Search PubMed⌕ Search

Biomedical subjects

C F Barker

Publications and source records attributed to C F Barker.

At least 19 recordsLinked to original sources
PubMed1992

Prevention of autoimmune diabetes in the BB rat by intrathymic islet transplantation at birth.

Spontaneous diabetes in the BioBreeding (BB) rat, like human type I diabetes, results from the destruction of pancreatic islets by autoreactive T lymphocytes recognizing beta cell-specific antigens. T cell tolerance is in part mediated by interactions of maturing thymocytes with antigens expressed in the thymic microenvironment; islets were therefore implanted into the thymus of neonatal diabetes-prone BB rats to determine whether exposure of T cell precursors to beta cell antigens could influence the development of diabetes. This treatment completely prevented diabetes and insulitis in the native pancreas. The effect may be the result of specific modulation of diabetogenic T cells maturing in an islet-bearing thymus.

Animals↗
PubMed1992

Direct assessment of the role of NK cells in autoimmune diabetes.

Considerable indirect evidence implicates participation of natural killer cells (NK) in the pathogenesis of diabetes in BB rats. The most convincing evidence derives from studies showing that anti-CD8 antibody effectively prevents both primary disease onset and autoimmune damage to transplanted islets. However, anti-CD8 treatment depletes both NK and cytotoxic T cells (CTL) since both cell types express the CD8 marker. To study directly the role of NK in diabetic BB rats we used MCA 3.2.3, a monoclonal antibody which selectively depletes normal Lewis rats of NK cells but not CTL. A regimen of ip injected antibody achieved rapid reduction of NK cells in diabetic and nondiabetic BB rats by FACS analysis. NK cell activity remained low in rats treated weekly as evidenced by YAC tumor cell killing. We next studied the effect of NK depletion on disease incidence in diabetes-prone BB rats of which about one half are expected to develop diabetes. Onset and incidence of diabetes in 3.2.3-treated and control antibody-treated aged matched litter mates were equal. These studies suggest that NK cells are not necessary for autoimmune islet destruction in spontaneously diabetic BB rats and support a role for CTL in pathogenesis of the disease.

Animals↗
PubMed1992

Magnetic resonance angiography of peripheral runoff vessels.

Recent improvements in magnetic resonance imaging techniques have made magnetic resonance angiography (MRA) a very useful adjunct to invasive angiography. Fifty-five limbs in 51 patients with occlusive peripheral vascular disease were studied with both MRA and contrast arteriography. The magnetic resonance and contrast arteriograms were read by radiologists and surgeons and separate interventional plans were based on each study. The MRA findings differed significantly from those of conventional arteriography in 26 limbs (48%). In every case MRA visualized all of the same vessels and hemodynamic stenoses seen on the contrast arteriogram. In 48% of the cases, however, MRA revealed additional findings. Thus the discrepancies in the two studies were always the result of the failure of the arteriogram to reveal all of the patent vessels seen on MRA. The additional information provided by MRA resulted in alteration of the interventional plan in 11 cases (22%). In nine cases (18%) target vessels suitable for use in a limb-salvage procedure were identified by MRA, although they had been missed by conventional arteriography. In all of these cases, intraoperative arteriograms confirmed the suitability of these vessels for use in technically successful bypass procedures. In two cases (4%) additional information provided by MRA identified a target runoff vessel for bypass grafting that proved to be a better alternative than the one that would have been chosen on the basis of contrast arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

A recent decrease in the time to development of monomorphous and polymorphous posttransplant lymphoproliferative disorder.

We have noted a decrease in the time to development of posttransplant lymphoproliferative disorder (PTLD) over the last two and one-half years in our multiorgan transplant program. From February 1965 until December 1990, 1622 transplants were performed including 1489 kidneys (KTxp), 87 livers (LTxp), and 46 pancreata. Between February 1965 and July 1988 (group 1), there were 1260 transplants performed and nine cases of either monomorphous PTLD (M-PTLD, n = 8) or polymorphous PTLD (P-PTLD, n = 1) were diagnosed. The mean time to development of PTLD was 163 +/- 128 weeks, all after KTxp. Five of these nine patients received haploidentical living-related grafts. All patients had presented with advanced disease, none had transplant nephrectomy, and all died of their disease. Between July 1988 and December 1990 (group 2), 362 transplants were performed, and four cases of M-PTLD and three cases of P-PTLD were recognized. Of the seven cases of PTLD in group 2, six developed within 90 days posttransplant (early PTLD). The mean time to development of PTLD was 11 +/- 16 weeks. This was significantly earlier than group 1 (P less than .01). Four of the five cases after KTxp had a 1 or 2 DR-matched donor. Five of these seven patients had serological evidence of recent Epstein-Barr Virus infection, and four of these five had received OKT3 and then developed early PTLD. In group 2, three patients are alive 7-15 months after KTxp nephrectomy, the remaining four have died. We hypothesize that risk factors for the development of PTLD may include heavy immunosuppression, including the use of OKT3, good DR matching, and active EBV infection. Treatment should include graft removal, if applicable, and reduction or cessation of immuno-suppression.

