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  • 1
    Electronic Resource
    Electronic Resource
    Islet Transplantation in Mice Differing in the I and S Subregions of the H-2 Complex (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 16 (1982), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Pancreatic islets from A.TH mice were transplanted into the spleen or streptozotocin (SZ)-diabetic A.TL mice. The two strains of mice are congenic inbred strains, differing only in the I and S subregions of the H-2 complex. The allogeneic islet grafts decreased blood glucose temporarily, but the islets were rejected after 21 ± 7 days (mean ± SD). The effect of skin presensitization was tested by giving both allogeneic and syngeneic skin grafts to each of a second set of A.TL mice before streptozotocin treatment and islet transplantation. The time course of rejection of the allogeneic islets in animals that received initial skin grafts was decreased to 8 ± 3 days. In both skin-presensitized and non-presensitized mice syngeneic islet grafts were able to restore normoglycaemia, even in animals that had previously rejected an islet allograft. These observations demonstrate that transplantation of pancreatic islet allografts across the I and S subregions of the H-2 complex is sufficient to induce rejection of the islets. The islet rejection was markedly accelerated by prior sensitization with allogeneic skin grafting. It is suggested that elements in allogeneic skin grafts serve as inducers of cytotoxic T-cell responses directed against gene products of the I and/or S subregions present on cells in the allogeneic islets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1982.tb00693.x
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  • 2
    Electronic Resource
    Electronic Resource
    Macrophages from High-Risk HLA-DQB1*0201/*0302 Type 1 Diabetes Mellitus Patients are Hypersensitive to Lipopolysaccharide Stimulation (2002)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 56 (2002), S. 0 
    Details
    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
    URL: http://dx.doi.org/10.1046/j.1365-3083.2002.01150.x
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  • 3
    Electronic Resource
    Electronic Resource
    Absence of H-2 genetic influence on streptozotocin-induced diabetes in mice (1982)
    Springer
    Diabetologia 23 (1982), S. 114-118 
    Details
    ISSN: 1432-0428
    Keywords: Mouse ; experimental diabetes ; streptozotocin ; H-2 system ; sex hormone ; insulitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five daily injections of streptozotocin (40 mg/kg) produced a delayed but progressively increasing level of hyperglycaemia in long term studies with male Naval Medical Research Institute mice and C3D2F1 (DBA 2 J male × C3H/ Tif female) F1 hybrid mice. The development of hyperglycaemia was paralleled by decreased amounts of pancreatic immunoreactive insulin as well as degranulation and necrosis of pancreatic B cells. Insulitis was found from days 9–25 after the first injection of streptozotocin. Compared with the F1 hybrid strain the parental inbred strains DBA 2 J and C3H/Tif demonstrated a certain resistance to streptozotocin. Development of hyperglycaemia did not differ in four congenic resistant lines of mice on the C57 BL/10 genetic background, indicating that major histocompatibility complex genes are not likely to determine susceptibility to streptozotocin-induced islet B cell damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01271171
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  • 4
    Electronic Resource
    Electronic Resource
    The World Health Organization International Collaborative Study for Islet Cell Antibodies (2000)
    Springer
    Diabetologia 43 (2000), S. 1282-1292 
    Details
    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
    URL: http://dx.doi.org/10.1007/s001250051524
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  • 5
    Electronic Resource
    Electronic Resource
    Antibodies directed against the pancreatic islet cell plasma membrane detection and specificity (1980)
    Springer
    Diabetologia 19 (1980), S. 445-451 
    Details
    ISSN: 1432-0428
    Keywords: Pancreatic islet cells ; cell suspensions ; islet cell surface antibodies ; cell surface immunofluorescence ; Protein A radioassay ; cell surface antigens ; autoimmunity ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rabbits were immunised with suspensions of viable, insulin-producing islet cells prepared from collagenase-isolated rat or ob/ob mouse pancreatic islets. Antibodies reactive with the surface of dispersed rat islet cells were present in both the rabbit anti-rat and the rabbit anti -ob/ob mouse islet sera as revealed by indirect immunofluorescence or by a radioligandassay using 125I-Protein A as a measure of cell bound IgG. In a competition assay the binding of 125I-Protein A was displaced in a concentration dependent manner by non-radioactive Protein A. Maximal displacement was found at concentrations of Protein A higher than 0.1 μg. added to 105 islet cells. Although not always detected by immunofluorescence there was a several-fold increase above normal rabbit serum of 125I-Protein A-binding to rat hepatocytes and spleen lymphocytes incubated with the islet cell antisera. Conversely, rabbit antisera against rat spleen lymphocytes or against a rat liver plasma membrane preparation reacted with rat islet cells. The rabbit anti-rat islet cell antiserum was absorbed to both spleen lymphocytes and hepatocytes until there was no binding of 125I-Protein A to either cell type. Islet specific antibodies were still present since this doubly absorbed antiserum induced cell surface immunofluorescence as well as 125I-Protein A-binding to rat islet cells. It is concluded that apart from common antigenic determinants immunisation with viable islet cells induces formation of antibodies directed against specific islet cell surface components.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281824
