[' ', '(c)', 'format', 'only', '1995', 'Dialog', 'Info.Sves.', 'All', 'rts.', 'reserv.', '0152448', 'IDENTIFYING', 'NO.:', '1P01NS315945-01A1l', '06003', 'AGENCY', 'CODE:', 'CRISP', 'ENDOTHELIN,', 'NICOTINE,', 'AND', 'CNS-DERIVED', 'ENDOTHELIAL', 'FUNCTION', 'PRINCIPAL', 'INVESTIGATOR:', 'HOFMAN,', 'FLORENCE', 'M', 'ADDRESS:', 'USC', 'SCH', 'OF', 'MEDICINE', '1333', 'SAN', 'PABLO', 'MCA', '246', 'LOS', 'ANGELES,', 'CA', '90033', 'PERFORMING', 'ORG.:', 'UNIVERSITY', 'OF', 'SOUTHERN', 'CALIFORNIA,', 'LOS', 'ANGELES,', 'CALIFORNIA', 'SPONSORING', 'ORG.:', 'NATIONAL', 'INST', 'OF', 'NEUROLOGICAL', 'DISORDERS', 'AND', 'STROKE', 'FY', ':', '94', 'TYPE', 'OF', 'AWARD:', 'New', 'Award', '(Type', '1)', 'SUMMARY:', 'Hypertension', 'and', 'cigarette', 'smoking', 'are', 'two', 'of', 'the', 'most', 'important', 'ischemic', 'stroke', 'risk', 'factors.', 'Endothelin,', 'a', 'vasoconstrictive', 'peptide', 'has', 'been', 'found', 'to', 'be', 'increased', 'in', 'the', 'plasma', 'of', 'hypertensive', 'patients', 'and', 'induces', 'hypertension', 'in', 'animals,', 'and', 'cigarette', 'smoking', 'ia', 'an', 'important', 'risk', 'stroke', 'risk', 'factor.', 'Furthermore,', 'patients', 'with', 'infection', 'or', 'other', 'inflammatory', 'processes', 'may', 'be', 'subjected', 'to', 'increased', 'stroke', 'risk.', 'The', 'goal', 'of', 'this', 'atudy', 'ia', 'therefore', 'to', 'determine', 'how', 'nicotine', 'and', 'endothelin,', 'plasma', 'factors', 'associated', 'with', 'atroke', 'risk', 'factors,', 'affect', 'specific', 'functions', 'of', 'endothelial', 'cells,', 'and', 'whether', 'inflammatory', 'cytokines,', '1.e.,', 'tumor', 'necrosis', 'factor', '(TNF),', 'IL-1', 'or', 'interferon', 'gamma', '(IFN-gamma),', 'modulate', 'this', 'activity.', 'To', 'achieve', 'this', 'goal', 'we', 'will', 'analyze', 'the', 'effects', 'of', 'nicotine', 'and', 'endothelin', 'on', 'endothelial', 'cells', 'derived', 'from', 'the', 'central', 'nervous', 'system', '(CNS).', 'CNS-derived', 'endothelial', 'cultures', 'have', 'been', 'established', 'in', 'this', 'laboratory', 'and', 'have', 'been', 'shown', 'to', 'be', 'greater', 'than', '98%', 'pure,', 'with', 'ganma-glutamine', 'transpeptidase', 'activity.', 'Endothelial', 'cella', 'will', 'be', 'examined', 'for', 'the', 'production', 'of', 'the', 'coagulation', 'factors', '(e.g.', 'plasminogen', 'activator', 'inhibitor-1', '(PAI-1),', 'tissue', 'plasminogen', 'activator', '(t-PA),', 'thrombomodulin,', 'prostacyclin,', 'tissue', 'factor', '(TF)),', 'vasoregulatory', 'factora', '(e.g.', 'endothelin', 'and', 'nitric', 'oxide),', 'and', 'cytokine', 'preduction', '(e.g.', 'IL-1', 'IL-6,', 'IL-8).', 'The', 'effects', 'of', 'endothelin', 'and', 