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Biomedical subjects

D B Kaufman

Publications and source records attributed to D B Kaufman.

At least 73 records · Page 4Linked to original sources
PubMed1989

Cold-storage preservation of the canine and rat pancreas prior to islet isolation.

Cold-storage preservation of the canine pancreas prior to islet isolation has previously been noted to reduce the intrasplenic islet autograft success rate; but the mechanism of this deleterious effect has not been determined. We undertook a study in both outbred dogs and Lewis (RT1-1) rats to determine the influence of cold-storage preservation interval, preservation solution, and flushing technique on islet yield and islet viability. The preservation solutions used were those that had proved most efficacious in preserving segmental canine pancreases--namely, the modifications of silica gel fractionated plasma (SGF-III and SGF-IV) and an hydroxyethylstarch/lactobionate solution (UW-1). In the first set of experiments, the traditional vascular flush was used; this was followed by storage at 4 degrees C. After brief periods of preservation (3 hr in the rat, 12 hr in the dog) there was a significant (P less than 0.006) reduction in islet yield. The reduced yields were similar with each solution tested, were made worse with increasing intervals of storage, and resulted in a significant reduction in autograft success rate. The second set of experiments examined the effect of using an intraductal flush prior to preservation, along with the effect of adding collagenase to the preservation fluid. Islet yields were maintained at control values in both animal models using preservation intervals of up to 24 hr. These islet yields produced auto- or isograft success rates similar to those obtained by transplanting freshly obtained tissue; verifying adequate islet viability. We recommend that a pre-storage ductal flush technique be used for cold-storage preservation of the pancreas prior to islet isolation and transplantation.

Animals↗
PubMed1989

Long-term survival following kidney transplantation in 100 type I diabetic patients.

Between December 1966 and April 1978, 265 uremic patients with type I diabetes received primary renal allografts at the University of Minnesota. One hundred of the diabetic patients were alive with a functioning graft 10 years after transplantation. The actual 10-year patient and primary graft functional survival rates overall were 40% and 32%, respectively. For recipients of HLA-identical sibling (n = 45), mismatched living-related (n = 121), and cadaver donor grafts (n = 99), the actual 10-year patient survival rates were 64%, 33%, and 36%, respectively, and the actual 10-year graft functional survival rates were 62%, 28%, and 22%, respectively. The differences in patient and graft survival rates between HLA-identical graft recipients and recipients of mismatched related and cadaver grafts were significant (P less than 0.001). Of the 100 patients who survived into a second decade, at 15 years posttransplant 51% were alive, and 41% had functioning grafts. For recipients of HLA-identical sibling, mismatched living-related donor grafts, and cadaver donor grafts who survived 10 years, 47%, 57%, and 43%, respectively, were alive at 15 years, and 31%, 45%, and 43%, respectively, had functioning grafts. For recipients who made it to the second decade, patient and primary graft survival rates thereafter were not statistically different by donor source. Twenty-three patients died in the second decade after transplantation, 10 of cardiovascular disease. Twenty-five patients lost graft function in the second decade, 19 from death with a functioning graft. In regard to diabetic complications, recurrence of diabetic nephropathy was common, but only two patients lost graft function solely for this reason. In 21 patients (42 eyes) followed prospectively for 10 years, visual acuity deteriorated in 26%, was stable in 64%, and improved in 10% of eyes. Neurophysiological test results indicated that correction of uremia does not stop the progression of diabetic neuropathy in recipients of kidney transplants alone. Even without cyclosporine, nearly two-thirds of recipients of HLA-identical kidney grafts, more than one-quarter of recipients of mismatched living-related donor grafts, and more than one-fifth receiving cadaver grafts enjoyed an extension of life for more than 10 years.

Age Factors↗
PubMed1989

Renal transplantation between living-related sibling pairs matched for zero-HLA haplotypes.

The functional survival rates of kidney grafts from zero-HLA haplotype-matched sibling pairs are similar to one-haplotype-matched pairs and superior to cadaver grafts. From January 1980 to March 1988, 318 primary renal transplants from sibling donors (151 matched for two, 130 for one, and 37 for zero HLA haplotypes), and 352 cadaver graft transplants were performed at the University of Minnesota. The renal graft survival rates at two years were 94%, 91%, and 94% for the 2, 1, and 0-haplotype pairs versus 75% for cadaver graft recipients (P less than 0.04). When analyzed across the different immunosuppression protocols the same trends held up, similar graft functional survivals for 1- and 0-haplotype-matched pairs both being superior to cadaver graft recipients. The graft functional survival rates at two years of recipients of 0-haplotype-matched sibling donor grafts (n = 37) was 94% versus 80% for recipients of cadaver donor grafts matched for greater than or equal to 4 HLA antigens. In addition, for recipients of 0-haplotype-matched grafts, hospital stay was shorter, fewer patients required dialysis posttransplant, and, despite a slightly higher incidence of rejection episodes (51% versus 40%, P = ns), the creatinine values one year posttransplant were significantly lower (1.5 mg/dl versus 1.9 mg/dl, P less than 0.02) than those of recipients of cadaver grafts matched for greater than or equal to 4 HLA antigens. These data support the use of cadaver grafts for patients not having a willing sibling donor, and the use of all willing sibling donors, whether or not they are a zero-haplotype match, for patients fortunate to have that family commitment.

Antilymphocyte Serum↗
PubMed1989

Effect of immunodepletion of MHC class II-positive cells from pancreatic islets on generation of cytotoxic T-lymphocytes in mixed islet-lymphocyte coculture.

