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Biomedical subjects

K Federlin

Publications and source records attributed to K Federlin.

At least 235 records · Page 13Linked to original sources
PubMed1987

Different effect of two immunomodulating agents cyclosporin A and ciamexon on the insulin metabolism of cultured mouse islets.

Ciamexon is a new immunomodulating agent with promising effects in treatment of newly-diagnosed insulin dependent diabetic patients. Ciamexon seems to have fewer adverse toxic properties than Cyclosporin A. Therefore, the effects of both substances on islet cell function were studied. Collagenase-isolated mouse islets were cultured free-floating for 3 or 7 days in medium RPMI 1640 plus 10% fetal calf serum in the presence of Cyclosporin A or Ciamexon (0.1 microgram/ml, 1 microgram/ml). Culture of the islets in the presence of 0.1 microgram/ml Ciamexon neither reduced the number of viable islets nor impaired insulin secretion as was found in Cyclosporin A. These results should be taken into account when treating early Type 1 diabetes or when transplanting islet cells.

Adjuvants, Immunologic↗
PubMed1987

[Endocrine rhythms in patients with rheumatoid arthritis: possible neurohormonal influence on immunological reactions].

Recent studies are reporting on an influence of ACTH and prolactin in physiological dosages on the intensity of the immune response in the animal model of adjuvant arthritis. Therefore, we studied the circadian secretion patterns of ACTH, cortisol and prolactin by measurements throughout a 24-hour cycle in two-hour intervals in patients with rheumatoid arthritis with different inflammatory activity of the disease. We only investigated patients who never before were treated with corticosteroids and drugs like gold, d-penicillamine or immunosuppressive drugs. The circadian secretion patterns of cortisol and ACTH were disturbed in most patients. High inflammatory activity was accompanied by severe disturbance of the circadian rhythm, whereas patients with low inflammatory activity showed a nearly normal secretion pattern. Also the measurements of prolactin showed a tendency of loss of circadian rhythm in relation to the inflammatory activity of the disease. According to the found changes of endocrine regulation of ACTH, cortisol and prolactin, an influence of mediators of inflammation on hypothalamic centers, analogous to endogenous pyrogen in fever should be discussed.

Adrenocorticotropic Hormone↗
PubMed1987

[Effect of autoimmune destruction and rejection on the function of transplanted islands of Langerhans in spontaneous diabetes in the BB rat].

In animals and human identical twin transplants the autoimmunity of naturally occurring diabetes may destroy transplanted islets, even if rejection is avoided. We studied the influence of transplant site (liver vs. kidney capsule) and pretransplant treatment (culture) on autoimmune damage and rejection of transplanted islets of Langerhans in BB-rats which spontaneously developed diabetes. Freshly isolated and in the liver transplanted islets were destroyed rapidly (on the base of autoimmune destruction, rejection or both). In contrary, the renal subcapsule shows to be immunologically privileged with long survival of transplants. Culture pretreatment of MHC-incompatible Lewis islets resulted in long survival of transplants, which was not true in case of MHC-compatible WF islets: immunological disparity of donor and recipient tissue might be most successful in preventing autoimmune damage and rejection.

Animals↗
PubMed1987

Ciamexon in the low dose streptozotocin induced diabetes of mice.

This article is concerned with suppression of the development of diabetes experimentally induced by multiple injections of subdiabetogenic doses of streptozotocin (4 x 45 mg/kg/d) in mice (CD 1 and C57B16). Streptozotocin injections were followed by hyperglycemia and mononuclear cell infiltration of islets (insulitis). Ciamexon is a new immuno-modulating agent with promising effects in experimental models of autoimmune diseases and practically no toxic side effects. When Ciamexon was given before streptozotocin treatment blood glucose levels in the parenteral glucose tolerance test were suppressed in a dose dependent way. 60 days after streptozotocin application the percentage of islets showing insulitis or even necrosis was reduced in the Ciamexon treated group compared to the streptozotocin only group. In contrast, Cyclosporin A had a detrimental effect on diabetes in this model although blood levels were proved to be in the therapeutic range. From these results we conclude that Ciamexon should be tested for its effect in human type I diabetes.

Adjuvants, Immunologic↗
PubMed1986

Clinical and biochemical aspects of the insulin autoimmune syndrome (IAIS).

