Defect of multidrug‐resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis

J Deleuze, E Jacquemin, C Dubuisson, D Cresteil, M Dumont, S Erlinger, O Bernard, M Hadchouel – 1 April 1996 – Disruption of the murine mdr2 (multidrug‐resistance) gene, which encodes a phosphatidylcholine flippase, leads to a hepatic disorder because of loss of biliary phospholipid secretion. Among the hereditary human cholestasis, a subtype of progressive familial intrahepatic cholestasis with high gamma‐glutamyltranspeptidase (GGT) serum activity shares histological, biochemical, and genetic features with mice lacking mdr2 gene expression (mdr2 ‐/‐ mice).

Hepatic mucosal mast cell hyperplasia in rats with secondary biliary cirrhosis

K P Rioux, K A Sharkey, J L Wallace, M G Swain – 1 April 1996 – Mast cells have been shown to play a role in many chronic inflammatory and fibrotic disorders. However, their possible contribution to the pathological changes that occur in liver cirrhosis is unknown. To explore this, we examined whether changes in hepatic mast cell number and mediator content were associated with fibrotic changes in experimental biliary cirrhosis. Rats were studied 7, 14, or 21 days after bile duct resection (BDR). Hepatic mast cells were identified by histochemical and immunohistochemical stains.

Etiology, evaluation, and outcome of jaundice in patients with acquired immunodeficiency syndrome

N Chalasani, C M Wilcox – 1 April 1996 – Although liver test abnormalities are frequently identified in patients with acquired immunodeficiency syndrome (AIDS), the causes, evaluation, and outcome of jaundice in these patients have not been systematically evaluated. From August 1, 1990 through September 1, 1994, all human immunodeficiency virus (HIV)‐infected patients with liver test abnormalities seen by the gastroenterology service at a large, inner‐city hospital were prospectively identified. Jaundice was defined as a serum bilirubin concentration ≥ 3 mg/dL.

Alcoholism in hereditary hemochromatosis revisited: Prevalence and clinical consequences among homozygous siblings

P C Adams, S Agnew – 1 April 1996 – The relationship between alcoholism and hereditary hemochromatosis remains controversial. Previous studies have included patients with alcoholic siderosis rather than hereditary hemochromatosis. In this retrospective study, the clinical features, iron status, alcohol history, liver histology, and long‐term survival were reviewed in 105 homozygotes for hemochromatosis using rigid diagnostic criteria including an HLA identical sibling with iron overload. Heavy alcohol consumption (>80 g ethanol/day) was found in 15% of hemochromatosis patients.

Hepatobiliary disposition of valproic acid and valproate glucuronide: Use of a pharmacokinetic model to examine the rate‐limiting steps and potential sites of drug interactions

C L Booth, G M Pollack, K L Brouwer – 1 April 1996 – Previous work in this laboratory has suggested that the nonlinear disposition of valproic acid (VPA) in the rat may be due to nonlinear distribution of VPA into the liver. The present study was undertaken to elucidate further the hepatobiliary disposition of VPA. VPA (0.1‐2 mmol/L) was incubated with isolated rat hepatocytes in vitro. Uptake of [3H]‐VPA was linear from 10 to 50 seconds, with minimal (<7 percent) biotransformation.

Behavior of various cholesterol crystals in bile from patients with gallstones

P Portincasa, K J van Erpecum, A Jansen, W Renooij, M Gadellaa, G P van Berge‐Henegouwen – 1 April 1996 – Besides classical plate‐like cholesterol monohydrate crystals, a variety of crystal shapes have recently been described in model biles but their relevance for human gallstone formation is unknown. We therefore studied crystallization behavior in gallbladder bile from cholesterol stone patients (54 untreated, 13 ursodeoxycholate‐treated) and 6 pigment stone patients.

Nitric oxide is not involved in hepatocyte killing by neutrophils activated by N‐formyl‐methionyl‐leucyl‐phenylalanine or phorbol myristate acetate in vitro

J G Wagner, P E Ganey, R A Roth – 1 April 1996 – Polymorphonuclear leukocytes (PMNS) have been implicated as cellular mediators of hepatic injury in models of inflammation in vivo. In vitro, hepatocyte killing by activated PMNs is mediated in part by proteases, but the role of nitric oxide is unknown. NO is produced by PMNs and hepatocytes and can act either to damage or protect in various models of toxicity. Therefore, we tested the hypothesis that NO is important in PMN‐mediated hepatocyte killing in vitro.

Inhibition of hereditary hepatitis and liver tumor development in Long‐Evans cinnamon rats by the copper‐chelating agent trientine dihydrochloride

K Sone, M Maeda, K Wakabayashi, N Takeichi, M Mori, T Sugimura, M Nagao – 1 April 1996 – Trientine dihydrochloride (trientine) is an alternative medicinal copper chelating agent for patients with Wilson's disease of penicillamine intolerance. We examined the effects of trientine on the spontaneous development of hepatitis and hepatic tumors, by its short‐ term and long‐term administration to Long‐Evans cinnamon (LEC) rats with an accumulation of copper in the liver, as animal models of Wilson's disease.

Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: A multicenter controlled trial

G V Gregorio, P Jara, L Hierro, C Diaz, A de la Vega, A Vegnente, R Iorio, F Bortolotti, C Crivellaro, L Zancan, H Daniels, B Portmann, G Mieli‐Vergani – 1 April 1996 – The comparative efficacy of prednisolone followed by interferon alfa (IFN‐α) versus IFN‐α alone in enhancing the rate of antibody to hepatitis B e antigen (anti‐HBe) seroconversion has not been evaluated in a large cohort of white children.

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