Changes in the localization of the rat canalicular conjugate export pump mrp2 in phalloidin‐induced cholestasis

Daniel Rost, Jürgen Kartenbeck, Dietrich Keppler – 30 December 2003 – Administration of phalloidin, one of the toxic peptides of the mushroom Amanita phalloides, leads to rapid and sustained cholestasis in rats. Although attributed to the interaction of phalloidin with microfilaments, the events leading to cholestasis are incompletely understood. The adenosine triphosphate (ATP)‐dependent, apical conjugate export pump, termed multidrug resistance protein 2 (Mrp2) or canalicular multispecific organic anion transporter, is the major driving force for bile salt‐independent bile flow.

Endothelial cells lining transjugular intrahepatic portasystemic shunts originate in hepatic sinusoids: Implications for pseudointimal hyperplasia

Arun J. Sanyal, Faridoddin Mirshahi – 30 December 2003 – The phenotype of the endothelial cells (ECs) in the pseudointima of transjugular intrahepatic portasystemic shunts (TIPS) and the mechanisms of pseudointima formation after TIPS were unknown. We hypothesized that TIPS were lined by hepatic sinusoidal ECs, which stimulated the migration of smooth muscle cells (SMCs) into the pseudointima and their proliferation.

Cryptogenic cirrhosis: Clinical characterization and risk factors for underlying disease

Stephen H. Caldwell, David H. Oelsner, Julia C. Iezzoni, Elizabeth E. Hespenheide, Emily H. Battle, Carolyn J. Driscoll – 30 December 2003 – We characterized 70 consecutive patients with cryptogenic cirrhosis to assess major risks for liver disease. Each patient was reevaluated for past alcohol exposure, scored by the International Autoimmune Hepatitis (IAH) score and assessed for viral hepatitis risks and risks for nonalcoholic steatohepatitis (NASH).

Zidovudine (AZT) causes an oxidation of mitochondrial DNA in mouse liver

José García de la Asunción, María L. del Olmo, Juan Sastre, Federico V. Pallardó, José Viña – 30 December 2003 – Zidovudine (3′‐azido‐2′,3′‐dideoxythymidine [AZT]) inhibits human immunodeficiency virus replication and delays progression of acquired immune deficiency syndrome. We have recently found that, in muscle, AZT causes oxidative damage to mitochondrial DNA (mtDNA) and other signs of mitochondrial oxidative damage. The aim of this work was to test if AZT causes oxidative damage to liver mtDNA.

The role of protein phosphatases in the expression of inducible nitric oxide synthase in the rat hepatocyte

Bradley S. Taylor, Shubing Liu, Raphael T. Villavicencio, Raymond W. Ganster, David A. Geller – 30 December 2003 – Previously, we demonstrated that nuclear factor‐κB (NF‐κB) mediates cytokine‐induced hepatic inducible nitric oxide synthase (iNOS) expression. NF‐κB activation is regulated by kinases and phosphatases whose function is only beginning to be understood. Therefore, experiments were performed to determine the role of protein phosphatases (PPase) in cytokine‐induced iNOS expression.

Determination of the chelatable iron pool of isolated rat hepatocytes by digital fluorescence microscopy using the fluorescent probe, phen green SK

Frank Petrat, Ursula Rauen, Herbert de Groot – 30 December 2003 – The intracellular pool of chelatable iron is considered to be a decisive pathogenetic factor for various kinds of cell injury. We therefore set about establishing a method of detecting chelatable iron in isolated hepatocytes based on digital fluorescence microscopy. The fluorescence of hepatocytes loaded with the fluorescent metal indicators, phen green SK (PG SK), phen green FL (PG FL), calcein, or fluorescein desferrioxamine (FL‐DFO), was quenched when iron was added to the cells in a membrane‐permeable form.

Growth inhibition by a triple ribozyme targeted to repetitive B2 transcripts

Tina M. Crone, Shani L. Schalles, Catharine M. Benedict, Weihua Pan, Ling Ren, Sarah E. Loy, Harriet Isom, Gary A. Clawson – 30 December 2003 – The B2 family represents a group of short repetitive sequences that are found throughout the rodent genome and are analogous to the human Alu sequences. Certain B2 subfamilies are transcribed by RNA polymerase III (pol III), and this transcription is in part controlled by the retinoblastoma protein.

P‐selectin mediates reperfusion injury through neutrophil and platelet sequestration in the warm ischemic mouse liver

Surinder S. Yadav, David N. Howell, Douglas A. Steeber, Robert C. Harland, Thomas F. Tedder, Pierre‐Alain Clavien – 30 December 2003 – Hepatic damage following ischemia‐reperfusion injury involves polymorphonuclear leukocytes (PMN) and platelet sequestration, however the mechanisms of adhesion remain elusive. In this study, using gene‐targeted deficient mice, we evaluated P‐selectin and its contribution to PMN and platelet adhesion in hepatic damage.

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