In vitro manipulation of pancreatic islets to decrease islet immunogenicity before transplantation has largely been directed at eliminating the major histocompatibility complex (MHC) class II-positive passenger leukocytes from the islets. The mixed islet-lymphocyte coculture (MILC) system was used to quantitate the efficacy of immunodepletion of MHC class II-positive cells from pancreatic islets in terms of reducing immunogenicity. With these experiments we compared the in vitro immunogenicity of MHC class II-depleted islets with untreated islets. B10.BR (H-2k) islets were treated with anti-Iak alloserum followed by complement. This treatment successfully eliminated MHC class II-positive cells from the islets, as demonstrated by indirect immunofluorescence techniques. Depleted islets generated slightly lower amounts of allospecific cytotoxic T-lymphocyte (CTL) activity when exposed to C57BL/6 (H-2b) splenocytes in the MILC than untreated control islets. Although the amount of CTL generated by the depleted islets was slightly less than that generated by untreated islets, there was significant stimulation of CTL by the MHC class II-depleted islets. Therefore, the presence or absence of MHC class II cells within the islet is unlikely to be the decisive factor contributing to islet immunogenicity.

Animals↗
PubMed1988

In vitro generated allospecific cytolytic T lymphocytes injure pancreatic islets.

The role of cytotoxic T lymphocytes in the rejection of pancreatic islet allografts remains poorly defined. The present study was designed to assess the ability of in vitro generated cytolytic T lymphocytes to produce allospecific functional and structural damage of mouse pancreatic islets. A mixed lymphocyte-islet coculture model (MLIC) has been developed, in which islets from DBA/2J mice (H-2d) stimulate the generation of allospecific cytolytic T lymphocytes (C57B1/6, H-2b), as measured by lysis of allospecific chromium-labeled tumor targets. Responder C57B1/6 splenocytes sensitized to DBA/2J islets were harvested from the MLIC on Day 5 and cocultured with either freshly isolated DBA/2J or B10.BR (H-2K) islets. Islet injury was determined by assessment of beta cell function after 8 hr (as measured by insulin release in response to a glucose challenge) and islet destruction after 24 hr of coculture with the sensitized splenocytes. Whereas coculture of third party B10.BR islets with MLIC-sensitized C57B1/6 anti-DBA splenocytes had no effect on insulin release or structure, incubation of allospecific DBA/2J islets with these splenocytes resulted in inhibition of insulin release after 8 hr and disintegration of the islets by 24 hr. The depletion of MLIC-sensitized C57B1/6 anti-DBA splenocytes with anti-Lyt2 monoclonal antibody, but not anti-L3T4 monoclonal antibody, prevented the allospecific destruction of fresh islets by the splenocytes in culture. This study suggests that allospecific, cytotoxic T lymphocytes may play an important role in the effector mechanism of pancreatic islet allograft destruction.

Animals↗
PubMed1988

A single-center experience of renal transplantation in thirteen Jehovah's Witnesses.

The beneficial effects of pretransplant blood transfusions on the success rate of renal transplantation have been so overwhelmingly emphasized that there is virtually no information on the fate of grafts in nontransfused patients transplanted during the last decade. Since 1979, all patients who have undergone renal transplantation at the University of Minnesota have routinely received random blood transfusions except Jehovah's Witnesses. Jehovah's Witnesses refuse transfusions but will accept renal allografts. From 1979 to May 30, 1987, primary renal allografts were placed in thirteen nontransfused Jehovah's Witnesses; six patients received kidneys from mismatched living-related donors, two patients received HLA-identical sibling grafts, and five patients received cadaveric renal allografts. The range of follow-up of the thirteen patients was 3-93 months, with a mean of 45 months and a median of 50 months. The outcomes after renal transplantation in Jehovah's Witnesses were compared with those of a paired control group (n = 25) matched for age, date of transplant, donor source, and diabetic status. The overall three-year actuarial patient and graft survival rates of the Jehovah's Witnesses were 83 per cent and 66 per cent, versus 80 per cent and 77 per cent for the controls. Although the outcomes after renal transplantation in Jehovah's Witnesses were similar to those of the control group, the Jehovah's Witnesses had an increased susceptibility to rejection episodes. The cumulative percentage of incidence of primary rejection episodes was 77 per cent at three months in the Jehovah's Witnesses versus 44 per cent at 21 months in the matched control group. The consequence of early allograft dysfunction from rejection was particularly detrimental to Jehovah's Witnesses who developed severe anemia (hemoglobin (Hgb)* 4.5 g per cent)-two early deaths occurred in the subgroup with this combination of problems. The overall results suggest that renal transplantation can be safely and efficaciously applied to most Jehovah's Witnesses but those with anemia who undergo early rejection episodes are a high-risk group relative to other transplant patients.

Actuarial Analysis↗
PubMed1988

Weight-corrected islet counts are predictive of outcome in the canine intrahepatic islet autograft model.

A combination of high-concentration collagenase digestion and density-gradient purification of canine pancreatic tissue made it possible to obtain relatively pure islets which could be quantified and the outcome of intrahepatic autotransplantation correlated with weight-corrected islet counts in the transplanted tissue. Of eleven dogs, seven achieved durable euglycaemia within 24 hours. All of these animals received islet doses of greater than 4,380 per kilogram of body weight. The remaining four animals became progressively hyperglycaemic necessitating sacrifice within one week; they all received islet doses of less than 4,380 per kilogram (p = 0.042). This model is therefore satisfactory for the investigation of preservation injury to islets and of allotransplantation because it identifies prospectively the transplants which ought to succeed, giving evidence for or against additional immune or ischaemic resistance to graft function.

Animals↗
PubMed1988

Retain and retrain.

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Dental Auxiliaries↗