the) (NML (NN:[741..747] enzyme) (HYPH:[747..748] -) (NN:[748..757] substrate)) (NN:[758..770] dissociation) (NN:[771..779] constant) (PRN (-LRB-:[780..781] -LRB-) (NP (NN:[781..783] Ks)) (-RRB-:[783..784] -RRB-))) (VP (TO:[785..787] to) (VP (VB:[789..791] be) (NP-PRD (CD:[792..795] 1.6) (NN:[796..802] microM))))) (SBAR-ADV (IN:[803..810] whereas) (S (NP-SBJ (NP (DT:[811..814] the) (NN:[815..827] dissociation) (NN:[828..836] constant)) (PP (IN:[837..839] of) (NP (DT:[840..843] the) (NML (NN:[844..850] enzyme) (HYPH:[850..851] -) (NN:[851..860] inhibitor)) (NN:[861..868] complex))) (PRN (-LRB-:[870..871] -LRB-) (NP (NN:[871..873] Ki)) (-RRB-:[873..874] -RRB-))) (VP (VBD:[875..878] was) (NP-PRD (CD:[879..883] 0.11) (NN:[884..890] microM)))))) (.:[890..891] .))) ;sentence 9 Span:892..1115 ;In contrast, 7-ethoxyresorufin O-deethylase activity (mediated by P-450c) in ;beta-naphthoflavone-induced rat hepatic microsomes was inhibited to a lesser ;extent (Ki = 2.4 microM) in relation to the Ks value (0.5 microM). ;[905..935]:substance:"7-ethoxyresorufin O-deethylase" ;[959..965]:cyp450:"P-450c" ;[970..989]:substance:"beta-naphthoflavone" ;[1056..1058]:quantitative-name:"Ki" ;[1061..1064]:quantitative-value:"2.4" ;[1065..1071]:quantitative-units:"microM" ;[1092..1094]:quantitative-name:"Ks" ;[1102..1105]:quantitative-value:"0.5" ;[1107..1113]:quantitative-units:"microM" (SENT (S (PP (IN:[892..894] In) (NP (NN:[895..903] contrast))) (,:[903..904] ,) (NP-SBJ (NP (NN:[905..922] 7-ethoxyresorufin) (NN:[923..935] O-deethylase) (NN:[936..944] activity)) (PRN (-LRB-:[946..947] -LRB-) (VP (VBN:[947..955] mediated) (NP (-NONE-:[955..955] *)) (PP (IN:[956..958] by) (NP-LGS (NN:[959..965] P-450c)))) (-RRB-:[965..966] -RRB-)) (PP-LOC (IN:[967..969] in) (NP (ADJP (NN:[970..989] beta-naphthoflavone) (HYPH:[989..990] -) (VBN:[990..997] induced)) (NN:[998..1001] rat) (JJ:[1002..1009] hepatic) (NNS:[1010..1020] microsomes)))) (VP (VBD:[1021..1024] was) (VP (VBN:[1026..1035] inhibited) (PP-EXT (TO:[1036..1038] to) (NP (DT:[1039..1040] a) (JJR:[1041..1047] lesser) (NN:[1048..1054] extent) (PRN (-LRB-:[1055..1056] -LRB-) (S (NP-SBJ (NN:[1056..1058] Ki)) (VP (SYM:[1059..1060] =) (NP (CD:[1061..1064] 2.4) (NN:[1065..1071] microM)))) (-RRB-:[1071..1072] -RRB-)))) (PP (IN:[1073..1075] in) (NP (NP (NN:[1076..1084] relation)) (PP (TO:[1085..1087] to) (NP (DT:[1088..1091] the) (NN:[1092..1094] Ks) (NN:[1095..1100] value) (PRN (-LRB-:[1101..1102] -LRB-) (NP (CD:[1102..1105] 0.5) (NN:[1107..1113] microM)) (-RRB-:[1113..1114] -RRB-)))))))) (.:[1114..1115] .))) ;sentence 10 Span:1116..1313 ;Spectral studies indicated that the efficiency of thioridazine binding in ;phenobarbital-induced microsomes was about 25-fold greater than in microsomes ; from beta-naphthoflavone-induced rat liver. ;[1166..1178]:substance:"thioridazine" ;[1191..1204]:substance:"phenobarbital" ;[1234..1254]:quantitative-value:"25-fold