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

The autoimmune polyglandular syndrome (APS) is characterized by a variable coexistence of several autoimmune diseases, affecting predominantly endocrine glands. In general two types of APS are distinguished. Type 1 APS is an autosomal recessive disorder often leading to insufficiency of the adrenal cortex, the parathyroid glands, and/or the gonads. This type of APS often affects the skin in form of chronic mucocutaneous candidiasis and ectodermal dystrophies (vitiligo, alopecia, keratopathy, dystrophy of dental enamel and nails). The second form of APS is a polygenic disease which usually involves the adrenal gland, the thyroid and the pancreatic beta-cells. In rare cases APS type 2 is associated with myasthenia gravis, autoimmune thrombocytopenic purpura, Sjogren's syndrome or rheumatoid arthritis. Here we describe a case of APS with the unusual combination of type 1 diabetes, secondary adrenocortical insufficiency, growth hormone deficiency, and primary hypothyroidism associated with lethal idiopathic giant cell myocarditis. The combination of APS and idiopathic giant cell myocarditis which is a rare, frequently fatal autoimmune disorder of myocardium affecting most commonly young individuals has not been reported so far.
Exp Clin Endocrinol Diabetes 2005 May
PMID:Autoimmune polyglandular syndrome associated with idiopathic giant cell myocarditis. 1592 18

Tako-tsubo-like left ventricular dysfunction phenomenon (TTP) has primarily been described in Japan and is characterized by transient left ventricular apical ballooning in the absence of coronary artery disease, associated with chest symptoms, electrocardiographic changes and minimal cardiac enzymes release. Aim of the present review is to summarize the current knowledge about TTP. TTP has been described predominantly in females. TTP occurs also outside Japan. Clinical symptoms comprise anginal chest pain, dyspnea and syncope. TTP occurs frequently after acute emotional or physical stress. Electrocardiographic ST- elevations may be present only for several hours. Then, normalization of the ST-segment occurs, followed by negative T waves, which persist for months. Arterial hypertension in TTP is found in up to 76%, hyperlipidaemia in up to 57%, diabetes mellitus in up to 12% and smoking in up to 18% of the patients. Several pathomechanisms have been proposed: myocardial stunning due to increased catecholamine levels, coronary vasospasm, atherosclerotic plaques rupture, myocarditis, catecholamine-induced hyperkinesis of the basal left ventricular segments and genetic. Patients with TTP should be monitored like patients with myocardial infarction. Care should be taken in the application of catecholamines and nitrates. Betablockers should be given in the acute and chronic phase, and possibly indefinitely to prevent recurrences. The prognosis of TTP is assumed to be good, but in the acute phase there are deaths due to multisystem organ failure, cardiogenic shock, ventricular fibrillation and ventricular rupture. The long term prognosis of TTP patients is largely unknown.
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PMID:Tako-tsubo-like left ventricular dysfunction: clinical presentation, instrumental findings, additional cardiac and non-cardiac diseases and potential pathomechanisms. 1598 8

Clozapine is a distinctive antipsychotic agent, having a unique clinical profile and an idiosyncratic safety profile. More so than with other agents, the weighting of its adverse event profile is critical, in order to counterbalance its clear clinical advantages. The safety issues with clozapine are in a number of areas, some of which are considered medical emergencies and potentially life-threatening. These include haematological (neutropenia and agranulocytosis), CNS (seizures), cardiovascular (myocarditis and cardiomyopathy), metabolic (diabetes), gastrointestinal and neuromuscular. Understanding the safety profile of clozapine allows an informed use of the agent that can maximise its clear clinical benefit and minimise the known risks.
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PMID:A review of clozapine safety. 1601 51

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

Virus infections and autoimmune disease have long been linked. These infections often precede the occurrence of inflammation in the target organ. Several mechanisms often used to explain the association of autoimmunity and virus infection are molecular mimicry, bystander activation (with or without epitope spreading), and viral persistence. These mechanisms have been used separately or in various combinations to account for the immunopathology observed at the site of infection and/or sites of autoimmune disease, such as the brain, heart, and pancreas. These mechanisms are discussed in the context of multiple sclerosis, myocarditis, and diabetes, three immune-medicated diseases often linked with virus infections.
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PMID:Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. 1641 24

