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Biomedical subjects

K V Richter

Publications and source records attributed to K V Richter.

At least 19 recordsLinked to original sources
PubMed1989

Histocompatibility and bone marrow transplantation (BMT).

Possible donors may be recommended by the following order: 1. HLA-identical twins (syngeneic) 2. HLA-identical siblings 3. HLA-haploidentical related donors The increased number of additional HLA-incompatibilities (HLA-A, -B, -DR) increases the risk of GVHD. 4. HLA-phenoidentical and MLC-negative unrelated donors The DRS for BMT includes the early HLA typing of the patient and of all related potential donors, covering all known antigens. Evidence on the basis of MLC should be available for cellular non-reactivity between donor and recipient cells, although this will be rarely possible with haploidentical related donors. Donor-specific HLA antibodies must not be detectable in the recipient. No generally accepted method has so far become available for consideration of minor histocompatibility antigens in the context of DRS for BMT.

Bone Marrow Transplantation↗
PubMed1988

Complement-mediated cytotoxic effects of islet cell surface antibodies in non-diabetic subjects with antecedent mumps infection and diabetic risk.

We studied sera of 24 selected non-diabetic subjects in whom an antecedent mumps infection with either complications and/or with onset at older age occurred 10-27 month ago regarding the capability to lyse rat islets of Langerhans in vitro. Thirteen subjects were characterized by diabetes associated HLA antigens DR3 and/or DR4 whereas 11 of them had none of these HLA antigens. Islet cell surface antibodies (ICSA) could be detected in 11 out of 24 subjects. Isolated pancreatic islets from 8-10 days old Wistar rats were incubated in freshly prepared human serum. The insulin leakage under the conditions of pharmacologic blockade of insulin secretion by means of epinephrine and propranolol provides a measure of complement-mediated cytotoxicity of human serum against rats islets in vitro. Out of a total of 24 subjects the sera of 11 of them exhibited cytotoxicity. Mean cytolytic insulin leakage was significantly higher in subjects with DR3 and/or DR4 in comparison with subjects without these HLA antigens (6.82 +/- 0.77% vs 3.90 +/- 0.48%; p less than 0.05). Ten out of the 11 subjects with cytotoxic sera had HLA DR3 and/or DR4 whereas DR3 was present in three out of 13 subjects with non-cytotoxic sera. There was no relationship between beta cell function in vivo (fasting C-peptide concentration and insulin response to oral glucose challenge) and the capability of patients sera to damage islet cells in vitro. In conclusion the pathogenetic role of mumps virus and cytotoxic ICSA and their possible relation to slow progressive beta-cell destruction has still to be ascertained.

Adolescent↗
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

Complement-dependent antibody mediated cytotoxicity (C'AMC) in patients with newly diagnosed insulin-dependent diabetes mellitus.

Serum activities of complement-dependent antibody mediated cytotoxicity (C'AMC) were determined in 36 consecutive patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM). The sequential exposure of 51Cr labeled neonatal rat islet cells to patient serum and rabbit complement revealed the presence of C'AMC in 28 IDDM subjects. The C'AMC titres ranged between 1:4 and 1:512 and were not related to the C'AMC activity of a given sample as measured at a standard dilution (1:4). In comparison to the clinical characteristics of 21 IDDM patients with negative C'AMC, higher C'AMC titres (greater than or equal to 1:32) were associated with a lower mean age at diagnosis of IDDM (12.2 +/- 2.1 vs. 19.0 +/- 2.3 years; p less than 0.05), with a higher frequency of infections up to 6 months prior to diagnosis (6 out of 11 vs. 3 out of 21 patients; p less than 0.05) and, although statistically not significant, a preponderance of female sex together with a decreased frequency of HLA-DR4. In contrast, fasting C-peptides levels, HLA-DR3 antigen frequency and Coxsackie B1-6 virus antibody titres were not related to the C'AMC titres. It is concluded that (1) C'AMC titration is superior to the detection of initial C'AMC levels for evaluating the strength of the complement-dependent humoral immune response towards islet cell surface (auto)antigen(s), and (2) infectious agents may be involved in eliciting a C'AMC response.

Adolescent↗
PubMed1987

Cytotoxic islet cell autoantibodies in newly diagnosed insulin-dependent diabetes mellitus: lack of correlation to age, residual beta cell function, HLA antigens and Coxsackie B virus antibodies.

In a cross-sectional study comprising of 56 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) serum was examined for the presence of complement-dependent antibody mediated cytotoxicity (C'AMC) by an improved assay measuring the release of 51Cr from freshly isolated normal rat islet cells prelabeled with the isotope. In the presence of complement, 35 (63%) IDDM sera specifically mediated cytotoxicity against islet cells. The degree of cell specificity was tested using prelabeled exocrine cells, but this cell type did not reveal any differences between the lytic effects of IDDM and control serum. At the time of clinical onset of IDDM the age of the patients, fasting and stimulated C-peptide levels, insulin requirement, HLA antigens, antibodies to Coxsackie B1-6 viruses, diabetes heredity, and, surprisingly, islet cell surface antibodies (ICSA) were not associated with C'AMC. It is concluded that the mere presence of C'AMC against rat islet cells at the time of diagnosis of IDDM is not indicative of a low residual B cell function and HLA-linked susceptibility to diabetes does not necessarily include enhancement of humoral anti-islet cell autoimmunity. More elaborate methods for quantitative detection of C'AMC and ICSA (e.g. in terms of titres) together with autoantibody subclass determination are needed to reveal possible associations between C'AMC and the clinical characteristics of IDDM.

