Transcriptional profiling after bile duct ligation identifies PAI‐1 as a contributor to cholestatic injury in mice

Hongtao Wang, Bhupinder P.S. Vohra, Yan Zhang, Robert O. Heuckeroth – 25 October 2005 – Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery.

Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus

Masataka Tsuge, Nobuhiko Hiraga, Hideki Takaishi, Chiemi Noguchi, Hiromi Oga, Michio Imamura, Shoichi Takahashi, Eiji Iwao, Yoshifumi Fujimoto, Hidenori Ochi, Kazuaki Chayama, Chise Tateno, Katsutoshi Yoshizato – 25 October 2005 – Studies of hepatitis B virus (HBV) mutants have been hampered by the lack of a small animal model with long‐term infection of cloned HBV. Using a mouse model in which liver cells were highly replaced with human hepatocytes that survived over a long time with mature human hepatocyte function, we performed transmission experiments of HBV.

Ethanol metabolism alters interferon gamma signaling in recombinant HepG2 cells

Natalia A. Osna, Dahn L. Clemens, Terrence M. Donohue – 25 October 2005 – We previously showed that IFNγ signal transduction was suppressed by ethanol in recombinant HepG2 cells (VL‐17A cells), which express alcohol dehydrogenase (ADH) and CYP2E1. We examined the mechanisms by which STAT1 phosphorylation is blocked by ethanol treatment in VL‐17A cells. Cells were exposed to 0 or 100 mmol/L ethanol for 72 hours. STAT1 phosphorylation was determined by Western blot after 1 hour IFNγ exposure.

Adipokines in NASH: Postprandial lipid metabolism as a link between adiponectin and liver disease

Giovanni Musso, Roberto Gambino, Marilena Durazzo, Giampaolo Biroli, Monica Carello, Emanuela Fagà, Giovanni Pacini, Franco De Michieli, Laura Rabbione, Alberto Premoli, Maurizio Cassader, Gianfranco Pagano – 25 October 2005 – Circulating levels of four adipokines (adiponectin, TNF‐α, leptin, and resistin) and the postprandial lipid and adiponectin responses to an oral fat load were assessed in 25 non‐obese, non‐diabetic patients with biopsy‐proven nonalcoholic steatohepatitis (NASH) and correlated with metabolic indices and liver histology.

Lamivudine plus interleukin‐12 combination therapy in chronic hepatitis B: Antiviral and immunological activity

Eirini I. Rigopoulou, Deepak Suri, Shilpa Chokshi, Ivana Mullerova, Steven Rice, Richard S. Tedder, Roger Williams, Nikolai V. Naoumov – 25 October 2005 – Interleukin‐12 (IL‐12) is an immunomodulatory cytokine that promotes cellular immunity. Pre‐clinical data suggest that IL‐12 inhibits hepatitis B virus (HBV) replication by stimulating interferon‐gamma (IFN‐γ) production.

Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients

Erwin Geuken, Dorien S. Visser, Henri G.D. Leuvenink, Koert P. de Jong, Paul M.J.G. Peeters, Maarten J.H. Slooff, Folkert Kuipers, Robert J. Porte – 25 October 2005 – The adenosine triphosphate (ATP)‐binding cassette (ABC)‐transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content.

Risk factors and comorbidities in primary biliary cirrhosis: A controlled interview‐based study of 1032 patients

M. Eric Gershwin, Carlo Selmi, Howard J. Worman, Ellen B. Gold, Mitchell Watnik, Jessica Utts, Keith D. Lindor, Marshall M. Kaplan, John M. Vierling, USA PBC Epidemiology Group – 25 October 2005 – Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology, often associated with other autoimmune conditions. Controlled studies have so far provided conflicting data on risk factors and comorbidity rates in PBC.

Mannose‐binding lectin in chronic hepatitis B virus infection

Wai Po Chong, Yuk Fai To, Wai Kee Ip, Man Fung Yuen, Tung Ping Poon, Wilfred H.S. Wong, Ching Lung Lai, Yu Lung Lau – 25 October 2005 – Mannose binding lectin (MBL) is a pattern‐recognition molecule of the innate immune system. The roles of MBL and its gene (mbl2) polymorphisms, −221X/Y and codon 54A/B, in hepatitis B virus (HBV) infection were investigated in this study.

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