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Biomedical subjects

B E Tuch

Publications and source records attributed to B E Tuch.

At least 91 records · Page 5Linked to original sources
PubMed1988

Recovery of human fetal pancreas after one year of implantation in the diabetic patient.

Between one and six cultured human fetal pancreata were allografted into five insulin-dependent diabetic recipients and their progress monitored for a year on each occasion. To prevent rejection the tissue was cultured for 1-3 weeks before transplantation, the HLA-DR antigens of the donor tissue were matched with those of the recipient when a single pancreas was used, and four of the recipients were immunosuppressed, three because of coexisting renal grafts. Graft function was observed transiently in one of the recipients. In three others human fetal pancreas was recovered 9-14 months after transplantation, although it was being slowly rejected during this time. Beta cells were present in the graft but did not function adequately to enable immunoreactive C-peptide to be measured in peripheral blood. The issues of rejection and immaturity of the human fetal pancreas will need to be surmounted if the potential of the human fetal pancreas to normalize blood glucose levels in diabetic man is ever to be realized.

C-Peptide↗
PubMed1987

Effect of phorbol and glucose on insulin secretion from the human fetal pancreas.

It has been reported previously that 12-0-tetradecanoylphorbol-13-acetate is capable of stimulating the release of insulin from adult and neonatal pancreatic tissue. The data from this study show that this agent at a concentration of 1.3 uM, in the presence of 2.8 mM glucose, was unable to cause significant secretion of insulin from cultured human fetal pancreatic explants. By contrast 20 mM glucose was able to cause a small but significant immediate increase in secretion of insulin, but was unable to maintain this response beyond ten minutes. When the two agents were combined, a synergistic effect was seen throughout the entire 50 minute period of stimulation. The reason for this synergism is unclear since, whilst both secretagogues were able to cause a rise in the levels of diacylglycerol, together no extra effect was observed.

Arachidonic Acid↗
PubMed1986

Long-term survival of human fetal pancreatic tissue transplanted into an insulin-dependent diabetic patient.

The explants of two human fetal pancreases of 15 weeks gestational age were cultured for 6-7 days before being implanted in a 29-year-old insulin-dependent diabetic woman who had received a renal graft two months previously. One pancreas was placed in the flexor muscles of the forearm whilst the other was implanted in an omental pouch. To reduce the chances of rejection the tissue was cultured in vitro, the donor of the tissue placed in the forearm was DR antigen matched with the recipient and the patient remained on cyclosporin and prednisone therapy. At 3 months a mass developed in the forearm muscle at the site of transplantation, and continued to grow. Biopsy at 13 months showed a small area of original pancreas surrounded by a large collection of mature lymphocytes and fibrous tissue. A and D cells could be seen around pancreatic ducts but B cells and acinar tissue were absent. At no stage during follow-up was plasma C-peptide detected in the recipient.

Administration, Oral↗
PubMed1986

Interferon-gamma induces the expression of HLA-A,B,C but not HLA-DR on human pancreatic beta-cells.

We examined the effect of interferon-gamma (IFN gamma) on expression of the major histocompatibility proteins on cultured human islet cells isolated from adult and fetal pancreas and from an insulinoma. While the pancreatic beta-cells from different sources varied in their responses to IFN gamma, in all instances the expression of HLA-A,B,C protein was increased. Pancreatic beta-cells did not express HLA-DR protein, before or after culture of the islets in IFN gamma, although HLA-DR protein expression was induced on some non-beta-cells. These findings are at variance with those reported with thyroid follicular cells, in which IFN gamma induced expression of HLA-DR. We, therefore, conclude that the interaction between the immune and the endocrine systems may be endocrine cell specific. The up-regulation of HLA-A,B,C protein on beta-cells by IFN gamma provides a mechanism for enhanced targetting to the beta-cells of autoreactive cytotoxic T-lymphocytes and, hence, for amplifying beta-cell destruction.

Adult↗
PubMed1986

Growth and hormonal content of human fetal pancreas passaged in athymic mice.

