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Biomedical subjects

R G Bretzel

Publications and source records attributed to R G Bretzel.

At least 217 records · Page 12Linked to original sources
PubMed1990

Protection of islets of Langerhans from interleukin-1 toxicity by artificial membranes.

Recently it has been reported that interleukin 1 may play a central role in the immune destruction of islets. Since the mass weight of interleukin-1 is close to that of insulin, destruction of transplanted islets may be possible although they are enclosed in membranes that prevent penetration by immune-competent cells and cyto-toxic antibodies. The present in vitro study showed that the encapsulated rat islets are protected from high doses of IL-1 (1000 ng) inside a hollow fiber membrane with a cutoff of 50,000 D. The function of islets in a free-floating culture, however, was suppressed in a dose-dependent manner (1000 ng/L; 20-30% of controls). Histologically, no damage of the free-floating or encapsulated islets was observed at 1000 ng of IL-1-containing medium. Islets washed out of the devices after 2 days of exposure to IL-1 showed no difference in glucose-stimulated insulin release when compared with islets not exposed that were kept in free-floating culture. It is suggested that an unspecific coating of the membranes by serum proteins (containing physiological IL-1 antagonists) may cause the protective effect.

Animals↗
PubMed1990

Treatment of rat pancreatic islets with MHC Ia antibody and complement prior to transplantation.

Rat pancreatic islets were treated with MHC Ia antigen monoclonal antibody and complement in order to lyse Ia antigen bearing cells within the islets. Ia antigen expression was significantly reduced after this treatment as shown by indirect immunofluorescence tests. Glucose stimulated insulin secretion and viability of the islets were not impaired. The partial reduction of the Ia antigen expression, however, did not provoke a prolongation of the graft acceptance after islet allotransplantation across a major histocompatibility barrier.

Animals↗
PubMed1990

Impact of culture and cryopreservation on MHC class II antigen expression in canine and porcine islets.

Canine and porcine islets were either cultured for 10 days at 37 degrees C or cryopreserved. The effect of these treatments on MHC class II antigen expression was examined by indirect immunofluorescence test using the class II monoclonal antibody 2MC3. Within untreated canine islets exclusively round shaped cells as leukocytes and monocyte/macrophage like cells with dendritic branches were positive with 2MC3. Porcine islets additionally exhibited strong immunofluorescence of the vascular endothelium. Tissue culture significantly reduced the class II antigen expression in both species. The majority of the untreated canine islets had between 5 and 19 2MC3 positive cells. Cell culture reduced the number of class II positive cells to a maximum of 3 and even 84.9% of the islets were completely negative for class II antigens. Porcine islets showed a total class II antigen loss of the vascular endothelium, whereas leukocytes and monocytes/macrophages remained class II antigen positive. Cryopreservation did not have clear-cut effects on the MHC expression in both species.

Animals↗
PubMed1990

Experiments on a new hollow fiber membrane for immuno isolated transplantation of islets of Langerhans.

Immunoisolated transplantation of xenogeneic islets could solve problems concerning the immunology of islet transplantation. This study presents results from in vitro and in vivo experiments in rodents by the use of a PEEK-hollow fiber. Glucagon secretion of encapsulated islets during a 48-hour-culture period sustained on the same level from day 2 to 28. There were no significant differences in glucose (16.7 mmol/l)-stimulated insulin release after 6, 14 or 28 days in culture. Contrary, intraperitoneal transplantation of 800 encapsulated islets resulted in a normoglycemia of 3.8 days (medium survival time) which was similar to that of not encapsulated controls. It was concluded that a more open ultrastructure of the membrane tested could result in a minimization of the diffusion distance and overcome principle geometric problems of the hollow fiber model.

Animals↗
PubMed1990

The evaluation of neutral density separation utilizing Ficoll-sodium diatrizoate and Nycodenz and centrifugal elutriation in the purification of bovine and canine islet preparations.

