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The role of K396 in the enzymatic catalysis and the antigenicity of the 65 kDa isoform of glutamate decarboxylase (GAD65) was analyzed using the K396R GAD65 mutant. GAD65 is a major autoantigen in Type 1 diabetes and autoantibodies directed to GAD65 are widely used markers for this disease. We found that (1) recombinant human GAD65 is fully enzymatically active; (2) the K396R mutation abolished GA
Antigen-specific T cells acquire a distinctive phenotype during activation, with characteristic acquisition of surface markers and patterns of gene expression. Early after antigen stimulation, CD4+ T lymphocytes increase their surface density of the CD4 marker, a trait which has been used to identify antigen-activated cells. The recent development of MHC tetramer technologies has greatly improved
Background: Patients with insulin-dependent diabetes mellitus (IDDM) have elevated risk for periodontitis (PD) relative to subjects without diabetes. Whether refractory PD in IDDM patients is related to autoimmunity as indicated by serum glutamic acid decarboxylase autoantibody GAD Ab levels or to host bacterial immunity as reflected by serum antibody titers to periodontal pathogens is unknown. Ai
The smaller isoform of glutamic acid decarboxylase, GAD65, is an important autoantigen implicated in the pathogenesis of type 1 diabetes whereas the larger isoform, GAD67 appears to play no major role. The primary difference between the two isoforms resides in the N-terminal part of the molecule including the GAD65 membrane-anchoring domain. The aim of this study was to generate mutants of the mem
The potential for using macaques to create a nonhuman diabetic model was investigated. The significant objectives were to determine a) prognosis of STZ induced permanent beta cell destruction in nonhuman primates, and b) the potential to use STZ treated animals in a model of autoimmune diabetes by following adoptively transferred lymphocytes into MHC identical macaques. Beta cell impairment was ac
Fritidsfisket är en viktig källa till rekreation samtidigt som företag inom fisketurism bidrar till utvecklingen av de kustnära regionerna. Sedan januari 2017 regleras fritidsfisket på torsk i västra Östersjön av en bag-limit. Det innebär att det är tillåtet att ta hem högst fem torskar per dag (tre under lekperioden, februari-mars). I det berörda området är många fisketurismföretag så kallade tur
Animal serum is often used to generate human macrophages in vitro. Since fetal calf serum (FCS) may complicate antigen uptake, processing and presentation on HLA molecules, we tested the ability of M-CSF to generate macrophages at low fetal calf serum conditions. Peripheral blood monocytes from 12 individuals were cultured 1-4 days with 0-100 ng/ml macrophage colony stimulating factor (M-CSF) at e
Retroviral vectors encoding glucose-responsive promoters driving furin expression may provide an amplified, glucose-regulated secretion of insulin. We constructed LhI*TFSN virus to encode a glucose-regulatable transforming growth factor α promoter controlling furin expression with a viral LTR promoter driving constitutive expression of furin-cleavable human proinsulin. Autologous BB rat vascular s
Recent advances in molecular and cell biology may allow for the development of novel strategies for the treatment and cure of type 1 diabetes. In particular, it is now possible to envisage restoration of insulin secretion by gene or cell-replacement therapy. The β-cell is, however, remarkably sophisticated, and many of the features of this highly differentiated secretory cell will have to be faith
Based on the presence of autoantibodies and a strong HLA linkage, type 1 diabetes is now classified as a chronic autoimmune disease. Many issues, however, remain unresolved. Although autoantibodies to GAD65, IA-2, and insulin are clearly markers for this disease, it is not known whether they contribute to pathogenesis or are simply the response to an existing underlying destructive process. Based
Objective. Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. Design. A population-based follow-up cohort study. Setting. Participants visited the primary health care cen
We describe a novel monoclonal antibody raised towards the N-terminus of the 65 kDa isoform of glutamate decarboxylase (GAD65). This N-GAD65 mAb is highly specific for GAD65 and can be used in a wide range of applications such as Western blot analysis, immunoprecipitation and immunocytochemistry. Full-length cDNAs coding for N-GAD65 mAb heavy and light chains were cloned and characterized by nucle
Recent clinical trials have pioneered the successful use of a nonsteroidal immunosuppressive regimen and established a basis for application in a routine clinical setting. In this study, a single islet transplant was not sufficient to regulate blood glucose levels, and a second transplant became necessary. A similar observation was made in our macaque islet transplant study, where animals after th
The problem of designing robust and noise-insensitive PI controllers for pressure-sensor based combustion-timing control was studied through simulation. Different primary reference fuels (PRF) and operating conditions were studied. The simulations were done using a physics-based, control-oriented model with an empirical ignition-delay correlation. It was found that the controllable region, in-betwThe problem of designing robust and noise-insensitive PI controllers for pressure-sensor based combustion-timing control was studied through simulation. Different primary reference fuels (PRF) and operating conditions were studied. The simulations were done using a physics-based, control-oriented model with an empirical ignition-delay correlation. It was found that the controllable region, in-betw
BB rats lose >50% of their islet sympathetic nerve terminals soon after diabetes onset, markedly impairing the glucagon response to activation of these nerves. In this study, we sought evidence that this degree of disease-induced nerve terminal damage affected their neuronal cell bodies. Increased galanin expression was used as a marker of the change of phenotype that occurs in neuronal cell bodie
Human type 1 diabetes mellitus (T1DM) arises through autoimmune destruction of pancreatic β cells and is modeled in many respects by the lymphopenic and spontaneously diabetic BioBreeding (BB) DRlyp-lyp rat Previously, preonset expression profiling of whole DRlyp-lyp pancreatic lymph nodes (PLN) revealed innate immune activity, specifically that of mast cells and eosinophils. Furthermore, we obser
The question of registering two images (or image volumes) acquired with different modalities, and thus exhibiting different contrast, at different positions is addressed based on an extension of global digital image (or volume) correlation. A specific comparison metric is introduced allowing the signature of the different phases to be related. A first solution consists of a Gaussian mixture to des
