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Diffusion of C-peptide but not proinsulin from islets in frozen sections of human pancreas identified by monoclonal antibodies

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

Immune complexes in insulin-dependent diabetes

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

Identification of an HLA-DQ β-chain related genomic sequence associated with insulin-dependent diabetes

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

Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2) : A randomized clinical trial—Rationale and design

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 fails to affect levels of islet cell surface antibodies and incidence of diabetes in the BB rat

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

Locus-specific detection of HLA-DQ and -DR antigens by antibodies against synthetic N-terminal octapeptides of the β chain

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

A prospective analysis of islet-cell cytotoxic antibodies in insulin-dependent diabetic children. Transient effects of plasmapheresis

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

In vitro lymphocyte recognition of islet cells following in vivo priming with allogeneic murine pancreatic islets

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

Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat

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

Spontaneous in vitro immunoglobulin secretion at the diagnosis of insulin-dependent diabetes

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 immune response in individuals with hla-dr specificities conferring susceptibility to insulin-dependent diabetes - A hypothesis

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

A β-cell glycoprotein of Mr 40 000 is the major rat islet cell immunogen following xenogenic immunisation

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

Autoantibodies to a 64-kilodalton islet cell protein precede the onset of spontaneous diabetes in the BB rat

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

Susceptibility to insulin-dependent diabetes defined by restriction enzyme polymorphism of HLA-D region genomic DNA

DNA fragments complementary to cloned sequences encoding HLA-D region class II antigen α- and β-chains were determined by clotting with DNA from HLA-typed members of 22 complete families, 12 of which had a proband with insulin-dependent diabetes mellitus (IDDM). Analysis of genotypes showed that the DNA sequences were linked to HLA-DR and permitted confirmation of recombinations in two families. D

LHC Dark Matter Working Group: Next-generation spin-0 dark matter models

Dark matter (DM) simplified models are by now commonly used by the ATLAS and CMS Collaborations to interpret searches for missing transverse energy (ET miss). The coherent use of these models sharpened the LHC DM search program, especially in the presentation of its results and their comparison to DM direct-detection (DD) and indirect-detection (ID) experiments. However, the community has been awa

Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice

We used the mouse passive transfer model to test whether islet cell antibodies affect β-cell function. The immunoglobulin (Ig) fraction of plasma from 5 islet cell surface antibody-positive, newly diagnosed insulin-dependent diabetic children or of a pool of plasma from 12 normal subjects was injected daily (7–16 mg IgG/day) for 14 days into normal immunosuppressed BALB/c mice. Insulin secretory r