Anomalies of naturally occurring CD4+ regulatory T cells (Treg) cause severe autoimmune/inflammatory diseases in humans and rodents. The transcription factor Foxp3 is currently the most specific marker for natural CD4+ Treg, but it would be useful if other Treg markers, particularly cell surface molecules, could be elucidated. We demonstrate in this study that the vast majority of Foxp3-expressing CD4+ T cells (whether CD25+ or CD25-) show constitutive high-level expression of glucocorticoid-induced TNFR family-related gene/protein (GITR). Transfer of T cell or thymocyte suspensions depleted of GITR(high) cells produces in BALB/c nude mice a wider spectrum and more severe forms of autoimmune diseases than does transfer of similar cell suspensions depleted of CD25+ CD4+ T cells only. Notably, mice that receive cells depleted of GITR(high) populations develop severe multiorgan inflammation that includes fatal autoimmune myocarditis resembling giant cell myocarditis in humans, accompanying high-titer anti-myosin autoantibodies. Similar transfer of GITR(high)-depleted cells from prediabetic NOD mice to NOD-SCID mice accelerates the development of diabetes and induces skeletal muscle myositis and other autoimmune/inflammatory diseases. We conclude that GITR(high), Foxp3-expressing natural Treg, containing both CD25+ and CD25- cell populations, contribute to preventing a variety of autoimmune/inflammatory diseases, and depletion of these cells allows the activation of even weak or rare autoreactive T cells yielding widespread severe autoimmune disease. Diseases induced in this way include many which have been suspected of an autoimmune etiology in humans without much evidence. GITR(high), Foxp3-expressing natural Treg represent a potential target for the treatment and prevention of these diseases.
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PMID:Control of autoimmune myocarditis and multiorgan inflammation by glucocorticoid-induced TNF receptor family-related protein(high), Foxp3-expressing CD25+ and CD25- regulatory T cells. 1658 68

The innate and adaptive immune responses have evolved distinct strategies for controlling different viral pathogens. Encephalomyocarditis virus (EMCV) is a picornavirus that can cause paralysis, diabetes, and myocarditis within days of infection. The optimal innate immune response against EMCV in vivo requires CD1d. Interaction of antigen-presenting cell CD1d with distinct natural killer T-cell ("NKT") populations can induce rapid gamma interferon (IFN-gamma) production and NK-cell activation. The T-cell response of CD1d-deficient mice (lacking all NKT cells) against acute EMCV infection was further studied in vitro and in vivo. EMCV persisted at higher levels in CD1d-knockout (KO) splenocyte cultures infected in vitro. Furthermore, optimal resistance to repeat cycles of EMCV infection in vitro was also shown to depend on CD1d. However, this was not reflected in the relative levels of NK-cell activation but rather by the responses of both CD4(+) and CD8(+) T-cell populations. Repeated EMCV infection in vitro induced less IFN-gamma and alpha interferon (IFN-alpha) from CD1d-deficient splenocytes than with the wild type. Furthermore, the level of EMCV replication in wild-type splenocytes was markedly and specifically increased by addition of blocking anti-CD1d antibody. Depletion experiments demonstrated that dendritic cells contributed less than the combination of NK and NKT cells to anti-EMCV responses and that none of these cell types was the main source of IFN-alpha. Finally, EMCV infection in vivo produced higher levels of viremia in CD1d-KO mice than in wild-type animals, coupled with significantly less lymphocyte activation and IFN-alpha production. These results point to the existence of a previously unrecognized mechanism of rapid CD1d-dependent stimulation of the antiviral adaptive cellular immune response.
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PMID:CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo. 1680 20

