Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A boy, now 22 months old, is described who presented at the age of 6 weeks with hypoglycaemic coma. The excretion pattern of organic acids in the urine was consistent with glutaric aciduria type II (GA II). A high energy diet low in fat and protein was given. Treatment with riboflavine resulted in an improvement of the metabolite profile, and the patient gained weight. However, a tendency to hypoglycaemia and severe hypotonia persisted. Due to muscle weakness, aggravated by infections, artificial ventilation was necessary during three periods. Serum carnitine level was low. Treatment with carnitine, started during the third period of artificial ventilation, led to some improvement of muscle strength, but he still could not breathe without support. Treatment with insulin, combined with further enrichment of the diet with glucose, resulted in an increase in muscular strength and in weight gain. Thirteen families with GA II have been described upto now. This is the first patient with a severe form of the disorder wo has survived the 1st year of life. Treatment and metabolic studies are presented.
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PMID:Glutaric aciduria type II: treatment with riboflavine, carnitine and insulin. 639 38

Seven cases of PCNP were studied; 5 females and 2 males, ages ranging from 21 to 68 years (mean 39). All had asymptomatic masses located in the head (3), body (2), isthmus (1) and tail (1). In 4 of them fine-needle aspiration (FNA) was done and showed a diagnostic pattern with papillary clusters as well as isolated epithelial cells with monomorphic appearance, round nuclei and inconspicuous nucleoli; 5 cases had a surgical resection and only 2 a biopsy due to unresectable tumors. Histologically, they showed the typical features of PCNP with solid, papillary, trabecular and cystic patterns. IHQ studies showed positivity for cytokeratin (n = 5), alpha-1-antitrypsin (n = 4), monoclonal NSE (n = 3), chromogranin (n = 3) and estrogen receptors (n = 1). All cases were negative for insulin, glucagon, somatostatin, EMA and CEA. DNA analysis done with an image analyzer showed 4 diploid tumors, 2 diploid-tetraploid an 1 aneuploid tumor. One patient died because of postoperative complications and the remaining 6 are alive with a mean follow-up of 17 months (2-36). We emphasize the diagnostic appearance of the tumor on FNA, and the low grade malignant potential of this neoplasm supported by the predominance of diploid tumors. Our IHQ findings suggest both an exocrine and endocrine differentiation.
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PMID:[Papillary and cystic tumors of the pancreas. Clinico-pathological, cytopathological, immunohistochemical, and nuclear ploidy study]. 808 43

It is well known that Down's syndrome patients frequently suffer from immune system diseases leading to the production of autoantibodies and the onset of correlated pathologies. These disorders become increasingly frequent as the patients grow older and the onset of one autoimmune disease often predisposes the development of others. Autoimmune thyroiditis is the most frequent disorder and appears to affect 39% of adult patients. Over the past years a number of reports have been published regarding the coexistence of various autoimmune diseases in DS patients, but little is still known about the relationship between these pathologies and celiac disease. In order to contribute to knowledge regarding the prevalence of this association, the authors report a case of a DS patient who developed diabetes mellitus, hypothyroidism and celiac disease at different times. This case provides further confirmation of the association between Down's syndrome and autoimmune pathologies. The authors feel that follow-up programmes for DS patients should include an evaluation of thyroid function and antithyroid antibodies given that the onset of glandular hypofunction may be very subtle. Furthermore, they should also include tests to assay glycemia, anti-pancreatic insula and anti-insulin antibodies for diabetes and AGA and EMA for celiac disease.
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PMID:[Diabetes, hypothyroidism and celiac disease in Down's syndrome. A case report]. 955 94

Coeliac disease has been reported to occur in 2-5 per cent of insulin-dependent diabetic patients (IDDM). Suitable non-invasive screening tests would allow identification of these patients. The aim of this study was to determine the value of the red cell distribution width (RDW) in detecting unrecognised coeliac disease in insulin-dependent diabetic patients (IDDM). All patients (n = 208) attending the Diabetic out-patient clinics at 2 adjacent centres who had a full blood picture and RDW carried out in the past 18 months were included. IDDM patients with an elevated RDW were identified and their charts were reviewed to determine if they had symptoms or laboratory abnormalities compatible with coeliac disease. They were invited to attend for serological screening. Ninety-five of 208 patients had an elevated RDW of whom 66 had non-insulin dependent diabetes mellitus and 29 had IDDM. Two of the 29 IDDM patients had died in the interim period. Six of the remaining 27 IDDM patients had previously been tested for serological markers associated with coeliac disease, of whom 1 had a positive antigliadin antibody titre (IgA-AGA 199 EU) and normal duodenal biopsy. Eighteen of the remaining 21 patients with IDDM consented to serological testing of whom only 1 had a positive titre of antiendomysial antibody (IgA-EMA) and villous atrophy. Although the RDW is known from previous studies to be a sensitive predictor for coeliac disease, this study has demonstrated its poor specificity in predicting IDDM patients who may have coeliac disease. The RDW is not recommended as a screening test for coeliac disease in patients with IDDM.
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PMID:Application of red cell distribution width to screening for coeliac disease in insulin-dependent diabetes mellitus. 1054 Jul 81

