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)

Coeliac disease is a chronic disease characterized by small bowel villous atrophy which impairs nutrient absorption and improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. Knowledge of the adult form of coeliac disease has greatly improved in recent years. Although this knowledge is not yet sufficiently widespread among referring clinicians, it has, over the past few years, allowed an increasing number of patients to be diagnosed with subclinical forms characterized by minor, transient or apparently unrelated symptoms. As a consequence, our views on the clinical and epidemiological aspects of this condition, the prevalence of which in the general population is believed to be close to 1 in 300, have changed and are still changing. Since it has been demonstrated that a strict gluten-free diet is protective against the complications of adult coeliac disease, it is important that even subclinical and silent forms are diagnosed and treated as early as possible. Non-invasive screening tests, such as anti-gliadin and anti-endomysium antibody estimation, should therefore be used systematically in groups considered to be at risk of coeliac disease. These include first-degree relatives of coeliac patients and patients with insulin-dependent diabetes mellitus, iron-deficiency anaemia, epilepsy with cerebral calcification, recurrent aphthous stomatitis and dental enamel hypoplasia. Other conditions will probably be identified in the near future.
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PMID:Coeliac disease in adults. 754 30

Dermatitis herpetiformis (DH) is a relatively rare skin disorder with an estimated incidence of 1:10,000 in the UK. It is characterized by urticarial plaques and blisters on the elbows, buttocks, and knees, although other sites may also be involved. The eruption tends to be persistent: only 10-15% of patients have spontaneous remission over a 25-year study period. The disease is characterized by the presence of IgA deposits in the upper dermis of uninvolved skin and the diagnosis should not be made in the absence of these deposits. Two-thirds of patients have a small intestinal enteropathy with villous atrophy as seen in coeliac disease (CD). However, the remaining third also show evidence of a gluten sensitivity in the intestine, as judged by increased lymphocytic infiltration of the epithelium. Villous atrophy also ensues after gluten challenge in those patients with previous normal villous architecture. The initial treatment of the rash is with one of the following three drugs, dapsone, sulphapyridine or sulphamethoxypyridazine. However, the rash also clears with gluten withdrawal. It must be stressed, however, that the average time to achieve significant reduction in drug requirements is 6 months and it can be over 2 years before drugs are no longer required. On re-introduction of gluten the eruption recurs. Patients with DH have a high incidence of auto-immune disorders, thyroid disease, pernicious anaemia, and insulin-dependent diabetes, and should be screened for those diseases on a yearly basis. As with coeliac disease there is also an increased incidence of lymphoma and a gluten-free diet appears to protect patients from this complication. The mechanism by which gluten causes the skin lesions has still to be elucidated, but current investigations implicate lymphocytes and cytokines in the pathogenesis. The original hypothesis of an antigen-antibody reaction in the skin with complement activation causing the skin lesions, may not be correct.
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PMID:Dermatitis herpetiformis. 754 32

It is known that certain combinations of alleles within the Human Leukocyte Antigen (HLA) Complex are associated with susceptibility or resistance to insulin-dependent diabetes mellitus (IDDM). The association of DR and DQ with IDDM has been well documented. Even though the association of specific DP alleles with some autoimmune diseases (i.e. juvenile rheumatoid arthritis [JRA] and celiac disease) has already been demonstrated, the role of HLA-DP genes in IDDM remains uncertain. A previous study conducted on a group of diabetic Venezuelan families with IDDM proband demonstrated that the HLA-DRB1*04-DQA1*03-DQB1*0302 and DRB1*03-DQA1*0501-DQB1*0201 combinations present a strong association with susceptibility to IDDM. The availability of this population enabled us to assess further susceptibility associated with other HLA class II alleles. We analysed HLA-DPA1 and DPB1 genes of 42 Venezuelan families with one IDDM proband and of 32 healthy families by oligotyping (PCR-SSO) using primers and probes from the XIth Histocompatibility Workshop. In contrast with previous data reported in other populations, the HLA DPA1*01-DPB1*0202 was the only haplotype significantly associated with IDDM in the Venezuelan population studied. In most cases the data showed this HLA DP allele combination as a part of the HLA DRB1*03-DQA1*0501-DQB1*0201 haplotype positively associated with IDDM, indicating a linkage disequilibrium between the alleles involved in this HLA DR-DQ-DP haplotype and as a consequence, a secondary role of HLA-DP genes in conferring susceptibility to the development of the disease. The analysis also indicates a non-significant increase of HLA DPA1*01-DPB1*0301 and DPA1*02-DPB1*1301 haplotypes among diabetics. However, both combinations were in 50% of the cases associated with the HLA DRB1*04-DQA1*03-DQB1*0302 haplotype. These data and their comparison with HLA DR-DQ-DP haplotypes in more homogeneous ethnic groups support the existence of a weak association of IDDM with specific HLA DP alleles and indicate how the distribution of these DP alleles could differ depending on the ethnic groups studied.
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PMID:HLA-DP and susceptibility to insulin-dependent diabetes mellitus in an ethnically mixed population. Associations with other HLA-alleles. 757 3

The genes of the human leukocyte antigen (HLA) region, the major histocompatibility complex (MHC) of humans, control a variety of functions involved in immune response and influence susceptibility to over 40 diseases. Theoretical studies in the development of models to determine the modes of inheritance of the HLA-associated diseases have led to a better understanding of the inheritance patterns in insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA-associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic factors. This review is presented using HLA-associated diseases, and in particular IDDM, as the example of interest, but the observations and techniques presented have direct relevance to the study of all human diseases with a complex genetic component. Three methods for localizing disease-predisposing genes are presented: (1) association studies, including population, family, and relative predispositional effects, (2) affected sib pair and other affected-relative methods, and (3) lod score analysis. A variety of complementary methods for studying the mode(s) of inheritance of the alleles at the disease-predisposing locus and for identifying the alleles and amino acids directly involved in the disease process also are presented.
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PMID:HLA disease associations: models for the study of complex human genetic disorders. 759 90

The complement system is an important part of non clonal or innate immunity that collaborates with acquired immunity to kill pathogens and to facilitate the clearance of immune complexes. The complement is made up of 20 distinct plasma proteins and 9 different membrane proteins. Three components, factor B, C2 and C4 (with 2 isotypes), are coded by polymorphic HLA-linked genes and are sometimes referred to as class III antigens, inherited as compact units called complotypes. The C4 genes are the most polymorphic, including a common null allele (Q0) at both the C4A and C4B loci. Other polymorphic complement factors (not linked to HLA) are C3 (2 common alleles), C6 and C7 (closely linked, with 3 and 2 alleles, respectively). A certain degree of polymorphism has also been described for complement receptors and membrane control proteins. No differences in functional activity are usually detected among different alleles. Immune-mediated diseases are associated with C4Q0, in particular: systemic lupus erythematosus and discoid-systemic lupus erythematosus, insulin-dependent diabetes mellitus, liver cirrhosis, celiac disease and IgA/IgG4 deficiency. Even if optimal HLA markers do become available, genetic counselling is usually not the ultimate goal for dealing with most of the HLA-associated common diseases, although their study could help to better delineate disease pathogenesis.
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PMID:Polymorphism of the complement components in human pathology. 794 94

Coeliac disease occurs more commonly in children with insulin-dependent diabetes mellitus (IDDM) than in the general population, but the prevalence of coeliac disease in adults with diabetes is unknown. We therefore screened an adult hospital-based diabetic population using IgA antigliadin antibody (IgA-AGA) to identify those patients requiring intestinal biopsy. In 1 year, 1789 patients (43% IDDM, 57% NIDDM) were screened, and 73 had raised IgA-AGA. Of these patients, 49 agreed to duodenal biopsy and 13 (10 IDDM) had coeliac disease. Selective IgA deficiency was found in eight patients, one of whom had coeliac disease. Of these 14 patients with newly diagnosed coeliac disease, four had microcytic anaemia, nine a low serum ferritin, and four a low albumin-corrected calcium. Eight patients had symptoms which improved on gluten withdrawal. Dietary compliance was maintained in 6/8 symptomatic patients, but only in 1/6 without symptoms. Included in the 1789 patients were four (all IDDM) with known coeliac disease. The overall prevalence of coeliac disease in adult patients with IDDM was 1:50 compared with 1:340 in NIDDM. Coeliac disease is common in adults with IDDM and may cause malabsorption and ill health. It should be suspected in any IDDM patient with gastrointestinal symptoms or unexplained anaemia.
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PMID:The prevalence of coeliac disease in adult diabetes mellitus. 798 59

The classical clinical picture of coeliac disease includes prolonged diarrhoea with failure to thrive. During the past two decades this type of active presentation of coeliac disease has decreased in many European countries, giving the impression that coeliac disease is a disappearing disease. However, this is not true. The disease can be found in older children with a more or less silent presentation. Silent coeliac disease can be detected by active screening with serological tests. Coeliac disease can be suspected in children suffering from mild gastrointestinal symptoms, such as abdominal pain, and in those with signs of nutritional deficiencies, as well as in children of first-degree relatives of already diagnosed coeliacs, patients with IgA-deficiency, patients suffering from dental enamel hypoplasia or dermatitis herpetiformis, and patients with some other disease known to be associated with coeliac disease, such as diabetes mellitus. According to the fundamental criteria of coeliac disease, the intestinal mucosa is flat when the individual is eating gluten-containing foods. However, this is not strictly true. Intolerance to gluten is obviously variable and the intestinal mucosa may be normal. This type of latent coeliac disease can be detected by analysing genetic markers, measuring antibodies in intestinal fluid or counting the density of intra-epithelial gamma/delta T cells which are increased greatly even in the latent phase of coeliac disease. Thus the general concept of the natural history of coeliac disease is changing.
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PMID:Changing clinical features of coeliac disease. 802 51

Celiac disease in children has been occasionally reported to be associated with various disorders such as arthritis, cutaneous vasculitis and diabetes mellitus. We report on a 12-year-old girl with celiac disease, diagnosed at 1 year of age, who developed systemic lupus erythematosus. This association has not yet been reported in children.
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PMID:Celiac disease associated with systemic lupus erythematosus. 804 53

We screened for celiac disease, by means of IgA class anti-endomysium antibodies (EmA), 383 consecutive adults with insulin-dependent diabetes mellitus (IDDM). Two control populations entered the study as well: 151 adults with biopsy proven celiac disease, as true positives; and 520 controls (healthy and diseased) as true negatives. IgA-EmA positivity was found in 145 of 151 (96%) celiac disease patients but in none of the controls (100% specificity). EmA were positive in 12 of 383 (3.13%) IDDM patients: 10 of these positives underwent intestinal biopsy, which showed either partial or total villous atrophy. Only one patient presented with gastrointestinal complaints, but severe iron deficiency was found in all. The IDDM celiac patients were started on a gluten-free diet: four refused both the diet and the follow-up protocol. Approximately one year after gluten withdrawal no significant change in the degree of diabetes control was observed, while an increased requirement for insulin was observed in three of four patients who strictly complied with the diet. The prevalence of biopsy-proven celiac disease among adult IDDM patients (1:38), eight times higher than that recently estimated for the general Italian population and the absence, except in one case, of gastrointestinal symptoms emphasizes the benefit of screening programs on populations at risk.
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PMID:Celiac disease and insulin-dependent diabetes mellitus. Screening in an adult population. 805 Mar 11

Peptide binding to DQ molecules has not previously been described. Here we report a biochemical peptide-binding assay specific for the DQ2 [i.e. DQ(alpha 1*0501, beta 1*0201)] molecule. This molecule was chosen since it shows a strong association to diseases such as celiac disease and insulin-dependent diabetes mellitus. Initially we radiolabelled some selected peptides and tested them for binding to affinity-purified DQ2 molecules. One of the peptides, a Mycobacterium bovis (MB) 65 kDa 243-255Y peptide, displayed a good signal-to-noise ratio and was thus chosen as an indicator peptide in the DQ2 binding assay. The MB 65 kDa 243-255Y peptide bound to DQ2 in a strictly pH-dependent fashion, with optimal binding around pH 5 and only weak binding at pH 7.4. The association of the MB 65 kDa 243-255Y peptide to DQ2 was slow, but once formed, the peptide-HLA complexes were very stable. The binding of peptides to DQ2 was specific, as shown in inhibition experiments with a panel of 47 peptides, differing in length, sequence, and origin. The binding of peptides to DR3 was tested in a similar assay with a Mycobacterium tuberculosis 65 kDa 3-13 peptide as the binding indicator. DQ2 and DR3 molecules bound to different sets of peptides. However, the peptide binding to DQ2 and DR3 showed, in general, similar characteristics with respect to pH dependence and kinetic parameters, indicating that the overall rules for peptide binding to DQ molecules are the same as those previously shown for human DR and murine I-A and I-E molecules.
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PMID:Binding of peptides to HLA-DQ molecules: peptide binding properties of the disease-associated HLA-DQ(alpha 1*0501, beta 1*0201) molecule. 818 96


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