Summary CV Publications Royal Devon & Exeter Foundation Trust 1 The Quadrant


RESEARCH FELLOW

19.01.89 - 30.9.91




















Hepatology.
Dr E. Elias, Dr J. Neuberger,
The Liver Unit, Queen Elizabeth Hospital, Birmingham.


My medical doctorate research involved the investigation of human intrahepatic biliary epithelial cells (HIBECs) as targets in primary biliary cirrhosis. HIBECs were isolated from diseased livers removed at transplantation and established in primary culture. Studies were undertaken to facilitate the long-term culture of these cells. A series of monoclonal antibodies was generated which recognise bile ducts of different sizes on histological sections. The results emphasized the heterogeneity of the biliary tree and demonstrated different patterns of staining in health and disease. The antigens to which these antibodies are directed have been partially characterized.

A chromium release cytotoxicity assay for use with HIBEC cultures was established and validated and has been employed to investigate bile salt cytotoxicity, lymphocyte cytotoxicity and ADCC. The results demonstrate that dihydroxy bile salts (including ursodeoxycholic acid) in particular are toxic to HIBECs in vitro.

The in vitro effect of TNFa, IFNg, IL-1, bile salts and steroids on the expression of ICAM-1 and HLA Class I & II on HIBECs has been studied along with the ability of HIBECs to present antigen to HLA-DR restricted T-cell clones. The expression of these surface antigens was demonstrated on HIBECs in vitro and their expression was up-regulated by incubation with pro-inflammatory cytokines. However, we were not able to demonstrate antigen presentation by these cells. Bile salts in non-cytotoxic concentrations did not affect the expression of the surface antigens studied.

Other work included examining HIBEC culture supernatants for chemotaxis to neutrophils and in collaboration with the department of Medicine II at Southampton University the ability of HIBECs to manufacture type IV collagenase/gelatinase.



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