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.

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.

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.

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.

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.

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).

A P Mowat – 1 June 1996

J Laurin, K D Lindor, J S Crippin, A Gossard, G J Gores, J Ludwig, J Rakela, D B McGill – 1 June 1996 – Non‐alcohol‐induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH.

F Kanai, Y Shiratori, Y Yoshida, H Wakimoto, H Hamada, Y Kanegae, I Saito, H Nakabayashi, T Tamaoki, T Tanaka, K Lan, N Kato, S Shiina, M Omata – 1 June 1996 – We have developed a recombinant replication‐defective adenovirus containing human α‐fetoprotein (AFP) promoter/enhancer to direct cell type‐specific expression of the herpes simplex virus thymidine kinase (HSVtk) gene to AFP‐producing hepatocellular carcinoma (HCC) cells.

L Capocaccia, A F Attili, O Riggio – 1 June 1996