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Biomedical subjects

K Reemtsma

Publications and source records attributed to K Reemtsma.

At least 109 records · Page 6Linked to original sources
PubMed1984

Prolongation of rat islet allograft survival by direct ultraviolet irradiation of the graft.

Ultraviolet irradiation of rat dendritic cells completely abrogated their allostimulatory capacity in a mixed lymphocyte reaction. Rat islets of Langerhans similarly irradiated remained hormonally functional when transplanted into syngeneic diabetic rats. Allogeneic transplantation across a major histocompatibility barrier of islets initially treated in vitro with ultraviolet irradiation resulted in prolonged allograft survival without the use of any immunosuppressive agents.

Animals↗
PubMed1984

Murine streptozotocin diabetes: influences of the major histocompatibility complex, genetic background and blood transfusion.

Major histocompatibility complex-linked immune response genes are thought to influence susceptibility to induction of both human insulin-dependent diabetes and murine streptozotocin-induced diabetes. To clarify this relationship, we administered streptozotocin intravenously in two doses (120 and 240 mg/kg body weight) on days 0 and 14, and monitored blood glucose until day 100 in young adult male mice of differing background genome and/or H-2 complex. In addition, we examined the effect of allogeneic whole blood transfusion on subsequent susceptibility to diabetes. B10 recombinant mice possessing the k allele at the centromeric H-2-K and I-A loci were most susceptible to diabetes induction. Variation in susceptibility of different inbred strains with the same major histocompatibility complex genotype suggested a rôle for non-major histocompatibility complex genes. Blood transfusion delayed the onset, but did not significantly reduce the incidence of, delayed hyperglycaemia. We conclude that, in this murine model, multiple genes within the outside the major histocompatibility complex influence multiple-dose streptozotocin-diabetes susceptibility, and that prior blood transfusion may modulate diabetes induction.

Animals↗
PubMed1984

Selective lymphoid irradiation and cyclosporin A in rat heart allografts.

Short-term peritransplant treatment utilizing 2-dose ALG and 1-dose Palladium-109-hematoporphyrin (PD-H) for selective lymphoid irradiation (SLI) leads to donor-specific permanent acceptance of heart allografts in the Fisher to Lewis rat model. The same treatment significantly prolongs survival of hearts transplanted to strongly histoincompatable , presensitized, and xenogeneic recipients. The purpose of this study was to evaluate synergistic effects of short-term, low-dose cyclosporin treatment and SLI in an attempt to develop a nontoxic protocol utilizing peritransplant treatment for immune preconditioning with minimal subsequent immunosuppression. Single-agent treatment alone with cyclosporin, ALG, or Pd-H resulted in a maximal mean graft survival time (MST) of 33 days. Immunosuppression with 1-dose Pd-H, 2-dose ALG, and low-dose cyclosporin (5 mg/kg) for 14 days doubled the MST to 78 days. Use of therapeutic-dose cyclosporin (20 mg/kg), given for just 3 days, was also quite effective, MST of 57 days with SLI and 43 days with ALG, but toxic; 3 of 12 recipients died of infection with functioning grafts. These results demonstrate that the use of low-dose cyclosporin over a short interval, when combined with peritransplant SLI, is a highly effective and safe method for prolonging heart allograft survival.

Animals↗
PubMed1984

Simple methods for direct antibiotic protection of synthetic vascular grafts.

Two simple methods for direct antibacterial protection of synthetic vascular grafts were investigated. In the first protocol the highly protein-bound antibiotics nafcillin (90% protein bound), cefazolin (80%), and cefamandole (70%) were added directly to preclotting blood. Knitted Dacron grafts preclotted in the presence of one of these drugs absorbed significant amounts. Although at high concentrations these antibiotics exhibited anticoagulant effects, significant antibacterial protection was obtained at lower antibiotic levels. Washing treated grafts for 6 hours failed to eliminate the antibacterial activity. Antibiotics remained on the grafts for at least 96 hours. In the second protocol knitted Dacron grafts were soaked in a suspension of silver-pefloxacin, a silver-nalidixic acid analogue with intense antistaphylococcic activity. Using 110Ag-labeled complexes, significant antibiotic activity was documented on the graft after 19 days of washing. Four nafcillin-treated prostheses, six silver-pefloxacin-coated grafts, and 11 control grafts were interposed in the infrarenal aorta of dogs and immediately challenged with an intravenous infusion of 1 X 10(7) Staphylococcus aureus. None of the four nafcillin-treated grafts was infected at 3 weeks. One of the six silver-pefloxacin-coated grafts grew staphylococci, and 9 of 11 controls had positive graft cultures for Staphylococcus when harvested. These studies suggest that prosthetic grafts can be simply coated at the time of implantation with antibiotics selected for appropriate binding and antibacterial characteristics to obtain an infection-resistant prosthesis.

