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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
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
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
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
Column perifusion of collagenase-isolated mouse pancreatic islets was used to study the dynamics of insulin release in experiments lasting for several hours. The methyl esters of L-leucine and L-arginine were synthetised. Whereas L-arginine methyl ester (L-arginine OMe) had no effect, L-leucine OMe stimulated the release of insulin. The effect of L-leucine OMe was maximal at 5 mmol/liter. Whereas
Sequences of different sizes are generated when DNA from homozygous HLA-Dw/DR typing cells are digested with restriction endonuclease and analyzed by hybridization with a HLA-D region class II antigen beta-chain cDNA probe. The patterns of hybridization were highly polymorphic but one endonuclease, BamHI, defined sequences unique to all HLA-Dw/DR specificities 1-8 except HLA-Dw/DR 2 and 6; however
The β-cell function, total islet volume, and number were studied in 1- to 18-month-old mice, together with the extractable pancreatic insulin and glucagon. The β-cell function, determined as the total amount of insulin released in response to glucose from the in vitro perfused pancreas showed an agerelated increase, without any differences in the kinetics of insulin secretion between young and old
ABSTRACT The pancreatic B‐cell function (glucose tolerance, C‐peptide release) and organ‐specific autoantibodies, including islet cell cytoplasmic and cell surface (mouse), were studied in 45 first‐degree relatives of patients with insulin‐dependent diabetes mellitus diagnosed before the age of 30 years. Compared to 107 healthy persons without any family history of either insulin‐dependent or non‐
The probable role of cell surface antigens in the development of juvenile diabetes necessitates a detailed study of the proteins expressed on the surface of pancreatic β-cells. A gene library composed of genes expressed in β-cells was constructed to provide a source of low abundance genes from those cells. Initial studies with this library have led to the isolation of three genes which share nucle
Litters of BB rats with an expected high and low incidence of insulin-dependent diabetes were followed from weaning until the age of about 140 days. Islet cell surface antibodies (ICSA) and lymphocyte antibodies (LA) were determined in a radioligand assay with fixed rat insulinoma (RIN 5F) cells, an insulin-secreting cell line, or spleen lymphocytes. In the low-incidence litter, 2 out of 14 rats h
An antiserum raised against the purified human erythrocyte glucose transporter specifically immunoprecipitated a major protein of Mr36 000 and a minor protein of Mr 58 000 from human pancreatic islets. The biosynthetic incorporation of [35S]methionine into the 36-kDa protein increased 2-3 fold in 16 mM D-glucose with 0.1 mM IBMX as compared to islets incubated in 3 mM D-glucose either with or with
The sensitivity and specificity of the assay for islet cell cytoplasmic antibodies in human serum were examined using cryostat sections from fresh frozen pancreas. The specificity of the assay was close to 100% while the sensitivity was 40%-98% depending on the pancreas used. Inter-observer variation was 12-27%. End-point titres of islet cell antibodies varied with the sensitivity of each pancreas
