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Biomedical subjects

I Rjasanowski

Publications and source records attributed to I Rjasanowski.

At least 37 records · Page 2Linked to original sources
PubMed1990

Autologous mixed lymphocyte reaction in newly diagnosed type-1 diabetes.

The autologous mixed lymphocyte reaction (AMLR) represents activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Deteriorations in AMLR have been reported in many autoimmune diseases and in diseases with a derangement in T cell regulatory function. We have studied AMLR in 23 newly diagnosed Type-1 diabetic patients and 32 healthy subjects. T and non-T cells were purified by rosetting mononuclear cells with sheep erythrocytes and separating the rosetted T cells from the nonrosetted non-T cells by density gradient centrifugation. Purity of T-lymphocytes isolated was 90% as determined by indirect immunofluorescent analysis with monoclonal antibodies. Proliferation of lymphocytes was measured in response to phytohaemagglutinin and of concanavalin A in a lymphocyte transformation test. In the present study, a deficient AMLR is demonstrated in patients with newly diagnosed Type-1 diabetes. Our data provide evidence for an aberrant immune regulation at the time of diabetes manifestation. The deficient AMLR may represent the in-vitro expression of an in-vivo process against pancreatic cells.

Adolescent↗
PubMed1990

Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes.

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.

Adult↗
PubMed1990

DQ beta restriction fragment length polymorphism in insulin dependent diabetes mellitus.

HLA DQ beta restriction fragment length polymorphisms (RFLP's) were compared in 43 patients with insulin dependent diabetes mellitus (IDDM), 51 healthy first grade relatives of IDDM patients and 27 controls without IDDM heredity in their families. We were able to demonstrate an association between the presence of a 12 kb BamHI restriction fragment (p less than 0.001) and 12 kb/4 kb (p less 0.01) or 12 kb/4.4 kb (p less than 0.001) BamHI fragment combinations and IDDM. But for these fragments and fragment combinations we also found increased frequencies in the healthy first grade relatives of IDDM patients. That means for the evaluation of the importance of the characterised "risk fragments" in practice it is necessary to follow up the manifestation of IDDM in this risk group.

Adolescent↗
PubMed1990

[The fructosamine test for the determination of nonenzymatic glycosylated serum proteins. A critical inspection of the method].

A modification of the original method of R.A. Johnson et al. for nonenzymatically glycated serum proteins (fructosamine test) is described. Problems of performance and optimization of the method as well as of calibration and the influence of protein composition on the results are discussed. Measuring is manually performed after a 8 min preincubation interval over a 1 min's period using the spectrophotometer "Spekol 220". Interserial precision was 3.2%. First clinical results demonstrate the possibility to assess glycemic control in type 1 diabetic patients over a integrated time interval.

Blood Proteins↗
PubMed1989

Persistence of anti-islet ADCC after manifestation of type-1 (insulin-dependent) diabetes.

ADCC (antibody-dependent cellular cytotoxicity) against xenogenic islets in vitro has frequently been found with mononuclear blood cells and heat inactivated autologous serum from newly diagnosed Type-1 diabetics. Anti-islet ADCC, as measured by enhanced 51Cr-release of islets after a 6h-incubation, leads to functional alteration of islets such as a decrease in insulin content and in leucine incorporation. In a follow-up investigation over at least three years it was demonstrated that anti-islet ADCC in vitro disappears, if there is no more C-peptide secretion in vivo. Furthermore, anti-islet ADCC has also not been found in long-term Type-1 diabetics who had no C-peptide secretion but an acutely stimulated immune system due to infectious diseases. An acute immunocytolytic process against pancreatic beta cells in vivo seems to be the precondition for anti-islet ADCC in vitro.

Adolescent↗
PubMed1989

Determination of islet cell surface antibodies in first-degree relatives of type 1 diabetic patients using rat insulinoma cells.

Titre of islet cell surface antibodies (ICSA) in 114 sera from healthy control probands and 177 sera from first-degree relatives of Type 1 diabetic patients was determined by indirect immunofluorescence using rat insulinoma (RIN) cells as target. All sera were tested at four dilutions (1/40-1/320). 10(5) RIN cells were incubated with 100 microliters diluted serum overnight at 4 degrees C followed by a 45 min-incubation with a FITC-labelled goat anti-human globulin. Titre curves were calculated by double logarithmic regression. ICSA titre was defined as the serum dilution producing cell surface fluorescence on 40% of RIN cells. Based on these data a serum is defined as ICSA positive when the ICSA titre calculated is higher than 1:142, quantil Q (0.97). Twenty-five out of 177 (14%) sera of first-degree relatives of Type 1 diabetes were ICSA positive with a mean titre of 1/393, range 1/145-1/1,740, while 2/114 (1.7%) control sera were weakly positive for ICSA. These data demonstrate the significantly increased ICSA prevalence in first-degree relatives of Type 1 diabetic patients. The present study suggests that RIN cells may represent a useful tool for standardization of ICSA assay.