Animals↗
PubMed1984

Pancreatic islet transplantation. Induction of graft acceptance by ultraviolet irradiation of donor tissue.

The effect of ultraviolet (UV) irradiation on the immunogenicity of rat pancreatic islets was examined in allograft and xenograft models. Direct UV irradiation (900 J/m2) of Lewis islets, isolated and hand-picked, does not alter pancreatic islet endocrine function in isograft experiments and results in indefinite islet allograft survival in streptozocin diabetic ACI rats without chronic immunosuppression. Direct UV irradiation, at an appropriate dose, also leads to indefinite islet xenograft survival of Lewis islets in B10-BR diabetic mice and prolonged survival of rat islets in Balb/C mice. When direct UV irradiation of islet allografts did not result in indefinite islet allograft prolongation [Wistar/Furth (W/F) to diabetic Lewis], the addition of brief peritransplant immunosuppression with cyclosporine (days 0, +1, and +2) resulted in permanent acceptance of islet allografts, a result not achieved by cyclosporine alone. The effectiveness of UV irradiation in abrogating islet allograft rejection in several experimental models is supported by in vitro studies showing that UV irradiation of stimulator cells, peripheral blood lymphocytes, splenocytes, and isolated rat dendritic cells abolishes any significant stimulation by such cells of totally histoincompatible thoracic duct responder lymphocytes. In vitro nonreactivity of mixed lymphocyte culture (MLC) with UV-irradiated stimulator cells and in vivo permanent allograft acceptance are reversed by the addition of a small number of untreated donor-type dendritic cells to either the MLC or the recipient bearing the permanent graft. The authors suggest that the primary effect of UV irradiation on immune alteration of islet allografts and xenografts is due to induction of a major metabolic change in the dendritic cells in the graft. This then leads to defective antigen presentation and results in either permanent or prolonged allograft and xenograft acceptance, depending on the degree of MLC stimulation between the islet donor and the diabetic recipient.

Animals↗
PubMed1984

The use of direct ultraviolet irradiation and cyclosporine in facilitating indefinite pancreatic islet allograft acceptance.

We have previously shown that direct ultraviolet (UV) irradiation of islets can reduce their immunogenicity without alteration of their endocrine function and effect prolonged survival of islet allografts in the Lewis-to-ACI strain combination without the use of immunosuppression. This study extends that work to investigate the survival of UV-irradiated Wistar-Furth islets in streptozotocin-diabetic Lewis rats, in which case the recipient is a relatively "high responder" to W/F alloantigens. Lewis recipients of 24-hr cultured W/F islets uniformly rejected islet allografts within one week of transplantation while the additional immunosuppression with cyclosporine (CsA) at 15 or 30 mg/kg on days 0, +1, and +2 was ineffective in prolonging islet allograft survival. Wistar-Furth islets, which were UV-irradiated at 850-900 J/m2 and cultured for 24 hr prior to transplantation, did not survive any longer than those in control animals receiving untreated islets (MST 5.5 +/- 1 day). When UV irradiation of islets was combined with recipient peritransplant treatment with CsA at 15 mg/kg on days 0, +1, and +2 islet allograft survival was markedly prolonged (MST of 18 +/- 4.1 days). Treatment of diabetic recipients of UV irradiated islets with an increased dose of CsA (30 mg/kg) during the same peri-transplant period (0, +1, +2 days) resulted in 100% islet allograft survival beyond 120 days. This data demonstrate the effectiveness and synergism between the use of the pretransplant UV irradiation of islet allograft and the peritransplant immunosuppression of the recipient with CsA in inducing prolonged islet allograft survival in "high responder" recipients, in which the singular use of either modality may be ineffective.

