Endotoxin‐induced mortality in bile duct—ligated rats after administration of reconstituted high‐density lipoprotein

Miguel E. Sewnath, Han H. M. Levels, Ronald Oude Elferink, Cornelis J. F. van Noorden, Fiebo J. W. ten Kate, Sander J. H. van Deventer, Dirk J. Gouma – 30 December 2003 – Cholestatic patients have substantial morbidity because of increased susceptibility to endotoxin (lipopolysaccharide [LPS]). Although reconstituted high‐density lipoprotein (rHDL) can bind and neutralize LPS, cholestasis is associated with a near complete absence of HDL. Effects of rHDL infusion on the outcome of LPS‐induced inflammatory responses in cholestatic rats were determined.

Risk factors for recurring hepatocellular carcinoma differ according to infected hepatitis virus—An analysis of 236 consecutive patients with a single lesion

Yukihiro Koike, Yasushi Shiratori, Shinpei Sato, Shuntaro Obi, Takuma Teratani, Masatoshi Imamura, Keisuke Hamamura, Yasuo Imai, Haruhiko Yoshida, Shuichiro Shiina, Masao Omata – 30 December 2003 – Patients with hepatocellular carcinoma (HCC) frequently experience intrahepatic HCC recurrence even after complete ablation of primary lesions. Because the oncogenic process may be different for hepatitis B viral (B‐viral) and hepatitis C viral (C‐viral) HCC, the present study was conducted to elucidate the factors contributing to HCC recurrence with respect to the infected hepatitis virus.

Retroviral gene transfer of signaling molecules into murine fetal hepatocytes defines distinct roles for the STAT3 and ras pathways during hepatic development

Yoshiaki Ito, Takaaki Matsui, Akihide Kamiya, Taisei Kinoshita, Atsushi Miyajima – 30 December 2003 – We recently demonstrated that oncostatin M (OSM) in the presence of glucocorticoid promotes development of fetal hepatic cells in a primary culture system. Our results also suggested that OSM transduces differentiation signals through gp130, a common subunit of the interleukin (IL)‐6 family cytokine receptors. However, an essential downstream pathway required for hepatic development remains unknown.

Pathophysiologic importance of E‐ and L‐selectin for neutrophil‐induced liver injury during endotoxemia in mice

Judy A. Lawson, Alan R. Burns, Anwar Farhood, Mary Lynn Bajt, Robert G. Collins, C. Wayne Smith, Hartmut Jaeschke – 30 December 2003 – Neutrophils can cause parenchymal cell injury in the liver during ischemia‐reperfusion and endotoxemia. Neutrophils relevant for the injury accumulate in sinusoids, transmigrate, and adhere to hepatocytes. To investigate the role of E‐ and L‐selectin in this process, C3Heb/FeJ mice were treated with 700 mg/kg galactosamine and 100 μg/kg endotoxin (Gal/ET).

Protein kinase activation by warm and cold hypoxia‐reoxygenation in primary‐cultured rat hepatocytes–JNK1/SAPK1 involvement in apoptosis

Dominique Crenesse, Jean Gugenheim, Joelle Hornoy, Karine Tornieri, Marina Laurens, Beatrice Cambien, Gaelle Lenegrate, Rafaele Cursio, Georges De Souza, Patrick Auberger, Catherine Heurteaux, Bernard Rossi, Annie Schmid‐Alliana – 30 December 2003 – Ischemia‐reperfusion procedures induced severe hepatic damages owing to different processes related to hypoxia and reoxygenation (H/R) phases, including the consecutive oxygen free radical (OFR) release. Stress‐activated protein kinases (SAPKs) could be activated by extracellular stimuli.

Transforming growth factor‐β induces apoptosis in rat FaO hepatoma cells via cytochrome c Release and oligomerization of Apaf‐1 to form a ∼700‐kd apoptosome caspase–processing complex

Caroline Freathy, David G. Brown, Ruth A. Roberts, Kelvin Cain – 30 December 2003 – In mammalian cells, non receptor‐mediated apoptosis occurs via the cytochrome c–dependent assembly of a ∼700‐kd apoptotic protease‐activating factor 1 (Apaf‐1)/caspase‐9 containing apoptosome complex. This initiates the postmitochondrial‐mediated effector caspase cascade. We now show that receptor mediated transforming growth factor β1(TGF‐β1)–induced apoptosis in rat hepatoma cells is accompanied by processing and activation of caspases‐2, ‐3, ‐7, and ‐8.

A Dose‐Ranging Study of Pegylated Interferon Alfa‐2b and Ribavirin in Chronic Hepatitis C

Paul Glue, Regine Rouzier‐Panis, Claude Raffanel, Ron Sabo, Samir K. Gupta, Margaret Salfi, Shiela Jacobs, Robert P. Clement – 30 December 2003 – The objectives of this study were to assess the safety, pharmacokinetics, and efficacy of pegylated interferon alfa‐2b (PEG‐Intron) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20‐68 years) with clinically compensated chronic hepatitis C virus (HCV) were enrolled into this open‐label, randomized, active controlled study.

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