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Biomedical subjects

E H Finke

Publications and source records attributed to E H Finke.

At least 37 records · Page 2Linked to original sources
PubMed1982

Prolongation of islet xenograft survival by in vitro culture of rat megaislets in 95% O2.

Individual rat islets could be aggregated into single megaislets in vitro and the megaislets remained morphologically and functionally intact after a 7-day period of culture in the presence of 95% O2 and 5% CO2. Cultured rat megaislets transplanted beneath the renal capsule of diabetic mice produced normoglycemia in the recipients and the survival of the xenografts was markedly prolonged by the 7-day exposure of a high oxygen tension. A single injection of antilymphocyte sera to mouse and rat lymphocytes into the recipients receiving cultured megaislets did not produce a further increase in the percentage of survival of the grafts at 70 days after transplantation. Lymphoid aggregates were present around xenografts of cultured negaislets at 60 and 90 days after transplantation. This lymphoid reaction did not interfere with the function of the xenografts since the recipients were normoglycemic and removal of the grafts resulted in a rapid return to a diabetic state. Intraportal and intrasplenic transplants of cultured rat megaislets did not survive as long as the xenografts of megaislets transplanted beneath the renal capsule. The renal subcapsule site apparently provided some immunological advantage for delaying acute rejection since transplants of individual, fresh rat islets survived for twice as long under the renal capsule as compared wtih intraportal transplants of fresh rat islets.

Animals↗
PubMed1982

An improved method for the isolation of islets from the beef pancreas.

An improved method for the isolation of islets from the beef and pig pancreas is described. The procedure involves the use of strips of Velcro that retain the partially-digested collagen during the isolation of islets by the collagenase technique. The spiny portion of the Velcro is ideally suited to retain the collagen and yet permit the separation of islets from the pancreatic parenchyma. A remarkably high yield of islets has been obtained from the beef and pig pancreas using this procedure.

Animals↗
PubMed1982

Prolongation of intrasplenic islet xenograft survival.

The spleen has been examined as a possible site for transplantation of rat islets into diabetic mice. Marked prolongation of islet xenograft survival in the spleen can be achieved with in vitro culture (24 C) and a single injection of either rabbit antiserum to mouse lymphocytes (MALS) alone or MALS and rabbit antiserum to rat lymphocytes (RALS) into the recipients. The percentage of survival of intrasplenic xenografts at 100 days was 16%, as compared with 70% when rat islet xenografts were transplanted via the portal vein. Further improvement in pretreatment regimens will be needed before the spleen can be used as an effective site for possible future islet allograft or xenograft transplants in man.

Animals↗
PubMed1981

Transplantation of insulin-producing tissue.

A series of new findings have shown that it is possible to prevent rejection of islet allografts and islet xenografts in animals without the continued use of immunosuppressive agents. The survival of allografts of rat islets has been prolonged for more than 100 days by in vitro culture of the islets at 24 degrees C for seven days prior to transplantation in conjunction with a single injection of rat antilymphocyte serum at the time of transplantation, Xenograft survival of rat islets transplanted into diabetic mice has been prolonged for more than 100 days by the use of culture of rat islets at low temperature, with a single injection of antiserums to mouse and rat lymphocytes at the time of transplantation. Rejection of established islet allografts in rats was induced by the injection of donor peritoneal exudate cells and donor T lymphocytes, whereas the injection of B lymphocytes did not induce rejection. The pretreatment regimens used for prolonging islet allograft and xenograft survival apparently destroy or alter passenger leukocytes in the grafts, and it would appear that these cells are needed for the induction of immune recognition by the recipient. Islet cells in mice express products of the H-2K and H-2D loci, but the cells do not express the I region (Ia) antigens. These new developments in the prevention of immune rejection of the islets raise the question as to whether these approaches may be applicable to the transplantation of islets into human subjects with diabetes.

Animals↗
PubMed1980

Prolongation of islet xenograft survival without continuous immunosuppression.

The survival of isolated rat islets transplanted into diabetic mice was prolonged markedly by maintaining the rat islets in vitro at 24 degrees C for 7 days before transplantation and administering to the recipients a single injection of antiserum to mouse and rat lymphocytes shortly before transplantation.

Animals↗
PubMed1980

Effect of culture on islet rejection.

