Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees

Marian E. Major, Harel Dahari, Kathleen Mihalik, Montserrat Puig, Charles M. Rice, Avidan U. Neumann, Stephen M. Feinstone – 27 May 2004 – To study determinants of clinical outcome following HCV infection, viral kinetics, immune events, and intrahepatic cytokine markers were compared in 10 naive chimpanzees. Four of the animals cleared HCV; 6 developed persistent infections. All animals developed similar acute infections with increasing viremia from 1 to 2 weeks, followed by alanine aminotransferase (ALT) elevations and seroconversion.

Susceptibility of murine periportal hepatocytes to hypoxia‐reoxygenation: Role for NO and Kupffer cell–derived oxidants

Hisashi Taniai, Ian N. Hines, Sulaiman Bharwani, Ronald E. Maloney, Yuji Nimura, Bifeng Gao, Sonia C. Flores, Joe M. McCord, Matthew B. Grisham, Tak Yee Aw – 27 May 2004 – Ischemia/reperfusion (I/R) is an important problem in liver resection and transplantation that is associated with hepatocellular dysfunction and injury. This study was designed to investigate whether a difference in hepatocyte susceptibility occurs in the periportal (PP) and/or perivenous (PV) zones in response to hypoxia/reoxygenation (H/R), and to delineate the mechanisms underlying this susceptibility.

Plasticity in the adult rat pancreas: Transdifferentiation of exocrine to hepatocyte‐like cells in primary culture

Jessy Lardon, Saskia De Breuck, Ilse Rooman, Leentje Van Lommel, Mogens Kruhøffer, Torben Orntoft, Frans Schuit, Luc Bouwens – 27 May 2004 – Under certain experimental conditions, hepatocytes can arise in the pancreas. It has been suggested that the pancreas retains a source of hepatocyte progenitor cells. However, such cells have not been yet identified in the adult pancreas. We describe here the transdifferentiation of primary rat pancreatic exocrine cells into hepatocyte‐like cells during 5 days of tissue culture in the presence of dexamethasone (DX).

Prediction of liver fibrosis in patients with features of the metabolic syndrome regardless of alcohol consumption

Fabrice Lainé, Claude Bendavid, Romain Moirand, Sabrina Tessier, Michèle Perrin, Anne Guillygomarc'h, Dominique Guyader, Emmanuelle Calon, Alain Renault, Pierre Brissot, Bruno Turlin, Yves Deugnier – 27 May 2004 – The aim of this study was to determine noninvasive predictive factors of significant liver fibrosis in patients with increased serum aminotransferases associated with features of metabolic syndrome (abdominal obesity, systemic hypertension, fasting hyperglycemia, and dyslipidemia). One hundred seventy‐three patients were prospectively examined, regardless of alcohol consumption.

Improvement of rat liver graft quality by pifithrin‐α–mediated inhibition of hepatocyte necrapoptosis

Amr M. El‐Gibaly, Claudia Scheuer, Michael D. Menger, Brigitte Vollmar – 27 May 2004 – Early graft dysfunction due to ischemia reperfusion injury remains a major clinical challenge in liver transplantation. Because apoptosis may contribute to graft dysfunction, we studied whether transient inhibition of p53 is capable of improving graft quality by reducing apoptotic cell death. Rat livers were harvested and stored for 24 hours or 48 hours in a 4°C solution containing either pifithrin‐α (PFT‐α), a specific p53‐inhibitor, or the vehicle dimethyl‐sulfoxide.

Hepatitis B virus X protein is essential for the activation of Wnt/β‐catenin signaling in hepatoma cells

Man‐Young Cha, Chang‐Myeong Kim, Young‐Min Park, Wang‐Shick Ryu – 27 May 2004 – Wnt/β‐catenin signaling contributes to diverse cellular functions, such as Drosophila wing development and colon carcinogenesis. Recently, stabilizing mutations of β‐catenin, a hallmark of Wnt signaling, were documented in significant numbers of primary hepatocellular carcinomas (HCC). However, whether the β‐catenin mutation leads to the activation of Wnt/β‐catenin signaling in hepatoma cells has not been established.

Pegylated interferon α therapy in acute hepatitis C: Relation to hepatitis C virus–specific T cell response kinetics

Sanaa M. Kamal, Alaa Ismail, Camilla S. Graham, Qi He, Jens W. Rasenack, Thomas Peters, Ahmed A. Tawil, Jutta J. Fehr, Khalifa El Sayed Khalifa, Mahmoud M. Madwar, Margaret James Koziel – 27 May 2004 – Pegylated interferon α (PEG IFN‐α) improves sustained virological response rates in chronic hepatitis C, but neither its role in acute hepatitis C nor the biologic basis for its action has been defined.

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