Herpesvirus 4, Human↗
PubMed1992

Indefinite survival of MHC class I-deficient murine pancreatic islet allografts.

To examine the immune response to class I-deficient allogeneic tissue, we used beta 2-microglobulin-deficient mice as graft donors. These mice lack cell surface class I major histocompatibility complex antigen expression. Pancreatic islet allografts from class I-deficient donors survived indefinitely in a majority of fully allogeneic BALB/c recipients. In contrast, host recognition of graft class I antigen was unnecessary for prompt destruction of skin allografts of for autoimmune damage of transplanted pancreatic islet grafts in nonobese diabetic mice. These studies provide evidence that intentional genetic elimination of immunologically relevant donor antigens may prove an effective strategy for preventing allograft rejection.

Animals↗
PubMed1992

Promotion of pancreatic islet allograft survival by intrathymic transplantation of bone marrow.

An important goal in the treatment of insulin-dependent diabetes by pancreatic islet transplantation is the development of strategies that allow permanent survival of islet allografts without continuous host immunosuppression. In this study, we demonstrate that inoculation of allogeneic bone marrow into the thymus of adult rats treated with a single dose of anti-lymphocyte serum induces an unresponsive state that permits survival of subsequent pancreatic islet allografts transplanted to an extrathymic site. This effect is donor specific, cannot be reproduced by systemic administration of bone marrow, and is associated with persistence of chimeric cells in the thymus of the recipient. In addition, lymph node cells from long-term recipients of intrathymic bone marrow display markedly reduced proliferative responses to donor alloantigens in mixed lymphocyte culture. Interaction of maturing thymocytes with foreign alloantigens may produce the unresponsiveness. This model offers a potential approach for establishing donor-specific allograft acceptance in adult recipients.

Animals↗
PubMed1992

Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow.

BACKGROUND: Induction of donor-specific tolerance to tissue or organ allografts can readily be achieved by administration of allogeneic bone marrow to neonatal rodents; however, in adult recipients induction of transplantation tolerance by this strategy generally requires intensive cytoablative conditioning. Described here is a novel method of promoting transplantation tolerance that involves inoculation of donor bone marrow into the thymus of transiently immunosuppressed adult recipients. METHODS: Prospective Wistar-Furth recipients were inoculated with allogeneic Lewis bone marrow cells (BMCs) either intrathymically or intravenously in conjunction with a single dose of antilymphocyte serum 2 to 3 weeks before receiving donor-strain cardiac allografts. Recipients were monitored for graft survival and examined for presence of hematopoietic chimerism. RESULTS: Intrathymic but not intravenous inoculation of donor BMCs led to permanent survival of donor-strain cardiac allografts, whereas third-party Dark agouti cardiac allografts were rejected promptly. Persistence of donor chimerism was demonstrated in the thymus of Wistar-Furth recipients of intrathymic Lewis BMCs for as long as 3 weeks after BMC inoculation. CONCLUSIONS: Intrathymic inoculation of BMCs concurrently with a single dose of antilymphocyte serum induces donor-specific unresponsiveness to rat cardiac allografts. The unresponsiveness may be the result of deletion or functional inactivation of alloreactive clones maturing in a thymus bearing donor alloantigen. Intrathymic inoculation of BMCs deserves further evaluation as a possible clinical strategy for the induction of transplantation tolerance.

Animals↗
PubMed1992

Normocalcemia thirteen years after successful parathyroid allografting in a recipient of a renal transplant.

Two months after receiving a cadaveric renal allograft, a 36-year-old woman received a parathyroid allograft from a living unrelated donor, who was haploidentical to the renal donor. Her preoperative 24-hour urinary excretion of calcium was 0.18 gm/24 hrs, and after operation it decreased to 0.004 gm/24 hrs, (normal, less than 0.20 gm/24 hrs). The C-terminal parathyroid hormone level increased from 155 pg/ml (normal, 275 to 675 pg/ml) to 327 pg/ml after operation. The N-terminal parathyroid hormone level in her grafted arm has varied between 2.5 to 10 times the level in her nongrafted arm. Thirteen years later, both allografts are functioning normally. To our knowledge, this is the longest functioning parathyroid allograft.

Calcium↗
PubMed1991

Nutritional support in renal failure.

