Alterations in enzymatic functions in hepatocytes and hepatocellular carcinomas from Ras‐transduced livers resemble the effects of insulin

R V Pearline, Y Lin, K J Shen, E M Brunt, W M Bowling, D G Hafenrichter, S Kennedy, M W Flye, K P Ponder – 1 October 1996 – An understanding of how oncogenes affect differentiated liver functions might lead to improved treatments for liver cancer or other disorders where liver‐specific functions are compromised. A retroviral vector that coexpressed β‐galactosidase (β‐gal) and activated Ras genes (Ras‐gal) was transduced into a small fraction of adult rat hepatocytes in vivo.

Subcellular distribution of glucocorticoid receptor in cultured rat and human liver‐derived cells and cell lines: Influence of dexamethasone

D Raddatz, M Henneken, T Armbrust, G Ramadori – 1 October 1996 – Glucocorticoid receptor (GR) distribution in isolated rat hepatocytes and nonparenchymal hepatic stellate cells, Kupffer cells, and liver fibroblasts with and without dexamethasone treatment was investigated by immunostaining and confocal laser scanning microscopy. In addition, human liver fibroblasts, Hep3B and HepG2 cells were investigated. Subcellular distribution of GR immunostaining was assessed semiquantitatively by digital image analysis.

Increasing hepatic cholesterol 7α‐hydroxylase reduces plasma cholesterol concentrations in normocholesterolemic and hypercholesterolemic rabbits

G Xu, G Salen, S Shefer, G C Ness, L B Nguyen, G S Tint, T S Parker, J Roberts, A K Batta, T S Chen, Z Zhao, X Kong – 1 October 1996 – The effect of bile acid depletion and replacement with glycodeoxycholic acid on plasma cholesterol concentrations, hepatic low‐density lipoprotein (LDL) receptor binding and messenger RNA (mRNA) levels, and hepatic activities and mRNA levels for 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase and cholesterol 7α‐hydroxylase was investigated in 19 New Zealand white (NZW) and 15 Watanabe heritable hyperlipidemic (WHHL) rabbits.

Meta‐analysis of interferon randomized trials in the treatment of viral hepatitis C: Effects of dose and duration

T Poynard, V Leroy, M Cohard, T Thevenot, P Mathurin, P Opolon, J P Zarski – 1 October 1996 – The aims of this study were to evaluate the benefits of higher doses or of longer duration in comparison with a standard interferon regimen (3 MU three times per week for 6 months) in chronic hepatitis C, and to assess the efficacy of interferon in acute hepatitis C. Meta‐analysis made use of the Peto et al. and the Der Simonian and Laird methods, with heterogeneity and sensitivity analyses.

Differential expression pattern of S‐adenosylmethionine synthetase isoenzymes during rat liver development

B Gil, M Casado, M A Pajares, L Bosca, J M Mato, P Martin‐Sanz, L Alvarez – 1 October 1996 – The pattern of expression of liver‐specific and extrahepatic S‐adenosylmethionine (SAM) synthetase in developing rat liver was established by determining steady‐state levels of the respective messenger RNAs (mRNAs) and protein content. Levels of liver‐specific SAM synthetase mRNA increased progressively from day 20 of gestation, increased 10‐fold immediately after birth, and reached a peak at 10 days of age, decreasing slightly by adulthood.

Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin

M F Fromm, D Busse, H K Kroemer, M Eichelbaum – 1 October 1996 – Cytochrome P450 (CYP) enzymes, which metabolize numerous drugs, are expressed both in liver and in extrahepatic tissues. CYP3A4 for example is present and inducible by rifampin in epithelial cells of the gastrointestinal tract. It has been shown that such prehepatic metabolism contributes substantially to total clearance of CYP3A4 substrates (e.g., cyclosporine) before and even more pronounced during enzyme induction.

Long‐term ganciclovir chemotherapy for congenital duck hepatitis B virus infection in vivo: Effect on intrahepatic‐viral DNA, RNA, and protein expression

C Luscombe, J Pedersen, E Uren, S Locarnini – 1 October 1996 – Long‐term antiviral chemotherapy using the nucleoside analogue ganciclovir was undertaken with the aim of eliminating hepadnaviral covalently closed circular (CCC) DNA from the livers of ducks that were congenitally infected with the duck hepatitis B virus (DHBV). Twenty‐ four weeks of ganciclovir therapy caused a substantial reduction in viremia, intrahepatic viral DNA replicative intermediates, and viral core proteins.

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