Animals↗
PubMed1983

Pancreatic islet allograft prolongation by donor-specific blood transfusions treated with ultraviolet irradiation.

Survival of allografts of islets of Langerhans in nonimmunosuppressed adult rats was prolonged by transfusions of donor blood irradiated with ultraviolet light before transplantation across a major histocompatibility barrier. This treatment is donor blood-specific and has produced greater than 160-day survival of transplanted islets without the administration of immunosuppressive agents.

Animals↗
PubMed1983

Vascular complications associated with percutaneous intra-aortic balloon pumping.

A percutaneous intra-aortic balloon pump (PIABP) was inserted in 112 patients. Successful placement was achieved in 102 patients, 67 of whom survived long enough to have the device removed. Vascular complications related to the PIABP were noted in 15 patients. Reversal of ischemic signs followed PIABP removal in six patients, but nine required femoral artery exploration for thrombectomy, repair of femoral laceration, or repair of false aneurysm. No patient died as a result of PIABP or correction of associated vascular complications, though five of the patients with vascular problems died of cardiac complications. Nine of ten survivors in this group were asymptomatic, and one had persistent paresthesias six months postoperatively. Most clinically significant vascular complications were due to the technique of balloon removal, and several modifications that were effected recently are expected to decrease the incidence of complications requiring surgical intervention.

Angina Pectoris↗
PubMed1983

Murine islet cryopreservation and corticosteroids: functional studies.

Knowledge of protective effects of corticosteroids on traumatized cells prompted us to test the potential benefit of islet cryopreservation in the presence of hydrocortisone. Neonatal murine islets were isolated by collagenase, followed by 2- to 3-day tissue culture. Precryopreservation glucose-stimulated (50-500 mg/dl) insulin release was 25-388% above basal (mean = 113%) in 18/20 fresh islet preparations. Subsequent freezing was done in RPMI 1640 medium plus 10% (v/v) heat-inactivated fetal calf serum and 10% (v/v) Me2SO with or without 1 mg/ml hydrocortisone at 0.25 degrees C per minute in a programmed freezing system, to -80 degrees C, and stored for greater than 60 days at -196 degrees C. Thawing, by transfer to room air, was followed by dilution, 4x (v/v), in 4 degrees C RPMI plus 10% protein, after which glucose-stimulated insulin release was reassessed, showing 56-280% response over basal in 3/8 steroid-treated preparation and 20-220% response in 3/10 control preparations. Basal insulin release was 0.72 ng/microgram protein/hr in fresh islets (N = 20) and 0.22 ng/microgram protein/hr after freeze-thawing. We conclude that functional islet survival by this method is approximately 30% and that hydrocortisone did not improve viability.

Adrenal Cortex Hormones↗
PubMed1983

Long-term function of duct-ligated and free-duct whole pancreas transplants.

This report compares endocrine and exocrine responses of "free-duct" and "duct-ligated" whole pancreas isografts in Lewis diabetic rats during a 1-year period of observation. Fasting blood sugar, serum amylase, serum insulin, pancreozymin-secretin test, and L-arginine tolerance test assays were performed prior to and at periodic intervals after transplantation. Histological examinations of transplanted and native pancreas were performed monthly on animals in each group. Whole pancreas transplantations led to immediate and sustained normalization of FBS and insulin levels. In the "duct-ligated" group there was a gradual but insignificant decrease of serum insulin levels after 9 months. Depressed serum amylase levels in diabetic rats were reversed in both groups. Isolated islet iso- and allografts also reversed depressed amylase levels. The results of pancreozymin-secretin tests in islet isografted animals supported the postulated trophic effect of endocrine pancreas on exocrine pancreas. Although both whole-pancreas transplant groups showed a normal response to GTT for 12 months after transplantation, the "duct-ligated" group showed a significantly lower response to L-arginine tolerance test than the "free duct" model as early as 4 months after transplantation, suggesting a defect in B-cell function in long-term "duct-ligated" graft. Serial histological examinations of transplanted pancreases revealed more rapid atrophy and more intense fibrosis of acinar tissue in the "duct-ligated" group than in the "free duct" group. These results suggest that a "free duct" pancreatic isograft maintains a more stable endocrine function in a long-term study than does the "duct-ligated" pancreas, and that exocrine dysfunction in diabetic rats may be related to the endocrine disorder which can be reversed by both islet cell and whole-organ pancreatic transplantation.