Although it is well-documented from theoretical studies that pathogens have the capacity to generate cycles, the occurrence and role of pathogens and disease have been poorly empirically studied in cyclic voles and lemmings. In screening for the occurrence of disease in cyclic vole and lemming populations, we found that a high proportion of live-trapped Clethrionomys glareolus, C. rufocanus, Microtus agrestis and Lemmus lemmus at high collective peak density, shortly before the decline, suffered from diabetes or myocarditis in northern Scandinavia. A high frequency of animals had abnormal blood glucose (BG) levels at the time of trapping (5-33%). In contrast, C. rufocanus individuals tested at a much lower overall density, and at an earlier stage relative to the decline in the following cycle, showed normal BG concentrations. However, a high proportion (43%) of a sample of these individuals kept in captivity developed clinical diabetes within five weeks, as determined by BG levels and a glucose tolerance test performed at that later time. A new picornavirus isolated from the rodents, Ljungan virus (LV), was assumed to cause the diseases, as LV-induced diabetes and myocarditis, as well as encephalitis and fetal deaths, were observed in laboratory mice. We hypothesize that LV infection significantly affects morbidity and mortality rates in the wild, either directly or indirectly, by predisposing the rodents to predation, and is at least involved in causing the regular, rapid population declines of these cyclic voles and lemmings. Increased stress at peak densities is thought to be an important trigger for the development of disease, as the occurrence of disease in laboratory mice has been found to be triggered by introducing stress to LV-infected animals.
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PMID:Diabetes and myocarditis in voles and lemmings at cyclic peak densities--induced by Ljungan virus? 1686 60

Tako-tsubo-like left ventricular dysfunction phenomenon (TTP) is characterized by transient left ventricular apical ballooning associated with symptoms, electrocardiographic changes and minimal cardiac enzyme release in the absence of coronary artery disease. Initially described in Japan, TTP occurs worldwide, predominantly in women and frequently after emotional or physical stress. Symptoms include anginal chest pain, dyspnea and syncope. Electrocardiographic ST elevations may be present only for several hours, and are followed by negative T waves that persist for months. Arterial hypertension is found in up to 76% of TTP patients, hyperlipidemia in up to 57% and diabetes mellitus in up to 12%. Potential pathophysiological mechanisms for TTP include catecholamine-induced myocardial stunning or hyperkinesis of the basal left ventricular segments, coronary vasospasm, plaque rupture, myocarditis and genetic factors. TTP patients should be monitored similarly to myocardial infarction patients because organ failure, cardiogenic shock, ventricular fibrillation or rupture may occur. Beta-blockers are indicated, whereas catecholamines and nitrates should be avoided. The long-term prognosis is unknown.
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PMID:Transient left ventricular dysfunction (tako-tsubo phenomenon): Findings and potential pathophysiological mechanisms. 1703 1

Coxsackievirus B3 (CVB3) is a picornavirus which causes myocarditis and pancreatitis and may play a role in type I diabetes. The viral genome is a single 7,400-nucleotide polyadenylated RNA encoding 11 proteins in a single open reading frame. The 5' end of the viral genome contains a highly structured nontranslated region (5'NTR) which folds to form an internal ribosome entry site (IRES) as well as structures responsible for genome replication, both of which are critical for virulence. A structural model of the CVB3 5'NTR, generated primarily by comparative sequence analysis and energy minimization, shows seven domains (I to VII). While this model provides a preliminary basis for structural analysis, the model lacks comprehensive experimental validation. Here we provide experimental evidence from chemical modification analysis to determine the structure of the CVB3 5'NTR. Chemical probing results show that the theoretical model for the CVB3 5'NTR is largely, but not completely, supported experimentally. In combination with our chemical probing data, we have used the RNASTRUCTURE algorithm and sequence comparison of 105 enterovirus sequences to provide evidence for novel secondary and tertiary interactions. A comprehensive examination of secondary structure is discussed, along with new evidence for tertiary interactions. These include a loop E motif in domain III and a long-range pairing interaction that links domain II to domain V. The results of our work provide mechanistic insight into key functional elements in the cloverleaf and IRES, thereby establishing a base of structural information from which to interpret experiments with CVB3 and other picornaviruses.
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PMID:Structure of the 5' nontranslated region of the coxsackievirus b3 genome: Chemical modification and comparative sequence analysis. 1707 14


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