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Biomedical subjects

C F Barker

Publications and source records attributed to C F Barker.

At least 127 records · Page 7Linked to original sources
PubMed1989

Prevention of recurrent diabetes in BB rats after islet transplantation by monoclonal antibody therapy.

Two immune responses imperil pancreatic islet allografts transplanted into subjects afflicted with autoimmune diabetes: 1) the well-described allograft response that is mounted against tissues bearing foreign transplantation antigens and 2) a recurrence of the beta-cell-specific autoimmune process responsible for the primary disease. To define the role of autoimmune response to transplanted islets, the possibility of a rejection response must be prevented. To accomplish this in spontaneously diabetic BB rats, we induced neonatal tolerance. We found that recurrent autoimmunity in tolerant BB rats can be prevented by treatment of recipients with the monoclonal antibody OX8 (specific for cytotoxic T-lymphocytes) but not W3/25 (specific for helper T-lymphocytes). These findings provide direct evidence for the role of OX8-bearing lymphocytes in autoimmune diabetogenesis.

Animals↗
PubMed1988

Prophylaxis of serious cytomegalovirus infection in renal transplant candidates using live human cytomegalovirus vaccine. Interim results of a randomized controlled trial.

We report the interim results of a randomized, double-blind, placebo-controlled, clinical trial of prophylactic, live, attenuated cytomegalovirus (CMV) vaccination (Towne strain of CMV) of renal transplant candidates (RTCs). One hundred seventy-two RTCs were treated and subsequently underwent transplantation and followed up for at least one year and up to five years after transplantation. Eighty-eight RTCs received vaccine, and 84 received placebo. Results were analyzed according to the prevaccination serologic status (anti-CMV antibody titer) of the recipient (R- or R+) and the donor (D- or D+). The overall incidence of CMV disease was highest in the R-D+ group and almost absent in the R-D- group. There was no difference in the incidence of CMV infection or disease between vaccinated and respective placebo control recipients in either the R-D+, R+D+, R+D-, or R-D- groups. In contrast, the severity of CMV disease was significantly decreased in R-D+ vaccinees vs R-D+ placebo-treated recipients. Moreover, in the R-D+ group, one- and five-year cadaver renal allograft actuarial survival rates were 73% and 62%, respectively, for CMV vaccinees vs 40% and 25%, respectively, for control placebo patients. We conclude that seronegative cadaver RTCs may benefit from vaccination with live, attenuated, Towne strain CMV vaccine before transplantation.

Adult↗
PubMed1988

Prevention of recurrent autoimmune diabetes in BB rats by anti-asialo-GM1 antibody.

BB rats exhibit a syndrome of spontaneous diabetes that has clinical and pathological characteristics analogous to those found in human insulin-dependent diabetes mellitus (IDDM). Islet tissue transplanted into spontaneously diabetic BB rats is uniformly destroyed by a recurrence of the autoimmune response that destroyed the diabetic subject's native islets. To examine recurrent autoimmune destruction of transplanted islets, it is necessary to exclude islet damage that might result from allograft rejection. We utilized neonatal tolerance induction to prevent rejection of Wistar-Furth (WF) (RT1u) islet allografts by spontaneously diabetic BB recipients. We determined that islet-recipient treatment with anti-asialo-GM1 (anti-AGM1) antibody prevents recurrent autoimmune diabetes that would otherwise destroy transplanted WF islet grafts. Anti-AGM1 therapy significantly decreased peripheral blood natural killer (NK) cell activity. These data suggest a role for NK cells in the pathogenesis of recurrent diabetes in neonatally tolerant BB rats.

Animals↗
PubMed1988

Immunoprediction of diabetes and evaluation of pancreatic islet transplantation during the prediabetic period.

