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Biomedical subjects

C F Barker

Publications and source records attributed to C F Barker.

At least 163 records · Page 9Linked to original sources
PubMed1983

Influence of islet and bone marrow transplantation on the diabetes and immunodeficiency of BB rats.

The results of islet transplantation in spontaneous autoimmune diabetes of BB rats were studied to determine whether this disease process might damage the transplanted islet tissue. Since BB rats are not genetically uniform, syngenetic grafts could not be used; therefore, allograft rejection was prevented by rendering BB rats immunologically tolerant of WF transplantation antigens by neonatal inoculation with bone marrow cells. Despite the resultant tolerant state, which permitted successful engraftment of WF skin allografts, the transplanted islets ameliorated the spontaneous diabetes of BB rats only briefly before they were destroyed by immune insulitis. BB rats from the diabetic stock were found to suffer from abnormalities in T lymphocytes and their subsets as well as defective immune response patterns. When analyzed with monoclonal antibodies specific for rat lymphocyte markers, BB rats of the diabetic stock were found to be lymphocytopenic. There was a reduction in helper T cells and a more severe deficit in the suppressor/cytotoxic subset. BB rats that were inoculated neonatally with bone marrow from normal donors were found to have a strikingly reduced incidence of diabetes. Moreover, the T cell functional, numerical, and microenvironmental defects that were present in noninoculated BB rats were restored in marrow-inoculated BB rats, findings possibly related to the decreased incidence of diabetes.

Animals↗
PubMed1983

Improvement of granulocyte adherence and in vivo granulocyte delivery by ascorbic acid in renal transplant patients.

Delivery of polymorphonuclear cells (PMN) to sites of bacterial invasion is a critical step in host defense. Renal transplant patients have a defect in PMN delivery caused by glucocorticoid immunosuppressive therapy that leads to increased susceptibility to infection. Because inhibited granulocyte adherence is often associated with poor delivery, the effects of propranolol and of ascorbic acid were measured for both of these functions. Propranolol caused a short-lived increase in adherence and no change in delivery in normal volunteers, so it was not studied in transplant patients. Ascorbic acid also failed to affect adherence in normal controls, but increased depressed adherence in transplant patients from a mean value of 27.7% to 48.0% when given daily for 3-4 weeks. PMN delivery increased to normal following 3-6 weeks of ascorbic acid, 4 g/day in a similar group of patients with low adherence prior to treatment. Pretreatment delivery was 3.06 X 10(5) and rose to 1.18 X 10(6) PMN after treatment (P less than 0.02), with no change noted in graft function. Thus, ascorbic acid treatment may improve PMN host defense in renal transplant patients.

Adult↗
PubMed1983

Influence of culturing on the functioning of major-histocompatibility-complex-compatible and incompatible islet grafts in diabetic mice.

Culturing B10.BR (H-2k) islets promotes their survival in major histocompatibility complex (MHC)-incompatible BALB/c (H-2d) mice, but not in MHC-compatible CBA (H-2k) animals. These results provide further evidence that MHC restriction is involved in transplantation immunity--i.e., that allografts are only recognized as foreign if they possess donor macrophages (or cells of this family), or if antigen-presenting cells MHC-compatible with the graft can be provided by the host.

Animals↗
PubMed1983

Effect of spontaneous diabetes on hormone release in BB/Phi rats: comparison between the isolated perfused pancreas/stomach/duodenum/spleen and the isolated perfused pancreas.

We have studied the effects of spontaneous diabetes in BB/Phi rats on hormone release in response to amino acids (15 mM) and to amino acids (15 mM) plus glucose (10 mM) from isolated perfused pancreas/stomach/duodenum/spleen (PSDS) and from isolated perfused pancreas (P) preparations. In the PSDS preparation, diabetes reduced total integrated insulin output by 97% (from 1146 +/- 198 to 40 +/- 24 ng/65 min, P less than 0.001), and glucagon output by about 50% (from 51.6 +/- 13.1 to 24.0 +/- 3.7 ng/65 min, P less than 0.05), whereas somatostatin output did not change (105.5 +/- 48.1 to 110.1 +/- 36.9 ng/65 min). In the P preparation, integrated glucagon output fell by 91% (from 97.9 +/- 26.8 to 8.6 +/- 4.8 ng/65 min, P less than 0.01) whereas integrated somatostatin output more than doubled (from 28.1 +/- 7.5 to 69.6 +/- 14.2 ng/65 min, P less than 0.05). Intestinal glucagon and somatostatin contributions were estimated by comparing hormone release from the PSDS with that from the P preparations. We conclude that in our nondiabetic BB/Phi rats, the pancreas was the only source for the release of glucagon and that the intestinal tract secreted more somatostatin than the pancreas. In the diabetic BB/Phi rats, pancreatic glucagon and insulin release was virtually abolished while glucagon secretion from the intestinal tract increased and somatostatin secretion decreased.

