PubMed:10217534 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10217534","sourcedb":"PubMed","sourceid":"10217534","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10217534","text":"Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity.\n1. Bioactivation of sulphamethoxazole (SMX) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity. We have therefore examined the cellular metabolism, disposition and conjugation of SMX and its metabolites in vitro. 2. Flow cytometry revealed binding of N-hydroxy (SMX-NHOH) and nitroso (SMX-NO) metabolites of SMX, but not of SMX itself, to the surface of viable white blood cells. Cellular haptenation by SMX-NO was reduced by exogenous glutathione (GSH). 3. SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine (CYS), GSH, human peripheral blood cells and plasma, suggesting that this is an important and ubiquitous bioinactivation mechanism. 4. Fluorescence HPLC showed that SMX-NHOH and SMX-NO depleted CYS and GSH in buffer, and to a lesser extent, in cells and plasma. 5. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX-NHOH and SMX-NO than those inducing loss of membrane viability, with SMX having no effect. Lymphocytes were significantly (P\u003c0.05) more sensitive to the direct cytotoxic effects of SMX-NO than neutrophils. 6. Partitioning of SMX-NHOH into red blood cells was significantly (P\u003c0.05) lower than with the hydroxylamine of dapsone. 7. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism. If an imbalance exists, haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur, and may result in drug hypersensitivity.","tracks":[{"project":"genia-medco-coref","denotations":[{"id":"C2","span":{"begin":24,"end":41},"obj":"NP"},{"id":"C3","span":{"begin":46,"end":49},"obj":"NP"},{"id":"C1","span":{"begin":24,"end":61},"obj":"NP"},{"id":"C4","span":{"begin":118,"end":141},"obj":"NP"},{"id":"C6","span":{"begin":346,"end":349},"obj":"NP"},{"id":"C7","span":{"begin":354,"end":357},"obj":"NP"},{"id":"C5","span":{"begin":346,"end":369},"obj":"NP"},{"id":"C9","span":{"begin":475,"end":478},"obj":"NP"},{"id":"C8","span":{"begin":418,"end":478},"obj":"NP"},{"id":"C10","span":{"begin":491,"end":501},"obj":"NP"},{"id":"C11","span":{"begin":571,"end":577},"obj":"NP"},{"id":"C12","span":{"begin":593,"end":620},"obj":"NP"},{"id":"C14","span":{"begin":625,"end":633},"obj":"NP"},{"id":"C15","span":{"begin":638,"end":644},"obj":"NP"},{"id":"C13","span":{"begin":625,"end":644},"obj":"NP"},{"id":"C16","span":{"begin":713,"end":716},"obj":"NP"},{"id":"C17","span":{"begin":751,"end":757},"obj":"NP"},{"id":"C19","span":{"begin":871,"end":879},"obj":"NP"},{"id":"C20","span":{"begin":884,"end":890},"obj":"NP"},{"id":"C18","span":{"begin":871,"end":890},"obj":"NP"},{"id":"C21","span":{"begin":960,"end":966},"obj":"NP"},{"id":"C23","span":{"begin":1070,"end":1078},"obj":"NP"},{"id":"C24","span":{"begin":1083,"end":1089},"obj":"NP"},{"id":"C22","span":{"begin":1070,"end":1089},"obj":"NP"},{"id":"C25","span":{"begin":1255,"end":1261},"obj":"NP"},{"id":"C26","span":{"begin":1299,"end":1307},"obj":"NP"},{"id":"C27","span":{"begin":1463,"end":1466},"obj":"NP"},{"id":"C29","span":{"begin":1470,"end":1473},"obj":"NP"},{"id":"C28","span":{"begin":1470,"end":1491},"obj":"NP"},{"id":"C30","span":{"begin":1496,"end":1501},"obj":"NP"},{"id":"C31","span":{"begin":1598,"end":1619},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-pron","subj":"C3","obj":"C2"},{"id":"R2","pred":"coref-ident","subj":"C4","obj":"C2"},{"id":"R3","pred":"coref-ident","subj":"C6","obj":"C4"},{"id":"R4","pred":"coref-pron","subj":"C7","obj":"C6"},{"id":"R5","pred":"coref-ident","subj":"C5","obj":"C1"},{"id":"R6","pred":"coref-ident","subj":"C9","obj":"C6"},{"id":"R7","pred":"coref-ident","subj":"C10","obj":"C9"},{"id":"R8","pred":"coref-ident","subj":"C15","obj":"C11"},{"id":"R9","pred":"coref-ident","subj":"C13","obj":"C8"},{"id":"R10","pred":"coref-ident","subj":"C16","obj":"C12"},{