Up‐regulation of heme‐binding protein 23 (HBP23) gene expression by lipopolysaccharide is mediated via a nitric oxide‐dependent signaling pathway in rat Kupffer cells

Stephan Immenschuh, Janina Stritzke, Shin‐ichiro Iwahara, Giuliano Ramadori – 30 December 2003 – Heme‐binding protein 23 (HBP23) is a cytosolic protein that binds the prooxidant heme with high affinity and has been implicated in the cellular protection against reactive oxygen species (ROS). Because lipopolysaccharide (LPS) stimulates macrophages to produce large amounts of ROS the gene expression of HBP23 was analyzed during treatment with LPS in cultured rat Kupffer cells (KC).

Ceramide induces caspase‐independent apoptosis in rat hepatocytes sensitized by inhibition of RNA synthesis

Brett E. Jones, Chau R. Lo, Anu Srinivasan, Karen L. Valentino, Mark J. Czaja – 30 December 2003 – Ceramide has been implicated as a second messenger in intracellular signaling pathways leading to apoptosis in nonhepatic cells. To determine whether ceramide can mediate hepatocyte apoptosis, the cytotoxicity of ceramide was determined in rat hepatocytes. The rat hepatocyte cell line, RALA255‐10G, and primary rat hepatocytes were completely resistant to toxicity from 10 to 100 μmol/L C2 ceramide.

Activation of mouse liver natural killer cells and NK1.1+T cells by bacterial superantigen‐primed Kupffer cells

Hiroshi Dobashi, Shuhji Seki, Yoshiko Habu, Takashi Ohkawa, Seiichiro Takeshita, Hoshio Hiraide, Isao Sekine – 30 December 2003 – Although bacterial superantigens have been well characterized as potent stimulators of T cells, their role in natural killer (NK)‐type cells remains largely unknown. In the present study, we examined the effect of bacterial superantigens on mouse liver NK cells and NK1.1 Ag+ (NK1+) T cells.

Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy

Yun‐Fan Liaw, Rong‐Nan Chien, Chau‐Ting Yeh, Sun‐Lung Tsai, Chia‐Ming Chu – 30 December 2003 – Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication, but its long‐term use may be associated with HBV tyrosine‐methionine‐aspartate‐aspartate (YMDD) motif mutation. To examine the clinical features and course after emergence of YMDD mutants, 55 patients who received lamivudine therapy over 104 weeks at our unit were assayed for YMDD mutation(s). Thirty‐two of them were found to have the YMDD mutation.

Antibody responses to hepatitis C virus hypervariable region 1: Evidence for cross‐reactivity and immune‐mediated sequence variation

Mario U. Mondelli, Antonella Cerino, Antonella Lisa, Sabrina Brambilla, Laura Segagni, Agostino Cividini, Morena Bissolati, Gabriele Missale, Giorgio Bellati, Annalisa Meola, Bruno Bruniercole, Alfredo Nicosia, Giovanni Galfrè, Enrico Silini – 30 December 2003 – Sequence heterogeneity of hepatitis C virus (HCV) is unevenly distributed along the genome, and maximal variation is confined to a short sequence of the HCV second envelope glycoprotein (E2), designated hypervariable region 1 (HVR1), whose biological function is still undefined.

Endothelin‐1 modulates intrahepatic resistance in a rat model of noncirrhotic portal hypertension

Patrick S. Kamath, Gertrude M. Tyce, Virginia M. Miller, Brooks S. Edwards, Duane K. Rorie – 30 December 2003 – Factors that increase resistance to blood flow through the hepatic sinusoids when portal hypertension occurs in the absence of significant hepatic fibrosis are not completely understood. Experiments were designed to test the hypothesis that endothelin‐1 (ET‐1) is one of the humoral factors that increases sinusoidal vascular resistance in a bile duct– ligated noncirrhotic portal hypertensive (BDL) rat.

MMP2 activation by collagen I and concanavalin A in cultured human hepatic stellate cells

Nathalie Théret, Kaisa Lehti, Orlando Musso, Bruno Clément – 30 December 2003 – Fibrosis occurs in most chronic liver injuries and results from changes in the balance between synthesis and degradation of extracellular matrix components. In fibrotic livers, there is a markedly increased activity of matrix metalloproteinase 2 (MMP2), a major enzyme involved in extracellular matrix remodeling. We have previously shown that hepatic stellate cells secrete latent MMP2 and that MMP2 activation occurs in coculture of hepatic stellate cells and hepatocytes concomitantly with matrix deposition.

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension

Michael J. Krowka, Robert P. Frantz, Michael D. McGoon, Cathy Severson, David J. Plevak, Russell H. Wiesner – 30 December 2003 – Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as “portopulmonary hypertension.” Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension.

Role of thyroid hormone in stimulating liver repopulation in the rat by transplanted hepatocytes

Ran Oren, Mariana D. Dabeva, Anthony N. Karnezis, Petko M. Petkov, Richard Rosencrantz, Jaswinder P. Sandhu, Steven F. Moss, Shaobai Wang, Ethel Hurston, Ezio Laconi, Peter R. Holt, Swan N. Thung, Liang Zhu, David A. Shafritz – 30 December 2003 – Recently, we reported near‐complete repopulation of the rat liver by transplanted hepatocytes using retrorsine (RS), a pyrrolizidine alkaloid that alkylates cellular DNA and blocks proliferation of resident hepatocytes, followed by transplantation of normal hepatocytes in conjunction with two‐thirds partial hepatectomy (PH).

Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

Abdelmajid Sabile, Gabriel Perlemuter, Fulvia Bono, Kyoko Kohara, France Demaugre, Michinori Kohara, Yoshiharu Matsuura, Tatsuo Miyamura, Christian Bréchot, Giovanna Barba – 30 December 2003 – Several lines of evidence suggest that hepatitis C virus (HCV) core protein may modulate cellular transduction signals and alter lipid metabolism. We have investigated the binding of HCV core protein to cellular proteins by combining 2 yeast hybrid, confocal, and surface plasmon resonance assays.

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