;PMID: 1391809 ;source_file_1421.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..34] = [t:0..34] ;1)sentence:[e:39..134] = [t:39..134] ;2)section:[e:138..211] = [t:138..211] ;3)section:[e:215..290] = [t:215..290] ;4)sentence:[e:294..481] = [t:294..481] ;5)sentence:[e:482..578] = [t:482..578] ;6)sentence:[e:579..766] = [t:579..766] ;7)sentence:[e:767..913] = [t:767..913] ;8)sentence:[e:914..1136] = [t:914..1136] ;9)sentence:[e:1137..1228] = [t:1137..1228] ;10)sentence:[e:1229..1340] = [t:1229..1340] ;11)section:[e:1344..1388] = [t:1344..1388] ;section 0 Span:0..34 ;Int J Hematol 1992 Aug;56(1):9-15 (SEC (FRAG (NNP:[0..3] Int) (NNP:[4..5] J) (NNP:[6..13] Hematol) (CD:[15..19] 1992) (CD:[20..27] Aug;56-LRB-) (CD:[27..28] 1) (-RRB-:[28..29] -RRB-) (CD:[29..31] :9) (IN:[31..32] -) (CD:[32..34] 15))) ;sentence 1 Span:39..134 ;N-RAS activation in the terminal stage of undifferentiated chronic ;myeloproliferative disease. ;[39..44]:gene-rna:"N-RAS" ;[81..133]:malignancy:"undifferentiated chronic myeloproliferative disease" (SENT (NP-HLN (NP (NN:[39..44] N-RAS) (NN:[45..55] activation)) (PP (IN:[56..58] in) (NP (DT:[59..62] the) (JJ:[63..71] terminal) (NN:[72..77] stage))) (PP (IN:[78..80] of) (NP (JJ:[81..97] undifferentiated) (JJ:[98..105] chronic) (JJ:[107..125] myeloproliferative) (NN:[126..133] disease))) (.:[133..134] .))) ;section 2 Span:138..211 ;Inokuchi K, Futaki M, Miyake K, Kuwabara T, Shinohara T, Dan K, Nomura T. (SEC (FRAG (NNP:[138..146] Inokuchi) (NNP:[147..148] K) (,:[148..149] ,) (NNP:[150..156] Futaki) (NNP:[157..159] M,) (NNP:[160..166] Miyake) (NNP:[167..168] K) (VBD:[168..169] ,) (NNP:[170..178] Kuwabara) (NNP:[179..180] T) (VBD:[180..181] ,) (NNP:[182..191] Shinohara) (NNP:[192..193] T) (,:[193..194] ,) (NNP:[195..198] Dan) (NNP:[199..200] K) (,:[200..201] ,) (NNP:[202..208] Nomura) (NNP:[209..211] T.))) ;section 3 Span:215..290 ;Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. (SEC (FRAG (NNP:[215..220] Third) (NNP:[221..231] Department) (IN:[232..234] of) (NNP:[235..243] Internal) (NNP:[244..252] Medicine) (,:[252..253] ,) (NNP:[254..260] Nippon) (NNP:[261..268] Medical) (NNP:[269..275] School) (,:[275..276] ,) (NNP:[277..282] Tokyo) (,:[282..283] ,) (NNP:[284..289] Japan) (.:[289..290] .))) ;sentence 4 Span:294..481 ;The relationship between activation of the N-RAS gene and the leukemic ;progression of undifferentiated chronic myeloproliferative disease (UCMPD) ;was investigated in a 71-year-old male. ;[337..342]:gene-rna:"N-RAS" ;[381..432]:malignancy:"undifferentiated chronic myeloproliferative disease" ;[434..439]:malignancy:"UCMPD" (SENT (S (NP-SBJ-1 (NP (DT:[294..297] The) (NN:[298..310] relationship)) (PP (IN:[311..318] between) (NP (NP (NP (NN:[319..329] activation)) (PP (IN:[330..332] of) (NP (DT:[333..336] the) (NN:[337..342] N-RAS) (NN:[343..347] gene)))) (CC:[348..351] and) (NP (NP (DT:[352..355] the) (JJ:[356..364] leukemic) (NN:[366..377] progression)) (PP (IN:[378..380] of) (NP (NP (JJ:[381..397] undifferentiated) (JJ:[398..405] chronic) (JJ:[406..424] myeloproliferative) (NN:[425..432] disease)) (NP (-LRB-:[433..434] -LRB-) (NN:[434..439] UCMPD) (-RRB-:[439..440] -RRB-)))))))) (VP (VBD:[441..444] was) (VP (VBN:[446..458] investigated) (NP-1 (-NONE-:[458..458] *)) (PP-LOC (IN:[459..461] in) (NP (DT:[462..463] a) (ADJP (NML (CD:[464..466] 