UNASSIGNED: TOXIC INDUSTRIAL @entity576 INDUCE LIVER INJURY, WHICH IS DIFFICULT TO DIAGNOSE WITHOUT INVASIVE PROCEDURES: Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be associated with the @entity82 pathology by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male @entity35 dosed with varying concentrations of three fibrogenic compounds ( @entity824 , @entity4314 , and @entity20587 ) and two non-fibrogenic compounds ( @entity35326 and @entity619 ) were conducted. @entity82 was definitively diagnosed by histopathology. The 67-plex gene panel accurately diagnosed @entity82 in both microarray and multiplexed-gene expression assays. @entity39 and inflammatory infiltration were comorbid with @entity82 . ANOVA with contrasts identified that 51 of the 67 predicted genes were significantly associated with the @entity82 phenotype, with 24 of these specific to @entity82 alone. The protein product of the gene most strongly correlated with the @entity82 phenotype (Pcolce) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (p<0.05). Semi-quantitative global mass spectrometry analysis of the plasma identified an additional 5 protein products of the gene panel which increased after fibrogenic toxicant administration: fibronectin, ceruloplasmin, @entity4117 , insulin-like growth factor binding protein, and a2-macroglobulin. These results support the data mining approach for identifying gene and/or protein panels for assessing @entity99 and may suggest bridging biomarkers for molecular mediators linked to histopathology.

Gene expression patterns associated with histopathology in XXXX .

@entity576 :: ('MESH:D064419', 'Disease') :: ['CHEMICALS'] @entity824 :: ('MESH:C006463', 'Chemical') :: ['allyl alcohol'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis', 'Fibrosis'] @entity4314 :: ('MESH:D002251', 'Chemical') :: ['carbon tetrachloride'] @entity39 :: ('MESH:D009336', 'Disease') :: ['Necrosis'] @entity20587 :: ('MESH:C009505', 'Chemical') :: ["4,4'-methylenedianiline"] @entity35326 :: ('MESH:C032036', 'Chemical') :: ['bromobenzene'] @entity619 :: ('MESH:D003907', 'Chemical') :: ['dexamethasone'] @entity4117 :: ('29169(Tax:10116)', 'Gene') :: ['vitronectin'] @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats'] @entity99 :: ('MESH:D056486', 'Disease') :: ['liver injury']
@entity99 :: (MESH:D056486,Disease) :: ['toxic liver fibrosis']