"id":"R11","pred":"coref-ident","subj":"C19","obj":"C14"},{"id":"R12","pred":"coref-ident","subj":"C20","obj":"C15"},{"id":"R13","pred":"coref-ident","subj":"C18","obj":"C13"},{"id":"R14","pred":"coref-ident","subj":"C21","obj":"C17"},{"id":"R15","pred":"coref-ident","subj":"C23","obj":"C19"},{"id":"R16","pred":"coref-ident","subj":"C24","obj":"C20"},{"id":"R17","pred":"coref-ident","subj":"C22","obj":"C18"},{"id":"R18","pred":"coref-ident","subj":"C25","obj":"C24"},{"id":"R19","pred":"coref-ident","subj":"C26","obj":"C23"},{"id":"R20","pred":"coref-ident","subj":"C27","obj":"C10"},{"id":"R21","pred":"coref-pron","subj":"C29","obj":"C27"},{"id":"R22","pred":"coref-pron","subj":"C30","obj":"C28"},{"id":"R23","pred":"coref-ident","subj":"C31","obj":"C28"}],"attributes":[{"subj":"C2","pred":"source","obj":"genia-medco-coref"},{"subj":"C3","pred":"source","obj":"genia-medco-coref"},{"subj":"C1","pred":"source","obj":"genia-medco-coref"},{"subj":"C4","pred":"source","obj":"genia-medco-coref"},{"subj":"C6","pred":"source","obj":"genia-medco-coref"},{"subj":"C7","pred":"source","obj":"genia-medco-coref"},{"subj":"C5","pred":"source","obj":"genia-medco-coref"},{"subj":"C9","pred":"source","obj":"genia-medco-coref"},{"subj":"C8","pred":"source","obj":"genia-medco-coref"},{"subj":"C10","pred":"source","obj":"genia-medco-coref"},{"subj":"C11","pred":"source","obj":"genia-medco-coref"},{"subj":"C12","pred":"source","obj":"genia-medco-coref"},{"subj":"C14","pred":"source","obj":"genia-medco-coref"},{"subj":"C15","pred":"source","obj":"genia-medco-coref"},{"subj":"C13","pred":"source","obj":"genia-medco-coref"},{"subj":"C16","pred":"source","obj":"genia-medco-coref"},{"subj":"C17","pred":"source","obj":"genia-medco-coref"},{"subj":"C19","pred":"source","obj":"genia-medco-coref"},{"subj":"C20","pred":"source","obj":"genia-medco-coref"},{"subj":"C18","pred":"source","obj":"genia-medco-coref"},{"subj":"C21","pred":"source","obj":"genia-medco-coref"},{"subj":"C23","pred":"source","obj":"genia-medco-coref"},{"subj":"C24","pred":"source","obj":"genia-medco-coref"},{"subj":"C22","pred":"source","obj":"genia-medco-coref"},{"subj":"C25","pred":"source","obj":"genia-medco-coref"},{"subj":"C26","pred":"source","obj":"genia-medco-coref"},{"subj":"C27","pred":"source","obj":"genia-medco-coref"},{"subj":"C29","pred":"source","obj":"genia-medco-coref"},{"subj":"C28","pred":"source","obj":"genia-medco-coref"},{"subj":"C30","pred":"source","obj":"genia-medco-coref"},{"subj":"C31","pred":"source","obj":"genia-medco-coref"}]},{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":528,"end":545},"obj":"cell_type"},{"id":"T2","span":{"begin":718,"end":746},"obj":"cell_type"},{"id":"T3","span":{"begin":800,"end":810},"obj":"protein"},{"id":"T4","span":{"begin":1165,"end":1176},"obj":"cell_type"},{"id":"T5","span":{"begin":1267,"end":1278},"obj":"cell_type"},{"id":"T6","span":{"begin":1313,"end":1328},"obj":"cell_type"}],"attributes":[{"subj":"T1","pred":"source","obj":"jnlpba-st-training"},{"subj":"T2","pred":"source","obj":"jnlpba-st-training"},{"subj":"T3","pred":"source","obj":"jnlpba-st-training"},{"subj":"T4","pred":"source","obj":"jnlpba-st-training"},{"subj":"T5","pred":"source","obj":"jnlpba-st-training"},{"subj":"T6","pred":"source","obj":"jnlpba-st-training"}]},{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":97},"obj":"Sentence"},{"id":"S2","span":{"begin":98,"end":262},"obj":"Sentence"},{"id":"S3","span":{"begin":263,"end":379},"obj":"Sentence"},{"id":"S4","span":{"begin":380,"end":546},"obj":"Sentence"},{"id":"S5","span":{"begin":547,"end":621},"obj":"Sentence"},{"id":"S6","span":{"begin":622,"end":837},"obj":"Sentence"},{"id":"S7","span":{"begin":838,"end":967},"obj":"Sentence"},{"id":"S8","span":{"begin":968,"end":1164},"obj":"Sentence"},{"id":"S9","span":{"begin":1165,"end":1279},"obj":"Sentence"},{"id":"S10","span":{"begin":1280,"end":1401},"obj":"Sentence"},{"id":"S11","span":{"begin":1402,"end":1558},