Cluster mannosides can inhibit mannose receptor–mediated tissue‐type plasminogen activator degradation by both rat and human cells

F Noorman, M M Barrett‐Bergshoeff, E A L Biessen, E van de Bilt, T J C van Berkel, D C Rijken – 30 December 2003 – Recently, we developed a series of cluster mannosides that were able to inhibit tissue‐type plasminogen activator (t‐PA) binding to the isolated mannose receptor. The mannoside with the highest affinity was able to inhibit t‐PA clearance by the liver in the rat.

A pilot study of recombinant interleukin‐2 for treatment of chronic hepatitis C

M Pardo, I Castillo, H Oliva, A Fernandez‐Flores, R Barcena, M A de Peuter, V Carreno – 30 December 2003 – The optimal and safer interleukin‐2 (IL‐2) dose for treatment of chronic hepatitis C virus (HCV) infection has been studied in 33 HCV‐RNA positive patients with chronic hepatitis C. Patients were randomly allocated to receive 5 days per week during 12 weeks IL‐2 doses of: 0.9 MIU (n = 10), 1.8 MIU (n = 10), or 3.6 MIU (n = 13). After 12 weeks, responder patients stopped treatment, whereas nonresponders received 12 additional weeks of IL‐2 at the next higher dose: 1.8, 3.6, or 5.4 MIU.

Hepatitis C and G co‐infection: Response to interferon therapy and quantitative changes in serum HGV‐RNA

J G McHutchison, O V Nainan, M J Alter, A Sedghi‐Vaziri, J Detmer, M Collins, J Kolberg – 30 December 2003 – Hepatitis G virus (HGV), a positive sense RNA virus, is distantly related to hepatitis C virus (HCV): its genetic organization and identity are consistent with the Flaviviridae family. Coinfection with HGV occurs in 10% to 20% of HCV‐infected subjects. These similarities raise two theoretical questions.

Long‐term longitudinal study of intrahepatic hepatitis C virus replication after liver transplantation

V di Martino, F Saurini, D Samuel, M Gigou, E Dussaix, M Reynes, H Bismuth, C Feray – 30 December 2003 – Recurrence of hepatitis C after liver transplantation is common and can lead to severe liver diseases. Although immunosuppression and high levels of viremia suggest a direct pathogenicity of hepatitis C virus (HCV), the relations between viral replication and long‐term histological course are still unknown. Thirty‐three patients with a mean histological follow‐up of 3.5 years (3 months ‐ 8.6 years) were analyzed. Nineteen patients were infected by genotype 1b.

Inhibition of hepatocellular carcinoma development in hepatitis B virus transfected mice by low dietary casein

Z Cheng, J Hu, J King, G Jay, T C Campbell – 30 December 2003 – In a comprehensive human ecological study, primary liver cancer has been shown to be highly significantly associated with 1) the prevalence of persistent infection with hepatitis B virus (HBV) and 2) plasma cholesterol concentrations that are, in turn, associated with the consumption of animal based foods. In rat studies, aflatoxin‐induced hepatocellular carcinoma is substantially prevented by decreasing the intake of animal based protein (casein), a hypercholesterolemic nutrient.

Exposure of primary rat hepatocytes in long‐term DMSO culture to selected transition metals induces hepatocyte proliferation and formation of duct‐like structures

E E Cable, H C Isom – 30 December 2003 – We previously showed that primary rat hepatocytes plated on a rat‐tail collagen coated dish and fed a chemically‐defined medium supplemented with 2% dimethylsulfoxide (DMSO) can be maintained in a well‐differentiated, non‐replicating state for periods of several months. In this study, we show that the addition of copper, iron, and zinc to the DMSO‐containing chemically defined medium induced DNA synthesis and cell replication during the first two months in culture without loss of hepatic differentiation.

Human hepatic myofibroblasts increase invasiveness of hepatocellular carcinoma cells: Evidence for a role of hepatocyte growth factor

V Neaud, S Faouzi, J Guirouilh, B Le Bail, C Balabaud, P Bioulac‐Sage, J Rosenbaum – 30 December 2003 – The stroma of hepatocellular carcinomas (HCC) is infiltrated with myofibroblasts (MFs). Preliminary in vivo data have suggested that liver MF express hepatocyte growth factor (HGF), a cytokine that has been implicated in several tumor models. Our aim was to investigate the role of MF and HGF in HCC. Cultured liver MF expressed HGF messenger RNA (mRNA) and secreted HGF in their medium, as shown by Western blot, immunoprecipitation, and enzyme‐linked immunosorbent assay (ELISA).

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