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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormally low circulating numbers and function of NK cells are associated with new onset type I diabetes. Since alpha interferon is a stimulator of NK function, enriched T and non-T lymphocytes were incubated with 0, 100 and 1,000 units/ml of recombinant alpha interferon (rIFN alpha) and natural killing against K562 and pancreatic islet cell targets was measured. The killing of K562 (1:20 target:effector ratio) cells by non-T cells incubated with 0, 100 and 1,000 units/ml of rIFN alpha in patients was decreased to 27% (p less than 0.014 vs control), 34% (p less than 0.001) and 39% (p less than 0.003) when compared to killing by normal control non-T cells (48%, 74% and 58% respectively). T cell mediated killing of K562 cells in patients was decreased to 3.9% (p less than 0.03), 5.3% and 6.6% (p less than 0.003) when compared to that of controls (8.7%, 10-8% and 22.6% respectively). Non-T cell mediated killing of islet cells (1:20 target:effector ratio) following treatment of effector cells with 0, 100 and 1,000 units/ml of rIFN alpha in patients was 19%, 27%, and 26% which was comparable to control subjects killing of 31%, 18% and 37% respectively. Similar data were obtained using T-cells as effectors. These data indicate that in new onset type I diabetes; (a) NK cell functional activity is diminished in both T and non-T lymphocyte subpopulations and (b) NK activity is suboptimally enhanced with rIFN alpha.
Diabetes Res 1988 Jan
PMID:Interferon responsiveness of natural killer cells in type I human diabetes. 340 65

The occurrence of HLA Class II expression by thyroid (and other endocrine) epithelia in autoimmune diseases suggests that these cells may facilitate their own destruction by immunogenically presenting autoantigens. This is supported by the findings that Class II+ thyrocytes can specifically stimulate virus-specific and autoreactive T cell clones, and that Class II expression by thyrocytes correlates with the occurrence of thyroid autoantibodies. A variety of factors may contribute to the regulation of Class II expression by thyrocytes: this is induced by interferon (IFN-gamma), and is enhanced by thyroid stimulating hormone (TSH) and by tumour necrosis factor (TNF). Conversely, epidermal growth factor (EGF) suppresses the induction of Class II in thyrocytes. This complex regulation is reflected in differences in HLA-D subregion expression between patients (DR greater than DP greater than DQ). The immune-based mechanisms of thyrocyte Class II regulation are clearly applicable to the on-going disease in an infiltrated thyroid, but the possibility of nonimmune Class II induction deserves attention, particularly in identifying factors which might contribute to the initial autoimmune attack. The possible involvement of such mechanisms in autoimmunity is supported by findings in Type I diabetes in which Class II+ islet beta cells can be found in the absence of infiltration. Further evidence is provided by the observation that a proportion of thyrocytes transformed with SV40 DNA constitutively express Class II molecules. Finally, the 'activated' state of capillary endothelial cells in organs subject to autoimmune attack suggests that they may play an important role in facilitating the autoreactive infiltration of the tissues.
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PMID:Thyrocyte HLA class II expression and regulation in relation to thyroid autoimmunity. 349 11

Examination of the interferon response of leukocytes in 119 patients with diabetes mellitus has demonstrated that interferon formation is influenced by a lot of factors. During counterbalancing of the metabolic disorders interferon formation was increased, being attended by marked clinical improvement of the patients. In the course of the treatment there was no rise in interferon production if the disease progressed rapidly and was accompanied by grave illnesses. The interferon response of leukocytes mirrors the gravity of metabolic abnormalities and can be used as an important prognostic test in the evaluation of the course of diabetes mellitus.
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PMID:[Interferon-synthesizing function of leukocytes in patients with diabetes mellitus]. 379 57

Adult male ICR Swiss mice develop insulin-dependent diabetes when infected with the D variant of encephalomyocarditis virus (EMC-D). In contrast, adult C57Bl/6 males are relatively resistant to the diabetogenic effects of this virus. We have been studying the role of interferon (IFN) in the pathogenesis of infection by EMC-D and development of virus-induced murine diabetes mellitus. The data show that when IFN beta or IFN gamma were administered four days after virus infection, the frequency and severity of diabetes were exacerbated in ICR Swiss mice, and the diabetic state was induced in the resistant C57Bl/6 strain. In addition, animals treated with either of the IFNs or the IFN-inducer poly I:C, developed symptoms of severe encephalomyocarditis. Analysis of ICR Swiss mouse tissues revealed that IFN-treatment resulted in virus replication in the heart and brain and the reappearance of the virus in the pancreas. It is concluded that under certain conditions, the diabetic state is exacerbated and the normal course of (EMC-D)-infection in mice is altered by IFN.
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PMID:Exacerbation of the pathogenesis of the diabetogenic variant of encephalomyocarditis virus in mice by interferon. 388 8

