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)

An important characteristic of autoimmune diseases is their association with major histocompatibility complex class I and class II alleles. In this study, we compared insulin-dependent diabetes mellitus (IDDM) with idiopathic dilated cardiomyopathy (IDC) from a strictly immunologic perspective. Although the target organs are different, being in one case the insulin-producing beta cells of the pancreas and in the other case the myocytes of the heart, many aspects of the tissue-specific immune destruction are common. Similar yet different Coxsackievirus B strains with either pancreotropic or cardiotropic specificity are able to perpetrate the first injury of the respective target tissue. Their shared capacity of inducing a superantigenic reaction further enhances the damage. Once previously secluded autoantigens are then exposed to the immune system, the tissue injury is completed via a more conventional type of immune response. On the basis of the compounded results we obtained, it is possible to propose that the same HLA-DQ molecules which are able to protect the individuals from IDDM (e.g., HLA-DQA1*0102, DQB1*0602) seem to favour the enteroviral attack to the myocardium, while alleles which confer the strongest susceptibility to IDDM (e.g., DQA1*0301, DQB1*0302), seem unable to sustain the immune attack against the heart.
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PMID:The same HLA-DQ alleles determine either susceptibility or resistance to different coxsackievirus-mediated autoimmune diseases. 1043 37

CAD is the most common cause of death in older men and was present in 44% of 664 men, mean age 80 years. Independent risk factors for new coronary events in older men include increasing age, prior CAD, cigarette smoking, hypertension, diabetes mellitus, high serum total cholesterol, and low serum HDL cholesterol. In older men with hypertension, echocardiographic LVH is a powerful independent predictor of new coronary events, atherothrombotic brain infarction, and CHF. In 554 older men with a mean age of 80 years, two-dimensional and Doppler echocardiography demonstrated that the prevalence of aortic stenosis was 14%, 1 + aortic regurgitation or greater was 31%, rheumatic mitral stenosis was 0.4, 1 mitral regurgitation or greater was 32%, mitral annular calcium was 35%, hypertrophic cardiomyopathy was 3%, idiopathic dilated cardiomyopathy was 1%, left atrial enlargement was 29%, LVH was 41%, and abnormal LVEF was 29%. The prevalence and incidence of CHF increase with age in older persons. The prevalence of a normal LVEF associated with CHF as a result of prior myocardial infarction or hypertension was 22% in men aged 60 to 69 years, 33% in men aged 70 to 79 years, 41% in men aged 80 to 89 years, and 47% in men aged 90 years or older.
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PMID:The older man's heart and heart disease. 1050 66

A line of nonobese diabetic (NOD) mice expressing the human diabetes-associated HLA-DQ8 transgene in the absence of mouse IAbeta failed to show spontaneous insulitis or diabetes, but rather developed dilated cardiomyopathy, leading to early death from heart failure. Pathology in these animals results from an organ- and cell-specific autoimmune response against normal cardiomyoctes in the atrial and ventricular walls, as well as against very similar myocytes present in the outermost muscle layer surrounding the pulmonary veins. Progression of the autoimmune process could be followed by serial ECG measurements; irradiation of young animals significantly delayed disease progression, and this effect could be reversed by adoptive transfer of splenocytes taken from older animals with complete heart block. Disease progression could also be blocked by cyclosporin A treatment, but was accelerated by injection of complete Fruend's adjuvant. The constellation of findings of spontaneously arising destructive focal lymphocytic infiltrates within the myocardium, rising titers of circulating anticardiac autoantibodies, dilation of the cardiac chambers, and gradual progression to end-stage heart failure bears a striking resemblance to what is seen in humans with idiopathic dilated cardiomyopathy, a serious and often life-threatening medical condition. This transgenic strain provides a highly relevant animal model for human autoimmune myocarditis and postinflammatory dilated cardiomyopathy.
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PMID:Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IAbeta knockout NOD mice. 1457 Sep 80

