Dexamethasone alters messenger RNA levels but not synthesis of collagens, fibronectin, or laminin by cultured rat fat‐storing cells

T Niki, D Schuppan, P J de Bleser, R Vrijsen, M Pipeleers‐Marichal, R Beyaert, E Wisse, A Geerts – 1 June 1996 – Glucocorticoids have been shown to suppress collagen synthesis and gene expression by fibroblasts. However, little is known about their effects on fat‐storing cells, the major matrix‐producing cells in liver fibrosis. In this study we investigated the effect of dexamethasone on the extracellular matrix expression by cultured rat fat‐storing cells.

Coagulation factor V levels as a prognostic indicator in fulminant hepatic failure

S Izumi, P G Langley, J Wendon, A J Ellis, R Pernambuco, R D Hughes, R Williams – 1 June 1996 – Data reported by Bernuau et al. have strongly supported the measurement of coagulation factor V as the best prognostic indicator in fulminant hepatic failure (FHF) and as the test on which selection for urgent liver transplantation should be made. In this study, we have measured plasma factor V in 110 patients with FHF, in grades I‐IV coma, in 88 of whom the etiology was acetaminophen overdose.

Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers

P Clavien, C A Camargo, R Gorczynski, M K Washington, G A Levy, B Langer, P D Greig – 1 June 1996 – Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes (PMN) may play a critical role in ischemia‐ reperfusion injury. To evaluate whether similar mechanisms are operative in human liver, six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were randomized for utilization of hepatic vascular exclusion (HVE) as a model of ischemia‐reperfusion injury.

The caffeine breath test does not identify patients susceptible to tacrine hepatotoxicity

R J Fontana, D K Turgeon, T F Woolf, M J Knapp, N L Foster, P B Watkins – 1 June 1996 – Therapy with tacrine, a promising new treatment for Alzheimer's disease, must be discontinued in up to 15% of patients because of hepatocellular toxicity. Recent studies using human liver microsomes have suggested that a single liver enzyme, cytochrome P450 1A2 (CYP1A2), catalyzes the major route of metabolism and elimination of tacrine, and also catalyzes the pathway(s) involved in the generation of reactive metabolites capable of covalent protein binding and cytotoxicity.

Biochemical epidemiology of gallbladder cancer

B L Strom, R D Soloway, J Rios‐Dalenz, H A Rodriguez‐Martinez, S L West, J L Kinman, R S Crowther, D Taylor, M Polansky, J A Berlin – 1 June 1996 – To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case‐control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico.

Hepatic sinusoidal endothelium heterogeneity with respect to mannose receptor activity is interleukin‐1 dependent

A Asumendi, A Alvarez, I Martinez, B Smedsrød, F Vidal‐Vanaclocha – 1 June 1996 – Using fluorescein isothiocyanate‐conjugated ovalbumin (OVA‐FITC), 125I‐mannan, or 125I‐invertase as specific ligands for the mannose receptor, we have quantified its activity in mouse and rat hepatic sinusoidal endothelium (HSE), under both basal conditions and after lipopolysaccharide (LPS) or human recombinant interleukin‐1β (IL‐1β) stimulations. Mouse treatment for 4 hours with 5 μg/kg IL‐1β significantly increased OVA‐FITC uptake by HSE.

Nonlinear kinetics after high‐dose omeprazole caused by saturation of genetically variable CYP2C19

K L Rost, I Roots – 1 June 1996 – Nonlinear kinetics of omeprazole and its metabolites were investigated after treatment with repeated high doses. Extensive metabolizers relating to cytochrome P450 2C19 (CYP2C19) activity received for 1 week either omeprazole at 40 mg/d (n = 14) or 60 mg/d omeprazole twice daily (n = 8). Five poor metabolizers (PMs) received 40 mg/d for 1 week. Comparison of omeprazole plasma kinetics between extensive metabolizers (EMs) and PMs after 40‐mg treatment revealed a dominant role of CYP2C19 over cytochrome P450 3A CYP3A in omeprazole metabolism.

Intensive care unit admissions with cirrhosis: Risk‐stratifying patient groups and predicting individual survival

J E Zimmerman, D P Wagner, M G Seneff, R B Becker, X Sun, W A Knaus – 1 June 1996 – Prognosis for acutely ill patients with cirrhosis is influenced by the severity of hepatic abnormalities and by dysfunction of other organ systems. The purpose of this study was to examine the usefulness of the Acute Physiology, Age, and Chronic Health Evaluation (APACHE III) prognostic system for risk‐stratifying groups of intensive care unit (ICU) patients with cirrhosis and in predicting individual survival.

Frequent expression of MUC1 apomucin on biliary epithelial cells of damaged small bile ducts in primary biliary cirrhosis and chronic viral hepatitis: An immunohistochemical study

M Sasaki, Y Nakanuma – 1 June 1996 – MUC1 apomucin is a specific target tumor antigen recognized by cytotoxic T cells in a major histocompatibility complex (MHC) unrestricted fashion in patients with pancreatic and breast cancer. This T‐cell‐mediated immune mechanism against MUC1 apomucin expressing cells has not been evaluated in nonneoplastic immune‐mediated diseases. Therefore, we immunohistochemically surveyed the expression of MUC1 apomucin on biliary epithelial cells of small bile ducts in various hepatobiliary diseases, including primary biliary cirrhosis (PBC).

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