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.

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.

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.

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.

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.

Detection of widespread hepatocyte infection in chronic hepatitis C

Vincent Agnello, György Ábel, Glenn B. Knight, Elizabeth Muchmore – 30 December 2003 – The controversial question of the extent of hepatocyte infection in chronic hepatitis C was re‐examined in both chimpanzees and humans using a newly modified in situ hybridization (ISH) method for detecting hepatitis C virus (HCV) RNA. The specificity of the methodology for distinguishing positive‐ and negative‐strand synthetic HCV RNA was at least six magnitudes greater than the reverse‐transcription polymerase chain reaction (RT‐PCR) assay for HCV.

Effects of bile duct ligation on hepatic expression of female‐specific CYP2C12 in male and female rats

Jiezhong Chen, Graham Robertson, Jacqueline Field, Christopher Liddle, Geoffrey C. Farrell – 30 December 2003 – Gender differences in hepatic sex steroid and drug metabolism result from hormonal regulation of specific cytochrome P450 genes (CYP). In male rats, bile duct ligation (BDL) is associated with down‐regulation of the male‐specific genes, CYP2C11 and CYP3A2, together with a decrease in serum testosterone levels and a two‐ to threefold increase in serum estradiol concentrations.

A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients

The Cancer of the Liver Italian Program (Clip) Investigators – 30 December 2003 – The clinical outcome of cirrhotic patients with hepatocellular carcinoma (HCC) depends both on the residual liver function and tumor characteristics. However, the relative prognostic weight of these variables is not well defined. The aims of this study were to verify the value of known prognostic factors and to devise a prognostic index more sensitive than the commonly used Okuda stage. A retrospective analysis of the cases of HCC diagnosed at 16 Italian institutions from 1990 to 1992 was performed.

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