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Biomedical subjects

B O Boehm

Publications and source records attributed to B O Boehm.

At least 91 records · Page 5Linked to original sources
PubMed1991

HLA-DR3 and variations of the T cell receptor beta gene in Graves' disease.

The association of Graves' disease with two allelic forms of the T cell receptor beta-chain gene (Bgl II restriction fragments 9.2/10.0 kb) was analysed in Caucasians suffering from Graves' disease (N = 54), randomly selected controls (N = 68), and HLA-DR3 homozygous typing control subjects (N = 12). While gene frequencies did not vary in the latter two groups, a significant reduction of 9.2 kb homozygosity was observed in patients with Graves' disease (11 vs 32%, chi 2 = 7.68, p less than 0.01, RR = 0.26). The excess of the 9.2/10.0 kb heterozygosity in patients, which is restricted to the DR3-positive individuals, did not reach significance. The increase in heterozygosity of genomic T cell receptor beta-chain polymorphisms may be attributed to the role the beta-chain plays in autoantigen recognition in Graves' disease.

Bacterial Proteins↗
PubMed1991

Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study.

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes.

Adolescent↗
PubMed1990

The HLA-DR4-associated DQw8 allele is confined to HLA-DR3/DR4 heterozygous type I (insulin-dependent) diabetics.

The HLA-DR4 specificity revealed a relative risk of 8.5 (chi 2 = 99.6; p less than 0.0001) when 193 type I diabetics were compared to 305 controls. Prevalence of the HLA-DR4-associated DQ types, i.e. DQw7 and DQw8, were determined, using a restriction fragment length polymorphism (RFLP) typing that combines the probe/enzyme combinations DQB/Taq I and DQB/Bam HI. The HLA-DQw8 specificity was confined to HLA-DR3/DR4 heterozygous patients when compared to controls (chi 2 = 4.9; p less than 0.025) or to all other DR4-heterozygous patients (chi 2 = 6.7; p less than 0.01). No association with HLA-DQw8 was seen in HLA-DR1/DR4 or HLA-DR"X"/DR4 (X not equal to 1,3,4) heterozygous patients. Due to the excess of HLA-DR3/DR4 patients the DQw8 allele is a risk factor in type I diabetics, but in HLA-DR1/DR4 and DRX/DR4 heterozygotes one might suggest that DQB1 and DRB combinations confer HLA-associated susceptibility.

Alleles↗
PubMed1990

TcR-alpha and TcR-beta dialellic RFLPs in insulin-dependent (type I) Caucasian diabetic patients.

We studied the association of a T-cell receptor (TcR) beta restriction fragment length polymorphism (RFLP) and a new TcR-alpha RFLP with insulin-dependent (Type I) diabetes mellitus. This study is part of our effort to find new non-HLA disease genes involved in this chronic organ-specific autoimmune disease. Distribution of a 9.2 kb and a 10.0 kb diallelic TcR beta 2 RFLP was not different in diabetics and controls. A new TcR-alpha RFLP, which gave a 2.7 kb Hind III restriction fragment (A2 allele) was found with a frequency of 0.78 in a population of 78 IDDM patients, compared to 0.68 in 68 control subjects (X2 = 3.62, p = 0.057). In 11 multiplex families studied, a high prevalence of the A2 allele was also observed, but cosegregation with the disease was not seen. Our data suggest that a TcR beta 2 RFLP is not associated with the disease, whereas a particular T-cell receptor alpha germline RFLP (A2 allele) is increased in Type I diabetics although formal proof of linkage is lacking. HLA typing reconfirmed that the HLA-DR4 specificity and the DQ allele HLA-DQw8 are primary risk markers in insulin-dependent (Type I) diabetes mellitus.

Alleles↗
PubMed1989

Restriction fragment polymorphisms of the HLA-DR, HLA-DQ, and insulin gene regions in IDDM: the GAW5 data.

