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Title: Vascular endothelial cell dysfunction in systemic sclerosis
Author: Holt, Cathy
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 1988
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Systemic sclerosis is a connective tissue disease of unknown aetiology, characterized by extensive vascular damage and an increased deposition of collagen. In addition, various immunological abnormalities have also been described in patients with the disease. This thesis has provided strong evidence in support of an immunologically mediated vascular pathogenesis in systemic sclerosis. This has been demonstrated by the occurrence of cytotoxicity of human vascular endothelial cells following co-culture with patient sera and normal peripheral blood mononuclear cells. Further characterization of the serum factor capable of causing endothelial cytotoxicity revealed that the responsible serum factor was monomeric IgG and was capable of binding to vascular endothelial cells, findings which are consistent with the cytotoxic factor being an antibody directed against the vascular endothelium. Further in vivo evidence of endothelial cell damage was demonstrated by the occurrence of elevated plasma levels of von Willebrand factor antigen in patients with systemic sclerosis. In addition, the presence of immune abnormalities including a high incidence of immune complexes and the occurrence of anticardiolipin antibodies was shown, thus emphasizing the autoimmune nature of systemic sclerosis. Finally, prostacyclin production by cultured vascular endothelial cells was investigated, during both 15 minute and 72 hour exposure to sera from patients with systemic sclerosis. In contrast to previous studies, no significant changes were detected between patient and control sera in their effect on endothelial cell prostacyclin release.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine Medicine