;PMID: 7864896 ;source_file_1795.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..53] = [t:0..53] ;1)sentence:[e:59..201] = [t:59..201] ;2)section:[e:205..256] = [t:205..256] ;3)section:[e:260..365] = [t:260..365] ;4)sentence:[e:369..432] = [t:369..432] ;5)sentence:[e:433..569] = [t:433..569] ;6)sentence:[e:570..703] = [t:570..703] ;7)sentence:[e:704..952] = [t:704..952] ;8)sentence:[e:953..1088] = [t:953..1088] ;9)sentence:[e:1089..1320] = [t:1089..1320] ;10)section:[e:1324..1368] = [t:1324..1368] ;section 0 Span:0..53 ;Biochem Biophys Res Commun. 1995 Feb 27;207(3):910-5. (SEC (FRAG (NNP:[0..7] Biochem) (NNP:[8..15] Biophys) (NNP:[16..19] Res) (NNP:[20..26] Commun) (,:[26..27] .) (CD:[28..32] 1995) (NNP:[33..36] Feb) (CD:[37..43] 27;207) (-LRB-:[43..44] -LRB-) (CD:[44..45] 3) (-RRB-:[45..46] -RRB-) (CD:[46..52] :910-5) (.:[52..53] .))) ;sentence 1 Span:59..201 ;Mode of action and resistance to azole antifungals associated with the ;formation of 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol. ;[92..109]:substance:"azole antifungals" ;[144..200]:substance:"14 alpha-methylergosta-8,24(28)-dien-3 beta,6 ;alpha-diol" (SENT (NP-HLN (NP (NP (NN:[59..63] Mode)) (PP (IN:[64..66] of) (NP (NN:[67..73] action)))) (CC:[74..77] and) (NP (NP (NN:[78..88] resistance)) (PP (TO:[89..91] to) (NP (NP (NN:[92..97] azole) (NNS:[98..109] antifungals)) (VP (VBN:[110..120] associated) (NP (-NONE-:[120..120] *)) (PP-CLR (IN:[121..125] with) (NP (NP (DT:[126..129] the) (NN:[130..139] formation)) (PP (IN:[141..143] of) (NP (CD:[144..146] 14) (NN:[147..182] alpha-methylergosta-8,24-LRB-28-RRB--dien-3) (NN:[183..189] beta,6) (NN:[190..200] alpha-diol))))))))) (.:[200..201] .))) ;section 2 Span:205..256 ;Kelly SL, Lamb DC, Corran AJ, Baldwin BC, Kelly DE. (SEC (FRAG (NNP:[205..210] Kelly) (NNP:[211..213] SL) (,:[213..214] ,) (NNP:[215..219] Lamb) (NNP:[220..222] DC) (,:[222..223] ,) (NNP:[224..230] Corran) (NNP:[231..233] AJ) (,:[233..234] ,) (NNP:[235..242] Baldwin) (NNP:[243..245] BC) (,:[245..246] ,) (NNP:[247..252] Kelly) (NNP:[253..256] DE.))) ;section 3 Span:260..365 ;Krebs Institute for Biomolecular Research, Department of Molecular Biology, ;University of Sheffield, UK. (SEC (FRAG (NNP:[260..265] Krebs) (NNP:[266..275] Institute) (IN:[276..279] for) (NNP:[280..292] Biomolecular) (NNP:[293..301] Research) (,:[301..302] ,) (NNP:[303..313] Department) (IN:[314..316] of) (NNP:[317..326] Molecular) (NNP:[327..334] Biology) (,:[334..335] ,) (NNP:[337..347] University) (IN:[348..350] of) (NNP:[351..360] Sheffield) (,:[360..361] ,) (NNP:[362..365] UK.))) ;sentence 4 Span:369..432 ;Azole antifungal compounds inhibit sterol 14 alpha-demethylase. ;[369..395]:substance:"Azole antifungal compounds" ;[404..431]:cyp450:"sterol 14 alpha-demethylase" (SENT (S (NP-SBJ (NN:[369..374] Azole) (JJ:[375..385] antifungal) (NNS:[386..395] compounds)) (VP (VBP:[396..403] inhibit) (NP (NN:[404..410] sterol) (CD:[411..413] 14) (NN:[414..431] alpha-demethylase))) (.:[431..432] .))) ;sentence 5 Span:433..569 ;They are used extensively for the treatment of immunocompromised patients ;where fungal infection is common and often results in death. (SENT (S (NP-SBJ-2 (PRP:[433..437] They)) (VP (VBP:[438..441] are) (VP (VBN:[442..446] used) (NP-2 (-NONE-:[446..446] *)) (ADVP (RB:[448..459] extensively)) (PP (IN:[460..463] for) (NP (NP (DT:[464..467] the) (NN:[468..477] treatment)) (PP (IN:[478..480] of) (NP (NP (JJ:[481..498] immunocompromised) (NNS:[499..507] patients)) (SBAR (WHADVP-1 (WRB:[508..513] where)) (S (NP-SBJ (JJ:[514..520] fungal) (NN:[522..531] infection)) (VP (VP (VBZ:[532..534] is) (ADJP-PRD (JJ:[535..541] common))) (CC:[542..545] and) (VP (ADVP (JJ:[546..551] often)) (VBZ:[552..559] results) (PP-CLR (IN:[560..562] in) (NP (NN:[563..568] death)))) (ADVP-1 (-NONE-:[568..568] *T*))))))))))) (.:[568..569] .))) ;sentence 6 Span:570..703 ;Resistance to the compounds is emerging, particularly in fungal pathogens ;obtained from AIDS patients undergoing prolonged therapy. ;[588..597]:substance:"compounds" (SENT (S (NP-SBJ (NP (NN:[570..580] Resistance)) (PP (TO:[581..583] to) (NP (DT:[584..587] the) (NNS:[588..597] compounds)))) (VP (VBZ:[598..600] is) (VP (VBG:[602..610] emerging) (,:[610..611] ,) (PP-LOC (ADVP (RB:[612..624] particularly)) (IN:[625..627] in) (NP (NP (JJ:[628..634] fungal) (NNS:[635..644] pathogens)) (VP (VBN:[645..653] obtained) (NP (-NONE-:[653..653] *)) (PP (IN:[654..658] from) (NP (NP (NN:[659..663] AIDS) (NNS:[664..672] patients)) (VP (VBG:[674..684] undergoing) (NP (VBN:[685..694] prolonged) (NN:[695..702] therapy)))))))))) (.:[702..703] .))) ;sentence 7 Span:704..952 ;We show here that cell growth arrest correlates with the accumulation of 14 ;alpha-methyl-ergosta-8,24(28)-dien-3 beta,6 alpha-diol in a yeast strain ;with a sterol 14 alpha-demethylase gene disruption, which mimics stringent ;treatment conditions. ;[778..836]:substance:"14 alpha-methyl-ergosta-8,24(28)-dien-3 beta,6 ;alpha-diol" ;[862..889]:cyp450:"sterol 14 alpha-demethylase" (SENT (S (NP-SBJ (PRP:[704..706] We)) (VP (VBP:[707..711] show) (ADVP (RB:[712..716] here)) (SBAR (IN:[717..721] that) (S (NP-SBJ (NML (NN:[722..726] cell) (NN:[727..733] growth)) (NN:[734..740] arrest)) (VP (VBZ:[741..751] correlates) (PP-CLR (IN:[753..757] with) (NP (NP (DT:[758..761] the) (NN:[762..774] accumulation)) (PP (IN:[775..777] of) (NP (CD:[778..780] 14) (NN:[781..817] alpha-methyl-ergosta-8,24-LRB-28-RRB--dien-3) (NN:[818..824] beta,6) (NN:[826..836] alpha-diol))))) (PP-LOC (IN:[837..839] in) (NP (NP (NP (DT:[840..841] a) (NN:[842..847] yeast) (NN:[848..854] strain)) (PP (IN:[855..859] with) (NP (DT:[860..861] a) (NML (NN:[862..868] sterol) (CD:[869..871] 14) (NN:[872..889] alpha-demethylase)) (NN:[890..894] gene) (NN:[895..905] disruption)))) (,:[905..906] ,) (SBAR (WHNP-1 (WDT:[908..913] which)) (S (NP-SBJ-1 (-NONE-:[913..913] *T*)) (VP (VBZ:[914..920] mimics) (NP (JJ:[921..930] stringent) (NN:[931..940] treatment) (NNS:[941..951] conditions))))))))))) (.:[951..952] .))) ;sentence 8 Span:953..1088 ;Cells can overcome the effect of such a block by a suppressor mutation in ;sterol delta 5,6 desaturation and acquire azole resistance. ;[1028..1034]:substance:"sterol" ;[1071..1076]:substance:"azole" (SENT (S (NP-SBJ (NNS:[953..958] Cells)) (VP (MD:[959..962] can) (VP (VP (VB:[963..971] overcome) (NP (NP (DT:[972..975] the) (NN:[976..982] effect)) (PP (IN:[983..985] of) (NP (JJ:[987..991] such) (DT:[992..993] a) (NN:[994..999] block)))) (PP-MNR (IN:[1000..1002] by) (NP (NP (DT:[1003..1004] a) (NN:[1005..1015] suppressor) (NN:[1016..1024] mutation)) (PP-LOC (IN:[1025..1027] in) (NP (NML (NN:[1028..1034] sterol) (SYM:[1035..1040] delta) (CD:[1041..1044] 5,6)) (NN:[1045..1057] desaturation)))))) (CC:[1058..1061] and) (VP (VB:[1063..1070] acquire) (NP (NN:[1071..1076] azole) (NN:[1077..1087] resistance))))) (.:[1087..1088] .))) ;sentence 9 Span:1089..1320 ;Plasmid-based complementation of sterol 14 alpha-demethylase defect does not ;alter the azole susceptibility of strains containing these suppressor ;mutations, showing resistance is due entirely to the delta 5.6 desaturase ;defect. ;[1122..1150]:substance:"sterol 14 alpha-demethylase" ;[1177..1182]:substance:"azole" ;[1292..1312]:substance:"delta 5.6 desaturase" (SENT (S (NP-SBJ (NP (ADJP (NN:[1089..1096] Plasmid) (HYPH:[1096..1097] -) (VBN:[1097..1102] based)) (NN:[1103..1118] complementation)) (PP (IN:[1119..1121] of) (NP (NML (NN:[1122..1128] sterol) (CD:[1129..1131] 14) (NN:[1133..1150] alpha-demethylase)) (NN:[1151..1157] defect)))) (VP (VBZ:[1158..1162] does) (RB:[1163..1166] not) (VP (VB:[1167..1172] alter) (NP (NP (DT:[1173..1176] the) (NN:[1177..1182] azole) (NN:[1183..1197] susceptibility)) (PP (IN:[1198..1200] of) (NP (NP (NNS:[1201..1208] strains)) (VP (VBG:[1210..1220] containing) (NP (DT:[1221..1226] these) (NN:[1227..1237] suppressor) (NNS:[1238..1247] mutations)))))) (,:[1247..1248] ,) (S-ADV (NP-SBJ (-NONE-:[1248..1248] *)) (VP (VBG:[1249..1256] showing) (SBAR (-NONE-:[1256..1256] 0) (S (NP-SBJ (NN:[1257..1267] resistance)) (VP (VBZ:[1268..1270] is) (ADJP-PRD (JJ:[1271..1274] due) (ADVP (RB:[1275..1283] entirely)) (PP (TO:[1284..1286] to) (NP (DT:[1287..1290] the) (NML (SYM:[1292..1297] delta) (CD:[1298..1301] 5.6) (NN:[1302..1312] desaturase)) (NN:[1313..1319] defect))))))))))) (.:[1319..1320] .))) ;section 10 Span:1324..1368 ;PMID: 7864896 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1324..1328] PMID) (::[1328..1329] :) (CD:[1330..1337] 7864896) (NN:[1338..1339] -LSB-) (NNP:[1339..1345] PubMed) (::[1346..1347] -) (NN:[1348..1355] indexed) (IN:[1356..1359] for) (NNP:[1360..1368] MEDLINE-RSB-)))