Mitogen‐activated protein kinase activation in hepatocyte growth factor–stimulated rat hepatocytes: Involvement of protein tyrosine kinase and protein kinase C

T Adachi, S Nakashima, S Saji, T Nakamura, Y Nozawa – 1 May 1996 – Hepatocyte growth factor (HGF) stimulated mitogen‐activated protein (MAP) kinases and MAP kinase kinase in primary cultured rat hepatocytes. Inhibitors for protein kinase C (PKC), Ro31‐8425, H‐7, and calphostin C, reduced HGF‐induced MAP kinase activity. A PKC activator, phorbol myristate acetate (PMA), induced MAP kinase activation in a concentration‐dependent manner. Protein tyrosine kinase (PTK) inhibitors, genistein, and ST638 also inhibited HGF‐induced MAP kinase activation.

Localization of α2‐macroglobulin protein and messenger RNA in rat liver fibrosis: Evidence for the synthesis of α2‐macroglobulin within Schistosoma mansoni egg granulomas

A M Tiggelman, W Boers, A F Moorman, P A J de Boer, C M Van der Loos, J P Rotmans, R A Chamuleau – 1 May 1996 – α2‐Macroglobulin (α2M) in the rat is a strong‐reacting acute‐phase protein with potent protease‐inhibiting and cytokine‐binding properties. Production of α2M is ascribed mainly to liver parenchymal cells. In the present study, we investigated, by means of immunohistochemistry and in situ hybridization, whether fibrosis in the rat liver induced by Schistosoma mansoni eggs leads to local production of α2M.

Hepatitis C virus genotypes, hepatitis, and hepatitis C virus recurrence after liver transplantation

Luca S. Belli, Enrico Silini, Alberto Alberti, Giorgio Bellati, Claudio Vai, Ernesto Minola, Gianfranco Rondinara, Luciano De Carlis, Margherita Asti, Domenico Forti, Gaetano Ideo – 1 May 1996 – Several genotypes of hepatitis C virus (HCV) have been recently identified by phylogenetic analysis, but their clinical relevance in the liver transplant setting is unknown. We evaluated the incidence and course of recurrent hepatitis C after transplantation in 50 patients who underwent transplantation for HCV‐related liver disease.

Regeneration of a transplanted liver after right hepatic lobectomy

Ravi S. Chari, Mark E. Baker, Sean R. Sue, William C. Meyers – 1 May 1996 – Liver regeneration has been described after heterotopic liver transplantation, small‐for‐size orthotopic liver transplantation and reduced‐size liver transplantation. In this report, we document the regenerative response of a whole liver transplant to major resection for the first time. A right hepatic lobectomy for liver ischemia was performed in a 30‐year‐old female after transplantation for autoimmune disease of the liver.

Liver‐targeted antiviral nucleosides: Enhanced antiviral activity of phosphatidyl‐dideoxyguanosine versus dideoxyguanosine in woodchuck hepatitis virus infection in vivo

B A Korba, H Xie, K N Wright, W E Hornbuckle, J L Gerin, B C Tennant, K Y Hostetler – 1 May 1996 – It would be desirable to develop antiviral agents that can be targeted to liver to enhance their antiviral effects and reduce nonhepatic toxicity. 2′,3′‐Dideoxyguanosine (ddG) has been found to be a potent and selective antihepatitis B agent both in vitro and in vivo. To evaluate ddG and its liver‐targeted analog, we synthesized a series of phosphatidyl‐ddGs and incubated them with 2.2.15 cells, which chronically produce hepatitis B virus.

Absence of the canalicular isoform of the MRP gene–encoded conjugate export pump from the hepatocytes in Dubin‐Johnson syndrome

J Kartenbeck, U Leuschner, R Mayer, D Keppler – 1 May 1996 – The Dubin‐Johnson syndrome is characterized by an inherited defect in the secretion of amphiphilic anionic conjugates from hepatocytes into the bile. We have recently identified the membrane protein mediating the adenosine triphosphate (ATP)‐dependent transport of glutathione and glucuronate conjugates as a multidrug‐resistance protein (MRP) and localized it to the canalicular as well as to the lateral hepatocyte plasma membrane.

Biliary malignancies in primary sclerosing cholangitis: Timing for liver transplantation

B Nashan, H J Schlitt, G Tusch, K J Oldhafer, B Ringe, S Wagner, R Pichlmayr – 1 May 1996 – Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease associated in 10% to 36% of those with hepatobiliary malignancies, which are, in the majority of cases, not known prior to transplantation. Diagnosis of carcinomas in a PSC setting at an early stage has not yet been achieved, because there are no differences in the age of patients or clinical course, particularly with regard to the time between diagnosis of PSC and detection of carcinomas.

Inhibitory actions of cyclic adenosine monophosphate and pertussis toxin define two distinct epidermal growth factor–regulated pathways leading to activation of mitogen‐activated protein kinase in rat hepatocytes

P Gines, X Li, S E Brown, T Nakamura, P S Guzelian, L E Heasley, R W Schrier, R A Nemenoff – 1 May 1996 – Increased intracellular cyclic adenosine monophosphate (cAMP) levels have been shown in some reports to inhibit and in other studies to stimulate growth factor‐mediated activation of the mitogen‐activated protein kinase (MAP kinase) pathway, depending on the cell type examined. The relationship between cAMP and MAP kinase in hepatocytes has not been examined.

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