SUMMARY The frequency of HLA-A3 and HLA-B14 antigens was significantly higher in a series of 51 patients with idiopathic haemochromatosis than in a control group, being respectively 78-4 versus 27 0 % and 25 5 versus 3 4 %. This finding strongly supports the suggestion that idiopathic haemochromatosis is a genetic disease and suggests that the gene(s) responsible for the disease may be linked to the histocompatibility genes.The aetiology of idiopathic haemochromatosis (IH) is controversial, most authors regarding this affection as an inborn error of metabolism (Sheldon, 1935), while others consider it to be an acquired disease (MacDonald, 1964). In this paper, we report the results of the determination of histocompatibility antigens in a series of patients with IH. The investigation showed a significant association of HLA-A3 and HLA-B14 antigens with IH, a finding which strongly supports the notion of hereditary transmission of the disease.
Methods
High yields of viable human hepatocytes were obtained by enzymatic perfusion of the left hepatic lobe of kidney donors and cultured alone or with an epithelial cell line derived from rat liver. In conventional cultures, human hepatocytes did not survive more than 2 to 3 weeks and by Day 8 decreased their ability to secrete albumin. When co-cultured, they survived for more than 2 months and secreted high levels of albumin even in a serum-free medium. This long-term survival appeared to correlate with production of an extracellular material which is rich in Type III collagen. In vitro phenotypic alterations of parenchymal cells were reversed by addition of rat liver cells and were characterized by recovery of cuboidal morphology, increased albumin secretion and a shift from Type I to Type III collagen deposition. Rat liver epithelial cells could not be replaced by nonhepatic epithelial cells. These observations suggest that when adult human hepatocytes are maintained in a culture which closely resembles their in vivo environment, they are capable of continuing to actively express specific cell functions.
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