J Greuet, L Pichard, J C Ourlin, C Bonfils, J Domergue, P Le Treut, P Maurel – 30 December 2003 – The influence of cell density and epidermal growth factor (EGF) on the expression and inducibility of cytochrome P450 (CYP) genes of the CYP3A and CYP1A families in adult human hepatocytes in primary culture has been evaluated. Only when cultured at subconfluence and in the presence of EGF did hepatocytes exhibit a proliferative response, assessed by measuring DNA synthesis and cyclin A accumulation.

S M Lemon, K Nishioka, S Mishiro, L Johnson – 30 December 2003

P Chaubert, R Gayer, A Zimmermann, C Fontolliet, B Stamm, F Bosman, P Shaw – 30 December 2003 – The molecular mechanisms of hepatocarcinogenesis are poorly understood. Only very recently has there been a suggestion of familial hepatocellular carcinoma (HCC). We have analyzed the status of the p16INK4(MTS1) gene, a cyclin‐dependent kinase inhibitor, in 26 patients with HCC of different etiologies. Four patients carried hemizygous germ‐line point mutations of the p16INK4(MTS1) gene, suggesting the existence of familial HCC involving this gene.

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.

30 December 2003

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.

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.

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.

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.

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).