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.

Germ‐line mutations of the p16INK4(MTS1) gene occur in a subset of patients with hepatocellular carcinoma

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.

Effect of cell density and epidermal growth factor on the inducible expression of CYP3A and CYP1A genes in human hepatocytes in primary culture

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.

Expression of costimulatory molecules B7‐1 (CD80) and B7‐2 (CD86) on human hepatocellular carcinoma

T Tatsumi, T Takehara, K Katayama, K Mochizuki, M Yamamoto, T Kanto, Y Sasaki, A Kasahara, N Hayashi – 30 December 2003 – Costimulation mediated by costimulatory molecules, such as B7‐1 and B7‐2, which are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)‐4 counter‐receptor, plays an important role in the induction of T cell‐mediated antitumor immunity.

Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity–determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection

K Chayama, A Tsubota, M Kobayashi, K Okamoto, M Hashimoto, Y Miyano, H Koike, M Kobayashi, I Koida, Y Arase, S Saitoh, Y Suzuki, N Murashima, K Ikeda, H Kumada – 30 December 2003 – Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are predictive factors of poor response to interferon therapy in patients with chronic hepatitis C. To further examine the factors predicting the response to interferon in patients with genotype 1b infection, we analyzed 110 consecutive patients with HCV who were treated with a total of 624 million units of lymphoblastoid interferon alfa.

Effects of extended cold preservation and transplantation on the rat liver microcirculation

H Imamura, A Brault, P M Huet – 30 December 2003 – Liver sinusoidal endothelial cell impairment and/or microcirculatory disturbances are thought to induce storage‐related graft failure; however, the respective roles of changes induced by extended cold preservation and transplantation, as well as their interactions, are still unknown.

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