Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetes mellitus (IDDM) results from selective autoimmune destruction of insulin producing beta-cells. T-cell reactivity and autoantibodies to several islet proteins such as insulin, GAD and IA-2 are associated with IDDM in mice and men. In NOD mice, the majority of T cells from insulitis specifically recognize the insulin B-chain peptide amino acid 9-22, in contrast to the periphery where the precursor frequency is much lower. It is important to note that these cells are diabetogenic. Surprisingly, the same insulin B-chain region contains epitopes recognized by protective T cells. In fact, autoimmune diabetes in NOD mice could be prevented by prophylactic treatment with this immunodominant T-cell epitope. In humans, however, no immunodominant regions of insulin have yet been defined. We have isolated and characterized a human insulin-specific T-cell clone that was derived from peripheral blood of a newly diagnosed IDDM patient. This patient displayed weakly positive primary T-cell responses to insulin. The peptide recognized by the clone was mapped to the insulin B chain (B:11-27). Functionally, the human insulin-specific CD4+ T cells displayed a Th1/0 like cytokine profile and were restricted by HLA-DR. The previously proposed alternative superantigen-like binding of insulin-B chain peptide outside of the peptide binding groove of HLA-DR could not be confirmed, since T-cell recognition was inhibited in competition experiments of insulin-B chain peptide with HLA-DR16 binding influenza peptide HA307-319. Our results indicate that human clonal T cells isolated from a recent onset IDDM patient recognize an epitope overlapping with the insulin B-chain region that is immunodominant and potentially therapeutic in NOD mice. This observation may be useful in studying the role of insulin-specific T cells in IDDM, and may eventually help to establish peptide-based immunotherapies in IDDM.
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PMID:Cloned T cells from a recent onset IDDM patient reactive with insulin B-chain. 965 96

The study of peptide binding to HLA class II molecules has mostly concentrated on DR molecules. Since many autoimmune diseases show a primary association to particular DQ molecules rather than DR molecules, it is also important to study the peptide-binding properties of DQ molecules. Here we report a biochemical peptide-binding assay for the type I diabetes-associated DQ8, i.e. DQ (alpha1*0301, beta1*0302), molecule. Affinity-purified DQ8 molecules were tested in peptide-binding assays using a radiolabelled influenza haemagglutinin (Ha) peptide encompassing positions 255-271(Y) as an indicator peptide. The Ha 255-271(Y) peptide bound to DQ8 in a pH-dependent fashion showing optimal binding around pH 5. The association kinetics were relatively slow and the resulting complexes were heat labile. The specificity of peptide binding to DQ8 was investigated in competitive inhibition experiments with a panel of 43 peptides of different lengths and sequences. The DQ8 molecules showed a different pattern of peptide binding compared to a previously studied DQ2 molecule. Peptides derived from thyroid peroxidase, HLA-DQ(alpha1*0301), HLA-DQ(alpha1*0302), retinol receptor and p21ras were among the high-affinity binders, whereas peptides derived from myelin basic protein were among the low-affinity binders. The sequence of the high-affinity peptides conformed with a previously published peptide-binding motif of DQ8.
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PMID:A peptide-binding assay for the disease-associated HLA-DQ8 molecule. 965 24

The influence of diabetes on susceptibility to influenza virus infection was examined in a mouse model in which RIP-Kb transgenic mice and their nontransgenic littermates were used as the diabetic and nondiabetic hosts, respectively. Influenza virus A/Phil/82 (H3N2) grew to significantly higher titers in the lungs of diabetic than nondiabetic mice. The extent of viral replication in the lungs was proportional to blood glucose levels in the mice at the time of infection, and the enhanced susceptibility of diabetic mice was reversed with insulin. Growth of A/HKx31 (H3N2) virus was also enhanced in diabetic mice, whereas the highly virulent strain A/PR/8/34 (H1N1) showed no difference in virus yields in diabetic and nondiabetic mice, even with low inocula. A/Phil/82 and A/HKx31 are sensitive to neutralization in vitro by the pulmonary collectin surfactant protein D (SP-D), whereas A/PR/8/34 is essentially resistant. Glucose is a ligand for SP-D, and neutralization of A/Phil/82 virus by SP-D was abolished in the presence of glucose at levels commonly found in diabetic mice. These findings suggest that in mice, and perhaps in humans, diabetes predisposes to influenza virus infection through compromise of collectin-mediated host defense of the lung by glucose.
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PMID:Increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defense of the lung by glucose? 965 39

Transgenic expression of the influenza virus hemagglutinin (HA) in the pancreatic islet beta cells of InsHA mice leads to peripheral tolerance of HA-specific T cells. To examine the onset of tolerance, InsHA mice were immunized with influenza virus A/PR/8 at different ages, and the presence of nontolerant T cells was determined by the induction of autoimmune diabetes. The data revealed a neonatal period wherein T cells were not tolerant and influenza virus infection led to HA-specific beta cell destruction and autoimmune diabetes. The ability to induce autoimmunity gradually waned, such that adult mice were profoundly tolerant to viral HA and were protected from diabetes. Because cross-presentation of islet antigens by professional antigen-presenting cells had been reported to induce peripheral tolerance, the temporal relationship between tolerance induction and activation of HA-specific T cells in the lymph nodes draining the pancreas was examined. In tolerant adult mice, but not in 1-week-old neonates, activation and proliferation of HA-specific CD8(+) T cells occurred in the pancreatic lymph nodes. Thus, lack of tolerance in the perinatal period correlated with lack of activation of antigen-specific CD8(+) T cells. This work provides evidence for the developmental regulation of peripheral tolerance induction.
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PMID:Ontogeny of T cell tolerance to peripherally expressed antigens. 1009 27