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  • 6
    Electronic Resource
    Electronic Resource
    New approaches to therapy and diagnosis of diabetes (1982)
    Springer
    Diabetologia 22 (1982), S. 61-67 
    Details
    ISSN: 1432-0428
    Keywords: Insulin preparations ; porcine insulin ; bovine insulin ; human insulin ; recombinant DNA ; insulin gene ; polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusion Not only has recombinant DNA added another source of insulin for treatment, but also, and perhaps more important, it has allowed the development of new techniques for studying the structure and function of the B cell at the gene level. We can only hope that this information will bring us closer to the understanding of the disease, so the diabetic patient may benefit from other measures of treatment than the classical replacement therapy introduced by Banting and Best 60 years ago [47].
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254830
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  • 7
    Electronic Resource
    Electronic Resource
    Analysis of islet cell antibodies on frozen sections of human pancreas (1983)
    Springer
    Diabetologia 25 (1983), S. 93-96 
    Details
    ISSN: 1432-0428
    Keywords: Islet cell antibodies ; indirect immunofluorescence ; insulin-dependent diabetes ; assay reproducibility ; assay precision
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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. End-point titration of the antibodies in two different laboratories using the same pancreas was significantly correlated (Spearman test p 〈 0.001). We conclude that a reliable determination of islet cell antibody titres in human serum requires careful characterization of the sensitivity and specificity of each pancreas used as a source of frozen sections, in the indirect immunofluorescence assay.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00250895
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  • 8
    Electronic Resource
    Electronic Resource
    A β-cell glycoprotein of Mr 40 000 is the major rat islet cell immunogen following xenogenic immunisation (1984)
    Springer
    Diabetologia 27 (1984), S. 70-73 
    Details
    ISSN: 1432-0428
    Keywords: Glycoprotein Mr 40 000 ; islet cell immunogen ; xenogenic immunisation ; antiserum R2 ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 in both rat islet and rat insulinoma cells. This glycoprotein is amphiphilic in character and probably represents a pancreatic β cell specific plasma membrane component. The results support previous observations in mouse β cells that a plasma membrane glycoprotein of Mr 40K constitutes a major islet cell immunogen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275650
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  • 9
    Electronic Resource
    Electronic Resource
    The low dose streptozotocin murine model of Type 1 (insulin-dependent) diabetes mellitus: Studies in vivo and in vitro of the modulating effect of sex hormones (1982)
    Springer
    Diabetologia 22 (1982), S. 194-198 
    Details
    ISSN: 1432-0428
    Keywords: Mouse ; experimental diabetes ; streptozotocin ; sex influence ; sex hormone ; islet cell cytotoxicity in vitro ; lymphocyte transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of sex on pancreatic islet B cell susceptibility to streptozotocin was studied in mice given multiple low doses of streptozotocin. Male C3 D2 F1 mice developed a steadily increasing blood glucose level after a lag period of about 3 weeks, in contrast to females who were resistant. Spleen cells from streptozotocin treated female animals produced hyperglycaemia in total body irradiated syngeneic female recipients, but only if the recipients were treated with testosterone. Testosterone treatment of donors did not affect blood glucose levels of recipients. Streptozotocin cytotoxicity in vitro determined by a 51Cr-release assay revealed an increased sensitivity to streptozotocin in dispersed islet cells from adult male animals as compared with cells from adult female mice. The incubation of islet cells from animals of either sex with testosterone, or oestradiol plus progesterone, did not enhance the susceptibility to streptozotocin. Islet cells from sexually immature male or female mice were less susceptible to streptozotocin. The results demonstrate that sex determines susceptibility to streptozotocin in vivo and in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00283752
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  • 10
    Electronic Resource
    Electronic Resource
    Islet cell antibodies — Theoretical and practical implications (1981)
    Springer
    Diabetologia 21 (1981), S. 431-435 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00257781
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