A 44-year old patient presented with recurrent hypoglycemic attacks after ingestion of carbohydrates. High insulin levels in the range of 350 microU/ml (normal range less than 20 microU/ml) were detected which rose to peak levels of 2,460 microU/ml (normal range less than 300 microU/ml) after oral glucose. The apparently high insulin concentrations were caused by insulin autoantibodies interfering in the radioimmunoassay (RIA) system (and thus with correct insulin quantitation). 125I-insulin added to the patient's serum was not bound to dextran-coated charcoal but was precipitated with antihuman IgG serum. The antibodies bound human, porcine, and bovine insulin with similar affinity. Following Sephadex G-50 gel filtration, the patient's insulin eluted after the void volume. Free insulin was extracted from serum using Sep-Pak C 18 cartridges and characterized by high pressure liquid chromatography (HPLC); it eluted similarly to synthetic human insulin. Quantitation of free insulin during a hypoglycemic attack (3.5 h after oral glucose, with a blood sugar of 20 mg/dl) showed an increased insulin level of 50 microU/ml. Insulin receptor concentration on erythrocytes was near the lower normal limit. We believe that the insulin antibodies present in this patient's serum (who supposedly never received insulin) led to the formation of a large circulating insulin pool, binding the insulin released after glucose stimulation, and causing hypoglycemias by delayed postprandial liberation of bound insulin.

Adult↗
PubMed1986

[Autoimmunity and viral infections in type-I diabetes mellitus].

Cytoplasmic islet-cell antibodies, insulin antibodies, islet-cell surface antibodies and islet-cell specific cytotoxicity were determined in serum of the following groups: 131 patients with type I diabetes, 19 with type II diabetes, 29 with mumps, 29 with enterovirus infections, 18 with measles and 28 healthy controls. Cytoplasmic islet-cell antibodies were found predominantly in type I diabetics. Islet-cell surface antibodies, on the other hand, were relatively frequently (60-80%) present in sera of both diabetics and patients with various virus infections. Islet-cell specific cytotoxicity in vitro was found not only in sera of diabetics, but also of patients with mumps or enterovirus infections. Sera of five patients with measles, however, had cytotoxic reactions comparable to those of the controls. These results suggest that cytotoxic antibody reactions against islet cells in vitro occur also in sera of non-diabetic patients. Under certain circumstances, infections which induce such immune reactions may be of significance in the pathogenesis of diabetes.

Adolescent↗
PubMed1986

Islet cell antibodies and the development of diabetes mellitus in relation to mumps infection and mumps vaccination.

Islet cell antibodies were investigated in 127 non-diabetic children after mumps infection and in four out of seven children who developed diabetes mellitus shortly after active mumps vaccination. Twenty-one of the children who had mumps and all four vaccinated children who were tested had islet cell cytoplasmic antibodies. In contrast, islet cell surface antibodies were detected in 43 out of 68 patients with mumps infection and in 32 out of 44 patients with other viral diseases. All but one mumps-infected child and all the other viral infected patients investigated did not develop diabetes mellitus. The mumps-infected ICA positive children did not show those HLA-frequencies associated with Type 1 diabetes.

Antibodies↗
PubMed1986

[Therapy of rheumatic diseases with inosiplex].

27 patients (13 rheumatoid arthritis, RA; 4 systemic lupus erythematosus, SLE; 5 systemic sclerosis, PSS; 5 undifferentiated connective tissue disease, UCTD) were treated with inosiplex for more than 23 months (7.7 +/- 1.3). Clinical improvement was impressive by the end of the first month of therapy in 7 patients with moderate active RA (p less than 0.01), and 5 of these patients treated for more than 8 months continued to do well (p less than 0.05). In contrast, patients with very active RA did not show any clear-cut improvement. In the other diseases studied, 5 patients responded rapidly (reduction in arthritis, improvement of pulmonary involvement). A concomitant rise in the T4/T8- (helper-/suppressor-) cell ratio with increased numbers of T4+-cells was observed in patients with RA and PSS. Our data suggest that some patients with rheumatic diseases may benefit from long-term treatment with inosiplex.

Adult↗
PubMed1985

An improved fluorochrome microassay for the detection of living and non-living intracellular bacteria in human neutrophils.