Although the effectiveness of influenza vaccination is established vaccination policies and their implementation differ considerably across Europe. Historically the selective policies for influenza vaccination were based on the proven efficacy of influenza vaccine in healthy volunteers, and recognition that influenza complications and death occur mostly in elderly people with chronic medical conditions. Healthcare providers are faced with increasingly aging populations and costly new technologies and are more likely to extend immunisation policies if new initiatives are cost effective compared with accepted measures. Few studies of vaccine effectiveness focus on elderly cohorts with and without high risk conditions. Accordingly, healthcare providers in Denmark, Sweden, The Netherlands and the UK may require further data on vaccine effectiveness in elderly people without high risk conditions before reconsidering their policies. Scandinavian countries may also require data demonstrating benefits in people with diabetes. Review of recent US studies indicates that the available data on vaccine effectiveness in preventing influenza-related hospitalisation and death are applicable in Europe, but vaccine costs and cost effectiveness, and the overall economic burden of inpatient and outpatient care, need to be assessed country by country.
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PMID:Socioeconomics of influenza and influenza vaccination in Europe. 1016 Apr 92

We conducted a randomized, double-blind trial to evaluate the safety and tolerability of a live attenuated cold adapted trivalent intranasal influenza vaccine, FluMist, compared with intranasal placebo when given in addition to a licensed trivalent injected inactivated influenza vaccine (TIV). The study population consisted of persons 65 years of age and older with chronic cardiovascular or pulmonary conditions or diabetes mellitus. During the 7 days post-vaccination, sore throat was reported on at least one day by 15% (15/100) of FluMist recipients compared with 2% (2/100) of intranasal placebo recipients (p = 0.001). No other reactogenicity symptom was statistically associated with receipt of FluMist. Among this group, FluMist was safe and well tolerated when administered with TIV.
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PMID:Safety of a trivalent live attenuated intranasal influenza vaccine, FluMist, administered in addition to parenteral trivalent inactivated influenza vaccine to seniors with chronic medical conditions. 1021 88

Rural health care delivery is often inferior to that of urban areas. Although health services do not have to be identical in the two settings, quality services appropriate for the needs of rural communities are imperative. Moreover, health education and promotion should be seen as an immediate and viable strategy for (a) reducing risk factors and health care needs, and (b) increasing the cost effectiveness of existing services. The appropriateness and prioritization of health care services and health education/promotion can only be realized if health professionals are aware of rural versus urban needs. To facilitate our knowledge of such differences, the mortality rates of the 10 leading causes of death were compared for each county in Ohio and differences between rural and urban mortality were analyzed. Counties were categorized according to "density" (persons per square mile) and "percent urban" (percent of county area classified as urban). The analysis demonstrated that there were no significant differences between rural and urban counties in mortality due to cancer, pulmonary disease, diabetes mellitus, atherosclerosis, and suicide. Mortality related to cardiovascular disease, cerebrovascular disease, accidents, and influenza/pneumonia was significantly higher in rural counties, while deaths due to chronic liver disease were significantly greater in urban counties.
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PMID:Difference in rural and urban mortality: implications for health education and promotion. 1029 26

Respiratory insufficiency developed in a man aged 68 after cardiac surgery and in a man aged 60 with COPD and a history of cigarette smoking after an attack of 'flu', while in a woman aged 70 with non insulin-dependent diabetes mellitus it had been present for years. All three had bilateral diaphragmatic paralysis. The diagnosis is based on the triad orthopnoea, paradoxical abdominal movements during respiration in the recumbent position and a decrease of the vital capacity in the horizontal as compared with the sitting position. The patients' physical condition could be improved with the aid of (noninvasive) ventilatory support.
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PMID:[Orthopnea: not always of cardiac origin]. 1042 61

For the past six years, the Arkansas Foundation for Medical Care, Inc. (AFMC), Health Care Quality Improvement Program (HCQIP), has focused primarily on inpatient projects. In 1996, we began expanding project information to include outpatient issues. Earlier ambulatory topics included management of thyroid disease, diabetes and flu immunization. This AFMC project focuses on the prevalence of facility resources to manage hypertension and asthma as part of quality improvement efforts for Medicare and Medicaid patients in Arkansas. AFMC understands that outpatient facilities frequently lack an infrastructure to conduct outpatient chart audits in an efficient and effective fashion. This difficulty in data acquisition reflects a significant barrier. Nevertheless, certain processes and structural elements can be assessed to improve management of common outpatient conditions.
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PMID:Beta blocker treatment following acute myocardial infarction: an effective but underutilized intervention. 1043 81

In 1973, WHO proposed that "excess mortality" be used for comparative assessment of the severity of influenza epidemics between countries. In this study, analysis of the data for deaths in Japan between 1980-1994 revealed excess mortality, which could be a useful indicator in Japan. There were six influenza epidemics, and statistically significant excess mortality rates were calculated in both deaths from acute respiratory diseases and all causes. The total number of excess deaths from acute respiratory diseases during influenza seasons for the 15 years was 13,931. Statistically significant excess mortality rates were also shown for other diseases, including ischemic heart disease, cerebro-vascular disease, diabetes, nephritis, chronic liver disease, malignant neoplasm, and chronic respiratory disease. Therefore, "excess mortality" is clearly present in recent years in Japan. In analyses of age-specific excess mortality rates, the epidemic was found to be most fatal to the aged. Further, the value of % excess (= excess rate divided by expected rate x 100) suggested that the number of deaths from all causes would be a more useful indicator than that from acute respiratory diseases. It was confirmed that excess mortality was applicable to regional surveillance of epidemic influenza.
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PMID:[Excess mortality from influenza epidemics in Japan, 1980-1994]. 1049 58


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