Based on Ph.D. thesis. / Includes bibliographical references (p. 201-216) and index.

Thesis (M.S.)--San Francisco State University, 2002. / Includes bibliographical references (leaves 29-54).

published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

Two major problems preventing the clinical application of pancreatic islet transplantation were investigated. The problem of allograft rejection was studied in rats, made diabetic by streptozotocin treatment. It was shown that DA rats given LEW renal allografts and treated with cyclosporine accepted their grafts, and subsequently developed a strain-specific unresponsive state that allowed successful transplantation of LEW islets without further immunosuppression, whilst BN islets were rejected normally. The effect was demonstrated to be independent of the site of islet transplantation, and, once an islet allograft had been accepted, it was possible to remove the original renal allograft without affecting the transplanted islets. The effect was shown to apply to another strain combination (LEW into PVG), and also to animals made unresponsive to renal allografts by another method (donor-specific blood transfusion). The problem of separation of adequate numbers of viable islets from the pancreas was studied in the rat, dog, pig and human. To aid the investigation, supravital staining techniques were developed, using neutral red to identify the islets, and fluorescein diacetate and ethidium bromide to assess islet viability. A variety of islet isolation techniques were investigated, and a new technique for isolation of islets from the dog pancreas, yielding up to 160,000 islets from 1 pancreas with a maximum purity of 80%, was developed. The structural integrity and in vitro function of the isolated islets was demonstrated, but it was not possible to prevent diabetes by autotransplantation of islets to the portal vein of pancreatectomised dogs. A method for isolation of islets from the human pancreas was developed from that used in the dog, yielding up to 80,000 islets from a whole pancreas, with a maximum purity of 40%. The technique was shown to be both simple and reliable. The structural integrity and in vitro function of the isolated islets was demonstrated, and the viability of the islets proven by successful transplantation under the kidney capsule of nude mice.

The use of organs from donors after circulatory death (DCD) has been recommended as one strategy to enlarge the donor pool and raise the transplant rate. However, DCD allografts had higher incidence of early post-transplant dysfunction. The general aim of this research project was to develop clinical and experimental strategies to reduce the incidence of early post-transplant dysfunction of kidney and liver allografts from DCD. First the ability of a clinical scoring system based on donor data for identifying DCD kidneys with high-risk of post-transplant dysfunction was evaluated using the Oxford and the UK National DCD kidney transplant cohorts. This works suggest that stratification of DCD kidneys before transplantation might allow early identification of kidneys in which lower graft function and survival could be expected if any additional therapeutic intervention is implemented. Second, as it has been suggested that hypothermic machine perfusion (HMP) may protect DCD kidneys from additional preservation injury and improve their outcome after transplantation, this work explored the benefit of HMP as preservation technique fo DCD kidneys in Oxford and discusses the potential of this technique for reducing the incidence of post-transplant dysfunction in DCD kidneys. The Oxford. Liver Group has provided evidence of the benefit of preservation with normothermic machine perfusion (NMP) on post-transplant function and survival of DCD liver allografts. In this work, the molecular mechanisms associated with this benefit were characterized using micro array technology. This analysis suggests that the beneficial effect ofNMP may be associated with the induction of the ischaemic preconditioning phenomenon and highlights a group of genes with potential for gene therapy. Finally, this works provides the "proof-of-concept" that the use of a non-mammalian viral vector for gene transfer of kidneys and livers during conventional cold preservation is feasible and is not associated with additional tissue injury.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Materials Science and Engineering." Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 171-191).

No description available.

No description available.

Thesis (M Nursing)--University of South Australia, 1997