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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 43 (2000), S. 1282-1292 
    ISSN: 1432-0428
    Keywords: Keywords Standards, ICA, GAD65, IA-2, diabetes, diagnostics, autoantibodies, islet cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Islet cell autoantibodies are a specific marker for Type 1 (insulin-dependent) diabetes mellitus. Standardisation of islet cell antibodies and the uniform reporting in International units is critical to research and the development of assays for islet cell autoantibodies as diagnostics.¶Methods. The suitability of a candidate serum to serve as the international standard for islet cell antibodies was studied by 19 participants in 8 countries. In addition, the purpose was to investigate whether the serum could also serve as a standard for antibodies to the 65 000 Mr isoform of glutamic acid decarboxylase (GAD65) and islet antigen-2 (IA-2). Control sera were included in the study to assess the validity of the various assay systems. The sera were lyophilized to World Health Organization criteria and the candidate serum assigned the ampoule code number 97/550.¶Results. The use of 97/550 was shown to notably reduce inter laboratory variability in the measurement of islet cell antibodies. In addition, there was a pronounced reduction in inter laboratory variability in the measurement of GAD65 and IA-2 antibodies. ¶Conclusions/interpretation. On the basis of the results reported here and with agreement of the participants, the preparation 97/550 has been established by the World Health Organization Expert Committee on Biological Standards for establishment as the first international standard for islet cell antibodies, with an assigned potency of 20 international units. In addition, 97/550 can serve as an international reference reagent for specific GAD65 antibodies, with an assigned potency of 100 units. It can also serve as a National Institute of Biological Standards and Control (NIBSC) reference reagent for IA-2 antibodies for evaluation of assays for this material. [Diabetologia (2000) 43: 1282–1292]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Levels of nonantigen-induced pro-inflammatory cytokines and prostaglandin in macrophages isolated from human leucocyte antigen (HLA)-matched type 1 diabetes mellitus patients, first-degree relatives and healthy controls were determined. We hypothesize that monocytes isolated from patients are sensitized or preactivated and therefore, have an altered response to in vitro stimulus compared with control groups as measured by levels of pro- and anti-inflammatory mediators. In this study, peripheral blood monocytes were differentiated to macrophages with macrophage-colony stimulating factor (M-CSF) to determine lipopolysaccharide (LPS)-stimulated tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-12 and prostaglandin E-2 (PGE-2) secretion from hetero- or homozygous HLA DQB1*0201 and *0302 type 1 diabetes mellitus patients, first-degree relatives and homozygous HLA DQB1*0602 healthy controls. LPS-stimulated secretion of TNF-α, IL-1β and IL-6 was immediate and markedly higher in the HLA-DQB1*0201/*0302 type 1 diabetes patients compared with all other groups including HLA-matched healthy first-degree relatives. In DQB1*0201/*0302 diabetes patients PGE-2 secretion was delayed but increased by LPS stimulation compared with HLA-matched healthy relatives. IL-12 was not detected at any condition. These data suggest that macrophages from DQB1*0201/*0302 type 1 diabetes patients are sensitized to secrete both cytokines and PGE-2 following nonantigenic stimulation. Sensitized macrophages may be important to high-risk DQB1*0201/*0302-associated type 1 diabetes.
    Type of Medium: Electronic Resource
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