71) (HYPH:[466..467] -) (NN:[467..471] year)) (HYPH:[471..472] -) (JJ:[472..475] old)) (NN:[476..480] male))))) (.:[480..481] .))) ;sentence 5 Span:482..578 ;Hematologically, it was difficult to differentiate the UCMPD from chronic ;myelogenous leukemia. ;[538..543]:malignancy:"UCMPD" ;[549..577]:malignancy:"chronic myelogenous leukemia" (SENT (S (ADVP (RB:[482..497] Hematologically)) (,:[497..498] ,) (NP-SBJ (PRP:[499..501] it)) (VP (VBD:[502..505] was) (ADJP-PRD (JJ:[506..515] difficult) (S-ADV (NP-SBJ (-NONE-:[515..515] *)) (VP (TO:[516..518] to) (VP (VB:[520..533] differentiate) (NP (DT:[534..537] the) (NN:[538..543] UCMPD)) (PP (IN:[544..548] from) (NP (JJ:[549..556] chronic) (JJ:[557..568] myelogenous) (NN:[569..577] leukemia)))))))) (.:[577..578] .))) ;sentence 6 Span:579..766 ;Chromosomal analysis revealed no Philadelphia chromosome (Ph1-), and DNA ;analysis revealed no BCR rearrangement (BCR-) either at the beginning or in ;the terminal stages of the disease. ;[613..636]:variation-event:"Philadelphia chromosome" ;[638..642]:variation-event:"Ph1-" ;[674..692]:variation-event:"BCR rearrangement" ;[674..677]:gene-rna:"BCR" ;[694..698]:variation-event:"BCR-" ;[694..697]:gene-rna:"BCR" (SENT (S (S (NP-SBJ (JJ:[579..590] Chromosomal) (NN:[591..599] analysis)) (VP (VBD:[601..609] revealed) (NP (NP (DT:[610..612] no) (NNP:[613..625] Philadelphia) (NN:[626..636] chromosome)) (NP (-LRB-:[637..638] -LRB-) (NN:[638..641] Ph1) (SYM:[641..642] -) (-RRB-:[642..643] -RRB-))))) (,:[643..644] ,) (CC:[645..648] and) (S (NP-SBJ (NN:[649..652] DNA) (NN:[653..661] analysis)) (VP (VBD:[662..670] revealed) (NP (NP (DT:[671..673] no) (NN:[674..677] BCR) (NN:[679..692] rearrangement)) (NP (-LRB-:[693..694] -LRB-) (NN:[694..697] BCR) (SYM:[697..698] -) (-RRB-:[698..699] -RRB-))) (PP (CC:[700..706] either) (PP (IN:[707..709] at) (NP (DT:[710..713] the) (NN:[714..723] beginning)) (PP-1 (-NONE-:[723..723] *RNR*))) (CC:[724..726] or) (PP (IN:[727..729] in) (NP (NP (DT:[730..733] the) (JJ:[734..742] terminal) (NNS:[743..749] stages)) (PP-1 (-NONE-:[749..749] *RNR*)))) (PP-1 (IN:[750..752] of) (NP (DT:[753..756] the) (NN:[758..765] disease)))))) (.:[765..766] .))) ;sentence 7 Span:767..913 ;We performed a tumorigenicity assay, using NIH3T3 cells, and molecular ;analysis, using the polymerase chain reaction (PCR) and direct sequencing. ;[859..869]:gene-protein:"polymerase" (SENT (S (NP-SBJ (PRP:[767..769] We)) (VP (VP (VBD:[770..779] performed) (NP=1 (DT:[780..781] a) (NN:[782..796] tumorigenicity) (NN:[797..802] assay)) (,:[802..803] ,) (S-MNR=2 (NP-SBJ (-NONE-:[803..803] *)) (VP (VBG:[804..809] using) (NP (NN:[810..816] NIH3T3) (NNS:[817..822] cells))))) (,:[822..823] ,) (CC:[824..827] and) (VP (NP=1 (JJ:[828..837] molecular) (NN:[839..847] analysis)) (,:[847..848] ,) (S-MNR=2 (NP-SBJ (-NONE-:[848..848] *)) (VP (VBG:[849..854] using) (NP (NP (NP (DT:[855..858] the) (NN:[859..869] polymerase) (NN:[870..875] chain) (NN:[876..884] reaction)) (NP (-LRB-:[885..886] -LRB-) (NN:[886..889] PCR) (-RRB-:[889..890] -RRB-))) (CC:[891..894] and) (NP (JJ:[895..901] direct) (NN:[902..912] sequencing))))))) (.:[912..913] .))) ;sentence 8 Span:914..1136 ;The DNA of leukemic cells at the beginning of the leukemic progression did ;not show any abnormalities, but at the terminal stage of the disease the DNA ;showed a point mutation in codon 12 (GGT----GCT) of the N-RAS