The primary aim of the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5) was to collect and analyze new data on DNA polymorphisms closely linked to the HLA-D region and the insulin gene. The probes and restriction enzymes described here were used by all ten participating labs, and the data from Southern blotting were interpreted and reported according to conventions developed for the Workshop. These DNA data on members of 94 families with two or more IDDM sibs constitute the largest such sample available. The data were used in most of the analyses presented at the Workshop meeting, and are available on request.

Chromosome Mapping↗
PubMed1989

Association of HLA antigens with progressive systemic sclerosis and morphea.

The HLA phenotype frequencies of 40 patients with progressive systemic sclerosis (PSS) and 42 patients with morphea (sclerodermia circumscripta) indicate a weak, HLA-linked genetic predisposition of the affected individuals (70 female, 12 male). An "opposite" HLA A1, B8 (high immune response) vs A3, B7, DR2 (low immune response) constellation in PSS and morphea supports the clinical subdivision of scleroderma into these different nosological entities, and may serve as a differential diagnostic tool and prognostic marker.

Female↗
PubMed1989

Re-evaluation of eye muscle autoantibody determination in Graves' ophthalmopathy: failure to detect a specific antigen by use of enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoblotting techniques.

Sera from 41 patients with Graves' ophthalmopathy were investigated for presence of autoantibodies directed against eye muscle preparations using different methods: 1. ELISA with pork eye muscle membrane preparations; 2. Immunoblotting with glycoprotein preparations from human eye muscle; 3. Indirect immunofluorescence with human eye muscle sections. The ELISA was not suitable for detection of specific immunoglobulin binding with sera from patients suffering from endocrine ophthalmopathy. Immunoblotting exhibited only nonspecific binding to some muscle proteins; it could be prevented by pre-adsorption procedures and was not different from the pattern observed with skeletal muscle as antigen. The indirect immunofluorescence technique revealed no binding of Graves' sera to human muscle sections, whereas sera containing antibodies against skeletal muscle bound to eye muscle as well. Thus far, an antigenic structure of eye muscle specific for Graves' ophthalmopathy is not detectable with the methodology used here. The possibility that retroorbital connective tissue may be the main target of the autoimmune process must be considered.

Animals↗
PubMed1989

Determination of islet cell antibodies using an ELISA system with a preparation of rat insulinoma (RIN A2) cells.

An enzyme-linked immunosorbent assay (ELISA) was established for the detection of islet cell antibodies in human sera. The antigen was prepared from rat insulinoma (RIN A2) cells. Cells were dissociated in lysis buffer and the lysate was centrifuged at 100,000 x g. The supernatant was used to coat microtiter ELISA plates (10 micrograms protein/ml in PBS pH 7.2). Non-specific binding sites on the plates were blocked with 2% PBS-BSA. Human test sera were preabsorbed on separate plates using 2% PBS-BSA and incubated on precoated plates at an optimal dilution of 1/10 in 60 mM PBS for 60 min at 37 degrees C. Phosphatase-labeled anti-human IgG serum and phosphatase substrate were applied and the reaction was stopped by adding 3 M NaOH. Out of 90 sera from type I diabetic patients, 47 (52.2%) reacted in the new ELISA whereas none of 15 type II diabetics, 50 sera containing non-islet specific antibodies or 100 normal controls were positive. In the same group of patients, ICA were positive in 63.3%. When both, the ELISA and conventional ICA testing were applied, the number of positives was increased to 83%. The ICA-ELISA with the above described antigen preparation provides a well standardized and reproducible test method which is highly specific for type I diabetes. It may therefore be useful for large screening procedures.

Adult↗
PubMed1988

Autoantibodies to adrenal medullary and thyroid calcitonin cells in type I diabetes mellitus--a prospective study.

Autoantibodies to adrenal medulla that gave a diffuse immunofluorescent staining pattern were detected in 17 out of 107 (16%) patients with newly diagnosed Type I diabetes mellitus, in 13 out of 178 (7%) patients with long lasting disease but in none of 80 mixed control sera tested. The antibodies were of IgG class and 31 of the 33 positive sera also fixed complement. In 32 out of 34 cases, detection of the antibodies was correlated with the presence in the serum of pancreatic islet cell antibodies (ICA). The specificity of adrenal medullary antibodies is distinct from ICA and from C-cell antibodies since their reactivity was not abolished by preabsorption with extracts from human insulinoma or thyroid C-cell carcinoma. The presence in the serum of antibodies to adrenal medulla is not related to a functional defect of the adrenal medulla, but this new specificity indicates a further autoimmune reaction related to the natural history of Type I diabetes.

