The effects of FR167653 in extended liver resection with ischemia in dogs

Junya Kobayashi, Izumi Takeyoshi, Susumu Ohwada, Kotaro Iwanami, Koshi Matsumoto, Minoru Muramoto, Yasuo Morishita – 30 December 2003 – Interleukin‐1 (IL‐1) and tumor necrosis factor (TNF) are cytokines commonly associated with inflammatory conditions such as hepatic injury after ischemia‐reperfusion. FR167653 has been characterized as a potent suppressant of IL‐1β and TNF‐α production. In this study, we evaluated the effect of FR167653 in an extended liver resection with ischemia in a dog model.

Liver transplantation for adult polycystic liver disease

Kim Swenson, Philip Seu, Milan Kinkhabwala, Melinda Maggard, Paul Martin, John Goss, Ronald Busuttil – 30 December 2003 – Polycystic liver disease, commonly associated with polycystic kidney disease, can result in massive hepatomegaly and debilitating symptoms. Surgical intervention for symptomatic polycystic liver disease has been associated with significant morbidity and inconsistent long‐term palliation; it is more appropriate in patients with a single dominant cyst or cysts which is/are confined to one lobe.

Noncirrhotic portal hypertension and nodular regenerative hyperplasia of the liver in dogs with mucopolysaccharidosis type I

Michael F. McEntee, Kathy N. Wright, Ian Wanless, Robert DeNovo, John F. Schneider, Robert Shull – 30 December 2003 – Nodular regenerative hyperplasia (NRH) is an uncommon hepatic lesion often associated with noncirrhotic portal hypertension (PHT). We have noted that NRH and PHT are frequent occurrences in a colony of dogs with the genetic storage disease, mucopolysaccharidosis I (MPS‐I). This observation provides the opportunity to study the histology and pathogenesis of NRH and noncirrhotic PHT in a new animal model.

Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

Anne Fournillier, Isao Nakano, Ludmila Vitvitski, Erik Depla, Olivier Vidalin, Geert Maertens, Christian Trépo, Genevieve Inchauspé – 30 December 2003 – Different delivery routes of plasmid DNA may result in the induction of differential humoral and cellular immunity. We have studied the influence of two main routes of plasmid injection, performed intramuscularly and intraepidermally using a gene gun, for the induction of immune responses specific to hepatitis C virus (HCV) envelope protein E2.

Protein phosphatase inhibition in normal and keratin 8/18 assembly–incompetent mouse strains supports a functional role of keratin intermediate filaments in preserving hepatocyte integrity

Diana M. Toivola, M. Bishr Omary, Nam‐on Ku, Olli Peltola, Hélène Baribault, John E. Eriksson – 30 December 2003 – The function and regulation of keratin 8 (K8) and 18 (K18), intermediate filament (IF) proteins of the liver, are not fully understood. We employed the liver damage induced by microcystin‐LR (MC‐LR), a liver‐specific inhibitor of type‐1 and type‐2A protein phosphatases, in normal and in keratin assembly–incompetent mouse strains as a model to elucidate the roles of IF phosphorylation in situ.

Role of alcohol in the progression of liver disease caused by hepatitis C virus infection

George Ostapowicz, Katrina J. Watson, Stephen A. Locarnini, Paul V. Desmond – 30 December 2003 – In patients with chronic hepatitis C, alcohol consumption has been proposed as a risk factor for the progression of liver disease; however, evidence for this remains conflicting. Two hundred thirty‐four anti–hepatitis C virus (HCV)–positive patients who had a liver biopsy performed within the past 24 months were studied. Demographic data and information on risk factors were recorded. A detailed lifetime alcohol consumption history was obtained.

Delayed fas‐mediated hepatocyte apoptosis during liver regeneration in mice: hepatoprotective role of TNFα

Tetsuo Takehara, Norio Hayashi, Eiji Mita, Tatsuya Kanto, Tomohide Tatsumi, Yutaka Sasaki, Akinori Kasahara, Masatsugu Hori – 30 December 2003 – Fas‐mediated apoptosis is one of the major death processes of hepatocytes in liver diseases. Although compensatory regeneration occurs during liver injury, it has not been determined whether regenerating hepatocytes die by the same apoptotic process as quiescent hepatocytes.

Hepatic stellate cells are not subjected to oxidant stress during iron‐induced fibrogenesis in rodents

Giuliana Montosi, Cinzia Garuti, Sabrina Martinelli, Antonello Pietrangelo – 30 December 2003 – Oxidant stress plays a key role in hepatic fibrogenesis. This study was undertaken to assess whether, during iron overload–associated liver fibrosis ain vivo, oxidant stress occurs in hepatic stellate cells (HSC) during active fibrogenesis. Gerbils were treated with iron‐dextran, and, after hepatic fibrosis developed, livers were subjected to various combination of in situ hybridization and immunocytochemistry analyses.

Characterization of the IGF axis components in isolated rat hepatic stellate cells

Jens‐Gerd Scharf, Thomas Knittel, Frank Dombrowski, Lars Müller, Bernhard Saile, Thomas Braulke, Heinz Hartmann, Giuliano Ramadori – 30 December 2003 – The insulin‐like growth factors I and II (IGF‐I, ‐II) are circulating peptides known to participate in the regulation of metabolism, growth, and cellular differentiation. In the present study, “early cultured” (days 2‐3 of culture) and “culture‐activated” (days 6‐7 of culture) rat hepatic stellate cells (HSCs) were analyzed for expression of individual components of the IGF axis.

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