966 research outputs found
Insulin as a Primary Autoantigen for Type 1A Diabetes
Type 1A diabetes mellitus is caused by specific and progressive autoimmune
destruction of the beta cells in the islets of Langerhans whereas the other cell
types in the islet (alpha, delta, and PP) are spared. The autoantigens of Type
1A diabetes may be divided into subgroups based on their tissue distributions:
Beta-cell-specific antigens like insulin, insulin derivatives, and IGRP (Islet-specific
Glucose-6-phosphatase catalytic subunit Related Peptide); neurendocrine antigens
such as carboxypeptidase H, insulinoma-associated antigen (IA-2), glutamic acid
decarboxylase (GAD65), and carboxypeptidase E; and those expressed
ubiquitously like heat shock protein 60 (a putative autoantigen for type 1 diabetes).
This review will focus specifically on insulin as a primary autoantigen, an essentia
l target for disease, in type 1A diabetes mellitus. In particular, immunization with
insulin peptide B:9-23 can be used to induce insulin autoantibodies and diabetes
in animal models or used to prevent diabetes. Genetic manipulation of the insulin
1 and 2 genes reciprocally alters development of diabetes in the NOD mouse,
and insulin gene polymorphisms are important determinants of childhood
diabetes. We are pursuing the hypothesis that insulin is a primary autoantigen
for type 1 diabetes, and thus the
pathogenesis of the disease relates to specific recognition of one or more peptides
Evidence for a neutral grain boundary barrier in chalcopyrites
Single grain boundaries in CuGaSe2 have been grown epitaxially. Hall measurements indicate a barrier of 30 40 meV to majority carrier transport. Nevertheless, local surface potential measurements show the absence of space charge around the grain boundary, i.e. it is neutral. Theoretical calculations [Persson and Zunger, Phys. Rev. Lett. 91, 266401 2003 ] have predicted a neutral barrier for the present S3 grain boundary. Thus, we have experimentally shown the existence of a neutral grain boundary barrier, however, smaller than theoretically predicte
Development Of An Adaptive Augmented Reality Qualification System For Manual Assembly And Maintenance
The manufacturing industry is facing various challenges today - globalization, fast-moving sales markets, short product life cycles, individualization, mass production and diversity of variants are trends that will continue or even increase in the future. Speed and flexibility in production are thus becoming important success factors for companies. To meet the demands of the market, there is a growing necessity to deploy employees flexibly within the production process. This increases the need for additional qualification of workers. By overlaying reality with virtual cues, Head-mounted displays (HMD) can present information in a situation-specific and location-linked manner. Data glasses also offer a high and convertible degree of support through the possibility of providing different media forms while both hands are available at the same time. Augmented Reality (AR) guidance systems are already available on the market and are suitable as permanent assistance systems, but only to a limited extent for qualification aspects. An industrially applicable qualification software that collects expert knowledge from skilled workers and then makes it available to new or inexperienced employees in an adaptive way that promotes learning is currently not available. This paper therefore presents the development of the software AQUA, which taps internal expertise with low effort and creates training courses that convey learning content to learners without over- or under-challenging them
Two Single Nucleotide Polymorphisms Identify the Highest-Risk Diabetes HLA Genotype: Potential for Rapid Screening
OBJECTIVE—People with the HLA genotype DRB1*0301-DQA1*0501-DQB1*0201/DRB1*04-DQA1*0301-DQB1*0302 (DR3/4-DQ8) are at the highest risk of developing type 1 diabetes. We sought to find an inexpensive, rapid test to identify DR3/4-DQ8 subjects using two single nucleotide polymorphisms (SNPs)
Retrospective Assessment of Islet Cell Autoantibodies in Pancreas Organ Donors
OBJECTIVE—Of deceased pancreas donors, 3–4% may have autoantibodies (AAb) to pancreatic islet cell antigens; these autoantibodies are well-established markers of type 1 diabetes. We investigated whether donor AAb positivity could affect the outcome of pancreas transplantation
Gad65 is recognized by t-cells, but not by antibodies from nod-mice
Since the 64kDa-protein glutamic acid decarboxylase (GAD) is one of the major autoantigens in T-cell mediated Type 1 diabetes, its relevance as a T-cell antigen needs to be clarified. After isolation of splenic T-cells from non-obese diabetic (NOD) mice, a useful model for human Type 1 diabetes, we found that these T-cells proliferate spontaneously when incubated with human GAD65, but only marginally after incubation with GAD67, both recombinated in the baculovirus system. No effect was observed with non-diabetic NOD mice or with T-cells from H-2 identical NON-NOD-H-2g7 control mice. It has been published previously that NOD mice develop autoantibodies against a 64kDa protein detected with mouse beta cells. In immunoprecipitation experiments with sera from the same NOD mice and 33S-methionine-labelled GAD, no autoantibody binding could be detected. We conclude firstly that GAD65 is an important T-cell antigen which is relevant early in the development of Type 1 diabetes and secondly that there is an antigenic epitope in the human GAD65 molecule recognized by NOD T-cells, but not by NOD autoantibodies precipitating conformational epitopes. Our results therefore provide further evidence that GAD65 is a T-cell antigen in NOD mice, being possibly also involved in very early processes leading to the development of human Type 1 diabetes
Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study
Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals
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