Acridine orange fluorescence may be used to distinguish living from non-living intracellular bacteria in individual glass-adherent neutrophil granulocytes (PMN). An improvement of the original assay (Smith and Rommel, 1977; Pantazis and Kniker, 1979) is described which allows differentiation between ingested and cell-adherent bacteria. It is shown that this differentiation is impossible with the original method using wet-mounted preparations. With the improved method, however, using dry-mounted preparations, cell-adherent as well as extracellular bacteria lose their fluorescence. Moreover, the fluorescence of cell nuclei and granula is reduced to a minimum. Phagocytosis kinetics and selective inhibition of the myeloperoxidase of PMN show that living intracellular bacteria fluoresce green and non-living bacteria red in such dry-mounted preparations. The preparations can be stored and interpreted for at least 2 months. Application of this method requires 0.1 ml blood or cell-rich body fluid per preparation and is fast and inexpensive.

Acridine Orange↗
PubMed1985

[Long-term therapy with human insulin. Clinical experiences].

During in-patient admission after metabolic stabilisation insulin treatment of 32 type-1-diabetics was changed from bovine insulin (Depot-Insulin Hoechst CR) to semisynthetic human insulin of the intermediary type (Depot-H-Insulin Hoechst). Out-patient follow-up over a period of 12 months showed constant satisfactory mean day blood sugar values and morning postprandial blood sugar. 14 patients, however, showed significantly increased fasting blood sugar values which could be adjusted after change of evening insulin injections to the longer acting NPH insulin without normal insulin admixture (Basal-H-insulin Hoechst). In addition, a slight but not significant reduction of daily insulin requirements could be noted. There was no change of the relation between morning and evening insulin dosage. Hypoglycaemias did not occur significantly more frequently and hypoglycaemic symptoms showed no alterations.

Adult↗
PubMed1985

Islet transplantation in experimental diabetes of the rat. X. Induction of cytotoxic antibodies and islet-cell-surface-antibodies after homologous islet transplantation in rats.

The mechanisms of islet allograft rejection are still unknown. 350 allogeneic rat islets (BDE/Han) were transplanted into the liver of Streptozotocin-diabetic rats (Lewis/Han). Animals were killed either on day 4, 7, 10 or 14. Immunofluorescence analysis for islet-cell-surface-antibodies (ICSA) was performed on BDE-islet-single-cells yielded by Collagenase-Dispase digestion. In order to detect cytoplasmic islet cell antibodies, immunofluorescence technique was used on BDE-pancreas cryosections. Cytotoxicity assay was tried out using 51Cr-release-test. After successful intraportal transplantation, rejection took place between day 7 and 10. ICSA could be observed on day 10 and 14. Cytoplasmic antibodies were not detected at any time. A specific cytotoxic activity in the recipient serum revealed itself on day 10 (23.0%) and day 14 (27.7%). Transplantation of freshly isolated allogeneic islets induced ICSA and cytotoxic antibodies. These results indicate an involvement of humoral mechanisms in islet allograft rejection.

Animals↗
PubMed1985

[Determination of alpha-2-macroglobulin concentration using immunologic and amidolytic methods in diabetics and kidney patients].

An increased alpha-2-macroglobulin level and a decreased functional capacity of the mononuclear phagocytic system in diabetics appears to be another important factor in the pathogenic cause of micro- and macro-angiopathy. Additionally, the disturbed immunobalance, especially in the micro-environment as well as the type and intensity of infections and inflammatory reactions are involved.

Diabetes Mellitus, Type 1↗
PubMed1985

Continuous subcutaneous insulin infusion therapy (CSII) influences cardiovascular responses to graded exercise in patients with autonomic diabetic neuropathy of the cardiovascular system (ADNCS).

We have demonstrated previously the effect of CSII on diabetics with ADNCS. In this study 16 Type-1-diabetics with ADNCS, 20 diabetics without ADNCS and 20 non diabetic controls were examined. Mean age and mean diabetes duration were similar in all groups. Graded exercise was performed in all patients using an ergometer cycle. In patients with ADNCS resting heart rate was significantly higher. The increase in heart rate during exercise was significantly lower, maximal tolerated work load was significantly reduced, and blood pressure-heart-rate multiplication as indirect measurement of oxygen uptake was significantly reduced too. The 16 diabetics with ADNCS were divided into 2 groups: 6 patients got CSII (12 months), 10 patients continued conventional s.c. therapy. After 6 and after 12 months graded exercise was performed again. The patients on s.c. therapy showed no improvement. 3 of the 6 CSII treated patients showed a significant improvement of the above mentioned parameters. Thus, in diabetics with ADNCS, CSII might not only influence the cardiovascular reflex tests, but might also have an effect on cardiovascular responses to graded exercise.

Autonomic Nervous System Diseases↗