Preclinical Evaluation of Two Human Anti–Hepatitis B Virus (HBV) Monoclonal Antibodies in the HBV‐Trimera Mouse Model and in HBV Chronic Carrier Chimpanzees

Rachel Eren, Ehud Ilan, Ofer Nussbaum, Ido Lubin, Dov Terkieltaub, Yossi Arazi, Ofer Ben‐Moshe, Alberto Kitchinzky, Shoshana Berr, Judy Gopher, Arie Zauberman, Eithan Galun, Danny Shouval, Nili Daudi, Ahamed Eid, Oded Jurim, Lars O. Magnius, Berit Hammas, Yair Reisner, Shlomo Dagan – 30 December 2003 – Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10−10 mol/L.

Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosis

Nils Kinnman, Anders Lindblad, Chantal Housset, Eva Buentke, Annika Scheynius, Birgitta Strandvik, Rolf Hultcrantz – 30 December 2003 – The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule‐1 (ICAM‐1) and liver cell‐type markers in liver cryosections in 11 patients with CF‐associated liver disease, and non‐CF controls with (n = 17) and without (n = 3) liver disease.

Rab3D, a small GTP–binding protein implicated in regulated secretion, is associated with the transcytotic pathway in rat hepatocytes

Janet M. Larkin, Bonnie Woo, Vijayan Balan, David L. Marks, Barbara J. Oswald, Nicholas F. LaRusso, Mark A. McNiven – 30 December 2003 – Rab3 isotypes are expressed in regulated secretory cells. Here, we report that rab3D is also expressed in rat hepatocytes, classic models for constitutive secretion. Using reverse transcriptase polymerase chain reaction (RT‐PCR) with primers specific for rat rab3D, we amplified a 151 base pair rab3D fragment from total RNA extracted from primary cultures of rat hepatocytes.

Long‐term follow‐up study of core gene deletion mutants in children with chronic hepatitis B virus infection

Yen‐Hsuan Ni, Mei‐Hwei Chang, Hong‐Yuan Hsu, Huey‐Ling Chen – 30 December 2003 – Core gene deletion mutants of hepatitis B virus (HBV) have been identified in adults. Because the acquisition of HBV occurs mainly in infancy and childhood in hyperendemic areas, this study aimed to learn the temporal profile of such mutants in children with chronic HBV infection. We have followed up 365 HBV‐infected children for more than 10 years and screened out HBV core gene deletion from their sera.

DNA‐based immunization produces Th1 immune responses to hepatitis delta virus in a mouse model

Yi‐Hsiang Huang, Jaw‐Ching Wu, Mi‐Hua Tao, Wan‐Jr Syu, Sheng‐Chieh Hsu, Wei‐Kuang Chi, Full‐Young Chang, Shou‐Dong Lee – 30 December 2003 – Hepatitis delta virus (HDV) superinfection is one of the major causes of fulminant hepatitis in endemic areas of hepatitis B virus (HBV) infection. Currently, there is no effective treatment or vaccine against HDV superinfection. DNA‐based immunization is a promising antiviral strategy to prevent or treat persistent viral infections. In this study, we investigated the immunological effects of DNA vaccines against HDV in BALB/c mice.

Bile acid synthesis in cultured human hepatocytes: support for an alternative biosynthetic pathway to cholic acid

Magnus Axelson, Ewa Ellis, Birgitta Mörk, Kristina Garmark, Anna Abrahamsson, Ingemar Björkhem, Bo‐Göran Ericzon, Curt Einarsson – 30 December 2003 – The biosynthesis of bile acids by primary cultures of normal human hepatocytes has been investigated. A general and sensitive method for the isolation and analysis of sterols and bile acids was used, based on anion exchange chromatography and gas chromatography–mass spectrometry (GC/MS). Following incubation for 5 days, 8 oxysterols and 8 C27 ‐ or C24 ‐bile acids were identified in media and cells.

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

Liam J. Fanning, John Levis, Elizabeth Kenny‐Walsh, Freda Wynne, Michael Whelton, Fergus Shanahan – 30 December 2003 – The aim of this study was to investigate the possibility of a significant relationship between human leukocyte antigen (HLA) class II and the clearance of hepatitis C virus (HCV). The study group consisted of 156 Irish women who iatrogenically received HCV 1b–contaminated Anti‐D immunoglobulin between May 1977 and November 1978. Thus, the study population was homogeneous in terms of gender, source of infection, and ethnicity.

Increased hepatic iron and cirrhosis: No evidence for an adverse effect on patient outcome following liver transplantation

Katherine A. Stuart, Linda M. Fletcher, Andrew D. Clouston, Steve V. Lynch, David M. Purdie, Paul Kerlin, Darrell H. G. Crawford – 30 December 2003 – It has been suggested that preexisting severe hepatic iron overload may adversely affect outcome after liver transplantation. The pathogenesis of iron overload in cirrhosis in the absence of hemochromatosis gene (HFE) mutations is poorly understood.

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