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  • 1
    Electronic Resource
    Electronic Resource
    The role of cytotoxic macrophages in non-obese diabetic mice: cytotoxicity against murine mastocytoma and beta-cell lines (1993)
    Springer
    Diabetologia 36 (1993), S. 1252-1257 
    Details
    ISSN: 1432-0428
    Keywords: Non-obese diabetic mice ; macrophage ; Type 1 (insulin-dependent) diabetes mellitus ; cytokine ; nitric oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cytotoxicity of macrophages from non-obese diabetic (NOD) mice against murine mastocytoma (P-815), and murine beta-cell lines having the NOD gene background (MIN6N-9a), were examined. Peritoneal exudate cells from 20-week-old mice showed higher cytotoxicity, measured as inhibition of thymidine uptake into P-815, than those from 12-week-old mice (p 〈0.01). In cyclophosphamide-injected mice, cytotoxicity of peritoneal exudate cells had increased at 8 days post-injection, at which time the mice were not diabetic. To confirm macrophage cytotoxicity against pancreatic cells and examine its cytolytic mechanism, the cytotoxicity of peritoneal exudate cells from cyclophosphamide-injected NOD mice against MIN6N-9a cells was measured by the chromium release assay. These peritoneal exudate cells showed higher cytotoxicity as compared to those of saline-injected mice (p 〈0.001). Macrophages were demonstrated to be the major component of peritoneal exudate cells (50%) by flowcytometric analyses. Cytotoxicity increased with macrophage enrichment by adhesion (p 〈0.01). Furthermore, a macrophage toxin, silica, completely blocked the cytotoxicity (p 〈0.001). Cytokines (interleukin 1 and tumour necrosis factor) and a nitric-oxide-producing vasodilator, sodium nitroprusside, were cytotoxic to MIN6N-9a cells but only sodium nitroprusside showed cytotoxicity when incubated for the same period as peritoneal exudate cells. Thus, macrophages play an important role in beta-cell destruction and soluble factors other than cytokines (e.g. nitric oxide) may be mediators of this early cytolytic process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400802
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Immunological aspect of non-obese diabetic mice: immune islet cell-killing mechanism and cell-mediated immunity (1984)
    Springer
    Diabetologia 27 (1984), S. 121-123 
    Details
    ISSN: 1432-0428
    Keywords: Non-obese diabetic mice ; cell-mediated cytotoxicity ; islet cells ; natural killer activity ; antibody-dependent cell-mediated cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The non-obese diabetic mouse is thought to be one of the best available animal models for human Type 1 (insulin-dependent) diabetes. By 51Cr release assay we investigated cell-mediated cytotoxicity to the islet cells of Balb/C mice, natural killer activity, and antibody-dependent cell-mediated cytotoxicity activity of spleen lymphocytes from pre-diabetic non-obese diabetic mice. The cell-mediated cytotoxicity to islet cells of non-obese diabetic mice was significantly higher than that of control ICR mice. In contrast, natural killer and antibody-dependent cell-mediated cytotoxicity activities of the spleen cells from the non-obese diabetic mice were significantly lower than those of ICR mice spleen cells. These results suggest that lymphocytes from non-obese diabetic mice were sensitized to the antigen of islet cells and that the non-specific cellular immunity of non-obese mice was reduced. They suggest also that this immune islet cell-killing mechanism may play an important role in the pathogenesis of diabetes in non-obese diabetic mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275666
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Cell-mediated cytotoxic islet cell surface antibodies to human pancreatic beta cells (1984)
    Springer
    Diabetologia 26 (1984), S. 30-33 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; islet cell surface antibodies ; cytotoxic antibodies ; antibody-dependent cell-mediated cytotoxcity ; human pancreatic B cells ; islet cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sera containing islet cell surface antibodies show a complement-dependent cytotoxic reaction against islet cells, but it has not yet been clarified whether islet cell surface antibodies exhibit cell-mediated cytotoxicity to these cells. By 51Cr release assay we investigated whether islet cell surface antibodies showed a cytotoxic reaction to human pancreatic B cells (JHPI-1 clone) in the presence of normal human lymphocytes. The sera from 14 islet cell surface antibody-positive, 16 islet cell surface antibody-negative Type 1 (insulin-dependent) diabetic patients and 18 islet cell surface antibody-negative healthy subjects were studied. Four sera containing islet cell surface antibodies showed specific cytotoxicity above the mean +3SD value of healthy subjects, and the mean specific cytotoxicity of islet cell surface antibody-positive sera differed significantly from that of both islet cell surface antibody-negative groups. These results suggest that this cell-mediated cytotoxic mechanism may play an important role in the pathogenesis of Type 1 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00252259
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    HLA class II is associated with the frequency of glutamic acid decarboxylase M r 65 000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus (1996)
    Springer
    Acta diabetologica 33 (1996), S. 108-113 
    Details
    ISSN: 1432-5233
    Keywords: Autoantigen ; Autoimmunity ; Insulin-dependent diabetes mellitus ; Human leukocyte antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and-DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1,23% long-duration type 1,56% slowly progressive type 1,3% type 2 patients, and 1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB1*08 allele (100%,Pc〈0.05). GAD65Ab frequencies in DQB1*0302, DQB1*0303, and DRB1*09-positive, long-duration type 1 patients were lower than those in short-duration type 1 patients (14%, 19%, and 20%,Pc〈0.02 compared with short-duration type 1, 90%, 75%, and 71%, respectively), while the frequency varied less in DQB1*04 individuals (44% and 30% in short- and long-duration type 1 patients, respecitively). These findings were also observed among patients with DRB1*04, i.e., the haplotype DRB1*0405-DQB1*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short- and long-duration type 1 patients, respectively), while DRB1*04xx-DQB1*0302 showed lower frequency in long-duration type 1 than short-duration (13% and 100%, respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this association might be affected by disease duration in Japanese type 1 patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569419
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    HLA class II is associated with the frequency of glutamic acid decarboxylase Mr 65 000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus (1996)
    Springer
    Acta diabetologica 33 (1996), S. 108-113 
    Details
    ISSN: 1432-5233
    Keywords: Key words  Autoantigen ; Autoimmunity ; Insulin-dependent diabetes mellitus ; Human leukocyte antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and -DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1, 23% long-duration type 1, 56% slowly progressive type 1, 3% type 2 patients, and 1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB1*08 allele (100%, Pc〈0.05). GAD65Ab frequencies in DQB1*0302, DQB1*0303, and DRB1*09-positive, long-duration type 1 patients were lower than those in short-duration type 1 patients (14%, 19%, and 20%, Pc〈0.02 compared with short-duration type 1, 90%, 75%, and 71%, respectively), while the frequency varied less in DQB1*04 individuals (44% and 30% in short- and long-duration type 1 patients, respectively). These findings were also observed among patients with DRB1*04, i.e., the haplotype DRB1*0405-DQB1*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short- and long-duration type 1 patients, respectively), while DRB1*04xx-DQB1*0302 showed lower frequency in long-duration type 1 than short-duration (13% and 100%, respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this association might be affected by disease duration in Japanese type 1 patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569419
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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