Adolescent↗
PubMed1988

Linkage of HLA-DR beta specific restriction fragment length polymorphisms with Graves' disease.

HLA-DR3 positive patients with Graves' disease (6 homozygotes, 7 heterozygotes, i.e. yielding 19 haplotypes) were studied by restriction fragment length polymorphism analysis using TaqI as restriction enzyme in order to look for polymorphisms in the HLA-DR3 allele of the human major histocompatibility complex. Polymorphic TaqI fragments of 11.6, 9.8 and 5.8 kb, each corresponding to HLA-DR beta sequences, were shown to differ in their prevalence in patients with Graves' disease and controls. The prevalence of DR3 polymorphisms in a total of 35 HLA-DR3-containing haplotypes was markedly different within patients with Graves' disease and Caucasian controls. Whereas a 11.6 kb fragment was rare in Graves' disease (2/19 haplotypes vs 8/16 in controls), the inverse ratio was found for a 9.8 kb fragment, with a prevalence of 17/19 and 8/16 haplotypes, respectively. A polymorphic fragment of 5.8 kb was exclusively seen in two DR3-containing haplotypes of patients with Graves' disease. Our data provide evidence that a DNA polymorphism of the HLA-DR beta genes, which is also reflected at the product level, is linked to Graves' disease.

Cell Line↗
PubMed1988

Biosynthetic human proinsulin, a new therapeutic compound for diabetics? A comparative study of biosynthetic human proinsulin with biosynthetic human insulin.

The biological activities of proinsulin, the endogenous precursor of insulin are different in comparison to insulin. Proinsulin has a longer biological half-life in serum and a much lower hypoglycemic potency. Biosynthetic human proinsulin has been suggested as an intermediate acting "insulin" in the treatment of diabetes mellitus, having the advantage of not including a retardation substance. For this reason it is important to establish a dose relationship in comparison to human insulin. Human proinsulin and human insulin were tested in 2 groups of healthy volunteers after i.v. application on a unit equivalent basis. 0.025, 0.05 and 0.1 units/kg of either compound were applied intravenously in a randomised order. Following human proinsulin application, the nadir of blood glucose showed a delay of 5-10 min. in comparison to insulin, however, the increase of blood glucose following the nadir was much more retarded after human proinsulin application. The antilipolytic effect of proinsulin was significantly stronger in comparison to insulin. No significant differences could be observed in the kinetics of beta-hydroxybutyrate levels and the counterregulatory response. Human proinsulin, based on a unit equivalent dosage, exerts a more pronounced hypoglycemic and antilipolytic effect, which is probably due to the longer biological half-life in comparison to insulin.

3-Hydroxybutyric Acid↗
PubMed1986

Classical and late-onset forms of congenital adrenal hyperplasia caused by 21-OH deficiency reveal different alterations in the C4/21-OH gene region.

Congenital adrenal hyperplasia (CAH) is due to defective adrenal cortisol biosynthesis. In most cases, deficiency of a P 450-C21 specific steroid hydroxylase impairing cortisol synthesis has been found. The disease is HLA-linked, and on clinical grounds it can be divided into two major forms, the classical and the non-classical type. Here, evidence is presented that the classical and the non-classical forms of CAH caused by 21-OH deficiency are due to different genetic alterations in the C4/21-OH gene region. In most cases of classical CAH associated with the HLA-Bw47 antigen, a specific and selective loss of the 21-OH B gene was observed with some interesting exceptions. Alterations in the 21-OH gene region in the non-classical forms of CAH, patients either HLA-B14; DR1 homo- or heterozygous, are different. Our data indicate the possibility of gene conversion events in this genomic region in non-classical CAH.

Adrenal Hyperplasia, Congenital↗