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A human HLA-DQ β-chain cDNA was used as a probe to identify and isolate a rat major histocompatibility antigen β-chain gene from a genomic library constructed in the vector λ Charon 28 using Wistar rat DNA (RT1u). The isolated exon of the rat gene (RT1.Bβ2) encoding a β-chain second domain was found to share 93% nucleotide homology with a mouse A β2 exon. Although the genomic organization of this
A cohort of 82 patients with Type 1 (insulin-dependent) diabetes was followed prospectively for 24 months, and 54 of them for 30 months, to study the relationship between fasting levels of immunoreactive C-peptide and titres of islet cell antibodies. After diagnosis, fasting C-peptide rose temporarily for 1-6 months of insulin therapy and declined continuously thereafter. While islet cell antibodi
Plasma levels of islet cell cytoplasmic and cytotoxic antibodies were determined in 10 children with insulin-dependent diabetes mellitus (IDDM) treated with plasmapheresis shortly after diagnosis, and in 9 children with IDDM treated by conventional means alone. Islet cell cytoplasmic antibody (ICA) titers were determined by indirect immunofluorescence using unfixed sections of human pancreas, and
Human proinsulin (HPI) and C-peptide (HCP) were visualized by specific monoclonal antibodies (Mab's) in the conventional indirect immunofluorescent assay for ICA (islet cell cytoplasmic antibodies) on frozen sections of human pancreas. Two different Mab's, GS-9A8 (anti-HPI, mouse IgG1) and GN-ID4 (anti-HPI/HCP, rat IgG2A), showed intense islet cell cytoplasmic staining. In contrast to the anti-HPI
Circulating immune complexes (IC) were studied in 40 newly-diagnosed insulin-dependent diabetics (IDDM), 40 long duration IDDM, and 16 healthy controls. IC were detected by the solid-phase Clq test (SP-Clq). IDDM patients at diagnosis (25%) showed a higher incidence of IC compared to the long duration IDDM patients (15%) and the control group (7%). There was no difference in the prevalence of circ
Restriction fragment length polymorphism detected by a cDNA probe for an HLA-DQ β-chain gene has revealed an HLA-DR4 linked BamH1 3.7 kb fragment which is rarely found among insulin-dependent diabetic patients. The present analysis demonstrates that the BamH1 3.7 kb fragment present on an HLA-DR4 positive chromosome in a healthy individual contains coding sequences for an HLA-DQ β-chain gene and t
Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore
Cortisone acetate (250 µg/kg·day) was given by im injections to 40 21-day-old diabetes-prone BB rats. The animals were followed longitudinally to determine islet cell surface antibodies (ICSA), as an expression of an abnormal immune reaction against the pancreatic islet cells and plasma glucose to estimate the degree of metabolic control. ICSA were detected 10-150 days before the diagnosis of diab
Antibodies against synthetic peptides representing the class-II antigen HLA-DR and -DQ β chain N-terminal sequences were prepared in rabbits. The two octapeptides only share two amino acids and enzyme-linked immuno-assays showed the antisera only to bind to its own antigen. Both peptide antisera detected a 29 kDa component in immunoblots of Raji and AL-34 cell plasma membrane proteins separated by
We determined the effects of plasmapheresis on cytotoxic antibodies to islet cells in 10 children (aged 11-16 yr) with newly diagnosed insulin-dependent diabetes mellitus (IDDM), as well as the plasma levels of antibodies over the next 30 mo and their relation to serum C-peptide concentrations. Complement-dependent, antibody-mediated cytotoxicity (C'AMC) in plasma was measured in a 51Cr release as
Lymphocytes from patients with insulin-dependent diabetes have been shown to be sensitized to pancreatic tissue antigens. Mice immunized with homologous pancreatic islets have been found to develop glucose intolerance and insulitis. Since lymphocytes may be involved in diabetogenesis, we wished to determine if lymph node cells from islet-immunized mice can recognize and respond to islet cells in v
The diabetic syndrome of the BB rat shows many homologies with that of human insulin-dependent diabetes and evidence that the onset of the disease is associated with the presence of autoantibodies, including islet cell surface antibodies. In this study, sera were sampled serially from weaning to 157 days of age from 26 BB rats in two low-incidence litters, and 22 rats of three high-incidence litte
Blood mononuclear cells obtained from 17 newly diagnosed insulin-dependent diabetic (IDDM) patients treated with insulin for 5-7 days were assessed for the number of spontaneous and pokeweed mitogen (PWM)-stimulated immunoglobulin-secreting cells in a reverse haemolytic plaque assay. The spontaneous in vitro immunoglobulin secretion was evanescent and decreased in individual patients within 1-4 mo
The genetic control of insulin-dependent diabetes as well as of other autoimmune endocrine disorders have not been defined. These disorders are often said to run in families but the mode of inheritance is not understood. A most intriguing aspect of insulin-dependent diabetes is its close association with the HLA-DR specificities 3 and/or 4. More than 90% of all caucasian IDDM have either one or bo
An antiserum (R2) was raised in a rabbit against dispersed Sprague Dawley rat islet cells. The R2 antiserum contains islet cell surface antibodies, which mediate complement-dependent cytotoxicity against islet cells resulting in a block of glucose induced insulin release. Immunoprecipitation and gel electrophoretic analysis showed that R2 specifically recognizes an Mr 40 000 glycoprotein present i
Spontaneous insulin-dependent diabetes mellitus (IDDM) in the BB rat is associated with the presence of antibodies to a 64-kilodalton rat islet cell protein. These protein antibodies appeared in young animals and remained for as long as 8 weeks before the clinical onset of IDDM. Antibodies to a 64-kilodalton human islet cell protein were found to be associated with human IDDM. Detection of the ant