Amylases↗
PubMed1983

Pancreatic polypeptide (PP) immunoreactivity in human parathyroid culture media.

Media from cultures of normal and abnormal human parathyroid fragments were assayed for parathyrin (PTH) and pancreatic polypeptide (PP) using sensitive radioimmunoassays. PP immunoreactivity was present in media (Day 6-7 in vitro) from cultures of 3/10 adenomas and 6/6 3 degrees hyperplastic glands (mean = 126. fmole/mg protein/day) (range = 6.-675.), and was not suppressed by 0 leads to 3 mM calcium challenge. PP was undetectable in media from cultures of one parathyroid carcinoma, one 1 degree hyperplasia, and one normal parathyroid. Medium C-terminal PTH levels were quite variable (26.-2,545,000. pg/mg protein/day). Presence of PP immunoreactivity in media from cultures of some hyperplastic parathyroids and some parathyroid adenomas suggests that PP may be released from these tissues in vitro. The significance of elevated PP levels in the MEA syndromes may be of special clinical relevance to this observation.

Adenoma↗
PubMed1983

Hypogastrinemia in streptozotocin diabetes with islet transplantation--reconstitution.

Gastrin is present in normal mammalian pancreatic islets, as well as in the antrum and duodenum. Serum gastrin levels are responsive to many physiologic and pharmacologic factors including hyperglycemia, somatostatin, and glucagon. To evaluate the effects of streptozotocin diabetes and islet transplantation on gastrin homeostasis, young, adult, male Lewis rats underwent streptozotocin diabetes alone (N = 14), diabetes plus intraperitoneal islet isografts (N = 22), or sham operation alone (N = 18). Streptozotocin reduced fasting gastrin immunoreactivity (107 pg/ml +/- 26 mean +/- SEM) compared to controls (256 pg/ml +/- 31) (P less than 0.001). Islet isotransplantation resulted in restoration of fasting gastrin immunoreactivity (230 pg/ml +/- 19) to levels significantly greater than diabetics (P less than 0.001) and comparable to control animals (P = NS). Normalization of serum gastrin levels occurred within one month of transplantation and persisted for up to 14 months. In addition, media from cultures of 4/7 dispersed neonatal rat pancreas cultures contained gastrin immunoreactivity. Streptozotocin diabetes produces hypogastrinemia; intraperitoneal islet isotransplantation normalizes fasting gastrin immunoreactivity. Rat islet culture medium contains gastrin-like immunoreactivity. Pancreatic islets would appear to produce or control a portion of circulating gastrin immunoreactivity.

Animals↗
PubMed1983

The immunologic and ultrastructural characterization of the cellular infiltrate in acute cardiac allograft rejection: prevalence of cells with the natural killer (NK) phenotype.

The inflammatory cell infiltrates in 15 endomyocardial biopsies serially obtained from a human cardiac allograft during a 1 1/2-year period were characterized. An indirect immunofluorescent technique with hybridoma-derived monoclonal antibodies which preferentially react with B lymphocytes (anti-Ia), mature T cells (OKT3, Leu 1), and helper (OKT4b,d) and supressor/cytotoxic (OKT8) T-cell subsets and with natural killer cells, macrophages, and granulocytes (OKM1) was used. During each of seven rejection episodes the overwhelming majority of infiltrating cells in the endomyocardial biopsy were OKM1+Ia. These cells displayed short microvilli, a moderate amount of cytoplasm, numerous mitochondria, a large amount of rough endoplasmic reticulum, Golgi, and an indented nucleus, that is, the ultrastructural features of large, granular lymphocytes. Thus, they morphologically and phenotypically resemble those lymphoid cells which have been shown to possess natural killer (NK) functions in man. Occasional Leu 1+OKT3+ cells, some of which were OKT8+, were also seen during acute rejection. In each instance following therapy and resolution of the rejection episode only rare OKM1+Ia- cells were present. At this time the majority of the cells were Leu 1+OKT3+OKT8+. Routine biopsies, performed at times without evidence of rejection, showed only reactivity for Ia antigens by the capillary endothelium. These studies demonstrate the prevalence of cells with the natural killer phenotype in this human cardiac allograft during episodes of acute graft rejection.

Acute Disease↗