Relation of disease activity during chronic hepatitis C infection to complexity of hypervariable region 1 quasispecies

N Yuki, N Hayashi, T Moribe, Y Matsushita, T Tabata, T Inoue, Y Kanazawa, K Ohkawa, A Kasahara, H Fusamoto, T Kamada – 30 December 2003 – We studied the heterogeneity in the E2/NS1 hypervariable region 1 of the hepatitis C virus (HCV) genome in relation to the natural course after infection. The subjects were composed of 38 chronic hepatitis C carriers who had been followed for 9 to 218 months after the onset of non‐A, non‐B (type C) hepatitis, being tested monthly for serum alanine aminotransferase levels.

Regulation of rat liver S‐adenosylmethionine synthetase during septic shock: Role of nitric oxide

M A Avila, J Mingorance, M L Martínez‐Chantar, M Casado, P Martín‐Sanz, L Boscá, J M Mato – 30 December 2003 – We investigated the modulation of rat liver S‐adenosylmethionine (SAM) synthetase in a model of acute sepsis. Our results show that animals treated with bacterial lipopolysaccharide experience a marked decrease in liver SAM synthetase activity. No changes were detected in the hepatic levels of SAM synthetase protein, suggesting that inactivation of the existing enzyme was the cause of the observed activity loss.

Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis

A J Czaja, M D Strettell, L J Thomson, P J Santrach, S B Moore, P T Donaldson, R Williams – 30 December 2003 – Susceptibility for type 1 autoimmune hepatitis has been associated with the major histocompatibility alleles DRB1*0301, DRB3*0101, DRB1*0401, and DRB4*0103, whereas the DRB1*1501 allele may protect from the disease. Our aim was to determine if these alleles or others influence clinical manifestations and prognosis. Eighty‐six white patients were evaluated prospectively for immune features and outcomes.

Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: Relationship of levels of autoantibodies to disease progression

Michael D. Van Norstrand, Michael Malinchoc, K. D. Lindor, T. M. Therneau, M. E. Gershwin, P. S. Leung, E. R. Dickson, H. A. Homburger – 30 December 2003 – We examined the clinical usefulness of measurements of antimitochondrial autoantibodies (AMA) in predicting disease progression in patients with primary biliary cirrhosis (PBC).

Bone metabolism in advanced cholestatic liver disease: Analysis by bone histomorphometry

Maureen M. J. Guichelaar, Michael Malinchoc, Jean Sibonga, Bart L. Clarke, J. Eileen Hay – 30 December 2003 – Despite the clinical importance of cholestatic osteopenia, little is known about its pathophysiologic mechanism. By tetracycline‐labeled histomorphometric analysis of bone biopsies taken at the time of liver transplantation, we prospectively evaluated bone resorption and formation in 50 consecutive patients with advanced primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).

Course and outcome of hepatitis C

Jay H. Hoofnagle – 30 December 2003 – The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post‐translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase).

Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti‐MDR1 ribozymes

Matthes Huesker, Yvonne Folmer, Michaela Schneider, Christine Fulda, Hubert E. Blum, Peter Hafkemeyer – 30 December 2003 – Human cancers, including hepatocellular carcinoma (HCC), are characterized by a high degree of drug resistance. The multidrug resistance (MDR) transporters MDR1‐P‐glycoprotein and MRP2 (multidrug‐associated protein 2) are expressed in almost 50% of human cancers, including HCCs. In this study, we analyzed the effect of anti‐MDR1 ribozymes, especially AFP promoter‐driven anti‐MDR1 ribozymes, to specifically chemosensitize HCC cells.

Insulin inhibits secretin‐induced ductal secretion by activation of PKC alpha and inhibition of PKA activity

Gene D. LeSage, Luca Marucci, Domenico Alvaro, Shannon S. Glaser, Antonio Benedetti, Marco Marzioni, Tushar Patel, Heather Francis, Jo Lynne Phinizy, Gianfranco Alpini – 30 December 2003 – Insulin stimulates canalicular bile flow by interaction with hepatocytes. Insulin regulates the function of a number of epithelia through activation and membrane translocation of Ca2+‐dependent PKC isoforms. No information exists regarding insulin regulation of ductal bile secretion.

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