Animals↗
PubMed1983

Analytical and functional studies on the T cells of untreated and immunologically tolerant diabetes-prone BB rats.

Lymphocyte profiles of untreated diabetes-prone BB rats (BBDP) and their normal marrow-inoculated tolerant littermates were determined with the aid of a fluorescence-activated cell sorter by using monoclonal antibodies specific for rat T cell (W3/13) and T cell subsets (W3/25, T helper; OX8, T cytotoxic/suppressor). In contrast to non-diabetes-prone rats and to their marrow-inoculated littermates, untreated BBDP rats were found to be T lymphocytopenic with reduced W3/25+ cells and with a major loss of OX8+ cells. Moreover, their lymphocytes displayed depressed alloreactivity that was not restored by addition of exogenous IL 2.

Animals↗
PubMed1983

Numerical and functional abnormaLity of T suppressor cells in diabetic rats.

Insulin-dependent diabetic patients have been reported to have abnormal suppressor T cell function. However, the importance of this abnormality in the etiology of the disease is difficult to evaluate, since the abnormality could be a result of hyperglycemia rather than a predisposing factor. A genetic condition in rats that closely resembles type I (insulin-dependent) diabetes mellitus made it possible to study their suppressor T cell status before they displayed the disease. Thus, monoclonal antibodies and a fluorescence-activated cell sorter were used to define lymphocyte subpopulations in these animals. In prediabetic rats the number of suppressor T cells was reduced strikingly. In vitro assays showed that lymphocytes from predisposed rats were also functionally deficient in regard to suppression. Susceptible rats inoculated with bone marrow cells from normal donors were protected from diabetes. Moreover, the numbers and functions of suppressor T cells in these marrow recipients were almost restored to normal. These observations indicate that a suppressor T cell abnormality is responsible for the hyperglycemia of diabetic rats and raises the possibility that the human disease has a similar etiology.

Animals↗
PubMed1982

Spontaneous diabetes in BB rats: evidence for a T cell dependent immune response defect.

Approximately 50% of BB rats develop insulinopenic hyperglycaemia and ketosis spontaneously in association with insulitis. Amelioration of the syndrome by immunosuppression suggests a cell mediated immune pathogenesis. Analysis of the cell-mediated immune profile of overtly diabetic and normoglycaemic diabetes prone BB rats indicates that they are lymphocytopenic relative to non-diabetes prone BB rats and that the T cell pool is particularly affected. Furthermore, lymphocytes from diabetic and diabetes prone BB rats, while producing normal responses to the T cell mitogen concanavalin A, do not respond when mixed in vitro with major histocompatibility complex incompatible lymphocytes. This anergy is not restored either by enriching the responding cell population for T cells or by adding exogenous T cell growth promoting factor. Thus BB rats have a numerical and regulatory deficit of their T cells which could be related to their propensity for diabetes.

Animals↗
PubMed1982

Evidence for major histocompatibility complex restriction in transplantation immunity.

Studies on the survival of histocompatibility-Y antigen (H-Y)-incompatible and skin-specific antigen (Skn)-incompatible skin grafts in mice, as well as those concerned with the survival of cultured parathyroid allografts in rats, indicate that grafts provoke a strong immune response only if they include donor macrophages (or Langerhans cells) or if major histocompatibility complex-compatible macrophages are available to react with cells bearing the foreign antigens.

Animals↗
PubMed1982

Percutaneous transluminal angioplasty treatment of renal transplant artery stenosis.

