Therapeutic serum concentrations of human alpha‐1‐antitrypsin after adenoviral‐mediated gene transfer into mouse hepatocytes

Mark A. Kay, Frank Graham, Frances Leland, Savio L. C. Woo – 1 March 1995 – Alpha‐1‐antitrypsin is a relatively common genetic deficiency that results in early emphysema. The liver as the natural source of most alpha‐1‐antitrypsin synthesis was the target organ selected for gene replacement therapy studies. Previous work used recombinant retroviral vectors that encode the human alpha‐1‐antitrypsin cDNA for ex vivo and direct in vivo transduction of hepatocytes in dogs and rodents. This approach led to low levels of the human protein in the serum of recipients.

Incidence of hepatocellular carcinoma in chronic hepatitis B and C: A prospective study of 251 patients

Susumu Takano, Osamu Yokosuka, Fumio Imazeki, Masami Tagawa, Masao Omata – 1 March 1995 – The incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included).

Is hepatitis B virus smarter than the immune system?

Marion Peters – 1 March 1995 – It has been suggested that mutations within immunodominant cytotoxic T‐lymphocyte (CTL) epitopes may be exploited by viruses to evade protective immune responses critical for clearance.1–4 Viral escape could originate from passive mechanisms, such as mutations within curcial CTL epitopes, either affecting major histocompatibility complex binding or T‐cell antigen receptor (TCR) recognition.

Conditional immortalization of gunn rat hepatocytes: An ex vivo model for evaluating methods for bilirubin‐UDP‐glucuronosyltransferase gene transfer

Ira J. Fox, Namita Roy Chowdhury, Sanjeev Gupta, Ravi Kondapalli, Michael L. Schilsky, Richard J. Stockert, Jayanta Roy Chowdhury – 1 March 1995 – Viral vectors and protein carriers utilizing asialoglycoprotein receptor (ASGR)‐mediated endocytosis are being developed to transfer genes for the correction of bilirubin‐UDP‐glucuronosyltransferase (bilirubin‐UGT) deficiency. Ex vivo evaluation of these gene transfer vectors would be facilitated by a cell system that lacks bilirubin‐UGT, but expresses differentiated liver functions, including ASGR.

Extramedullary erythropoiesis in human liver grafts

Hans Jürgen Schlitt, Sabine Schäfers, Andrea Deiwick, Kai‐Uwe Eckardt, Torsten Pietsch, Wolfram Ebell, Björn Nashan, Burckhardt Ringe, Kurt Wonigeit, Rudolf Pichlmayr – 1 March 1995 – Extramedullary erythropoiesis in the adult is very rare and is generally confined to situations of severe bone marrow irritation or replacement. In this study, we describe the occurrence of intrahepatic erythropoiesis in patients who have received a liver allograft and who have no evidence of bone marrow dysfunction.

Growth hormone, insulinlike growth factor‐1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease

Anthony Donaghy, Richard Ross, Alexander Gimson, Sian Cwyfan Hughes, Jeffrey Holly, Roger Williams – 1 March 1995 – The liver is the major source of circulating insulinlike growth factor‐I (IGF‐I) and has been suggested as a major source of at least two of the major binding proteins that modify its bioavailability.

An anesthetized model of lethal canine galactosamine fulminant hepatic failure

Timothy D. Sielaff, Michael Y. Hu, Mark D. Rollins, Joseph R. Bloomer, Bruce Amiot, Wei‐Shou Hu, Frank B. Cerra – 1 March 1995 – A reproducible large animal model of fulminant hepatic failure was developed in the anesthetized dog by the administration of the amino sugar D‐galactosamine. Galactosamine in 5% dextrose in water (D5W), was given as an intravenous bolus to 10 young male dogs weighing 27 to 30 kg. Three dogs that received an equal volume of D5W alone served as controls.

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