This study evaluates the potential of a neutral density separation technique using iodinated gradient media in combination with Ficoll or alone at two different densities for the purification of bovine and canine islets isolated by a continuous digestion-filtration technique. In addition, centrifugal elutriation is applied to the purification of isolated bovine islets. A single density layer of Ficoll-sodium diatrizoate or Nycodenz at densities of 1.080 g/ml or 1.085 g/ml resulted in an recovery of 47.4% to 77.4% bovine islet volume with bovine islet purities ranging from 43.5% to 49.0%. The use of a single density layer of Ficoll-sodium diatrizoate at 1.080 g/ml and Nycodenz at 1.085 g/ml resulted in recoveries of 86.4% and 56.2% canine islet volume with canine islet purities of 58% and 63.5%, respectively. The bovine islet enriched fraction (flow rates 50-90 ml/min at a rotor speed of 200 rpm) obtained by centrifugal elutriation was 20.0 +/- 3.5% pure, the average recovery of bovine islet volume obtained by centrifugal elutriation was 59.0 +/- 10.7%. It is suggest that a further refinement of factors like osmolality, viscosity, pH, ionic composition and temperature of iodinated density gradient media may allow continued improvement of islet purity and recovery obtained by the simple neutral density separation technique.

Animals↗
PubMed1990

Immunopathological findings and thyroid autoantibodies in thyroid autonomy.

Different phenomena under consideration, lymphocytic and macrophagic infiltration and increased thyrocyte class I and class II antigen expression, normally ascribed to autoimmune thyroid disease (Graves' disease; Hashimoto's thyroiditis) were frequently found in thyroid glands with autonomous nodules, too. Contrary, nodular formations in the vast majority of nodular goiters were not associated with these immunopathological findings. Furthermore, thyroid microsomal, anti-peroxidase and TSH-receptor antibodies although at low frequency rates, were only detected in cases of autonomous nodules but not in cases of nodular goiters. From these findings we conclude that the immune phenomenon observed in thyroid autonomy could not be a consequence of nodular formations but that at least in some cases of thyroid autonomy immunopathogenic mechanisms may play an important role. Based on the fact that class I hyper-expression was more common and that a stronger correlation of cell infiltration with increased class I than with increased class II expression on thyrocytes existed we propose, that if the initial event of the autoimmune process is indeed increased class II expression, this stimulus may more likely originate from increased non-thyrocyte class II positivity (for example dendritic or endothelial cells) than from thyrocyte class II positivity. But, if aberrant class II expression is not the initial stimulus, another candidate could be the increased thyrocyte class I expression observed, probably due to the action of interferon alpha and/or beta induced by any unknown stimulus (viruses?).

Antibodies, Monoclonal↗
PubMed1989

Islet transplantation in experimental diabetes of the rat. XII. Effect on diabetic retinopathy. Morphological findings and morphometrical evaluation.

Digest-preparations of rat retinal vasculature were examined with respect to single capillary alterations and diffuse changes in cellular composition. Retinas of streptozotocin-diabetic rats revealed single micro-aneurysms, degenerated capillaries, strand formation, microthromboses and further lesions, occurring sooner than previously described. A severe loss of pericytes and a slight increase in endothelial cell number resulting in an increase in E/P-ratio were observed, all effects becoming more pronounced with longer duration of diabetes. Syngeneic islet transplantation could prevent all of the described alterations if carried out soon after diabetes induction. If performed six months later it was able to almost restore the normal cellular composition while pathomorphological lesions could be arrested or reversed only partially.

Animals↗
PubMed1989

Bovine islets of Langerhans. Potential source for transplantation?

Two methods are described for large-scale isolation of islets from the bovine pancreas. With the single-endpoint technique the average number of islets isolated from a 73.3-g pancreas sample was 150,560, representing an estimated total islet volume of 0.391 ml. Pancreases processed by the continuous digestion-filtration method yielded an average of 246,229 islets from a 93.9-g pancreas sample, representing an estimated total islet volume of 0.458 ml. Isolated bovine pancreatic islets demonstrated a well-preserved endocrine cell ultrastructure, responded to acute stimulation with propionic acid, and temporarily reversed experimental diabetes in mice.

Animals↗