The autoimmune diabetic syndrome of the biobreeding (BB) rat currently constitutes the best animal model for human type I diabetes. Since prediction of human beings at high risk for development of diabetes by immunologic and physiologic parameters is not possible at present, we investigated the feasibility of immunoprediction of diabetes in normoglycemic BB diabetes-prone (BBdp) rats. Peripheral blood lymphocyte counts (PBLC) accurately predicted future development of diabetes in a cohort of 50 BBdp rats (100% specificity, 95.8% sensitivity for PBLC less than 3800/mm3). We also assessed the fate of normal islets transplanted from MHC-compatible non-diabetes-prone Wistar Furth (WF) donors in the prediabetic milieu of BBdp hosts that were known on the basis of their PBLC destined either to become diabetic or to remain normoglycemic. In 13 BBdp rats in which diabetes was predicted the native pancreatic beta cells were eliminated at 35 days of age with streptozocin and replaced with transplanted WF islets. Neonatally induced tolerance of WF antigens prevented rejection. After successful islet transplantation, spontaneous diabetes occurred in 100% (5/5) of the rats in which the development of diabetes was predicted. The identical protocol in eight rats predicted not to have diabetes resulted in permanent normoglycemia in all. We conclude that normal islets are susceptible to anti-islet autoimmunity after transplantation in the prediabetic period.

Animals↗
PubMed1987

Elevated levels of a lymphocyte subset accurately predict the diabetic state in the BB rat.

The frequency of Ia antigen bearing W3/13 positive lymphocytes from the blood of 68 bio-breeding (BB) diabetes-prone rats was analyzed with monoclonal antibodies to determine whether elevated levels of these cells could predict which animals would subsequently become hyperglycemic. Selecting a value of greater than or equal to 4.00% as elevated, the sensitivity of this assay in predicting diabetes was 85%, while the specificity was 83%. We believe that elevated levels of Ia antigen bearing W3/13 positive lymphocytes reflect an ongoing immune process and accurately predict the likelihood of developing spontaneous hyperglycemia when obtained from a high risk population.

Animals↗
PubMed1987

Gamma interferon induces novel expression of Ia antigens by rat pancreatic islet endocrine cells.

Pancreatic endocrine cells normally express only Class I gene products of the major histocompatibility complex (MHC). Recently it has been shown that in both patients with recent onset type I diabetes and acutely diabetic BB rats, residual islet beta cells express Class II MHC antigens. In an attempt to define a potential inducer of this aberrant Class II antigen expression, we have investigated the effect of in vitro incubation of rat isolated pancreatic islets with the lymphokine gamma interferon (IFN-gamma) on MHC antigen expression. Our results demonstrate that in vitro exposure to IFN-gamma induces novel expression of Class II antigens on the surface of rat islet endocrine cells and increases the level of pre-existing Class I antigen expression.

Animals↗
PubMed1987

Percutaneous transluminal angioplasty. The procedure of choice in the hypertensive renal allograft recipient with renal artery stenosis.

A retrospective review of 547 renal transplants performed over a six-year period revealed allograft renovascular hypertension secondary to RTAS in 39 (7.1%) patients. Percutaneous transluminal angioplasty (PTA) resulted in immediate cure or improvement in 76% of the patients, increasing to 83% in patients with functioning kidneys at a mean follow-up period of 30 months (1-72 months). The renal artery stenosis (RTAS) was equally distributed between living-related and cadaver kidney recipients and did not appear to be more prevalent in end-to-end or end-to-side anastomoses. The blood pressures fell from pre-PTA levels of 167 +/- 22 mmHg systolic to 141 +/- 23.7 post-PTA and 102 +/- 11 mmHg diastolic pre-PTA to 88 +/- 12 mmHg post-PTA (P less than 0.01). Of 25 cured or improved patients, 24 are on significantly less hypertensive medication. Two patients died of causes unrelated to the PTA and only one patient lost a kidney because of the procedure. Compared with operation, PTA is a safer and more effective procedure for the initial treatment of RTAS.

Adult↗
PubMed1987

[Effect of autoimmune destruction and rejection on the function of transplanted islands of Langerhans in spontaneous diabetes in the BB rat].

In animals and human identical twin transplants the autoimmunity of naturally occurring diabetes may destroy transplanted islets, even if rejection is avoided. We studied the influence of transplant site (liver vs. kidney capsule) and pretransplant treatment (culture) on autoimmune damage and rejection of transplanted islets of Langerhans in BB-rats which spontaneously developed diabetes. Freshly isolated and in the liver transplanted islets were destroyed rapidly (on the base of autoimmune destruction, rejection or both). In contrary, the renal subcapsule shows to be immunologically privileged with long survival of transplants. Culture pretreatment of MHC-incompatible Lewis islets resulted in long survival of transplants, which was not true in case of MHC-compatible WF islets: immunological disparity of donor and recipient tissue might be most successful in preventing autoimmune damage and rejection.

Animals↗