Hepatitis C virus persistence in human hematopoietic cells injected into SCID mice

Jean‐Pierre Bronowicki, Marie‐Anne Loriot, Valérie Thiers, Yves Grignon, Anna Linda Zignego, Christian Bréchot – 30 December 2003 – The issue of infection of peripheral blood mononuclear cells (PBMC) by the hepatitis C virus (HCV) has potentially important implications, but is still debated. We have used the severe combined immunodeficiency (SCID) mouse model to test for the persistence of HCV in PBMC. Hematopoietic cells isolated from 14 subjects infected by HCV were inoculated intraperitoneally into SCID mice.

Multiple genetic alterations, 4q28, a new suppressor region, and potential gender differences in human hepatocellular carcinoma

Christine Hammond, Lennox Jeffers, Brian I. Carr, Daniela Simon – 30 December 2003 – Primary hepatocellular carcinomas (HCCs) of different etiologies were studied to determine the rate of alteration of several genetic regions previously associated with the HCC phenotype. The focus of our study was to identify the frequency of genetic alterations within individual HCCs and their distribution among male and female cases.

Prospective study of interferon therapy for compensated cirrhotic patients with chronic hepatitis C by monitoring serum hepatitis C RNA

Yasushi Shiratori, Osamu Yokosuka, Ryo Nakata, Masashi Ihori, Katsutaro Hirota, Tetsuro Katamoto, Tadao Unuma, Ken'ichi Okano, Yusei Ikeda, Masanori Hirano, Tateo Kawase, Susumu Takano, Kazunori Matsumoto, Yasuo Ohashi, Masao Omata – 30 December 2003 – Because interferon therapy exhibits low efficacy for cirrhotic patients infected with hepatitis C virus, this prospective study was conducted to determine effective interferon regimens tailored to treatment response by monitoring HCV RNA status.

Hepatocellular carcinoma cell lines from diethylnitrosamine phenobarbital‐treated rats. characterization and sensitivity to endothall, a protein serine/threonine phosphatase‐2A inhibitor

Jean‐Paul Thièry, Istvàn Blazsek, Stéphane Legras, Sylvie Marion, Michel Reynes, Aurora Anjo, René Adam, Jean Louis Misset – 30 December 2003 – Primary hepatocellular carcinoma (HCC) is probably one of the most common fatal forms of liver cancer. We have established permanent cell lines from diethylnitrosamine/phenobarbital induced primary rat liver carcinomas to study new anticancer therapies. The rat hepatocellular carcinoma cell lines (HR‐2, HR‐3, and HR‐4) have been maintained in culture for over 3 years. They form tumors when transplantedscorim into young syngeneic rats.

Increased circulating leptin in alcoholic cirrhosis: Relation to release and disposal

Jens H. Henriksen, Jens Juul Holst, Søren Møller, Kim Brinch, Flemming Bendtsen – 30 December 2003 – Leptin is a cytokine peptide that decreases appetite and thereby food intake and increases energy expenditure. It is produced in fat cells, but recent animal experiments have shown expression of leptin in modified stellate hepatic cells.

Formation of 4‐hydroxynonenal adducts with cytochrome c oxidase in rats following short‐term ethanol intake

Juanjuan Chen, Neal C. Robinson, Steven Schenker, Teri A. Frosto, George I. Henderson – 30 December 2003 – This study addresses the role of the lipid peroxidation product, 4‐hydroxynonenal (HNE), in ethanol‐related damage of cytochrome c oxidase (COX) in vivo. It utilizes an animal model with acute ethanol exposure in which HNE levels in liver mitochondria are strikingly increased. Pregnant female Sprague‐Dawley rats were administered 5 doses of ethanol (4 gm/kg, po at 12‐hour intervals) beginning on day 17 of gestation and were sacrificed on day 19.

Enhancement of mdr2 gene transcription mediates the biliary transfer of phosphatidylcholine supplied by an increased biosynthesis in the pravastatin‐treated rat

Massimino Carrella, Douglas Feldman, Susanna Cogoi, Annalisa Csillaghy, Paul A. Weinhold – 30 December 2003 – An increase of biliary lipid secretion is known to occur in the rat under sustained administration of statin‐type 3‐hydroxy‐3‐methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors. The present study has addressed critical mechanisms of hepatic lipid synthesis and phosphatidylcholine (PC) biliary transport in the rat fed with a 0.075% pravastatin diet for 3 weeks.

Increased heme oxygenase‐1 gene expression in liver cells and splanchnic organs from portal hypertensive rats

Mercedes Fernandez, Herbert L. Bonkovsky – 30 December 2003 – Heme oxygenase (HO) catalyzes the conversion of heme into biliverdin, iron, and carbon monoxide (CO). Two isoforms of HO have been identified: the inducible HO‐1 and the constitutive HO‐2. CO, like nitric oxide, is an endogenous vasodilator that could contribute to modulation of systemic and local vascular tone. The aim of the present study was to determine the expression of HO isoforms in liver cells and splanchnic organs from portal hypertensive (PH) and sham‐operated (SO) rats.

Fibroblast activation protein: A cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis

Miriam T. Levy, Geoffrey W. McCaughan, Catherine A. Abbott, John E. Park, Anne M. Cunningham, Erika Müller, Wolfgang J. Rettig, Mark D. Gorrell – 30 December 2003 – Fibroblast activation protein (FAP) is a cell surface–bound protease of the prolyl oligopeptidase gene family expressed at sites of tissue remodelling. This study aimed to delineate the expression of FAP in cirrhotic human liver and examine its biochemical activities. Seventeen cirrhotic and 8 normal liver samples were examined by immunohistochemistry and reverse‐transcriptase polymerase chain reaction (RT‐PCR).

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