While the usefulness of the human fetal pancreas transplanted into diabetic humans has yet to be realized, its transplantation into nude mice has revealed some of its potential. In this animal the organ grows in size, during which time differentiation of its endocrine component and maturation of the insulinogenic response to glucose occurs. The results reported in this article expand these results by providing data on the weight and both the insulin and glucagon content of these passaged organs. Human fetal pancreata of gestational age 14-19 wk were implanted subcutaneously (s.c.) in nude mice and maintained in vivo for 5-54 wk (absolute age 19-68 wk). The implants were then removed and their insulin and glucagon content determined. Both the weight of these implants and their insulin content were positively correlated with the absolute age of the tissue (weight: r = 0.61, P less than 0.001; insulin content: r = 0.62, P = 0.0003). The glucagon content bore no relationship to the age. The maximum level of insulin extracted from 30 passaged human fetal pancreata was 0.8 U, a level far below the daily insulin requirements in adult humans. It is suggested that an explanation for this is the site of transplantation used. To compare the s.c. site with the renal subcapsular space, the explants of four fetal pancreata were evenly divided between these two sites. After 11-13 wk, the implants were removed. Those beneath the renal capsule were larger and contained a greater amount of insulin and glucagon than those transplanted s.c.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Maturation of the response of human fetal pancreatic explants to glucose.

The release of insulin from the human pancreas in response to glucose is known to be either poor or absent in the fetus, whereas in the infant and adult, the response is much greater. The maturation of this response was examined systematically in this study using pancreases that were initially obtained at 14-20 weeks gestation and maintained either in culture alone or by passaging them in diabetic nude mice. Stimulation with glucose was carried out in vitro using tissue of ages ranging from 14 to 58 weeks. A response to glucose was initially seen at 25 weeks and this dramatically increased in the fetal tissue that had reached an age of 55 weeks or more. One of the nude mice used for passage developed normoglycaemia and when the pancreatic implant of age 52 weeks was removed, diabetes recurred. Our findings support the idea of the use of human fetal pancreatic tissue in the treatment of diabetes mellitus.

Age Factors↗
PubMed1985

Typing of human fetal organs for the histocompatibility antigens A, B and DR.

In the transplantation of human fetal pancreatic explants into diabetic man, the importance of matching the histocompatibility antigens of donor and recipient to decrease the chances of rejection is unknown. Before this question can be answered human fetuses must be tissue typed. We have shown that lymphocytes harvested from fetal liver, thymus, bone marrow and spleen can be successfully HLA DR typed in 64% and A and B typed in 57% of 58 fetuses aged 15 wk or more. Typing should ideally be carried out on unseparated T and B cells. Best results were achieved if all four of the above organs were available and more than one million viable cells were able to be harvested for typing. Whilst the DR antigens could be typed from all tissues, the A and B antigens could be typed, with few exceptions only from thymus, spleen and bone marrow. The efficacy of matching the histocompatibility antigens of recipient and donor fetuses, especially the DR antigens can now be tested in the human diabetic being transplanted with pancreatic explants.

Diabetes Mellitus↗
PubMed1984

Histologic differentiation of human fetal pancreatic explants transplanted into nude mice.

The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the tissue being cultured in vitro before implantation. These implants coalesced and grew. They were removed at intervals up to 37 wk later and showed selective differentiation of endocrine tissue that normally occurs in the fetus and neonate, with formation of bipolar, mantle, and mature islets. There was growth of this endocrine tissue with significantly more islets than in the freshly stained fetal pancreas assuming an average dimension larger than 150 micron, which is the reported mean diameter of a neonatal islet. Duct and fibrous tissue remained viable, but there was no definitive acinar tissue seen. The pancreata uncultured before implantation reached a larger size than that attained by those implants cultured before being transplanted, the difference probably being the amount of ductular and mesenchymal tissue still present. Of those glands cultured before transplantation, the longer the period of culture, the smaller the size the implants reached. Culture beyond 3 wk in vitro made it difficult to macroscopically locate the implant. These data show that, in human fetal pancreas removed from its usual environment, both selective differentiation of the endocrine component and growth of the islets can occur.

Animals↗