'nicotine', 'will', 'be', 'analyzed', 'in', 'the', 'absence', 'and', 'presence', 'of', 'inflammatory', 'cytokines', '(e.g.', 'TNF,', 'IL-1,', 'IFN-ganma)', 'and', 'negative-regulatory', 'cytokines', '{(e.g.', 'IL-4,', 'transforming', 'growth', 'factor', 'Beta', '(TGFBeta)).', 'Coagulation', 'factors', 'will', 'be', 'identified', 'using', 'ELISA', 'and', 'functional', 'aszay3.', 'Vasoregulatory', 'factors', 'will', 'be', 'measured', 'by', 'immunocytochemical', 'techniques,', 'and', 'the', 'enzymatic', 'assay', 'to', 'identify', 'nitric', 'oxide', 'synthase', 'activity.', 'Cytokine', 'synthesis', 'and', 'secretion', 'will', 'be', 'determined', 'using', 'in', 'aitu', 'hybridization,', 'Northern', 'blot', 'analysis,', 'immunostaining', 'and', 'ELISA', 'techniques.', 'TNF', 'receptor', 'regulation', 'will', 'be', 'monitored', 'using', 'flow', 'cytometry:', 'membrane', 'signalling', 'will', 'be', 'examined', 'by', 'measuring', 'phosphokinase', '¢,', 'phospholipase', 'C', 'and', 'phospholipase', 'C', 'and', 'phospholipase', 'A', 'enzymatic', 'activity.', 'The', 'data', 'obtained', 'from', 'these', 'studies', 'will', 'determine', 'how', 'hemostatic', 'functions', 'are', 'altered', 'by', 'nicotine', 'and', 'endothelin', 'and', 'how', 'inflammatory', 'eytokines', 'in', 'the', 'local', 'cerebral', 'microenvironment', 'affect', 'cNS-derived', 'endothelial', 'cell', 'activity.', 'This', 'information', 'will', 'provide', 'new', 'insights', 'into', 'the', 'brain', 'regulation', 'of', 'hemostasis', 'and', 'lead', 'to', 'specific', 'therapeutic', 'measures', 'capable', 'of', 'altering', 'brain', 'hemostasis', 'function', 'to', 'reduce', 'stroke', 'risk.', '6/7/50', 'DIALOG(R)File', '266:Fed.', 'Res.', 'in', 'Progress', '(ce)', 'format', 'only', '1995', 'Dialog', 'Info.Sves.', 'All', 'rts.', 'reserv.', '0152053', ':', '-', 'IDENTIFYING', 'NO.:', '5R29NS30S66-03', 'AGENCY', 'CODE:', 'CRISP', 'CHOLINERGIC', 'RECEPTORS', 'IN', 'MANDUCA', 'SEXTA', 'PRINCIPAL', 'INVESTIGATOR:', 'TRIMMER,', 'BARRY', 'A', 'ADDRESS:', 'TUFTS', 'UNIVERSITY', 'MEDFORD,', 'MA', '02155', 'PERFORMING', 'ORG.:', 'TUFTS', 'UNIVERSITY', 'BOSTON,', 'BOSTON,', 'MASSACHUSETTS', 'SPONSORING', 'ORG.:', 'NATIONAL', 'INST', 'OF', 'NEUROLOGICAL', 'DISORDERS', 'AND', 'STROKE', 'FY', ':', '94', 'FONDS:', '$93,725', 'TYPE', 'OF', 'AWARD:', 'Noncompeting', 'Continuation', '(Type', 'Ss)', 'SUMMARY:', 'The', 'long-term', 'objectives', 'of', 'this', 'preposal', 'are', 'to', 'determine', 'how', 'transmitters', 'transfer', 'information', 'between', 'neurons,', 'how', 'individual', 'neurons', 'integrate', 'and', 'respond', 'to', 'this', 'information,', 'and', 'how', 'this', 'processing', 'TEST', 'OTIS', ' ']