Adolescent↗
PubMed1988

Phagocytic activity of blood cells in diabetic risk probands and newly diagnosed type 1 diabetics.

The phagocytic activity of granulocytes and mononuclear blood cells was compared in probands at risk for insulin-dependent Type 1 diabetes mellitus and in newly diagnosed diabetics before and during short-term insulin treatment. Healthy persons without family history of Type 1 diabetes were used as controls. Furthermore, the relationship between phagocytic activity and the proportion on monocytes in the granulocyte- and mononuclear blood cell fractions was estimated. The phagocytic activity of the mononuclear cells from the risk subjects was reduced. This observation suggests that defective phagocytosis might be important in the pathogenesis of Type 1 diabetes. But the phagocytic activity of mononuclear cells from newly diagnosed diabetics was not severely impaired and was fully normal under insulin treatment. We found no differences in the phagocytic activity of the granulocytes between patients and healthy probands. The proportion of monocytes in the mononuclear cell fraction was significantly enhanced in newly diagnosed diabetics and remained high throughout the 6-month period of insulin therapy. We assume that the increased monocyte level and the phagocytic activity of mononuclear cells in diabetics are not related to each other. But the increased monocyte level could also be interpreted as a compensatory reaction against the impaired phagocytic activity observed in the risk probands.

Adolescent↗
PubMed1988

Effect of lymphocytes and serum from probands before and after manifestation of type 1 (insulin-dependent) diabetes on rat islets in vitro.

In a two-year follow-up study neonatal rat islets have been shown to be affected in vitro by lymphocytes and complement-inactivated serum obtained from newly diagnosed Type 1 (insulin-dependent) diabetic patients and probands who are at high risk for developing the disease. The effect was measured by 51Cr-release of the islets treated with the proband's serum after a 6 h-incubation with lymphocytes of the same donor. Nineteen newly diagnosed diabetic patients, 23 persons at risk and 11 control probands were studied. There was no appreciable cytotoxic activity in the control probands (with one exception) and in 7 out of the 19 newly diagnosed diabetics. Five of the diabetes-susceptible probands developed diabetes mellitus during the investigation period. Anti-islet cytotoxicity of lymphocytes was found in these individuals at least 8 months before diagnosis of Type 1 diabetes. The cytotoxic effect disappeared at various time intervals after disease manifestation. Islet cytotoxicity was intermittently found with lymphocytes from further 13 probands at risk, sometimes for more than one year. Our data indicate that mononuclear cells from probands who are at high risk for developing Type 1 diabetes can exert cytotoxicity on xenogenic neonatal islets in the presence of their own serum.

Adolescent↗
PubMed1988

Complement component 3 (C 3) and diabetes mellitus.

Complement factor 3 (C3) phenotype and allele frequencies were defined in 312 patients with Type 1 diabetes (IDDM), 256 patients with Type 2 diabetes mellitus (NIDDM), 114 apparently healthy first-degree relatives of Type 1 diabetics, in 10 families (29 members) with a familial history of Type 1 or Type 2 diabetes, and 512 controls (blood donors). All persons investigated were Europeans. There is no evidence to suggest that genes linked to C3 influence susceptibility to Type 1 and Type 2 diabetes and to their late complications. C3 levels in blood plasma were found to be slightly elevated in both types of diabetes. But the C3 concentrations varied considerably within the groups. C3 split products were demonstrable in a high percentage in the blood plasma of freshly manifested Type 1 diabetic persons as well as in Type 1 diabetics with a duration of the disease of 1 to 3 years. C3 proteolysis could also be found in plasma of Type 2 diabetics (26%).

Adolescent↗
PubMed1988

Restriction-fragment-length-polymorphisms close to the human insulin gene on chromosome 11 and their possible relation to diabetes mellitus in a GDR population.

A polymorphic DNA sequence flanking the 5'-region of the human insulin gene was studied by means of Southern blot hybridization techniques in 92 diabetic and non-diabetic individuals in order to investigate the possible relation of their allelic variants to certain types of diabetes. DNA was isolated from nucleated blood cells and digested with the restriction endonucleases EcoRI or Bg1 I. Only two classes of alleles were found (U and L). The small L-allele was predominantly found with the following frequency: 0.64 in controls, 0.795 in insulin-dependent diabetics, and 0.625 in non-dependent patients. It could be demonstrated that the L-allele and IDDM are associated. These data suggest that this allele seems to be a genetic marker for insulin-dependent diabetes mellitus. The putative function of the polymorphic region in the aetiology of diabetes mellitus and the possible genes being in linkage disequilibrium with it are not known so far.