Cardiac transplantation is the gold standard therapy for patients below 60 years presenting with severe heart failure (HF) despite maximal medical therapy, who have no other surgical option and no contraindications to this procedure. We evaluated our experience with this important form of heart failure therapy. Between February 1987 and December 2002, 32 patients, aged 37 +/- 16 years, 19 males, with ejection fraction of 18 +/- 7%, underwent heart transplantation in our center. Seven (22%) patients were in NYHA class IV with hemodynamic support. Seventeen (53%) patients had idiopathic dilated cardiomyopathy (DCM), 7 (22%) had ischemic DCM, 3 (9%) had valvular DCM and the remainder had other causes of left ventricular dysfunction. Overall survival rate was 68% at first year post-transplantation, 59% at 5 years and 59% at 10 years. One year after cardiac transplantation, 95% of patients were in NYHA class I and the rest were in NYHA class II. Among the 13 patients who died, in five (18%) death occurred during the first month: the most frequent cause was hemodynamic failure. Causes of late death were: allograft vasculopathy (n = 3), allograft rejection (n = 1), infection (n = 1), sudden death (n = 1), hemodynamic failure (n = 1) and bradyarrhythmia (n = 1). Among the patients followed for more than one year, only three died. Early complications were: infection (8 episodes, 7 of respiratory location), right heart failure (3 patients), pericardial effusion (5 patients) and others (7 patients). Late complications were: a) allograft rejection: 17 (53%) patients, 72 episodes (10 ISHLT grade 3, 6 of whom were treated with intravenous corticotherapy, 8 grade 2 and 54 grade 1); b) infections: 19 (59%) patients; 35 episodes, 25 requiring hospitalization: 10 (28%) involving the respiratory tract, 6 (17%) the oropharynx, 5 (14%) the urinary tract, 4 (11%) the skin and 10 (28%) of undetermined location; c) chronic allograft rejection: 6 (19%) patients; d) arterial hypertension: 14 (45%) patients; d) renal failure: 5 (16%) patients; e) diabetes: 2 (6%) patients; f) cancer: 2 (6%) patients. Patients with severe heart failure and a very poor prognosis who underwent cardiac transplantation in our hospital showed marked improvement in functional capacity and quality of life and had an overall survival similar to the results of international heart transplantation registries. Complications during follow-up were similar to those usually described in the literature.
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PMID:Heart transplantation. A Portuguese hospital center's experience. 1537 3

The prognosis of dilated cardiomyopathy due to hypertension (HT-DCM) is surprisingly unknown, particularly in the absence of coronary disease and diabetes. We aimed at investigating the long-term outcome and the predictors of mortality in patients with left ventricular systolic dysfunction exclusively due to hypertension. From October 1995 to May 2001, 90 consecutive patients with echocardiographic fractional shortening (FS) < 30% and 29 control patients with FS > or = 30% were included. Obstructive coronary disease was excluded by dipyridamole myocardial perfusion imaging in all patients and coronary angiography in 60. After a mean follow-up of 4.3+/-1.6 years, the total mortality rate of HT-DCM was twice as much higher than that of patients without left ventricular systolic dysfunction (P = 0.01). In HT-DCM, the 5-year mortality rate was 26%. Univariate analyses selected age and creatinine for being positively related to mortality, and body mass index, FS and blood pressure during follow-up for being negatively related to mortality. Neither the improvement of left ventricular FS nor the decrease in left ventricular mass index was related to survival. Multivariate analysis identified (hazard ratio; 95% confidence interval) age (1.08; 1.02-1.13), body mass index (0.86; 0.75-0.98), and baseline FS (0.88; 0.78-0.98) as independent predictors of mortality. In conclusion, poor survival in HT-DCM can be anticipated by the severity of left ventricular systolic dysfunction and advanced age. Instead of ominous signs, high blood pressure and body mass may predict a more favourable prognosis.
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PMID:The long-term outcome of patients with hypertensive cardiomyopathy. 1571 81

Transthoracic Doppler echocardiographic-derived coronary flow reserve is an useful hemodynamic index to assess dysfunction of coronary microcirculation. Isolated coronary microvascular abnormalities are overt by reduced coronary flow reserve despite normal epicardial coronary arteries. These abnormalities may occur in several diseases (arterial hypertension, diabetes mellitus, hypercholesterolemia, syndrome X, aortic valve disease, hypertrophic cardiomyopathy and idiopathic dilated cardiomyopathy). The prognostic role of impaired microvascular coronary flow reserve has been shown unfavourable especially in hypertrophic or idiopathic dilated cardiomyopathies. Coronary flow reserve reduction may be reversible, for instance after regression of left ventricular hypertrophy subsequent to valve replacement in patients with aortic stenosis, after anti-hypertensive treatment or using cholesterol lowering drugs. Coronary flow reserve may increase by 30% or more after pharmacological therapy and achieve normal level >3.0. In contrast to other non invasive tools as positron emission tomography, very expensive and associated with radiation exposure, transthoracic Doppler-derived coronary flow reserve is equally non invasive but cheaper, very accessible and prone to a reliable exploration of coronary microvascular territories, otherwise not detectable by invasive coronary angiography, able to visualize only large epicardial arteries.
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PMID:The non-invasive documentation of coronary microcirculation impairment: role of transthoracic echocardiography. 1608 Jul 92

Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM has been described in about 20-30% of cases, with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. A similar pattern of humoral and cellular immune dysregulation has been described in other autoimmune diseases. There is considerable evidence that genetic factors play an important role in the pathogenesis of DCM, either as contributors to the susceptibility to environmental factors or as determinants of functional and structural changes that characterize the phenotypic expression of the disease.Yet, it is not known whether the susceptibility to immunologically mediated myocardial damage reflects the presence of genetic risk factors shared by other autoimmune diseases. Preliminary investigations suggest, that this is the case, because the frequency of autoimmune disorders other than DCM was higher in first-degree relatives of the subjects with DCM including juvenile diabetes, rheumatoid arthritis, thyroiditis, psoriasis, and asthma. The nature of the genetic risk is undetermined and probably involves genes in the major histocompatibility (MHC) locus as well as other susceptibility loci. Therefore, the authors started their investigation with the search for MHC class 2 DQ polymorphisms in the peripheral blood of patients with DCM in parallel to the search for new interesting susceptibility loci by the use of the microarray analysis regarding genes responsible for inflammatory and autoimmune diseases. By this approach a new insight in the familial clustering of other autoimmune diseases in patients with DCM and in genetic predisposition can be expected.
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PMID:Inflammatory dilated cardiomyopathy (DCMI). 1617 Jun 86

Over 100 million prescriptions were filled for statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) in 2004. Statins were originally developed to lower plasma cholesterol in patients with hypercholesterolemia and are the most effective drugs on the market in doing so. Because of the discovered pleiotropic effects of statins, the use has expanded to the treatment of many other conditions, including ventricular arrythmias, idiopathic dilated cardiomyopathy, cancer, osteoporosis, and diabetes. The elderly population is growing. Therefore, it is estimated that the number of statin users will also increase. Fortunately, the use of statins is relatively safe with few side effects. Myopathy is the most common side effect with symptoms ranging from fatigue, weakness, and pain to symptoms associated with rhabdomyolysis which is a life-threatening condition. The development of statin-induced rhabdomyolysis is rare occurring in approximately 0.1% of patients; however, the occurrence of less severe symptoms is underreported and may be 1-5% or more. Physical exercise appears to increase the likelihood for the development of myopathy in patients taking statins. It is thought that as many as 25% of statin users who exercise may experience muscle fatigue, weakness, aches, and cramping due to statin therapy and potentially dismissed by the patient and physician. The mechanisms causing statin-induced myopathy have not been elucidated; however, research efforts suggest that apoptosis of myofibers may contribute. The mitochondrion is considered a regulatory center of apoptosis, and therefore its role in the induction of apoptosis will be discussed as well as the mechanism of statin-induced apoptosis and myopathy.
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PMID:Statin-induced apoptosis and skeletal myopathy. 1688 96

To determine whether statin therapy improves survival in patients with heart failure (HF) secondary to nonischemic dilated cardiomyopathy (non-IDC), data from 1,024 patients with non-IDC (New York Heart Association functional class III and IV HF) and left ventricular ejection fraction < or =0.35 who were enrolled in the BEST were analyzed. The association of statin therapy at the initial screening visit with all-cause and cardiovascular mortality was evaluated using multivariate Cox proportional hazards models. After adjusting for age, gender, race, systolic blood pressure, total cholesterol, New York Heart Association functional class IV, estimated glomerular filtration rate, current cigarette smoking, left ventricular ejection fraction, angiotensin-converting enzyme inhibitor use, antiplatelet therapy, diabetes mellitus, treatment group (beta blocker or placebo), and hypertension, statin use was independently associated with decreased all-cause mortality (hazard ratio 0.38, confidence interval 0.18 to 0.82, p = 0.0134) and also with decreased cardiovascular death (hazard ratio 0.42, confidence interval 0.18 to 0.95, p = 0.037). In conclusion, in patients with moderate or severe HF due to non-IDC entered into BEST, statin therapy at entry was independently associated with a decrease in all-cause and cardiovascular mortality.
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PMID:Effect of statin therapy on survival in patients with nonischemic dilated cardiomyopathy (from the Beta-blocker Evaluation of Survival Trial [BEST]). 1749 77

Nonenzymatic glycosylation or glycation of amino groups in peptides and proteins by D-glucose is a universal reaction with important implications for the pathogenesis of many diseases including diabetes mellitus. Here a general approach is reported to synthesize site specifically glucose-derived N-glycated peptides. Therefore, model peptides H-AKASASFL-NH(2), H-AKASADFL-NH(2), H-ASKASKFL-NH(2), and H-AKDSASFL-NH(2) were synthesized on solid phase by Fmoc chemistry using Fmoc-Lys(4-methyltrityl)-OH in positions 2 or 3 to be glycated. After completion of the synthesis, the acid labile 4-methyltrityl-group was cleaved with 1% TFA in DCM and the free amino groups were glycated by the Lobry de Bruyn reaction using 2,3:4,5-di-O-isopropylidene-aldehydo-beta-D-arabino-hexos-2-ulo-2,6-pyranose on solid phase. After TFA treatment, the crude peptides were obtained in high yields and purities above 80%. Minor by-products were well separated on reversed-phase HPLC.
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PMID:Solid-phase synthesis of glucose-derived Amadori peptides. 1788 44


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