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Biomedical subjects

C F Barker

Publications and source records attributed to C F Barker.

At least 109 records · Page 6Linked to original sources
PubMed1990

Induction of donor-specific unresponsiveness by intrathymic islet transplantation.

The application of isolated pancreatic islet transplantation for treatment of diabetes mellitus has been hampered by the vulnerability of islet allografts to immunologic rejection. Rat islet allografts that were transplanted into the thymus of recipients treated with a single injection of anti-lymphocyte serum survived indefinitely. A state of donor-specific unresponsiveness was achieved that permitted survival of a second donor strain islet allograft transplanted to an extrathymic site. Maturation of T cell precursors in a thymic microenvironment that is harboring foreign alloantigen may induce the selective unresponsiveness. This model provides an approach for pancreatic islet transplantation and a potential strategy for specific modification of the peripheral immune repertoire.

Animals↗
PubMed1990

The effect of islet cell culture in vitro at 24 degrees C on graft survival and MHC antigen expression.

A period of in vitro culture prior to transplantation has been shown to prolong the survival of many types of MHC-incompatible endocrine grafts. The effectiveness of this strategy has been attributed to a selective depletion of intragraft antigen-presenting cells. We report that in vitro culture at 24 degrees C results in a significantly better survival of rat isolated islet allografts than does culture at 37 degrees C. Using in vitro assays of APC activity, we were unable to detect differences in the quantity of residual intraislet APCs between 24 degrees C and 37 degrees C culture preparations. In contrast, islet endocrine cells cultured at 24 degrees C evidenced a reduced level of cell surface class I MHC antigen expression and were significantly less vulnerable to lysis in vitro by CTL. These findings suggest that culture at 24 degrees C produces islet alterations other than APC depletion, and that its beneficial effect on graft survival correlates with a reduction in endocrine cell class I MHC antigen expression.

Animals↗
PubMed1990

Pancreatic and islet autotransplantation.

The techniques of segmental pancreatic autotransplantation and intraportal islet autografting have been reported to prevent diabetes after resection of the diseased pancreas. Unless total pancreatectomy is done, transplant function cannot be assessed without measuring insulin in the venous effluent. Islet infusion appears to be a more uncertain technique than segmental autotransplantation, probably because of technical difficulties in obtaining sufficient islets. Both methods have serious potential for morbidity and mortality, which must be balanced against the possible benefits of improved glucose homeostasis. In segmental autografts we recommend an intraperitoneal transplant site with iliac vessel anastomosis, and a lateral pancreaticojejunostomy to provide ductal drainage. For islet transplantation we recommend extreme caution and the use of only very pure islet preparations for portal vein infusions. There is insufficient long-term follow-up of patients with successful auto- or allotransplants to be certain that secondary complications of diabetes will be less than those of patients on insulin therapy. Further experience is necessary before the long-term functional survival of segmental or islet autografts will be known.

Adult↗
PubMed1989

Discriminating rejection from CMV infection in renal allograft recipients using flow cytometry.

The ability to distinguish among rejection, cytomegalovirus (CMV) infection, and cyclosporin toxicity in the symptomatic renal allograft recipient remains one of the major issues in clinical transplantation. The practical application of immunologic monitoring of peripheral blood lymphocytes through the use of fluorescently labeled monoclonal antibodies and single-color flow cytometry has been limited by the inability to demonstrate significant correlations between the levels of specific T-cell subset populations and the cause of impaired renal function. In the present study using two-color analysis, we monitored the expression of interleukin-2 receptor (IL-2R) and HLA-DR antigen on the T-cells of a group of 51 renal cadaveric allograft recipients receiving cyclosporin, azathioprine, and prednisone for an average of 4 months after transplantation. We found that the proportion of CD3+ cells coexpressing IL-2R increased above baseline during 12 out of 14 rejection episodes that took place during the course of the study (P less than 10(-6)). Alternatively, we found that the proportion of cells coexpressing HLA-DR antigen on CD2+ cells increased above baseline during 11 out of 11 CMV infections (P less than 10(-6)). There was no correlation between the level of IL-2R+CD3+ cells and CMV infection or between the level of CD2+DR+ cells and rejection. These relationships showed a high degree of sensitivity and specificity when used to discriminate among possible etiologies for decreased renal function in the symptomatic patient.

Adolescent↗
PubMed1989

Late failure of reversed vein bypass grafts.

Late failure of reversed vein bypass grafts is preceded by the appearance of stenotic lesions, which progress to total occlusion. These lesions appear either as intrinsic graft lesions or as new arteriosclerotic lesions in contiguous arteries. The present study summarizes the University of Pennsylvania experience with these lesions in 521 vein grafts inserted from 1979 to 1985. The grafts were grouped according to the site of the distal anastomosis; 231 above-knee popliteal (FP AK), 171 below-knee popliteal (FP BK), and 119 tibial (FT). The overall incidence of stenotic lesions was essentially identical with the three grafts (21%), but the relative incidence of intrinsic graft to arterial lesions was higher with the more distal grafts. The most common graft lesions developed adjacent to the proximal anastomosis, which is the narrowest part of a reversed vein graft. The popliteal artery was the most common site of outflow stenosis. There was negligible incidence of tibial lesions. The most common inflow arterial lesion was located in the common femoral and iliac arteries. The superficial femoral artery (SFA) was a rare site of inflow stenosis, even though it was at risk because 96 grafts originated from the SFA or popliteal artery. Sixty-seven per cent of the graft and 52% of the arterial lesions were treated successfully by percutaneous transluminal angioplasty; the rest had minor surgical revisions. This resulted in a 19%, 10%, and 9% improvement in 5-year patency for the FT, FP BK, and FP AK bypasses. These results justify an aggressive policy of graft surveillance to identify and treat stenotic graft lesions before graft occlusion.

Graft Occlusion, Vascular↗
PubMed1989

Modulation of the major histocompatibility complex antigen and the immunogenicity of islet allografts.

Modulation of major histocompatibility complex (MHC) antigen by parenchymal cells and "passenger leukocytes" is a common feature of allograft rejection. To assess its significance we have examined the fate of antigen-presenting cell (APC)-depleted pancreatic islet allografts subsequent to increasing their expression of MHC antigens by in vitro exposure to the lymphokine interferon-gamma (gIFN). While most untreated grafts survived indefinitely, gIFN-exposed grafts were acutely rejected. Using in vitro islet cell-lymphocyte coculture assays, we attempted to dissect the underlying mechanism of enhanced islet cell immunogenicity resulting from gIFN treatment. We determined that gIFN exposure did not affect the capacity of islet cells to serve as APC for T lymphocytes, however islet cell exposure to gIFN was associated with enhanced vulnerability to allogeneic cytotoxic T lymphocyte (CTL) lysis in vitro by an CD5+ (OX-19+), CD8+ (OX-8+), CD4- (W3/25-), class I-restricted CTL. On the basis of these findings, we conclude that antigenic modulation can be a decisive factor in the survival of engrafted tissues by augmenting the interaction of the graft antigens with cytolytic effector T lymphocytes.

Animals↗