IRS‐2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes

Angela M. Valverde, Isabel Fabregat, Deborah J. Burks, Morris F. White, Manuel Benito – 24 November 2004 – To assess the role of insulin action and inaction in the liver, immortalized hepatocyte cell lines have been generated from insulin receptor substrate (IRS)‐2−/− and wild‐type mice. Using this model, we have recently demonstrated that the lack of IRS‐2 in neonatal hepatocytes resulted in insulin resistance.

Randomized trial of leuprorelin and flutamide in male patients with hepatocellular carcinoma treated with tamoxifen

Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire (GRETCH) – 24 November 2004 – The growth of hepatocellular carcinoma (HCC) is thought to be dependent on androgens, as androgen receptors are present in most of these tumors. The aim of this multicenter trial was to assess the effect of antiandrogens in patients who have advanced HCC. Male patients with advanced HCC were randomized into 2 groups treated with (1) leuprorelin (3.75 mg/mo subcutaneously), flutamide (750 mg/d orally), and tamoxifen (30 mg/d orally) or (2) tamoxifen alone (30 mg/d orally) administered until death.

Comparison of adefovir and tenofovir in the treatment of lamivudine‐resistant hepatitis B virus infection

Florian van Bömmel, Thomas Wünsche, Stefan Mauss, Petra Reinke, Alexandra Bergk, Dirk Schürmann, Bertram Wiedenmann, Thomas Berg – 24 November 2004 – Adefovir dipivoxil was recently approved for the treatment of wild‐type and lamivudine‐resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine‐resistant HBV infection.

Transcription factor HNF‐6/OC‐1 inhibits the stimulation of the HNF‐3α/Foxa1 gene by TGF‐β in mouse liver

Nicolas Plumb‐Rudewiez, Frédéric Clotman, Hélène Strick‐Marchand, Christophe E. Pierreux, Mary C. Weiss, Guy G. Rousseau, Frédéric P. Lemaigre – 24 November 2004 – A network of liver‐enriched transcription factors controls differentiation and morphogenesis of the liver. These factors interact via direct, feedback, and autoregulatory loops. Previous work has suggested that hepatocyte nuclear factor (HNF)‐6/OC‐1 and HNF‐3α/FoxA1 participate coordinately in this hepatic network. We investigated how HNF‐6 controls the expression of Foxa1.

Inhibition of T‐cell responses by hepatic stellate cells via B7‐H1–mediated T‐cell apoptosis in mice

Ming‐Chin Yu, Cheng‐Hsu Chen, Xiaoyan Liang, Lianfu Wang, Chandrashekhar R. Gandhi, John J. Fung, Lina Lu, Shiguang Qian – 24 November 2004 – In the injured liver, hepatic stellate cells (HSCs) secrete many different cytokines, recruit lymphocytes, and thus participate actively in the pathogenesis of liver disease. Little is known of the role of HSCs in immune responses. In this study, HSCs isolated from C57BL/10 (H2b) mice were found to express scant key surface molecules in the quiescent stage.

Low‐grade steatosis and major changes in portal flow as new prognostic factors in steroid‐treated alcoholic hepatitis

Christophe Duvoux, Catherine Radier, Françoise Roudot‐Thoraval, François Maille, Marie‐Christine Anglade, Jeanne Tran Van Nhieu, Isabelle Rosa, Sylvie Hospitel, Issam Abd‐Alsamad, Véronique Sitruk, Olivier Seror, Marianne Ziol, Hughes Blondon, Daniel Dhumeaux, Jean‐Philippe Richardet – 24 November 2004 – The aim of this study was to assess the prevalence and prognostic value of major alterations of portal flow in patients with steroid‐treated alcoholic hepatitis. Fifty patients with severe, histologically proven alcoholic hepatitis were enrolled.

Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity

Jeffrey D. Browning, Lidia S. Szczepaniak, Robert Dobbins, Pamela Nuremberg, Jay D. Horton, Jonathan C. Cohen, Scott M. Grundy, Helen H. Hobbs – 24 November 2004 – Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), its pathogenesis and clinical significance remain poorly defined. In this study, we examined and compared the distribution of hepatic triglyceride content (HTGC) in 2,287 subjects from a multiethnic, population‐based sample (32.1% white, 48.3% black, and 17.5% Hispanic) using proton magnetic resonance spectroscopy.

Transplantation of bone marrow cells reduces CCl4‐induced liver fibrosis in mice

Isao Sakaida, Shuji Terai, Naoki Yamamoto, Koji Aoyama, Tsuyoshi Ishikawa, Hiroshi Nishina, Kiwamu Okita – 24 November 2004 – We investigated the effect of bone marrow cell (BMC) transplantation on established liver fibrosis. BMCs of green fluorescent protein (GFP) mice were transplanted into 4‐week carbon tetrachloride (CCl4)–treated C57BL6 mice through the tail vein, and the mice were treated for 4 more weeks with CCl4 (total, 8 weeks).

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