Inhibition of rat liver fibrogenesis through noradrenergic antagonism

Liliane Dubuisson, Alexis Desmoulière, Boris Decourt, Laetitia Evadé, Christiane Bedin, Liliane Boussarie, Laurence Barrier, Michel Vidaud, Jean Rosenbaum – 30 December 2003 – The effect of adrenergic innervation and/or circulating catecholamines on the function of liver fibrogenic cells is poorly understood. Our aim was to investigate the effects of noradrenergic antagonism on carbon tetrachloride (CCl4)‐induced liver fibrosis in rats. Two weeks of CCl4 induced a ∼5‐fold increase in the area of fibrosis as compared with controls.

A20 protects mice from D‐galactosamine/lipopolysaccharide acute toxic lethal hepatitis

Maria B. Arvelo, Jeffrey T. Cooper, Christopher Longo, Soizic Daniel, Shane T. Grey, Jerome Mahiou, Eva Czismadia, Graziella Abu‐Jawdeh, Christiane Ferran – 30 December 2003 – Apoptosis of hepatocytes is a seminal feature of fulminant hepatic failure. We show that the anti‐apoptotic protein A20 is upregulated in hepatocytes by pro‐inflammatory stimuli and functions to protect from apoptosis and limit inflammation by inhibiting NF‐κB.

Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications

Sheng‐Chieh Hsu, Wan‐Jr Syu, I‐Jane Sheen, Hui‐Ting Liu, King‐Song Jeng, Jaw‐Ching Wu – 30 December 2003 – The mechanisms that link genotypes of hepatitis D virus (HDV) with clinical outcomes have not yet been elucidated. Genotypic variations are unevenly distributed along the sequences of hepatitis delta antigens (HDAgs). Of these variations, the packaging signal at the C‐terminus has a divergence of 74% between genotypes I and II.

Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa‐2b plus ribavirin

Maria Buti, Francisco Sanchez‐Avila, Yoav Lurie, Carlos Stalgis, Auristela Valdés, Maria Martell, Rafael Esteban – 30 December 2003 – Pegylated interferon (peginterferon) alfa‐2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa‐2b and ribavirin in 55 patients.

The resistance of P. acnes–primed interferon γ–deficient mice to low‐dose lipopolysaccharide‐induced acute liver injury

Yoshiaki Shimizu, Julie A. Margenthaler, Keith Landeros, Naoki Otomo, Gerard Doherty, M. Wayne Flye – 30 December 2003 – Endotoxin has been identified as a principal mediator of sepsis, often with resulting multiple organ failure. Although interferon γ (IFN‐γ) has a central role in controlling bacterial infection through the activation of macrophages and T lymphocytes, it can also enhance the harmful effects of the inflammatory response.

NF‐κB inhibition sensitizes hepatocytes to TNF‐induced apoptosis through a sustained activation of JNK and c‐Jun

Hailing Liu, Chau R. Lo, Mark J. Czaja – 30 December 2003 – Hepatocyte resistance to tumor necrosis factor α (TNF)‐induced apoptosis is dependent on activation of the transcription factor nuclear factor κB (NF‐κB). To determine the mechanism by which NF‐κB protects against TNF toxicity, the effect of NF‐κB inactivation on the proapoptotic c‐Jun NH2‐terminal kinase (JNK) signaling pathway was examined in the rat hepatocyte cell line RALA255‐10G.

Synergistic effect of basic fibroblast growth factor and vascular endothelial growth factor in murine hepatocellular carcinoma

Hitoshi Yoshiji, Shigeki Kuriyama, Junichi Yoshii, Yasuhide Ikenaka, Ryuichi Noguchi, Daniel J. Hicklin, James Huber, Toshiya Nakatani, Hirohisa Tsujinoue, Koji Yanase, Hiroo Imazu, Hiroshi Fukui – 30 December 2003 – The growth of any solid tumor depends on angiogenesis. Among the known angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), are potent and representative factors involved in tumor development. It has been reported that bFGF and VEGF showed a synergistic effect in both in vitro and in vivo angiogenesis.

M6P/IGF2R tumor suppressor gene mutated in hepatocellular carcinomas in Japan

Yoshihiko Oka, Robert A. Waterland, J. Keith Killian, Catherine M. Nolan, Hong‐Seok Jang, Keiji Tohara, Seigo Sakaguchi, Tsuneyoshi Yao, Akinori Iwashita, Yutaka Yata, Terumi Takahara, Shin‐ichiro Sato, Kazuyuki Suzuki, Tomoyuki Masuda, Randy L. Jirtle – 30 December 2003 – Mannose 6‐phosphate/insulin‐like growth factor II receptor (M6P/IGF2R) tumor suppressor– gene mutation is an early event in human hepatocellular carcinoma (HCC) formation in the United States, but its role in hepatocarcinogenesis in Japan is unclear.

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