Adequate protein intake is necessary in renal failure to reduce morbidity. The desire to avoid dialysis should not be a justification to starve patients, particularly because fed patients have better survival rates in acute renal failure. The treatment techniques for renal failure may be used secondarily as a delivery route for nutrients.

Acute Kidney Injury↗
PubMed1991

Intrathymic islet transplantation in the spontaneously diabetic BB rat.

Recently it was demonstrated that pancreatic islet allografts transplanted to the thymus of rats made diabetic chemically are not rejected and induce specific unresponsiveness to subsequent extrathymic transplants. The authors report that the thymus can also serve as an effective islet transplantation site in spontaneously diabetic BB rats, in which autoimmunity and rejection can destroy islets. Intrathymic Lewis islet grafts consistently reversed hyperglycemia for more than 120 days in these rats, and in three of four recipients the grafts promoted subsequent survival of intraportal islets. In contrast intraportal islet allografts in naive BB hosts all failed rapidly. The authors also show that the immunologically privileged status of the thymus cannot prevent rejection of islet allografts in Wistar Furth (WF) rats sensitized with donor strain skin and that suppressor cells are not likely to contribute to the unresponsive state because adoptive transfer of spleen cells from WF rats bearing established intrathymic Lewis islets fails to prolong islet allograft survival in secondary hosts.

Animals↗
PubMed1991

Anti-CD2 monoclonal antibodies alter cell-mediated immunity in vivo.

The antimurine CD2 mAb 12-15 was administered intravenously to investigate the role of CD2 in cell-mediated immunity in vivo. The anti-CD2 mAb was able to diminish the contact sensitivity response to the hapten trinitrophenyl and was most effective when administered during the efferent or elicitative phase of immunity. Antibody treatment was also able to inhibit in vivo priming for subsequent generation of secondary, TNP-specific CTL in vitro. This inhibitory effect was most effective in the afferent or early phase of immunity. Indeed antibody could be injected at least 3 weeks prior to in vivo antigen priming, and the subsequent CTL response was still suppressed. Additional experiments showed a well-defined dose-response relationship between the amount of anti-CD2 administered and subsequent immunosuppression. Control experiments showed that other isotype-matched antibodies were not suppressive and that the anti-CD2 was not merely shifting the kinetics of the CTL response. Further experiments revealed that in vivo mAb treatment could also inhibit the subsequent development of primary, alloantigen-specific CTL in vitro while the mixed lymphocyte reaction (MLR) remained unchanged. FACS analysis revealed a marked downmodulation of CD2 in vivo, a small and variable decrease in CD8, and essentially no change in CD3 or CD4 after treatment with anti-CD2. The F(ab')2 fragment was not able to downmodulate CD2 or to suppress CTL activity at the doses tested. These results support a major role for CD2 in diverse aspects of cell-mediated immunity affecting both CD4+ and CD8+ effector T cells. The anti-CD2 mAb functions not by deleting or depleting relevant cell populations but rather by altering the array of cell surface receptors and subsequent responses to antigenic challenge.

Animals↗
PubMed1991

Adrenal suppression and steroid supplementation in renal transplant recipients.

The use of increased dosages of glucocorticoids during periods of physiologic stress in allograft recipients represents a clinical dilemma in that the short-term exogenous therapy required may significantly impair wound healing and immunocompetence. To investigate whether "stress steroids" are actually necessary, a prospective study was conducted in 40 renal allograft recipients admitted with significant physiologic stress. Stress categories included sepsis, metabolic abnormalities, and surgery. These patients received only their baseline prednisone immunosuppression (5-10 mg/day) and no supraphysiologic or stress doses of glucocorticoids. The clinical course of the patients revealed no evidence of adrenal insufficiency. There was no mortality, increase in hospital stay, or eosinophilia. Five episodes of hyponatremia and seven instances of hypotension were attributed to primary disease processes and responded promptly to specific treatment without steroid supplementation. Biochemical evaluation during stress revealed suppression of ACTH levels in 74.5% of episodes, elevation of urinary free cortisol levels in 79.1% of episodes, and elevation of isolated serum cortisol levels in 55.9% of episodes. This suggested that these patients had physiologically adequate adrenal function. The cosyntropin stimulation test overestimated the incidence and degree of clinically significant adrenal dysfunction (63% of patients) and was not a useful indication of a requirement for additional glucocorticoids. We conclude that functional adrenal suppression is uncommon in renal allograft recipients receiving baseline prednisone immunosuppression (5-10 mg/day) and that the demands of physiologic stress are met by a combination of endogenous adrenal function plus exogenous, baseline, immunosuppressive doses of glucocorticoids. Supra-physiologic or high doses of so-called "stress steroids" are not required. The cosyntropin stimulation test has significant clinical limitations and did not serve to alter clinical care.

Adrenal Glands↗