Since June 1979, percutaneous transluminal angioplasty (PTA) has been the procedure of choice for renal transplant artery stenosis (RTAS) at the Hospital of the University of Pennsylvania. Of 241 renal allograft recipients, 17 (7%) when studied by arteriogram because of suspected RTAS proved to have significant stenosis (the mean reduction in luminal width for the group being 68%) and underwent PTA. RTAS was equally prevalent in cadaver and related kidney allografts and was no less common in HLA-identical related donor grafts, arguing against the importance of immune factors in etiology. RTAS was equally prevalent whether the anastomotic technique was end to end or end to side. However, when RTAS occurred after end to side anastomoses, it was usually postanastomotic. Fifteen of 17 of the attempts at dilation by PTA were successful by angiographic analysis. Thirteen of the 15 successfully dilated patients had long-term allograft survival and in all of these instances blood pressure (BP) was decreased after PTA. After a mean of 67 weeks, BP decreased from a systolic of 184 +/- 24 mm Hg pre-PTA to 135 +/- 15 mm Hg (P less than 0.001) and from a diastolic of 115 +/- 10 mm Hg pre-PTA to 87 +/- 11 mm Hg (P less than 0.001). The majority of patients continue to require antihypertensive drugs but in a less vigorous regimen than pre-PTA. Serum creatinine level fell following PTA from 1.9 +/- 0.6 to 1.7 +/- 0.5 mg/100 ml (P less than 0.01). Repeat angiographic study was done in nine patients, an average of 61 weeks after PTA, and no recurrent RTAS was identified. Three minor complications of PTA occurred but none led to long-term sequelae. Thus, we believe PTA of RTAS is relatively safe, carrying less mortality and morbidity than operative treatment, and is capable of improving BP control and renal allograft function.

Adult↗
PubMed1982

Transplantation of islets and bone marrow cells to animals with immune insulitis.

The results of islet transplantation in an animal model of spontaneous immune insulitis were studied to see whether this disease process might damage transplanted tissue. Since the insulitis occurs only in "BB" rats (which are not genetically uniform) syngeneic grafts could not be used, therefore allograft rejection was avoided by rendering "BB" rats tolerant of WF transplantation antigens by inoculating them neonatally with WF bone marrow cells. Despite the resultant tolerant state, which permitted successful engraftment of WF skin and islets transplanted to artificially diabetic "BB" rats, tolerant "BB" rats with spontaneous diabetes accepted transplanted WF islets only briefly before they were destroyed by immune insulitis. "BB" rats were found to have abnormalities in immune response (delayed skin graft rejection and decreased alloreactivity in mixed lymphocyte response). "BB" rats that were treated neonatally with WF bone marrow. Moreover, "BB" rats inoculated with WF bone marrow neonatally were found less likely to become diabetic than untreated "BB" controls. It is suggested that the chimeric state (persistence of WF bone marrow cells) may be responsible for the improved immune response and perhaps for the decreased susceptibility to diabetes.

Animals↗
PubMed1982

Treatment of acute peripheral arterial and graft thromboses with low-dose streptokinase.

Seventeen patients with acute peripheral arterial or graft occlusion were treated with local low-dose intra-arterial streptokinase. The series includes eight patients with native vessel occlusion, six patients with vein graft occlusion, two patients with prosthetic graft occlusion, and one patient with renal allograft artery occlusion. The duration of occlusion prior to streptokinase therapy varied from 2 hours to 5 weeks. The treatment was successful in 14 of the 17 instances. In conjunction with the successful thrombolytic therapy, percutaneous transluminal angioplasty was performed subsequently in 10 of the patients and reconstructive surgery in three. One major and five minor hemorrhagic complications occurred and were considered to be secondary to the streptokinase therapy. In follow-up of up to 9 months, 11 of the 14 successfully treated patients continued to have a good result, without any indication of recurrent arterial occlusion. Two patients have died of causes unrelated to thrombolytic therapy and one patient required bypass grafting for recurrent thrombosis. None of the successfully treated patients lost a limb. Of the three patients in whom thrombolysis was unsuccessful, two required amputation. Local intra-arterial low-dose streptokinase appears to be a promising alternative to immediate operative treatment in carefully selected cases of arterial occlusion. Definitive treatment of the underlying cause of the thrombus usually is required and changes of success may be enhanced by the thrombolytic therapy.

Adult↗
PubMed1982

Invited commentary: an overview of pancreas transplantation--biologic aspects.

The clinical results of vascularized pancreas transplants have improved somewhat during the last 5 years, the but technical problems of handling the pancreatic duct remain difficult. Clinical isolated islet allografts have rarely if ever succeeded. Rejection appears to be a more severe problem in pancreas or islet transplants than in other pancreas transplants. Nevertheless, if nonendocrine cells can be completely removed, transplanted beta-cells might have prolonged survival, since they probably lack Ia antigens that may be necessary to evoke an immune response. An additional biologic problem is the possible destruction (independent of rejection) of transplanted islet cells by autoimmune insulitis. This has been found to occur in spontaneously diabetic rats who received transplanted islets. Study of this animal model may provide important clues to the etiology and treatment or prevention of diabetes.

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