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↗
PubMed1985

Metabolic, hormonal, and immunological alterations in subjects with antecedent mumps infection.

Since mumps virus seems to be one of the most likely candidates in viral etiology of insulin-dependent diabetes (IDDM) we studied the possible relationship of glucose tolerance (75 g oGTT), beta cell function, diabetes associated HLA antigens, haptoglobin phenotype, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in 125 subjects with antecedent mumps infection. Impaired glucose tolerance (IGT) was diagnosed in 3.2% (n = 4) but onset of diabetes did not appear within 14 months after mumps infection. There was no relationship between glucose tolerance and complications of antecedent mumps infection (e.g. pancreatitis, meningitis, orchitis). The prevalence rate of ICA was 76%. ICSA were detectable in about 36% of children and 62% of the adults tested (p less than 0.01). There was no relationship between ICA/ICSA and diabetes-associated HLA antigens, haptoglobin phenotype or beta cell function (fasting C-peptide and insulin response to 75 g oGTT). However, adults with circulating ICA were characterized by a significantly lower insulin response to glucose. Fifty two "risk" subjects characterized by IGT, diabetes associated HLA antigen(s), ICA or ICSA either alone or combined were studied again 26 months after mumps infection. No symptomatic diabetes appeared and IGT was diagnosed in one case only. ICA and ICSA persisted in more than 50% of subjects in whom ICA or ICSA were present 14 months after mumps infection. Since the used immunological techniques do not clearly distinguish organ-specific from non-organ-specific antibodies the results must be interpreted with caution. To summarize, the preliminary results do not support a close temporal relationship between mumps infection and the onset of IDDM. The pathogenetic role of mumps virus and ICA/ICSA and their possible relation to a slow progressive beta cell destruction has still to be determined.

Adult↗
PubMed1982

Multiple sclerosis--relation between HLA haplotype A25, B18 and disease progression.

The HLA typing of 100 patients with multiple sclerosis (MS) and their differentiation according to the dynamics of the disease, the type of course and the degree of defect showed the following results: a significant increase in frequency of HLA B7 (P less than 0.05), independent of the severity of illness, a 4-fold increased frequency of the HLA haplotype A25, B18 with augmented occurrence in slight to moderate severity of the disability degree (P less than 0.05), less so in the dynamics of the disease, and only partially so in the relapsing-remittent course. These HLA constellations provide only a hint at the prognosis of MS; the findings could be an expression of the heterogeneity of the disease.

Gene Frequency↗
PubMed1982

[Chronicity of non-A, non-B hepatitis. Evaluation of the clinical course with special reference to the types of distribution of HLA antigens and clinical criteria].

The progression of acute viral hepatitis non-A, non-B in a group of young female patients with well defined disease was evaluated retrospectively over a period of 21/2 years. The histologically proved chronification rate was 39 per cent. It was looked for a correlation between some parameters in the acute phase of the disease, the distribution of HLA antigens, and the progression to chronicity. There were no statistically ensured differences of HLA antigens between patients with chronic hepatitis non-A, non-B, patients with healed acute one, patients with chronic hepatitis type B, and the normal population. The level of transaminases within the acute phase of the illness did not allow to draw any conclusion for the further progression of the disease. But icteric patients seemed to develop chronic disease more seldom. In this time, the reason of the high chronification rate after infection by hepatitis virus(es) non-A, non-B is not yet clear.

Adolescent↗
PubMed1978

Specificities of heterologous antisera against human leukaemia cells. 1. Reactions against leukaemia cells.

Rabbit or goat antisera directed to ALL, CLL, AML and CML cells were investigated in cytotoxicity tests with different leukaemia and normal cells as targets. After absorptions with erythrocytes and spleen cells from allogeneic donors the antisera killed only leukaemia cells. There was no reaction with remission leukocytes or blood leukocytes from normal donors. Anti-ALL-Sera reacted in 35 out of 49 tests with ALL cells from 13 patients. Apparently the ALL antisera which were directed to the T cell subtype of ALL preferentially affected ALL cells of this subtype. Cross reactions with cells from CLL, AML and CML were not found. Anti-CLL-sera reacted in 10 out of 12 tests with CLL cells from 4 donors, and in 4 out of 20 tests with ALL cells from 7 donors and also with the cells of a CML patient. AML cells from two patients were not killed. Antisera against AML and CML showed extensive cross reactions with cells of myelocytic and lymphocytic leukaemias. Absorption tests demonstrated the presence of two antibody specificities in AML antisera, one of which being directed to a common antigen of AML and ALL cells and another against an antigen of myelocytic leukaemia cells.

Antibodies, Neoplasm↗