gene. ;[926..940]:malignancy:"leukemic cells" ;[1030..1059]:malignancy:"terminal stage of the disease" ;[1078..1092]:variation-type:"point mutation" ;[1096..1104]:variation-location:"codon 12" ;[1106..1109]:variation-state-original:"GGT" ;[1113..1116]:variation-state-altered:"GCT" ;[1125..1130]:gene-rna:"N-RAS" (SENT (S (S (NP-SBJ (NP (DT:[914..917] The) (NN:[919..922] DNA)) (PP (IN:[923..925] of) (NP (NP (JJ:[926..934] leukemic) (NNS:[935..940] cells)) (PP-TMP (IN:[941..943] at) (NP (NP (DT:[944..947] the) (NN:[948..957] beginning)) (PP (IN:[958..960] of) (NP (DT:[961..964] the) (JJ:[965..973] leukemic) (NN:[974..985] progression)))))))) (VP (VBD:[986..989] did) (RB:[990..993] not) (VP (VB:[994..998] show) (NP (DT:[1000..1003] any) (NNS:[1004..1017] abnormalities))))) (,:[1017..1018] ,) (CC:[1019..1022] but) (S (PP-TMP (IN:[1023..1025] at) (NP (NP (DT:[1026..1029] the) (JJ:[1030..1038] terminal) (NN:[1039..1044] stage)) (PP (IN:[1045..1047] of) (NP (DT:[1048..1051] the) (NN:[1052..1059] disease))))) (NP-SBJ (DT:[1060..1063] the) (NN:[1064..1067] DNA)) (VP (VBD:[1068..1074] showed) (NP (NP (DT:[1075..1076] a) (NN:[1078..1083] point) (NN:[1084..1092] mutation)) (PP-LOC (IN:[1093..1095] in) (NP (NP (NN:[1096..1101] codon) (CD:[1102..1104] 12)) (PRN (-LRB-:[1105..1106] -LRB-) (NP (NP (NN:[1106..1109] GGT)) (PP (SYM:[1109..1113] ----) (NP (NN:[1113..1116] GCT)))) (-RRB-:[1116..1117] -RRB-)) (PP (IN:[1118..1120] of) (NP (DT:[1121..1124] the) (NN:[1125..1130] N-RAS) (NN:[1131..1135] gene)))))))) (.:[1135..1136] .))) ;sentence 9 Span:1137..1228 ;Interestingly, a codon 13 mutation (GGT----GTT) was also detected by ;tumorigenicity assay. ;[1155..1163]:variation-location:"codon 13" ;[1164..1172]:variation-event:"mutation" ;[1174..1177]:variation-state-original:"GGT" ;[1181..1184]:variation-state-altered:"GTT" (SENT (S (ADVP (RB:[1137..1150] Interestingly)) (,:[1150..1151] ,) (NP-SBJ-1 (DT:[1152..1153] a) (NML (NN:[1155..1160] codon) (CD:[1161..1163] 13)) (NN:[1164..1172] mutation) (PRN (-LRB-:[1173..1174] -LRB-) (NP (NP (NN:[1174..1177] GGT)) (PP (SYM:[1177..1181] ----) (NP (NN:[1181..1184] GTT)))) (-RRB-:[1184..1185] -RRB-))) (VP (VBD:[1186..1189] was) (ADVP (RB:[1190..1194] also)) (VP (VBN:[1195..1203] detected) (NP-1 (-NONE-:[1203..1203] *)) (PP-MNR (IN:[1204..1206] by) (NP (NN:[1207..1221] tumorigenicity) (NN:[1222..1227] assay))))) (.:[1227..1228] .))) ;sentence 10 Span:1229..1340 ;These observations suggest that the activated N-RAS gene contributes to the ;hematologic progression of UCMPD. ;[1276..1281]:gene-rna:"N-RAS" ;[1334..1339]:malignancy:"UCMPD" (SENT (S (NP-SBJ (DT:[1229..1234] These) (NNS:[1236..1248] observations)) (VP (VBP:[1249..1256] suggest) (SBAR (IN:[1257..1261] that) (S (NP-SBJ (DT:[1262..1265] the) (VBN:[1266..1275] activated) (NN:[1276..1281] N-RAS) (NN:[1282..1286] gene)) (VP (VBZ:[1287..1298] contributes) (PP-CLR (TO:[1299..1301] to) (NP (NP (DT:[1302..1305] the) (JJ:[1307..1318] hematologic) (NN:[1319..1330] progression)) (PP (IN:[1331..1333] of) (NP (NN:[1334..1339] UCMPD))))))))) (.:[1339..1340] .))) ;section 11 Span:1344..1388 ;PMID: 1391809 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1344..1348] PMID) (::[1348..1349] :) (CD:[1350..1357] 1391809) (IN:[1358..1359] -LSB-) (NNP:[1359..1365] PubMed) (HYPH:[1366..1367] -) (JJ:[1368..1375] indexed) (IN:[1376..1379] for) (NNP:[1380..1388] MEDLINE-RSB-)))