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Biomedical subjects

C F Barker

Publications and source records attributed to C F Barker.

At least 181 records · Page 10Linked to original sources

Spontaneous diabetes in rats: destruction of islets is prevented by immunological tolerance.

Spontaneous diabetes occurring in "BB" rats (derived from a colony of outbred Wistar rats) is the result of destruction of pancreatic islets by infiltrating mononuclear cells (insulitis) and may be a disease very similar to human juvenile onset diabetes. Both diseases probably have an autoimmune etiology. Evidence is presented that islets transplanted to diabetic BB rats are destroyed by the original disease process. Inoculation of bone marrow from normal (nondiabetes-susceptible) rat donors into neonatal BB recipients usually prevented the development of hyperglycemia.

Animals↗

Prevention of diabetes in rats by bone marrow transplantation.

Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation.

Animals↗

Studies of the immediately vascularized skin allograft.

In order to evaluate the effect of the nature of revascularization on survival rates of skin allografts, a rat model was devised which provided simultaneous and immediate establishment of arterial and venous blood supply to a composite skin-renal allograft. For 5 days after transplantation the skin portion of the composite grafts appeared normal, with minimal inflammation in 11 recipients. From 6 to 11 days, in 6 rats, active rejection developed with a marked inflammatory reaction of the skin-kidney interface. In 10 rats in which the composite grafts remained in the secondary hosts for 12--21 days rejection of the skin was complete. The renal portion of all composite grafts appeared normal in all three panels and all recipients of composite grafts rejected subsequent orthotopic skin grafts in an accelerated manner, with median survival time of 8.2 +/- 0.3 days compared with 11.5 +/- 0.7 days in untreated Fisher leads to Lewis controls. These results demonstrate that the skin on the composite graft retained its immunogenicity, that immediately vascularized skin allografts between AgB compatible rats will be rejected in a normal time and that anatomical factors are not sufficient to account for the difference in survival times between skin and solid organs.

Animals↗

Granulocyte function in recipients of renal transplant from live related donors and from cadavers.

Granulocyte adherence, chemotaxis, phagocytosis, and bactericidal activity were studied in patients receiving renal transplants to determine whether defects in granulocyte function can explain increased susceptibility to infection. Five points were studied: preoperatively; immediately after transplantation; at the time of any rejection crises (when the patient was receiving large doses of prednisone and azathioprine); at discharge; and six months postoperatively with stable renal function. The major defect was depressed granulocyte adherence early postoperatively and at the time of rejection crises, when prednisone dosage was maximal. Chemotactic activity improved progressively after transplantation despite large doses of prednisone and azathioprine and was supranormal at the time of rejection crises. Phagocytosis was enhanced early postoperatively and at the time of rejection crises. Bactericidal activity was unaffected by renal transplantation and immunosuppressive therapy in recipients of transplants from live related donors, but was depressed in recipients of cadaveric kidneys.

Azathioprine↗

Inadvertent transplantation of a melanoma.

A cadaver renal allograft recipient with normal function for over 3 years developed metastatic melanoma and died within months despite cessation of immunosuppression and allograft nephrectomy. Two additional immunotherapeutic modalities were attempted when it became obvious that the tumor was not a de novo malignancy but rather an inadvertently transplanted one. Neither reexposure to the allograft antigens nor administration of alloantiserum from the patient who had received and rejected the mate of the kidney from the same donor affected the rapid growth of the melanoma in our patient. Of extreme interest is that a focus of melanoma was found in the allograft removed from the surviving patient.

Adult↗

Bilateral complete ureteral obstruction secondary to an abdominal aortic aneurysm with perianeurysmal fibrosis: diagnosis by computed tomography.

The sixteenth case of bilateral ureteral obstruction with anuria secondary to an abdominal aortic aneurysm with perianeurysmal fibrosis is presented. The details of this case clearly indicate the need for a combined vascular and urologic approach to patients with this disorder. A complete preoperative evaluation, including excretory urography, retrograde pyeloureterography, aortography and, when indicated, venacavography, may determine renal and vascular abnormalities that will allow a more definitive and successful management of this difficult problem. Furthermore, we believe that the use of computed tomography is an invaluable tool to define this retroperitoneal disease process and its precise relationship to the ureters.

Aged↗