Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma

K Kurokohchi, M Carrington, D L Mann, T B Simonis, M A Alexander‐Miller, S M Feinstone, T Akatsuka, J A Berzofsky – 1 May 1996 – The expression of the HLA class I molecules on the cell surface was investigated in hepatocellular carcinoma (HCC) cell lines using complement‐mediated cytotoxicity (CMC) and flow cytometric analysis. Although HLA‐A antigens were detected by CMC in all cell lines tested, HLA‐B and ‐C antigens were not detectable in six of seven HCC cell lines. These results were also confirmed by flow cytometric analysis focusing on HLA‐Bw4 and Bw6 public antigens.

Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis

G S Baroni, L D'Ambrosio, P Curto, A Casini, R Mancini, A M Jezequel, A Benedetti – 1 May 1996 – Interferon gamma (IFN‐γ) inhibits in vitro the activation of hepatic stellate cells (HSC), the primary extracellular matrix‐producing cells in liver fibrosis. This study was undertaken to determine in vivo the effect of IFN‐γ in the rat model of liver fibrosis induced by dimethylnitrosamine (DMN), where HSC activation represents an early response to cell injury. Rats were killed after 1 or 3 weeks of treatment with DMN, IFN‐γ, DMN + IFN‐γ, or saline.

Ultracentrifugation systematically overestimates vesicular cholesterol levels in bile

P K Yuet, D Blankschtein, J M Donovan – 1 April 1996 – To accurately determine the cholesterol (Ch) distribution between mixed micelles and vesicles in lithogenic bile, both ultracentrifugation and gel chromatography with the correct intermixed micellar/vesicular bile salt concentration (IMC) have been proposed. We have systematically compared both separation techniques with physiological model biles to ascertain their quantitative separation ability.

Intrahepatic hepatitis C RNA levels do not correlate with degree of liver injury in patients with chronic hepatitis C

P H McGuinness, G A Bishop, D M Painter, R Chan, G W McCaughan – 1 April 1996 – The balance between a direct cytopathic effect by hepatitis C virus (HCV) and immune‐mediated injury remains unclear. This report aims to test the following hypotheses: (1) that intrahepatic HCV load would correlate with the degree of liver injury; (2) that interferon alfa (IFN‐α) would decrease intrahepatic HCV‐RNA levels. Liver tissues (n = 56) were obtained from 47 patients with chronic HCV (9 before and after IFN‐α therapy).

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.

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.

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.

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.

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.

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