"obj":"Sentence"},{"id":"S12","span":{"begin":1559,"end":1728},"obj":"Sentence"}],"attributes":[{"subj":"S1","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S2","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S3","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S4","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S5","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S6","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S7","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S8","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S9","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S10","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S11","pred":"source","obj":"pubmed-sentences-benchmark"},{"subj":"S12","pred":"source","obj":"pubmed-sentences-benchmark"}]},{"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":0,"end":20},"obj":"other_name"},{"id":"T2","span":{"begin":24,"end":41},"obj":"other_organic_compound"},{"id":"T3","span":{"begin":50,"end":61},"obj":"other_organic_compound"},{"id":"T4","span":{"begin":63,"end":96},"obj":"other_name"},{"id":"T5","span":{"begin":118,"end":135},"obj":"other_organic_compound"},{"id":"T6","span":{"begin":137,"end":140},"obj":"other_organic_compound"},{"id":"T7","span":{"begin":165,"end":176},"obj":"other_organic_compound"},{"id":"T8","span":{"begin":192,"end":211},"obj":"other_name"},{"id":"T9","span":{"begin":241,"end":244},"obj":"other_organic_compound"},{"id":"T10","span":{"begin":346,"end":349},"obj":"other_organic_compound"},{"id":"T11","span":{"begin":358,"end":369},"obj":"other_organic_compound"},{"id":"T12","span":{"begin":475,"end":478},"obj":"other_organic_compound"},{"id":"T13","span":{"begin":491,"end":494},"obj":"other_organic_compound"},{"id":"T14","span":{"begin":528,"end":545},"obj":"cell_type"},{"id":"T15","span":{"begin":571,"end":574},"obj":"other_organic_compound"},{"id":"T16","span":{"begin":603,"end":614},"obj":"peptide"},{"id":"T17","span":{"begin":616,"end":619},"obj":"peptide"},{"id":"T18","span":{"begin":625,"end":628},"obj":"other_organic_compound"},{"id":"T19","span":{"begin":638,"end":641},"obj":"other_organic_compound"},{"id":"T20","span":{"begin":697,"end":705},"obj":"amino_acid_monomer"},{"id":"T21","span":{"begin":707,"end":710},"obj":"amino_acid_monomer"},{"id":"T22","span":{"begin":713,"end":716},"obj":"peptide"},{"id":"T23","span":{"begin":718,"end":746},"obj":"cell_type"},{"id":"T24","span":{"begin":800,"end":810},"obj":"protein_family_or_group"},{"id":"T25","span":{"begin":841,"end":858},"obj":"other_name"},{"id":"T26","span":{"begin":871,"end":874},"obj":"other_organic_compound"},{"id":"T27","span":{"begin":884,"end":887},"obj":"other_organic_compound"},{"id":"T28","span":{"begin":900,"end":903},"obj":"amino_acid_monomer"},{"id":"T29","span":{"begin":908,"end":911},"obj":"peptide"},{"id":"T30","span":{"begin":960,"end":966},"obj":"tissue"},{"id":"T31","span":{"begin":971,"end":991},"obj":"other_name"},{"id":"T32","span":{"begin":1010,"end":1029},"obj":"other_name"},{"id":"T33","span":{"begin":1070,"end":1073},"obj":"other_organic_compound"},{"id":"T34","span":{"begin":1083,"end":1086},"obj":"other_organic_compound"},{"id":"T35","span":{"begin":1143,"end":1146},"obj":"other_organic_compound"},{"id":"T36","span":{"begin":1165,"end":1176},"obj":"cell_type"},{"id":"T37","span":{"begin":1234,"end":1251},"obj":"other_name"},{"id":"T38","span":{"begin":1255,"end":1258},"obj":"other_organic_compound"},{"id":"T39","span":{"begin":1267,"end":1278},"obj":"cell_type"},{"id":"T40","span":{"begin":1299,"end":1302},"obj":"other_organic_compound"},{"id":"T41","span":{"begin":1313,"end":1328},"obj":"cell_type"},{"id":"T42","span":{"begin":1376,"end":1389},"obj":"other_organic_compound"},{"id":"T43","span":{"begin":1393,"end":1400},"obj":"other_organic_compound"},{"id":"T44","span":{"begin":1463,"end":1466},"obj":"other_organic_compound"},{"id":"T45","span":{"begin":1583,"end":1594},"obj":