Induction of endotoxin tolerance in transgenic mouse liver expressing creatine kinase

E Hatano, A Tanaka, S Iwata, S Satoh, T Kitai, S Tsunekawa, T Inomoto, H Shinohara, B Chance, Y Yamaoka – 1 September 1996 – The liver plays an important role in maintaining homeostasis during endotoxin‐triggered systemic inflammatory response. To study the effects of phosphocreatine on hepatic energy metabolism after endotoxin administration, we used transgenic mice whose livers express creatine kinase (CK). CK catalyzes a phosphocreatine/creatine reaction, that is, an adenosine triphosphate (ATP) reservoir system.

PK 11195 aggravates 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine‐induced hepatic porphyria in rats

O Fonia, R Weizman, R Coleman, E Kaganovskaya, M Gavish – 1 September 1996 – There is evidence to suggest that peripheral‐type benzodiazepine receptors (PBR) are involved in porphyrin transport during erythroid differentiation, and it is possible that these receptors have an important role in heme biosynthesis. We examined the biochemical and ultrastructural alterations in rat liver following experimentally induced acute hepatic porphyria, as well as the effects of the administration of a selective PBR ligand, PK 11195.

Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine

R Ling, D Mutimer, M Ahmed, E H Boxall, E Elias, G M Dusheiko, T J Harrison – 1 September 1996 – We describe mutations in the hepatitis B virus (HBV) polymerase gene in viruses which reactivated in two patients during therapy with ‐2′‐deoxy‐ 3′‐thiacytidine, or lamivudine (3TC), and following orthotopic liver transplantation for chronic hepatitis B.

An algorithm for the grading of activity in chronic hepatitis C

P Bedossa, T Poynard – 1 August 1996 – Histological activity reflects the global assessment of basic necroinflammatory lesions and is a criterion of major importance in chronic hepatitis C. The aim of this study was to propose and test the accuracy of a simple algorithm that generates a single activity score based on basic pathological features. A panel of 10 pathologists reviewed 363 chronic hepatitis C liver biopsies and graded the activity of hepatitis according to their own experience (reference activity).

Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential

S Arii, M Mise, T Harada, M Furutani, S Ishigami, M Niwano, M Mizumoto, M Fukumoto, M Imamura – 1 August 1996 – The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly.

Interferon γ down‐regulates cytochrome P450 3A genes in primary cultures of well‐differentiated rat hepatocytes

M Tapner, C Liddle, B Goodwin, J George, G C Farrell – 1 August 1996 – Administration of interferons of both the γ and alfa/β classes down‐regulates hepatic cytochrome P450 (CYP) genes when administered to humans or rats. In male rats, interferons decrease expression of CYP3A2 at a pretranslational level, but because interferons also release other cytokines in vivo, it is unclear whether this is a direct effect on hepatocytes. We therefore examined the effects of rat recombinant interferon γ (IFN‐γ) on CYP3A2, other 3A genes, and 2C11 in stable primary cultures of male rat hepatocytes.

Nimodipine, a dihydropyridine‐type calcium channel blocker, prevents alcoholic hepatitis caused by chronic intragastric ethanol exposure in the rat

Y Iimuro, K Ikejima, M L Rose, B U Bradford, R G Thurman – 1 August 1996 – It has been shown recently that inactivation of Kupffer cells prevents free radical formation and early alcohol‐induced liver injury, and that hypoxia subsequent to a hypermetabolic state caused by activated Kupffer cells is likely involved in the mechanism. Calcium is essential for the activation of Kupffer cells, which contain L‐type voltage‐dependent Ca2+ channels.

Regulation of the last two enzymatic reactions in cholesterol biosynthesis in rats: Effects of BM 15.766, cholesterol, cholic acid, lovastatin, and their combinations

A Honda, S Shefer, G Salen, G Xu, A K Batta, G S Tint, M Honda, T C Chen, M F Holick – 1 August 1996 – The Smith‐Lemli‐Opitz syndrome is a common inherited birth disorder caused by markedly reduced 7‐dehydrocholesterol δ7‐reductase activity, the final enzyme in the cholesterol biosynthetic pathway. BM 15.766 (4‐[2‐[1‐(4‐chlorocinnamyl)piperazin‐4‐yl]ethyl]‐benzoic acid) inhibits 7‐dehydrocholesterol delta 7‐reductase activity, reduces plasma cholesterol levels, and increases 7‐dehydrocholesterol levels to reproduce the biochemical abnormalities of the syndrome in rats.

Functional differences between hepatocytes and biliary epithelial cells in handling polymeric immunoglobulin A2 in humans, rats, and guinea pigs

S Sakisaka, K Gondo, M Yoshitake, M Harada, M Sata, K Kobayashi, K Tanikawa – 1 August 1996 – Immunoglobulin A (IgA) in bile plays an important role in preventing the biliary tract from infection. In the present study, to clarify the functional differences between hepatocytes and biliary epithelial cells (BEC) in handling polymeric IgA2 (pIgA2), the major and important IgA in bile, we have determined in different species the binding characteristics of 125I‐labeled pIgA2 to tissue sections of human, rat, and guinea pig livers.

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