Adult↗
PubMed1987

5-year follow-up study of C-peptide secretion in newly diagnosed type I diabetics: relations to HLA-phenotype, insulin requirement and metabolic control.

50 HLA-typed insulin-dependent diabetics were studied at the time of diabetes onset and after 1, 2, 3 and 5 years with regard to C-peptide secretion after combined stimulation with glucose and glucagon, insulin requirement and glycaemic control index. The mean decrease of the residual B-cell reserve was observed within two years. C-peptide secretion was correlated with better metabolic control and lower insulin requirement after more than one year of diabetes duration, but had no influence on this at the time of diabetes onset. The C-peptide response sometimes varied between non response and high response in one individual from one investigation to the next. There was no prognostic value of C-peptide secretion at diabetes onset for the further development of B-cell function. We found a significantly longer persistence of B-cell function in patients who were older and in those with mild symptoms at diabetes onset. The presence of HLA B8, DR3 antigens was correlated with severe ketoacidosis at manifestation and a more pronounced destruction of B-cell function.

Adolescent↗
PubMed1987

Islet cell surface antibodies (ICSA) in subjects with a previous mumps infection--a prospective study over a 4 year period.

It has been suggested that the mumps virus may be involved in the etiopathogenesis of Type-I diabetes mellitus. Most studies have analyzed this relationship retrospectively. We, however, carried out a prospective study over a 4 year period after a mumps infection in two age groups (16 years and under [group A no = 32] and over 16 years [group B no = 18]). These subjects with "diabetic risk factors" (impaired glucose tolerance, low insulin response, ICSA and/or HLA-DR3/DR4) were selected from 1581 registered cases, in whom an antecedent mumps infection had occurred in 1980 and 1981. Glucose tolerance and insulin secretion did not change significantly during 4 years after a mumps infection. Overt diabetes was not observed in any of the cases. One year after a mumps infection 35% of children and 63% of adolescents/adults exhibited ICSA (control subjects = 5%; a serum was considered ICSA-positive if more than 25% of the intact rat islet cells showed distinct cell surface immunofluorescence). After 4 years the percentage of subjects with ICSA decreased significantly to 13% and 14%, resp. Only 21% of ICSA-positive sera were found to be cytotoxic on rat islet cells (51Cr-release assay). No relationship could be evaluated between complications resulting from a mumps infection and the appearance of ICSA. There was no correlation between ICSA, glucose tolerance, and insulin secretion. In fact, our prospective study did not reveal any relationship between a mumps infection and Type-I diabetes. ICSA would seem to be of no predictive value.

Adolescent↗
PubMed1986

The role of insulin antibodies in insulin treatment of type I diabetes.

We investigated equilibrium plasma binding patterns of insulin in 45 juvenile diabetics treated with conventional insulin preparations. Insulin binding parameters were evaluated by Scatchard analysis of the binding data. Stable diabetics had significantly lower equilibrium dissociation constants than labile, thus suggesting an enhanced insulin depot effect due to stronger insulin binding. Correlation of insulin binding data with a glycemic control index yielded a positive relationship between insulin antibody binding and the degree of glycemic control. Insulin neutralization as detected by a relationship between maximum binding capacity of high affinity antibodies and insulin requirement could only be found if patients with poor diabetes control were excluded. Similarly, the well-known promoting influence of residual beta-cell functional capacity (assessed by C-peptide levels) on diabetic stability was observed only after exclusion of patients with higher insulin antibody binding. These data suggest that insulin antibodies are influencing insulin treatment of diabetics in a dual way. They may neutralize therapeutic insulin but at the same time they exert an insulin-sparing action by improvement of diabetes control. Occasionally the latter effect may abolish the correlation between diabetes control and beta-cell functional capacity.

Adolescent↗
PubMed1985

Validity of WHO criteria for classification of newly diagnosed diabetics.

In order to assess the validity of WHO criteria for the discrimination between Type I and Type II diabetes a cross-sectiona clinical study was performed in 84 normweight newly diagnosed diabetics with a mean age of 22 years. Taking into consideration clinical and biochemical characteristics of the carbohydrate and fat metabolism, the therapeutic requirement to maintain euglycemic metabolic control, the residual beta-cell function, the HLA phenotype and islet cell antibodies (ICA, ICSA) it could be shown that none of the tested criteria has the ability to distinguish between the types with absolute certainty. As shown by the frequency of the different markers in relation to the therapeutic requirements for euglycemic metabolic control as well as by the correlation analysis between the variables the discriminating validity of the markers decreased in the following sequence: diabetes associated HLA phenotype, residual beta-cell function, proneness to ketosis, age at onset, relative body weight. Neither the characteristics of the carbohydrate and fat metabolism nor the presence of islet cell antibodies contributed much to the differentiation between insulin-dependent and noninsulin-dependent diabetes.

Adolescent↗