30 December 2003

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.

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.

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

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.

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.

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.

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.

A Michalak, R F Butterworth – 30 December 2003 – There is increasing evidence that alterations of glutamatergic function are implicated in the pathogenesis of central nervous system consequences of acute liver failure.

T Ueki, J Fujimoto, T Suzuki, H Yamamoto, E Okamoto – 30 December 2003 – The c‐met proto‐oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC).