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

In the past few years, several studies have unravelled a novel pathway of antigen presentation to T cells of the mammalian immune system. The antigens are presented by CD1, which appears to have evolved to present glycolipid antigens to alphabeta T cells. CD1-restricted T cells are frequently autoreactive, and can promptly release key regulatory cytokines such as IL-4 and IFN-gamma. They have been implicated in a variety of autoimmune diseases including type I diabetes and lupus, in intracellular bacterial infections, and in tumor rejection. They are likely to be involved at the early, innate phase of these immune responses, providing a unique model to study the interface between the innate and adaptive immune systems.
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PMID:Innate and adaptive functions of the CD1 pathway of antigen presentation. 979 14

Antiglomerular basement membrane (anti-GBM) disease is characterized by a linear deposition of immunoglobulins along the glomerular basement membrane. A 67-year-old man with a recently discovered monoclonal gammopathy of unknown significance (MGUS) presented with microscopic hematuria, nephrotic-range proteinuria, and rapidly deteriorating renal function after a pneumonia. Renal histology showed a crescentic glomerulonephritis; immunohistology showed intense linear staining of the GBM with immunoglobulin A (IgA) and moderate linear staining with kappa and lambda light chains. Screening for systemic disease, including diabetes mellitus, lupus erythematodes disseminatus, cryoglobulinemia, was negative. Serological tests for detection of anti-GBM antibodies were positive for IgA class and negative for IgG. Further examination indicated a bronchial carcinoma T2N2M0. This clinical report adds new information to the spectrum of anti-GBM disease and suggests that neoplasia may be associated with unusual exposure of and/or immune response to epitopes in the GBM.
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PMID:IgA antiglomerular basement membrane disease associated with bronchial carcinoma and monoclonal gammopathy. 1007 3

The presentation of peptide antigens to T-cells by MHC Class II proteins is a central process in cellular and humoral immune responses. Blockade of this presentation event via synthetic ligands that bind to disease-associated MHCs (such as DR1 and DR4) may be useful for the treatment of autoimmune diseases such as rheumatoid arthritis, Type 1 diabetes, multiple sclerosis, lupus erthymatosis and Graves disease. Recently reported synthetic ligands for DR1 and DR4 are short modified peptides (2-7 mers) capable of competing at nanomolar concentrations with antigenic peptides for the DR (MHC) binding groove.
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PMID:DR (MHC class II) ligands: an approach to rheumatoid arthritis therapeutics. 1019 51

Genome-scale analysis in type 1 diabetes has resulted in a number of non-major histocompatibility complex loci of varying levels of statistical significance. In no case has a specific gene been proven to be the source of genetic linkage at any candidate locus. Comparative analysis of the position of loci for type 1 diabetes with candidate loci from other autoimmune/inflammatory diseases shows considerable overlap. This supports a hypothesis that the underlying genetic susceptibility to type 1 diabetes may be shared with other clinically distinct autoimmune diseases such as systemic lupus erythemastosus, multiple sclerosis, and Crohn's Disease.
Diabetes 1999 Jul
PMID:Comparative genetics of type 1 diabetes and autoimmune disease: common loci, common pathways? 1038 38

Although the short- and medium-term (5-10 years) outcome of patients with lupus nephritis has been studied extensively, there are very few data on the second and subsequent decades. We studied outcome in 110 local patients investigated at a single centre before 1986, who all had potential follow-up of more than 10 years (actual 2-31 years, median 15.5 years). At last follow-up, 40 patients were dead and 70 alive, nine of whom were on maintenance dialysis or transplanted, actuarial survivals being 84%, 72%, 62%, 61% and 54% at 5, 10, 15, 20 and 25 years for the group as a whole. Survival was better in the cohort 1976-86 (n = 60) than in that from 1963-75 (n = 50) (90, 81 and 76% vs. 78, 56 and 43% at 5, 10 and 15 years, p < 0.001). Sepsis (12) and myocardial infarction (8) were the principal causes of death. Of living patients with renal function, 38% had normal urine and renal function, 11 were off all treatment (19%), 62% had persistent proteinuria and 18% had reduced but generally stable renal function. Renal failure, in those patients who developed it, occurred during the first decade and none of 67 patients actually followed more than 10 years subsequently went into renal failure. Induction treatment was with prednisolone, combined with azathioprine in more severe forms of nephritis, and from the middle 1970s to 1986, 30 with methylprednisolone and in 12 cases plasma exchange. Seventeen other patients were treated using oral cyclophosphamide during the 1960s. No patient received i.v. cyclophosphamide as induction therapy, although nine patients had this form of treatment later, largely because of non-compliance. Serious complications of lupus and/or its treatment occurred in 49%: sepsis in 32, ischaemic heart disease in 20, thrombosis in one and avascular necrosis of bone in eight. In contrast, fracturing osteoporosis occurred in only three, and cataracts requiring surgery and diabetes mellitus in none. The very long-term outlook of lupus nephritis, especially its more severe forms, has improved, but that with current management strategies only a minority of patients are able to stop treatment altogether, and the incidence of serious complications is high.
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PMID:The very long-term prognosis and complications of lupus nephritis and its treatment. 1039 9

Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases.
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PMID:The role of genetic factors in autoimmune disease: implications for environmental research. 1050 33

Systemic lupus erythematosus (SLE) is a multiphenotypic autoimmune disease. The hallmark of SLE is the production of anti-double-stranded DNA autoantibodies and the deposition of immune complexes in target tissues such as the kidney, skin, and brain. Additional phenotypic traits are the presence of arthritis, anemia, central nervous system involvement, and a variety of autoantibodies. Females of childbearing age are particularly at risk. Recent genetic analysis of murine SLE shows that susceptibility is under complex polygenic control. It is also apparent that environmental factors contribute to the induction and exacerbation of SLE. We describe here the genotypic and phenotypic characterization of a group of recombinant inbred strains of SLE-prone mice that were derived from NZB and NZW progenitors, the parental strains of the classic female F1 hybrid lupus model. Recombination and reassortment of these ancestral genomes resulted in the NZM (New Zealand mixed) strains with strain-specific patterns of renal disease penetrance and other autoimmune traits such as Coombs positive anemia and neurologic deficits. Multiple susceptibility loci of the ancestral strains demonstrate that SLE is inherited as a threshold trait. Because some of these loci co-localize with the susceptibility loci of the insulin-dependent diabetes of nonobese diabetic strain, it is apparent that there are disease-specific as well as autoimmunity-promoting genes. It is proposed that the NZM strains, particularly those with reduced disease penetrance or partial genotypes, provide an improved genetic model for assessment of the effects of environmental agents on SLE and autoimmunity.
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PMID:New Zealand mixed mice: a genetic systemic lupus erythematosus model for assessing environmental effects. 1050 36

The history of antiarrhythmic therapy reveals these agents to be associated with a high incidence of toxicity. Although several agents have ocular effects, amiodarone is the most widely recognized for producing adverse effects in the eyes. Corneal microdeposits are almost ubiquitous in patients being treated with amiodarone. However, they are, for the most part, benign and produce no changes in visual acuity. Lack of microdeposits should prompt the physician to investigate whether there is a problem with drug absorption or adherence to therapy. Other effects on the eye have been reported including optic neuropathy, but no causal link has been proved with amiodarone. The population of patients treated with amiodarone often have ischemic disease and/or diabetes, which affect retinal and optic nerve health. Many antiarrhythmic agents also affect lung function. The frequent association of procainamide with a lupus-like syndrome, where half the cases develop pleural-pericardial involvement, may require discontinuation of that drug. Although beta blockers and to a lesser degree, calcium antagonists, may cause bronchospasm in some patients, this is not usually a major clinical problem. Again, it is amiodarone that has the most widespread reputation for causing pulmonary toxicity. Although infrequent (< 1% incidence), it generates the most fear as it is sometimes fatal. Because of the lack of a diagnostic "gold standard," it is often overdiagnosed, placing patients at risk from overlooked congestive heart failure and infections and from recurrent arrhythmias after drug withdrawal. Patients with pre-existing pulmonary disease appear to be more at risk. Common features include indolent onset of cough, malaise and fever associated with patchy peripheral infiltrates, and severely decreased diffusion capacity. Several cases of pulmonary toxicity have had inordinately high serum desethylamiodarone to amiodarone ratios. Most cases recover with cessation of amiodarone therapy. Steroids are commonly used, but are of unproved efficacy. In terms of its toxicity, amiodarone remains the most feared of the antiarrhythmic agents. In the future, a better understanding of its pharmacokinetics, mechanisms of toxicity, and optimal dosing regimens should provide a possibility of better strategies for avoidance, early diagnosis, and more directed therapy of toxicities associated with amiodarone.
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PMID:Clinical organ toxicity of antiarrhythmic compounds: ocular and pulmonary manifestations. 1056 58

Emphysematous cystitis (EC) is a rare condition in which gas-forming organisms are active in the bladder wall and lumen. Most of the cases have been described in patients suffering from diabetes mellitus due to glucosuria and subsequent anaerobic fermentation of glucose. To our knowledge this condition has never been described in association with systemic lupus erythematosus (SLE). We report here the first case of EC during the course of a chronic lupus cystitis (LC) in a woman suffering from SLE and type-I diabetes mellitus.
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PMID:Lupus cystitis: a possible additive risk factor for emphysematous cystitis in diabetes mellitus: discussion about one case. 1119 30

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3[1,25-(OH)2D3], exerts immunosuppressive activity. At a cellular and molecular level, the hormone preferentially targets helper T cell activity (Th1) by inhibiting the secretion of both IL-2 and IFN-gamma by Th1 and by suppressing the secretion pro-Th1 cytokine IL-12 by antigen-presenting cells. The active metabolite further inhibits class II antigen expression and enhances suppressor cell activity. In animal models of autoimmunity, 1,25-(OH)2D3 prevents the development of experimental autoimmune encephalomyelitis, reduces the incidence of diabetes, and attenuates murine lupus. The hormone also prolongs graft survival in animal models of transplantation. In humans, non-classical use of 1,25-(OH)2D3 has led to an anti-proliferative effect in psoriasis, antineoplastic effect in prostate cancer, and immunomodulatory effect in scleroderma. The development of less hypercalcemic analogs might open a new therapeutic area for vitamin D3.
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PMID:1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. 1076 31


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