Inhibition of rat hepatocyte proliferation by transforming growth factor β and glucagon is associated with inhibition of ERK2 and p70 S6 kinase

Mark Dixon, Loranne Agius, Stephen J. Yeaman, Christopher P. Day – 30 December 2003 – Stimulation of hepatocyte proliferation by epidermal growth factor (EGF) and insulin is inhibited by transforming growth factor β (TGF‐β) and by glucagon. It is also suppressed by inhibitors of various protein kinases, including rapamycin, which blocks activation of p70 S6 kinase (p70S6k), PD98059, which inhibits the activation of extracellular‐regulated kinase (ERK), and SB 203580, an inhibitor of the p38 mitogen‐activated protein kinase (p38 MAPK).

Delineation of a novel hepatic route for the selective transfer of unesterified sterols from high‐density lipoproteins to bile: Studies using the perfused rat liver

Sander J. Robins, Joan M. Fasulo – 30 December 2003 – Cholesterol is principally excreted from the body in bile as unesterified cholesterol (UC). Using the unesterified plant sterol, sitostanol (SIT), as a nonexchangeable analog for UC, we have found that high‐density lipoproteins (HDL), but not low‐density lipoproteins, provide a vehicle for the direct delivery of cholesterol to bile.

Macronutrient preference, dietary intake, and substrate oxidation among stable cirrhotic patients

H. Isobel Davidson, Rosemary Richardson, Donald Sutherland, O. James Garden – 30 December 2003 – Anorexia in liver disease is common; however, its association with aberrant metabolism and the type of cirrhosis has not been considered. Dietary intake, nutritional status, fasting substrate oxidation, and macronutrient preference were examined in controls (n = 18) and 65 patients with hepatocellular (n = 31) or biliary cirrhosis (n = 34).

Three cases of severe subfulminant hepatitis in heart‐transplanted patients after nosocomial transmission of a mutant hepatitis B virus

Lieven Stuyver, Sija De Gendt, Jean Fran Cadranel, Caroline Van Geyt, Georges Van Reybroeck, Richard Dorent, Iranj Gandjbachkh, Michel Rosenheim, Frederic Charlotte, Pierre Opolon, Jean Marie Huraux, Françoise Lunel – 30 December 2003 – Fulminant and severe viral hepatitis are frequently associated with mutant hepatitis B virus (HBV) strains. In this study, the genetic background of a viral strain causing severe subfulminant outcome in heart‐transplanted patients was studied and compared with viral hepatitis B strains that were not linked to severe liver disease in the same setting.

Effects of iron loading on pathogenicity in hepatitis C virus–infected chimpanzees

Suzanne E. Bassett, Adrian M. Di Bisceglie, Bruce R. Bacon, R. Mark Sharp, Sugantha Govindarajan, Gene B. Hubbard, Kathleen M. Brasky, Robert E. Lanford – 30 December 2003 – Elevated iron levels have been associated with raised serum alanine transaminase (ALT) levels in hepatitis C virus (HCV)‐infected humans. However, it is not clear if HCV infection causes increased iron accumulation by the liver or if the severity of HCV infection is actually worsened by higher iron levels in the host.

Interferon alfa receptor expression and growth inhibition by interferon alfa in human liver cancer cell lines

Hirohisa Yano, Akihiro Iemura, Makoto Haramaki, Sachiko Ogasawara, Akiko Takayama, Jun Akiba, Masamichi Kojiro – 30 December 2003 – Type I interferon (IFN) receptor consists of two chains (Hu‐IFN‐αR1 and Hu‐IFN‐αR2), and Hu‐IFN‐αR2 takes a soluble (Hu‐IFN‐αR2a), short (Hu‐IFN‐αR2b), or long (Hu‐IFN‐αR2c) form. We examined the expression of type I IFN receptor, the growth‐suppression effect of IFN‐α, and their relationship in 13 liver cancer cell lines.

Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood

Eva‐Maria Wolber, Rainer Ganschow, Martin Burdelski, Wolfgang Jelkmann – 30 December 2003 – The liver is the main production site of the hormone thrombopoietin (TPO), the major regulator of megakaryopoiesis. To investigate the role of an impaired TPO gene expression in the pathogenesis of thrombocytopenia in pediatric patients suffering from liver failure, we measured hepatic TPO mRNA in children with acute or chronic end‐stage liver disease undergoing orthotopic liver transplantation.

Expression of delta F508 cystic fibrosis transmembrane conductance regulator protein and related chloride transport properties in the gallbladder epithelium from cystic fibrosis patients

Nathalie Dray‐Charier, Annick Paul, Jean‐Yves Scoazec, Danielle Veissière, Martine Mergey, Jacqueline Capeau, Olivier Soubrane, Chantal Housset – 30 December 2003 – Cystic fibrosis transmembrane conductance regulator (CFTR), the cystic fibrosis (CF) gene product, functions as an adenosine 3′,5′‐cyclic monophosphate (cAMP)‐regulated chloride channel in the apical membrane of biliary epithelial cells, including gallbladder epithelial cells. It has been shown that ▵F508, the most common CF mutation, impedes CFTR trafficking to the apical surface of epithelial cells.

Genetic aberrations detected by comparative genomic hybridization in hepatocellular carcinomas: Their relationship to clinicopathological features

Noriyoshi Kusano, Kei Shiraishi, Keiko Kubo, Atsunori Oga, Kiwamu Okita, Kohsuke Sasaki – 30 December 2003 – To elucidate cytogenetic alterations underlying human hepatocellular carcinomas (HCCs), we used a comparative genomic hybridization (CGH) method to analyze 41 cases of hepatocellular carcinoma (HCC) including 15 well differentiated HCCs, 14 moderately differentiated HCCs, and 12 poorly differentiated HCCs. Of these, 27 patients were chronically infected with hepatitis C virus (HCV), and the remaining patients were positive for hepatitis B virus (HBV).

Regulation of hepatic transport systems involved in bile secretion during liver regeneration in rats

Thera A. Vos, Jenny E. Ros, Rick Havinga, Han Moshage, Folkert Kuipers, Peter L. Jansen, Michael Müller – 30 December 2003 – We investigated the expression of hepatic transport systems involved in bile secretion during liver regeneration after partial hepatectomy (PH) in rats. Initial studies showed maximal BrdU incorporation 24 hours after PH. Therefore, transporter expression and bile secretion were analyzed in detail at this time. The mRNA levels of the multidrug resistance genes mdr1a andmrp1 slightly increased, whereas mdr1b mRNA levels showed an extensive increase after PH.

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