In order to diminish or prevent rejection of transplanted allogeneic islets of Langerhans, in vitro culture was used. After digestion of the rat pancreas and Ficoll separation, islets were handpicked to be free of vascular and ductal tissue. Phenol red in the culture medium imparted a pink color to the islets when observed with a diffuse green light against a black background. Islets cultured at room temperature (24 degrees C) remained functionally and morphologically intact for 1--4 wk. Insulin secretion was 1--3 microU per islet per hour, increasing to 16 microU per islet per hour at 37 degrees C. Culture alone resulted in a modest prolongation of function across a major histocompatibility barrier, Wistar Furth to Lewis (mean survival time, 11.6 +/- 1.2 vs. 7.2 +/- 0.5 days). However, one injection of antilymphocytic serum (ALS) into 10 recipients at the time of transplantation prolonged survival to greater than 100 days in nine rats. In the combination ACI to Lewis, also a major barrier, the same regimen prolonged function to greater than 100 days in five out of five recipients. Injection of donor peritoneal exudate cells resulted in prompt rejection of islets. These results suggest that culture and ALS either damage or alter passenger leukocytes in the donor tissue, thereby preventing rejection of the islets.

Animals↗
PubMed1979

Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS.

Isolated rat islets remain morphologically and functionally intact during a 7-day period of in vitro culture at 24 degrees C. In vitro culture of islets at 24 degrees C for 7 days prior to transplantation, in conjunction with a single injection of antiserum to lymphocytes into the diabetic recipient, results in islet allograft survival of 100 days when the islets are transplanted across a major histocompatibility barrier.

Animals↗
PubMed1979

Prolongation of islet allograft survival.

Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if "hand-picked," clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier.

Animals↗
PubMed1978

Elevated levels of pancreatic polypeptide in obese-hyperglycemic mice.

The concentration and distribution of pancreatic polypeptide (PP) was studied in hyperglycemic obese (ob/ob) mice and homozygous (+/+) controls. By radioimmunoassay, the concentration of PP in the pancreas of ob/ob mice was greater both in the duodenal lobe (70.7%) and in the body and tail (66.3%) when compared to identical areas of control pancreases. Analysis of immunostained pancreatic tissue indicated that the number of PP cells per islet cross-section was significantly increased (58%) in the ob/ob tissue. The calculated total number of PP cells per average islet was elevated three times in the ob/ob islet. However, the proportion PP cell volume relative to the islet volume in ob/ob was one-half that of control islets. These results clearly demonstrate an elevation in both the number of PP cells per islet and the concentration of PP in the diabetic ob/ob murine pancreas.

Animals↗
PubMed1976

Long-term perfusion of isolated rats islets in vitro.

A perfusion system is described for long-term maintenance of isolated rat islets in vitro. This system permits the monitoring of the pattern, rate, and amount of insulin secretion following repeated, acute stimulations with glucose during the period of culture. Fibroblastic proliferation did not occur, thus making is possible to reclaim the islets for biochemical and morphologic studies at the conclusion of the experiments. Maintenance of the islets with a low concentration of glucose (1.0 mg./ml.) resulted in a marked decline in insulin secretion following acute stimulations with glucose (5.0 mg./ml.) during an eight-day interval. Stimulation with 10 mM theophylline and 5.0 mg./ml. glucose on day 9 resulted in enhanced insulin release. The decline in glucose sensitivity occurred even more rapidly when the islets were maintained in the presence of a lower concentration of glucose (0.5 mg./ml.). The pattern of insulin release was altered with an absence of a first phase of secretion. Adenylate cyclase activity of islets maintained with 0.5 mg./ml. glucose for four days was significantly decreased in comparison with islets from fed rats and islets maintained with 2.5 mg./ml. glucose. A means of maintaining the same biphasic pattern and amount of glucose-induced insulin release was achieved by using alternating levels of glucose (1.5 and 2.5 mg./ml) for maintenance of the islets during a 36-day interval.

Adenylyl Cyclases↗
PubMed1975

Cinemicrographic studies on beta granule movement in monolayer culture of islet cells.

Monolayer cultures of adult rat islets were used for cinemicrographic studies on the movement of beta granules in the cytoplasm of beta cells. Stimulation of insulin release by glucose produced a significant increase in the amount of beta granule movement in the cultured cells. Disruption of the microtubular system with vinblastine or stabilization of microtubules with deuterium oxide inhibited the induction of granule movement by glucose. Incubation of the cultures in the absence of calcium inhibited glucose-induced movement of beta granules, whereas the subsequent addition of calcium permitted movement to occur. The addition of epinephrine also inhibited glucose-induced beta granule movement. In the presence of nonstimulating levels of glucose, movement of beta granules was present. The amount of movement varied from cell to cell suggesting a difference in base line activity of individual beta cells. The movement of individual beta granules was saltatory in type, and the average rate of movement was 1.5 mum. per second. The study demonstrated that directed movement of beta granules occurs following stimulation with glucose and adds further support to the hypothesis that the microtubular-microfilamentous system is involved in the intracellular translocation of beta granules to the cell surface where they are released by emiocytosis.

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