greater than" ;[1275..1294]:substance:"beta-naphthoflavone" (SENT (S (NP-SBJ (JJ:[1116..1124] Spectral) (NNS:[1125..1132] studies)) (VP (VBD:[1133..1142] indicated) (SBAR (IN:[1143..1147] that) (S (NP-SBJ (NP (DT:[1148..1151] the) (NN:[1152..1162] efficiency)) (PP (IN:[1163..1165] of) (NP (NN:[1166..1178] thioridazine) (NN:[1179..1186] binding))) (PP-LOC (IN:[1188..1190] in) (NP (ADJP (NN:[1191..1204] phenobarbital) (HYPH:[1204..1205] -) (VBN:[1205..1212] induced)) (NNS:[1213..1223] microsomes)))) (VP (VBD:[1224..1227] was) (ADJP-PRD (ADJP (ADVP (QP (RB:[1228..1233] about) (CD:[1234..1236] 25) (HYPH:[1236..1237] -) (RB:[1237..1241] fold))) (JJR:[1242..1249] greater)) (PP (IN:[1250..1254] than) (PP-LOC (IN:[1255..1257] in) (NP (NP (NNS:[1258..1268] microsomes)) (PP (IN:[1270..1274] from) (NP (ADJP (NN:[1275..1294] beta-naphthoflavone) (HYPH:[1294..1295] -) (VBN:[1295..1302] induced)) (NN:[1303..1306] rat) (NN:[1307..1312] liver))))))))))) (.:[1312..1313] .))) ;sentence 11 Span:1314..1447 ;This finding is consistent with the relative capacity of thioridazine to ;inhibit oxidase activities catalyzed by P-450b and P-450c. ;[1372..1384]:substance:"thioridazine" ;[1396..1403]:substance:"oxidase" ;[1429..1435]:cyp450:"P-450b" ;[1440..1446]:cyp450:"P-450c" (SENT (S (NP-SBJ (DT:[1314..1318] This) (NN:[1319..1326] finding)) (VP (VBZ:[1327..1329] is) (ADJP-PRD (JJ:[1330..1340] consistent) (PP (IN:[1341..1345] with) (NP (NP (DT:[1346..1349] the) (JJ:[1351..1359] relative) (NN:[1360..1368] capacity) (S-1 (-NONE-:[1368..1368] *ICH*))) (PP (IN:[1369..1371] of) (NP (NN:[1372..1384] thioridazine))) (S-1 (NP-SBJ (-NONE-:[1384..1384] *)) (VP (TO:[1385..1387] to) (VP (VB:[1388..1395] inhibit) (NP (NP (NN:[1396..1403] oxidase) (NNS:[1404..1414] activities)) (VP (VBN:[1415..1424] catalyzed) (NP (-NONE-:[1424..1424] *)) (PP (IN:[1425..1427] by) (NP-LGS (NN:[1429..1435] P-450b) (CC:[1436..1439] and) (NN:[1440..1446] P-450c)))))))))))) (.:[1446..1447] .))) ;sentence 12 Span:1448..1613 ;Mixed-function oxidase activities catalysed by other P-450s were also ;inhibited by thioridazine, although to a lesser extent than those catalysed ;by forms b and c. ;[1463..1470]:substance:"oxidase" ;[1501..1507]:cyp450:"P-450s" ;[1532..1544]:substance:"thioridazine" ;[1599..1606]:cyp450:"forms b" ;[1599..1604]...[1611..1612]:cyp450:"forms"..."c" (SENT (S (NP-SBJ (NP (NML (VBN:[1448..1453] Mixed) (HYPH:[1453..1454] -) (NN:[1454..1462] function)) (NN:[1463..1470] oxidase) (NNS:[1471..1481] activities)) (VP (VBN:[1482..1491] catalysed) (NP (-NONE-:[1491..1491] *)) (PP (IN:[1492..1494] by) (NP-LGS (JJ:[1495..1500] other) (NNS:[1501..1507] P-450s))))) (VP (VBD:[1509..1513] were) (ADVP (RB:[1514..1518] also)) (VP (VBN:[1519..1528] inhibited) (PP (IN:[1529..1531] by) (NP-LGS (NN:[1532..1544] thioridazine))) (,:[1544..1545] ,) (PP (IN:[1546..1554] although) (PP (TO:[1555..1557] to) (NP (NP (DT:[1558..1559] a) (JJR:[1560..1566] lesser) (NN:[1567..1573] extent)) (PP (IN:[1574..1578] than) (NP (NP (DT:[1579..1584] those)) (VP (VBN:[1586..1595] catalysed) (NP (-NONE-:[1595..1595] *)) (PP (IN:[1596..1598] by) (NP-LGS (NP (NML-1 (NNS:[1599..1604] forms)) (NN:[1605..1606] b)) (CC:[1607..1610] and) (NP (NML-1 (-NONE-:[1610..1610] *P*)) (NN:[1611..1612] c)))))))))))) (.:[1612..1613] .))) ;sentence 13 Span:1614..1806 ;Thus, the 6 beta- and 16 beta-hydroxylations of androst-4-ene-3,17-dione in ;hepatic microsomes from untreated rats were inhibited to a similar extent ;(I50S = 52 and 43 microM, respectively). ;[1663..1687]:substance:"androst-4-ene-3,17-dione" ;[1767..1771]:quantitative-name:"I50S" ;[1774..1776]:quantitative-value:"52" ;[1781..1783]:quantitative-value:"43" ;[1784..1790]:quantitative-units:"microM" (SENT (S (ADVP (RB:[1614..1618] Thus)) (,:[1618..1619] ,) (NP-SBJ-3 (NP (DT:[1620..1623] the) (NML (NML (NML (CD:[1624..1625] 6) (SYM:[1626..1630] beta)) (HYPH:[1630..1631] -) (NML-2 (-NONE-:[1631..1631] *P*))) (CC:[1632..1635] and) (NML (NML (CD:[1636..1638] 16) (SYM:[1639..1643] beta)) (HYPH:[1643..1644] -) (NML-2 (NNS:[1644..1658] hydroxylations))))) (PP (IN:[1659..1661] of) (NP (NN:[1663..1687] androst-4-ene-3,17-dione))) (PP-LOC (IN:[1688..1690] in) (NP (NP (JJ:[1691..1698] hepatic) (NNS:[1699..1709] microsomes)) (PP (IN:[1710..1714] from) (NP (JJ:[1715..1724] untreated) (NNS:[1725..1729] rats)))))) (VP (VBD:[1730..1734] were) (VP (VBN:[1736..1745] inhibited) (NP-3 (-NONE-:[1745..1745] *)) (PP (TO:[1746..1748] to) (NP (DT:[1749..1750] a) (JJ:[1751..1758] similar) (NN:[1759..1765] extent))) (PRN (-LRB-:[1766..1767] -LRB-) (S (NP-SBJ (NN:[1767..1771] I50S)) (VP (SYM:[1772..1773] =) (NP (NP (CD:[1774..1776] 52) (NML-1 (-NONE-:[1776..1776] *P*))) (CC:[1777..1780] and) (NP (CD:[1781..1783] 43) (NML-1 (NN:[1784..1790] microM)))) (,:[1790..1791] ,) (ADVP (RB:[1792..1804] respectively)))) (-RRB-:[1804..1805] -RRB-)))) (.:[1805..1806] .))) ;sentence 14 Span:1807..1930 ;The 7 alpha- and 16 alpha-hydroxylase pathways were approximately only half ;as susceptible to inhibition by thioridazine. ;[1811..1820]...[1834..1845]:substance:"7 alpha-"..."hydroxylase" ;[1825..1845]:substance:"16 alpha-hydroxylase" ;[1917..1929]:substance:"thioridazine" (SENT (S (NP-SBJ (DT:[1807..1810] The) (NML (NML (NML (NML (CD:[1811..1812] 7) (SYM:[1814..1819] alpha)) (HYPH:[1819..1820] -) (NML-1 (-NONE-:[1820..1820] *P*))) (NML-2 (-NONE-:[1820..1820] *P*))) (CC:[1821..1824] and) (NML (NML (NML (CD:[1825..1827] 16) (SYM:[1828..1833] alpha)) (HYPH:[1833..1834] -) (NML-1 (NN:[1834..1845] hydroxylase))) (NML-2 (NNS:[1846..1854] pathways))))) (VP (VBD:[1855..1859] were) (ADJP-PRD (QP (RB:[1860..1873] approximately) (RB:[1874..1878] only) (RB:[1879..1883] half) (RB:[1884..1886] as)) (JJ:[1888..1899] susceptible) (PP (TO:[1900..1902] to) (NP (NP (NN:[1903..1913] inhibition)) (PP (IN:[1914..1916] by) (NP (NN:[1917..1929] thioridazine))))))) (.:[1929..1930] .))) ;sentence 15 Span:1931..2099 ;These findings demonstrate the capacity of thioridazine to inhibit a range ;of P-450-dependent drug oxidations, with those catalysed by forms b and c ;most susceptible. ;[1975..1987]:substance:"thioridazine" ;[2010..2015]:cyp450:"P-450" ;[2026..2030]:substance:"drug" ;[2068..2075]:cyp450:"forms b" ;[2068..2073]...[2080..2081]:cyp450:"forms"..."c" (SENT (S (NP-SBJ (DT:[1931..1936] These) (NNS:[1937..1945] findings)) (VP (VBP:[1946..1957] demonstrate) (NP (NP (DT:[1958..1961] the) (NN:[1963..1971] capacity)) (PP (IN:[1972..1974] of) (NP (NN:[1975..1987] thioridazine))) (S-ADV (NP-SBJ (-NONE-:[1987..1987] *)) (VP (TO:[1988..1990] to) (VP (VB:[1991..1998] inhibit) (NP (NP (DT:[1999..2000] a) (NN:[2001..2006] range)) (PP (IN:[2007..2009] of) (NP (ADJP (NN:[2010..2015] P-450) (HYPH:[2015..2016] -) (JJ:[2016..2025] dependent)) (NN:[2026..2030] drug) (NNS:[2031..2041] oxidations)))) (,:[2041..2042] ,) (PP (IN:[2044..2048] with) (S-NOM (NP-SBJ (NP (DT:[2049..2054] those)) (VP (VBN:[2055..2064] catalysed) (NP (-NONE-:[2064..2064] *)) (PP (IN:[2065..2067] by) (NP-LGS (NP (NML-1 (NNS:[2068..2073] forms)) (NN:[2074..2075] b)) (CC:[2076..2079] and) (NP (NML-1 (-NONE-:[2079..2079] *P*)) (NN:[2080..2081] c)))))) (ADJP-PRD (RBS:[2082..2086] most) (JJ:[2087..2098] susceptible))))))))) (.:[2098..2099] .))) ;sentence 16 Span:2100..2262 ;The present study strongly suggests that drug interactions elicited by ;thioridazine are most likely a consequence of inhibitory interactions with ;P-450 enzymes. ;[2142..2146]:substance:"drug" ;[2172..2184]:substance:"thioridazine" ;[2248..2261]:cyp450:"P-450 enzymes" (SENT (S (NP-SBJ (DT:[2100..2103] The) (JJ:[2104..2111] present) (NN:[2112..2117] study)) (ADVP (RB:[2119..2127] strongly)) (VP (VBZ:[2128..2136] suggests) (SBAR (IN:[2137..2141] that) (S (NP-SBJ (NP (NN:[2142..2146] drug) (NNS:[2147..2159] interactions)) (VP (VBN:[2160..2168] elicited) (NP (-NONE-:[2168..2168] *)) (PP (IN:[2169..2171] by) (NP-LGS (NN:[2172..2184] thioridazine))))) (VP (VBP:[2185..2188] are) (ADVP (RBS:[2189..2193] most) (RB:[2195..2201] likely)) (NP-PRD (NP (DT:[2202..2203] a) (NN:[2204..2215] consequence)) (PP (IN:[2216..2218] of) (NP (NP (JJ:[2219..2229] inhibitory) (NNS:[2230..2242] interactions)) (PP (IN:[2243..2247] with) (NP (NN:[2248..2253] P-450) (NNS:[2254..2261] enzymes)))))))))) (.:[2261..2262] .))) ;section 17 Span:2266..2310 ;PMID: 2604739 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2266..2270] PMID) (::[2270..2271] :) (CD:[2272..2279] 2604739) (NN:[2280..2281] -LSB-) (NNP:[2281..2287] PubMed) (::[2288..2289] -) (NN:[2290..2297] indexed) (IN:[2298..2301] for) (NNP:[2302..2310] MEDLINE-RSB-)))