Factors regulating tumor pressure in hepatocellular carcinoma and implications for tumor spread

T Tanaka, N Yamanaka, T Oriyama, K Furukawa, E Okamoto – 30 December 2003 – This study was performed to investigate factors determining tumor pressure (TP) in hepatocellular carcinoma (HCC) and a correlation of pressure gradient between TP and portal vein pressure (PVP) with tumor spread. TP and hepatic tissue pressure (HTP) were measured in 70 patients who underwent hepatic resection for HCC. Changes in TP after hepatic artery occlusion (HAO) or portal vein occlusion (PVO) were observed.

Dose‐dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa

N P Lam, A U Neumann, D R Gretch, T E Wiley, A S Perelson, T J Layden – 30 December 2003 – To determine if the clearance of hepatitis C genotype 1 virus (HCV) is dependent on the dose of interferon alfa‐2b (IFN‐α2b), the acute clearance of HCV after a single dose of either 3, 5, or 10 mIU of IFN‐α was compared in patients with chronic hepatitis C. HCV‐RNA levels following IFN‐α administration were measured. At 24 hours, mean percentage serum viral reduction was 41.4%, 63.7%, and 85.5% for 3, 5, and 10 mIU, respectively (P < .001).

Transferrin receptor recycling in rat hepatocytes is regulated by protein phosphatase 2A, possibly through effects on microtubule‐dependent transport

M Runnegar, X Wei, N Berndt, S F Hamm‐Alvarez – 30 December 2003 – To understand the regulation of receptor‐mediated endocytosis in hepatocytes, we have used two specific inhibitors of serine‐threonine protein phosphatases (PP), microcystin (MCYST) and okadaic acid (OKA) as probes to alter protein phosphorylation in hepatocytes. We have then examined the impact of these changes on the specific binding and uptake of transferrin (Tf) in hepatocytes. The measurement of PP activity in hepatocyte lysates showed that OKA and MCYST shared a common inhibition of protein phosphatase 2A (PP2A).

Glycine protects against hepatocyte killing by KCN or hypoxia by preventing intracellular Na+ overload in the rat

R Carini, G Bellomo, M De Cesaris, E Albano – 30 December 2003 – Glycine has been shown to prevent hepatocyte death induced by anoxia and by several toxic agents. However, the mechanisms responsible for such a cytoprotective effect have not yet been entirely clarified. We have previously shown that an uncontrolled increase in intracellular Na+ is critical for hepatocyte killing induced by adenosine triphosphate (ATP) depletion.

Cholesterol supplementation prevents necrosis and inflammation but enhances fibrosis in alcoholic liver disease in the rat

A A Nanji, A Rahemtulla, T Daly, S Khwaja, L Miao, S Zhao, S R Tahan – 30 December 2003 – Based on studies that show a role for the low‐density lipoprotein (LDL)‐receptor in arachidonic acid delivery and eicosanoid synthesis in macrophages, the present study investigated the effect of cholesterol supplementation on pathological changes and thromboxane (TX) synthesis in alcoholic liver injury. Male Wistar rats were intragastrically fed ethanol with either corn oil or fish oil for 1 month. Control rats received isocaloric amounts of dextrose instead of ethanol.

Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis

Y Matsuda, K Matsumoto, A Yamada, T Ichida, H Asakura, Y Komoriya, E Nishiyama, T Nakamura – 30 December 2003 – Liver fibrosis/cirrhosis is characterized by hyper‐accumulation of fibrous tissue components and is commonly observed in later or terminal states of chronic hepatic diseases. In ongoing work, we found that the administration of human recombinant hepatocyte growth factor (hrHGF) suppressed the onset of liver fibrosis/cirrhosis in several distinct models and accelerated the recovery from liver fibrosis/cirrhosis in rats.

Nonparenchymal cells from regenerating rat liver generate interleukin‐1α and ‐1β: A mechanism of negative regulation of hepatocyte proliferation

R Boulton, A Woodman, D Calnan, C Selden, F Tam, H Hodgson – 30 December 2003 – Following experimental partial hepatectomy of 70% in the rat, there is a semisynchronized surge of hepatocyte proliferation that ceases after 48 to 72 hours. Little is known about the determinants governing the termination of the proliferative phase, although transforming growth factor (TGF) β has been implicated as an important inhibitor of hepatocyte replication in this model.

Targeted nucleotide exchange in the alkaline phosphatase gene of HuH‐7 cells mediated by a chimeric RNA/DNA oligonucleotide

B T Kren, A Cole‐Strauss, E B Kmiec, C J Steer – 30 December 2003 – Although a variety of methods has been devised for modification of hepatic genes, none has been effective for long‐term correction of genetic disorders. In this study, we employed a recently described novel experimental strategy for site‐directed nucleotide exchange in genomic DNA of HuH‐7 human hepatoma cells. A chimeric 2′‐O‐methylated‐RNA/DNA oligonucleotide containing sequences complementary to 25 bases of the alkaline phosphatase gene was constructed as a duplex containing a G to A substitution at nucleotide 935.

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