Mitochondrial permeability transition in acetaminophen‐induced necrosis and apoptosis of cultured mouse hepatocytes

Kazuyoshi Kon, Jae‐Sung Kim, Hartmut Jaeschke, John J. Lemasters – 14 October 2004 – Acetaminophen overdose causes massive hepatic failure via mechanisms involving glutathione depletion, oxidative stress, and mitochondrial dysfunction. The ultimate target of acetaminophen causing cell death remains uncertain, and the role of apoptosis in acetaminophen‐induced cell killing is still controversial. Our aim was to evaluate the mitochondrial permeability transition (MPT) as a key factor in acetaminophen‐induced necrotic and apoptotic killing of primary cultured mouse hepatocytes.

Occult hepatitis B virus infection in a North American adult hemodialysis patient population

Gerald Y. Minuk, Dong Feng Sun, Rebecca Greenberg, Manna Zhang, Kimberly Hawkins, Julia Uhanova, Adam Gutkin, Kevin Bernstein, Antonio Giulivi, Carla Osiowy – 14 October 2004 – Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units. A possible contributing factor is the presence of occult HBV (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty‐one adult hemodialysis patients were screened for occult HBV.

Can Turner syndrome teach us about the pathogenesis of chronic cholestasis?

Piotr Milkiewicz, Jenny Heathcote – 14 October 2004 – The mechanisms that cause the female predominance of primary biliary cirrhosis (PBC) are uncertain, but the X chromosome includes genes involved in immunological tolerance. We assessed the rate of X monosomy in peripheral white blood cells from 100 women with PBC, 50 with chronic hepatitis C, and 50 healthy controls, by fluorescence in‐situ hybridisation.

Leflunomide protects from T‐cell–mediated liver injury in mice through inhibition of nuclear factor κB

Motoaki Imose, Masahito Nagaki, Kiminori Kimura, Shinji Takai, Motohiro Imao, Takafumi Naiki, Yosuke Osawa, Takahiko Asano, Hideki Hayashi, Hisataka Moriwaki – 28 September 2004 – Leflunomide is a novel immunosuppressive and anti‐inflammatory agent for the treatment of autoimmune disease. The aim of this study was to investigate whether leflunomide protects from liver injury induced by concanavalin A (Con A), a T‐cell–dependent model of liver damage. BALB/c mice were injected with 25 mg/kg Con A in the presence or absence of 30 mg/kg leflunomide.

Intact signaling by transforming growth factor β is not required for termination of liver regeneration in mice

Shoshiro Oe, Eric R. Lemmer, Elizabeth A. Conner, Valentina M. Factor, Per Levéen, Jonas Larsson, Stefan Karlsson, Snorri S. Thorgeirsson – 22 September 2004 – Transforming growth factor β (TGF‐β) is a potent inhibitor of hepatocyte proliferation in vitro and is suggested to be a key negative regulator of liver growth.

Antifibrotic effects of a tissue inhibitor of metalloproteinase‐1 antibody on established liver fibrosis in rats

Christopher J. Parsons, Blair U. Bradford, Clark Q. Pan, Ellen Cheung, Michael Schauer, Andreas Knorr, Barbara Krebs, Sabine Kraft, Stefan Zahn, Bodo Brocks, Nikki Feirt, Baisong Mei, Myung‐Sam Cho, Roopa Ramamoorthi, Greg Roldan, Paul Ng, Peggy Lum, Claudia Hirth‐Dietrich, Adrian Tomkinson, David A. Brenner – 22 September 2004 – Liver fibrosis is characterized by increased synthesis, and decreased degradation, of extracellular matrix (ECM) within the injured tissue.

Opioid receptor blockade reduces Fas‐induced hepatitis in mice

Martial Jaume, Sébastien Jacquet, Pierre Cavaillès, Gaëtane Macé, Lionel Stephan, Catherine Blanpied, Cécile Demur, Pierre Brousset, Gilles Dietrich – 22 September 2004 – Fas (CD95)‐induced hepatocyte apoptosis and cytotoxic activity of neutrophils infiltrating the injured liver are two major events leading to hepatitis. Because it has been reported that opioids, via a direct interaction, sensitize splenocytes to Fas‐mediated apoptosis by upregulating Fas messenger RNA (mRNA) and modulated neutrophil activity, we assumed that opioids may participate in the pathophysiology of hepatitis.

A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations

Scott T. Magness, Ramón Bataller, Liu Yang, David A. Brenner – 22 September 2004 – Activation of hepatic stellate cells (HSCs) and other resident mesenchymal cells into myofibroblasts expressing alpha smooth muscle actin (αSMA) and collagen I is a key event in liver fibrogenesis. However, the temporal expression profiles of αSMA and collagen I genes in these cells is unknown.

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era

Kim M. Olthoff, Robert S. Brown, Francis L. Delmonico, Richard B. Freeman, Sue V. McDiarmid, Robert M. Merion, J. Michael Millis, John P. Roberts, Abraham Shaked, Russell H. Wiesner, Michael R. Lucey – 21 September 2004 – A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses.

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