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Biomedical subjects

K Federlin

Publications and source records attributed to K Federlin.

At least 181 records · Page 10Linked to original sources

[Recurrent hypoglycemia in the insulin autoimmune syndrome].

A 72-year-old man with recurrent hypoglycaemia was suspected of having an insulinoma. But several diagnostic methods (computed tomography; mesenteric and coeliac angiography; sella imaging) did not reveal any tumour. 72-hour hunger test did not precipitate any spontaneous hypoglycaemia. A falling insulin-glucose ratio spoke against an insulin-producing tumour. Reactive symptomatic hypoglycaemia occurred 4.5 hours after an oral glucose test. Measurement of insulin concentration demonstrated a slow but pronounced increase (3500 microU) over an already raised initial value (816 microU/ml), typical of prediabetic metabolic regulation. Demonstration of insulin autoantibodies confirmed the diagnosis of an insulin autoimmune syndrome, which has a good prognosis. The patient became free of symptoms on a regimen of frequent small, carbohydrate-poor but fat and bulk-rich meals. Hypoglycaemia recurred when the diet was not observed.

Aged↗

[Insulin and immunology--a correlation].

In comparison to former decenniums the relations between insulin and immunology have changed and continued to develop. Still up to 20 years ago the immunological side effects of an insulin therapy stood well to the fore concerning the clinical interest, nowadays, however, they are the autoantibodies against insulin and it is the role of insulin for a functioning immune system, which is not in the least exactly recognized.

Animals↗

Effects of ganglioside (Cronassial) treatment on MHC Ia antigen expression and allograft survival of pancreatic islets in diabetic rats.

Streptozotocin-diabetic BdII rats were treated daily with 20 mg/kg body weight gangliosides for ten days beginning two days before transplantation. This treatment did not prolong allograft survival of untreated Lewis islets. Culture treatment of isolated Lewis islets with gangliosides (100 micrograms/ml in RPMI 1640) for one day resulted in a significant reduction of MHC Ia antigen positive cells but not of class I antigens within the islets. Transplantation of the ganglioside pretreated islets into non-immunosuppressed BdII recipients prolonged allograft survival to 12 days only in one of five animals.

Animals↗

Relationship between CD5+ B lymphocytes and the activity of systemic autoimmunity.

We studied the relationship between CD5+ B cells and the activity of the disease process in patients with autoimmune diseases. In rheumatoid arthritis (RA), levels of CD5+ B cells were associated with autoantibody production as determined by serum rheumatoid factor and antinuclear antibodies. In addition, CD5+ B cells were significantly correlated with C-reactive protein, and data from longitudinal studies showed a marked influence of corticosteroid treatment on numbers of CD5+ B cells. Patients with systemic lupus erythematosus (SLE) had slightly elevated levels of CD5+ B cells as compared with normals, but a close association with measures of an active disease was not observed. In a group of patients with type I diabetes mellitus, CD5+ B cells were detected in patients with anti-islet cell antibodies. Our results suggest that CD5+ B cells are related to the activity of the autoimmune process and can be modulated by therapy in patients with RA. Although CD5+ B cells do not seem to have a major role in SLE, polyclonal activation might affect this B cell subset as well in this disease. Further studies are needed to define the precise role of CD5+ B cells in organ-specific autoimmunity.

Adrenal Cortex Hormones↗

Impaired agglutination of IgM resulting from non-enzymatic glycation in diabetes mellitus.

Non-enzymatic glycation of circulating immunoglobulin G, A and M, measured by boronic acid affinity chromatography was found to be significantly increased in diabetes mellitus. The mean value of glycated IgM was already high in the control group: 49.58% (+/- 10.3% SD) and increased up to a mean value of 61.00% (+/- 8.5%) in the diabetic group. Similarly IgG and IgA glycation was significantly higher in the diabetic group than in controls: IgG 21.6% (+/- 3.4%) vs. 14.1% (+/- 2.9%; P less than 0.01); IgA 14.7% (+/- 4.9%) vs. 7.7% (+/- 1.3%; P less than 0.01). To investigate how glycation would alter IgM function, serum proportions from diabetic patients with blood group O were separated into glycated and non-glycated fractions by affinity chromatography and, adjusted to the same concentrations, tested against group A1 erythrocytes. Agglutination, which is mainly an IgM-mediated reaction, was significantly lower in the glycated than in the non-glycated fraction of IgM. The correlation between glycation of IgM and the reduction of agglutination titres in the glycated fraction was significant (r = 0.88, P less than 0.001). We conclude that impaired IgM function may be caused by non-enzymatic glycation in diabetes mellitus with possible consequences for host resistance in the early phase of infection.

Agglutination↗

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↗

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↗

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↗

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↗

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↗