"other_name"},{"id":"T46","span":{"begin":1602,"end":1619},"obj":"other_organic_compound"},{"id":"T47","span":{"begin":1706,"end":1727},"obj":"other_name"}],"attributes":[{"subj":"T1","pred":"source","obj":"GENIAcorpus"},{"subj":"T2","pred":"source","obj":"GENIAcorpus"},{"subj":"T3","pred":"source","obj":"GENIAcorpus"},{"subj":"T4","pred":"source","obj":"GENIAcorpus"},{"subj":"T5","pred":"source","obj":"GENIAcorpus"},{"subj":"T6","pred":"source","obj":"GENIAcorpus"},{"subj":"T7","pred":"source","obj":"GENIAcorpus"},{"subj":"T8","pred":"source","obj":"GENIAcorpus"},{"subj":"T9","pred":"source","obj":"GENIAcorpus"},{"subj":"T10","pred":"source","obj":"GENIAcorpus"},{"subj":"T11","pred":"source","obj":"GENIAcorpus"},{"subj":"T12","pred":"source","obj":"GENIAcorpus"},{"subj":"T13","pred":"source","obj":"GENIAcorpus"},{"subj":"T14","pred":"source","obj":"GENIAcorpus"},{"subj":"T15","pred":"source","obj":"GENIAcorpus"},{"subj":"T16","pred":"source","obj":"GENIAcorpus"},{"subj":"T17","pred":"source","obj":"GENIAcorpus"},{"subj":"T18","pred":"source","obj":"GENIAcorpus"},{"subj":"T19","pred":"source","obj":"GENIAcorpus"},{"subj":"T20","pred":"source","obj":"GENIAcorpus"},{"subj":"T21","pred":"source","obj":"GENIAcorpus"},{"subj":"T22","pred":"source","obj":"GENIAcorpus"},{"subj":"T23","pred":"source","obj":"GENIAcorpus"},{"subj":"T24","pred":"source","obj":"GENIAcorpus"},{"subj":"T25","pred":"source","obj":"GENIAcorpus"},{"subj":"T26","pred":"source","obj":"GENIAcorpus"},{"subj":"T27","pred":"source","obj":"GENIAcorpus"},{"subj":"T28","pred":"source","obj":"GENIAcorpus"},{"subj":"T29","pred":"source","obj":"GENIAcorpus"},{"subj":"T30","pred":"source","obj":"GENIAcorpus"},{"subj":"T31","pred":"source","obj":"GENIAcorpus"},{"subj":"T32","pred":"source","obj":"GENIAcorpus"},{"subj":"T33","pred":"source","obj":"GENIAcorpus"},{"subj":"T34","pred":"source","obj":"GENIAcorpus"},{"subj":"T35","pred":"source","obj":"GENIAcorpus"},{"subj":"T36","pred":"source","obj":"GENIAcorpus"},{"subj":"T37","pred":"source","obj":"GENIAcorpus"},{"subj":"T38","pred":"source","obj":"GENIAcorpus"},{"subj":"T39","pred":"source","obj":"GENIAcorpus"},{"subj":"T40","pred":"source","obj":"GENIAcorpus"},{"subj":"T41","pred":"source","obj":"GENIAcorpus"},{"subj":"T42","pred":"source","obj":"GENIAcorpus"},{"subj":"T43","pred":"source","obj":"GENIAcorpus"},{"subj":"T44","pred":"source","obj":"GENIAcorpus"},{"subj":"T45","pred":"source","obj":"GENIAcorpus"},{"subj":"T46","pred":"source","obj":"GENIAcorpus"},{"subj":"T47","pred":"source","obj":"GENIAcorpus"}]},{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":80,"end":96},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":245,"end":261},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1210,"end":1219},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1677,"end":1680},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1711,"end":1727},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0000605"},{"id":"A2","pred":"mondo_id","subj":"T1","obj":"0005271"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0000605"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"0005271"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0000605"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0012833"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0000605"},{"id":"A8","pred":"mondo_id","subj":"T7","obj":"0005271"},{"subj":"T1","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T3","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T5","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T6","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T7","pred":"source","obj":"PMID_GLOBAL"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"genia-medco-coref","color":"#9f93ec","default":true},{"id":"jnlpba-st-training","color":"#a0ec93"},{"id":"pubmed-sentences-benchmark","color":"#ec93ba"},{"id":"GENIAcorpus","color":"#93d4ec"},{"id":"PMID_GLOBAL","color":"#ecea93"}]}]}}