Walter F. Ballinger

Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats

SummaryIsolated pancreatic islets were transplanted isogeneically into the subcutaneus tissue, peritoneum and portal vein of diabetic rats. Implantation of islets subcutaneously did not modify the diabetic state. Intraperitoneal islets ameliorated the effects of diabetes but normal urine volumes, blood glucose and urine glucose levels were not achieved. Direct injection of islets into the portal vein resulted in normal urine volumes, normoglycemia and abolition of glycosuria in the rats studied. These effects have been maintained 2 months later. — It is suggested that the portal environment may be the most effective site for transplanted pancreatic islets.

A Morphologic Study of Intrahepatic Portal-vein Islet Isografts

Isologous pancreatic islets were implanted into the portal vein of rats with streptozotocin-induced diabetes. At intervals of from one to 32 days after transplantation, the intraheptic islet grafts were examined histologically and ultrastructurally, and their vascular supply was determined by later perfusion studies. Implanted islets were found widely dispersed throughout the liver in peripheral interlobular portal venules and surrounded by vacuolated liver cells containing large stores of glycogen. The endocrine cells were structurally normal in each interval examined. By the third day after transplantation the beta cells were depleted of secretory granules in aldehyde-fuchsin preparations. Regranulation returned by the 14th day and was associated with secretory organelle hypertrophy and hyperplasia. Islet cells were found outside the portal areas in direct apposition to hepatocytes forming distinct desmosomes by the first day. While hemoperfusion of the grafts occurred from the moment of implantation into the portal venule, a ual vascular supply derived from periportal arterial and venous sources developed by the 11th day after transplantation, establishing full vascularization of the grafts. Preliminary work is presented to show that an active ingrowth of nerves in the islet graft occurs in association with the process of vascularization.

Pancreatic islet banking: The transplantation of frozen-thawed rat islets transported between centers

Abstract This report describes the feasibility of islet banking for the purpose of transporting isolated islets from one center to another for transplantation. Adult rat islets survived freezing to −196 °C when 0.25 °C/min was used as the cooling rate, 7.5 °C/min as the warming rate, and when the hyperosmotic protective agent was carefully removed. We were able to show that islets isolated and frozen in one center and transplanted in another center returned diabetic animals to clinical normalcy (fasting normoglycemia, aglycosuria, and weight maintenance). However, as measured by a glucose tolerance test three months after transplantation, these animals had an impaired early insulin release when compared with animals who received fresh islet transplants. Diabetic animals that received islets frozen at a cooling rate of 1.0 °C/min remained diabetic as measured by our clinical parameters. Thus specific definition of conditions used for cryopreservation is important in developing methods suitable for islet banking.

Effects of cold storage on the function of isolated pancreatic islets.

Abstract Isolated pancreatic islets from Lewis rats were stored at 4 °C for periods up to 96 hr. A normal pattern of insulin secretion in response to high glucose concentrations was demonstrated in islets stored for up to 48 hr but not in islets stored for longer than this time. The 4 °C environment may be adequate for temporary storage of isolated pancreatic islets but is not suitable for their long-term preservation.

Cortisol 2i-acetate: apparently abnormal plasma levels in patients with rheumatoid arthritis

Abstract Cortisol acetate has been isolated from pooled plasma from patients with rheumatoid arthritis and its identity confirmed by I-R spectroscopy. On the assumption that the difference between the total Porter-Silber chromogens and the enzymatically determined corticosteroid level represents cortisol 21-acetate, an average of 63% of the total consisted of the acetylated compound in the rheumatoid arthritis patients, but only 8% in the control group. Evidence in support of this assumption is presented and the results suggest a metabolic abnormality of clinical significance since acetylation may affect the availability at tissue sites and delay or inhibit biological activity.