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Renal allograft survival was prolonged in rabbits, a species in which antibody mediated hyperacute rejection can occur, by administering large quantities of donor specific F(ab')(2) alloantibody. In 13 control animals, onset of uremia with histological evidence of rejection occurred at a mean of 6.0 days. Eight of eight rabbits actively immunized and seven of nine rabbits passively immunized with unmodified donor specific IgG alloantibody hyperacutely rejected an allografted kidney. Four rabbits treated with non-specific F(ab')(2) for one week acutely rejected an allografted kidney at a mean of 6.2 days. In 12 recipient rabbits receiving 100-500 mg of donor specific F(ab')(2) alloantibody for a mean of 8.5 days, onset of uremia was delayed to a mean of 14.5 days following transplantation. Recipients were selected so that the donor specific F(ab')(2) alloantibody employed had no activity against recipient antigens. This selection maximized the antigenic difference between the donor and recipient, and also assured us that the donor specific F(ab')(2) was directed against antigens present in the donor but absent in the recipient. Passive administration of donor specific F(ab')(2) allowed antibody mediated suppression of a specific immune response to occur without risk of hyperacute rejection. However, the onset of rejection could not be delayed indefinitely by this treatment. The experimental conditions employed and the difficulties encountered closely resemble those which will occur for clinical utilization of passive immunological enhancement.

Immunoglobulins and complement are deposited in the glomerular mesangium of rats with progressive glomerulosclerosis secondary to chemically induced diabetes mellitus. Isotransplantation of a kidney from a rat diabetic for 6 mo into a normal recipient results within 2 mo in the disappearance of IgG, IgM, and ß1C from the mesangium and arrest or reversal of the light microscopic glomerular lesions. Kidneys isotransplanted from normal donors into diabetic rats developed mesangial matrix thickening and deposition of IgG, IgM) and ß1C in the mesangium. No glomerular changes occur upon transplantation of a normal kidney into a normal rat. These findings indicate that diabetic glomerular changes in the rat are reversible and are secondary to the diabetic state rather than to the inducing agent.

A mechanism of immune glomerular injury is described based on the fixation of antibody (Ab) to an antigen (Ag) that has localized in the glomerular mesangium. Rabbits were given, intravenously (i.v.), aggregated human IgG (AHIgG) or albumin (AHSA) and 10 h later, when the Ag by immunofluorescent microscopy was present in the mesangium, a kidney was removed and transplanted into a normal rabbit. The recipient then received, i.v., rabbit anti-HIgG or anti-HSA. Within minutes of Ab infusion, glomeruli of the donor kidney had polymorphonuclear (PMN) infiltration that over the next few hours became marked and was associated with glomerular cell swelling. At 24 h a decrease in PMN's and early mesangial proliferation was seen. By 3 days there was marked mesangial hypercellularity and increased mesangial matrix. Within minutes after Ab administration rabbit IgG, C3, and fibrin were seen in the glomerular mesangium. There was a fall in complement titer by 1 min after Ab infusion that was due to complement consumption by the donor kidney. Complement then returned to normal levels by 48 h. Significant glomerular injury did not occur (a) in the recipient's own kidney, (b) from Ag administration and transplantation without recipient Ab administration, or (c) from transplantation and Ab administration without prior Ag administration. These studies demonstrated that Ag localized in the glomerular mesangium can react with circulating Ab and complement resulting in severe glomerular injury.

SummaryRabbits thymectomized and appendectomized at birth, and challenged with bovine gamma globulin at 7-9 weeks of age, produce much lower titers of antibody than sham-operated animals. The titers of this group were also significantly lower than those of rabbits subjected to thymectomy alone, appendectomy alone, or combined thymectomy and splenectomy. The suppression of antibody-producing capacity in the thymecto-mized-appendectomized animals was paralleled by lack of lymphoid tissue development and by low levels of circulating lymphocytes through the period of study.

Diabetes was induced in Lewis rats with streptozotocin. Six to nine months later glomeruli showed significant mesangial matrix thickening; by immunofluorescent microscopy large quantities of IgG, (β1C and in some instances, IgM were seen in a mesangial distribution. Sustained normoglycemia was then achieved in nine of these animals by successful pancreatic islet isotransplantation. Three months following transplantation five of these animals had decreased mesangial matrix while four had no further progression of glomerular lesions. All had a marked decrease in IgG, IgM and β iC in the mesangium. In contrast, untreated diabetic rats, over the same time period, demonstrated progressive mesangial thickening and focal tuft sclerosis. Immunoglobulins and complement were in the mesangium in quantities equal to or greater than seen in earlier biopsies. Thus, successful pancreatic islet transplantation in the rat results in regression or arrest of the diabetic glomerular lesion.

Using a modification of the collagenase digestion, Ficoll gradient separation technique, we isolated the islets of Langerhans from fresh human pancreata removed from braindead cadavers. Comparison of the tissue insulin/amylase ratios between whole pancreas and isolated material revealed a significant purification of islet from acinar tissue. Also, islets isolated by this technique, when incubated in vitro , incorporated radiolabeled amino acid precursors into acid-alcohol-soluble islet proteins, thus indicating their viability and protein hormonal synthesis capabilities. Pig pancreata were processed by a similar technique, and the isolated material was transplanted to pigs with diabetes induced by total pancreatectomy. The mean survival time of the 11 pancreatectomized pigs that received an islet transplant was 15.3 days, while 13 pancreatectomized control pigs had a mean survival time of 6.0 days. Control pigs had no detectable circulating insulin 2 days after pancreatectomy. The pancreatectomized pigs that received an islet transplant, although remaining hyperglycemic, had insulin levels ranging from 5 to 14 μU/ml for up to 25 days after transplantation. The present studies demonstrate the feasibility of an approach designed for our ultimate goal—the large scale isolation and transplantation of islets in man.

A congenital duodenal diaphragm was encountered in an adult previously treated with gastroenterostomy for vascular compression of the duodenum. Impediment of a normal embryologic process results in the former lesion whereas the latter may arise secondarily as a result of debilitation. Survival into adulthood depends on the presence of a perforation within the diaphragm. The difficulties in establishing the correct diagnosis clinically, radiographically, and at exploration may lead to inadequate treatment. A duodenotomy with excision is the procedure of choice for duodenal diaphragm. A duodenojejunal bypass provides satisfactory treatment for vascular compression of the duodenum.

The ability to differentiate renal allograft rejection from other causes of impaired renal function using [125]fibrinogen was evaluated using a rabbit renal transplantation model. By measuring radioactivity over the kidney and comparing it to that over the heart, rejection could clearly be differentiated from renal artery or vein thrombosis, hydronephrosis or ischemic damage.