The content of interferon in plasma and interferon reaction of leukocytes (IRL) were studied in 28 children with initial stages of diabetes mellitus. IRL in these children was found to be the same as in controls. Some kinds of insulin: zink-insulin, protamine-zink-insulin, insulin-protamine as well as vincristin were capable of reducing in vitro the interferon-producing activity of leukocytes 3--6 fold. The content of interferon in plasma was determined in 22 children: in 20 of them the concentration of interferon was below 10 units/ml, in 2 was 10 units/ml.
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PMID:[The interferon system in children with the initial stages of diabetes mellitus]. 615 95

Two patients with newly diagnosed insulin dependent diabetes mellitus were treated with human leukocyte interferon based on the hypothesis that the diabetes was induced by an active viral infection in the pancreatic islets and could be arrested. High peak levels of serum interferon were achieved (100-200 U/ml) with minimal systemic side effects. There was no sustained therapeutic benefit as measured by increased production of endogenous insulin, or of C-peptide, or by a lower requirement for exogenous insulin. Further trials with interferon treatment should be undertaken only if evidence of active viral infection (culture, antigen detection) can be associated with insulin dependent diabetes onset and these markers followed during treatment.
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PMID:Human leukocyte interferon treatment of two children with insulin dependent diabetes. 616 82

The M variant of encephalomyocarditis virus (EMC) produces a disease similar to human insulin-dependent diabetes mellitus in some but not all strains of mice. This diabetogenic M variant was found to induce fivefold more interferon than non-diabetogenic strains of EMC in cultures of mouse L 929 fibroblasts. When interferon induced by the M variant was added to monolayers of B cells from both diabetes-'susceptible' CD-1 mice and 'resistant' C57 bl/6 mice before EMC infection, B cell damage and virus replication were delayed. In addition, viral production in B cell cultures from C57 bl/6 mice was reduced five- to tenfold. A similar effect was not found when cultures from CD-1 mice were treated with interferon. Thus, interferon might play an important role in modulating the severity of the initial infection of B cells.
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PMID:Effect of interferon on encephalomyocarditis virus infection of cultured mouse pancreatic B cells. 618 60

The current study used a murine model of diabetes induced by the D variant of encephalomyocarditis virus (DEMC) to determine the protective effect of exogenous antiviral agents. Antivirals, which were found to inhibit the development of DEMC virus cytopathic effect in L-929 cell monolayers, were administered intraperitoneally beginning 12 h prior to DEMC virus challenge. Arildone (500 mg/kg per day) or murine interferon (3.2 X 10(6) IU/kg per day) significantly reduced the incidence of hyperglycemia at 4 days after virus challenge. The incidences of hyperglycemia were 96% in untreated, 62% in arildone, and 0% in interferon treated mice. In other experiments we found that interferon (1.6 X 10(6) IU/kg per 12 h X 3) significantly protected mice against diabetes when administered at the time of virus infection or beginning 12 h afterwards. This effect was associated with reductions in average viral titers in the heart and pancreas of infected animals relative to untreated, infected mice. The results of these studies suggest that picornavirus induced diabetes may be prevented or ameliorated by the use of antiviral agents.
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PMID:Modification of encephalomyocarditis virus-induced diabetes in mice by antiviral agents. 619 26

Plaque purification of the M variant of encephalomyocarditis (EMC) virus resulted in the isolation of two stable variants: one diabetogenic and designated D and the other nondiabetogenic and designated B. When the D variant was inoculated into SJL/J male mice, hypoinsulinemia and hyperglycemia developed in > 90% of the animals. In contrast, none of the mice inoculated with the B variant developed diabetes. Histologic examination of pancreata from mice infected with the D variant revealed insulitis and necrosis of beta cells, whereas islets from mice infected with the B variant showed little, if any, change. When islets were assayed for infectious virus, approximately 10 times more virus was recovered from animals inoculated with the D as compared with the B variant. Moreover, approximately 60% of islet cells from mice infected with the D variant contained viral antigens when stained with fluorescein-labeled anti-EMC virus antibody, whereas < 5% of islet cells from animals infected with the B variant contained viral antigens. Co-infection experiments showed that the induction of diabetes by the D variant was inhibited by the B variant. When the B and D variants were mixed together at B:D ratios of 1, 9, and 99, diabetes developed in 60, 11, and 0% of the mice, respectively. Tissue-culture experiments revealed that the B variant induced considerably more interferon than the D variant, and studies in animals showed that interferon appeared earlier and in greater amounts in the circulation of mice infected with the B as compared with the D variant. These studies suggest that the induction of interferon by the B variant is, at least in part, responsible for the inhibition of diabetes by the D variant.
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PMID:Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus. 625 75

The diabetogenic strain of encephalomyocarditis virus (D virus) was propagated in several continuous cell lines. Each virus stock was tested for its ability to produce diabetes in mice and induce L-cell interferon (IFN-beta). The effect of insulin on virus replication and IFN-beta induction was also determined. It was found that the severity of the diabetes and the amount of IFN-beta produced was dependent on the cell line used for virus propagation. Virus synthesis was augmented and IFN-beta production was altered in insulin-treated cell cultures. It is concluded that D virus either consists of more than one virus or that its diabetes and IFN-beta inducing characteristics are unstable.
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PMID:Alteration of diabetes and interferon induction by the diabetogenic strain of encephalomyocarditis virus through cell passage. 629 May 77


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