Rab3 GTPases regulate exocytosis of neurons, endocrine and exocrine cells. In the present paper, we report a system to measure the guanine nucleotide status of Rab3 proteins in living cells. The assay is based on the ability of the Rab3 interacting molecule RIM to extract selectively the GTP-bound form of Rab3. Using this system, we found that approx. 20% of wild-type Rab3A, -B, -C or -D transfected in the insulin-secreting cell line HIT-T15 is in the GTP-bound conformation. The pool of activated Rab3 is decreased under conditions that stimulate exocytosis or by co-expression of the Rab3 GTPase-activating protein. In contrast, co-expression of Mss4 or Rab3-GEP (guanine nucleotide exchange protein) increases by approx. 3-fold the GTP-bound pool of Rab3 isoforms. Rab3-GEP is very similar to MADD, a death domain-containing protein that associates with the type 1 tumour necrosis factor receptor. We observed that the death domain of Rab3-GEP is involved in intramolecular interactions and that deletions or mutations that affect this domain of the protein impair the nucleotide exchange activity towards Rab3. We propose that the death domain of Rab3-GEP acts as a molecular switch and co-ordinates multiple functions of the protein by exchanging its binding partners.
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PMID:The death domain of Rab3 guanine nucleotide exchange protein in GDP/GTP exchange activity in living cells. 1185 34

Coeliac disease and type 1 diabetes mellitus can frequently coexist, presumably due to a common genetic predisposition. The present study was designed to evaluate the frequency of coeliac disease among Hungarian diabetic children and to study the effect of gluten-free diet on glycaemic control. A total of 205 diabetic children (age range 2.0-17.0 years, median 11.6 years) were screened for coeliac disease by determination of IgA-endomysium (EMA) antibodies. In the positive cases, a jejunal biopsy was performed and, in addition to routine histology, the number of intraepithelial gamma/delta T-cells was also determined. Insulin requirement, glycosylated haemoglobin level and body mass index of diabetic children with coeliac disease were determined before and 3 months after the introduction of gluten-free diet. IgA-EMA was positive in 24 cases, 17 of them (8.3% of all diabetic children) had a subtotal villous atrophy and thus coeliac disease was diagnosed. In all but two of these children, the mean number of gamma/delta T-cells was elevated (above 7 cells/mm). Of the remaining seven patients with positive EMA but normal villous structure, five (2.4%) had elevated number of epithelial gamma/delta T-cells, indicating probable latent coeliac disease. The insulin requirement of the children had significantly increased 3 months after the introduction of gluten-free diet (median values 0.64 versus 0.48 U/kg per day, P<0.05). Median body mass indices also showed significant elevation after this period (16.8 versus 14.2 kg/m(2), P<0.05) CONCLUSION: the frequency of coeliac disease was high in the studied group. Introduction of a gluten-free diet improved the somatic development of these children. A latent form of coeliac disease is also frequent in children with type 1 diabetes mellitus.
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PMID:Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus. 1248

We report a case of a 56-year-old male with a primary large cell neuroendocrine renal carcinoma. Grossly, the left kidney was enlarged by a solid tumor that measured 145 x 125 x 100 mm. Histologically, the tumor consisted of large cells with a moderate to abundant amount of eosinophilic cytoplasm. The nuclei were irregular, some of them with finely or coarsely granular chromatin, others with vesicular chromatin and prominent nucleoli. The tumor cells showed multiple mitotic figures (up to 32 mitoses/10 HPF). In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was solid-alveolar, trabecular and cribriform. Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for synaptophysin, CD56 and CD57. Cytokeratin AE1/AE3, vimentin and CD10 were positive only focally. Chromogranin showed weak cytoplasmic positivity in rare tumor cells. Cytokeratin CAM5.2, cytokeratin 34betaE12, BerEP 4, EMA, TTF-1, cytokeratin 7, cytokeratin 20, calretinin, serotonin, somatostatin, gastrin, calcitonin, glukagon and insulin were negative. Primary large cell neuroendocrine carcinoma of the kidney is a rare tumor. To the best of our knowledge, only 3 cases of a tumor of this type have been reported to date.
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PMID:Primary large cell neuroendocrine carcinoma of the kidney. 1957 58

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
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PMID:New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. 2008 58

OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
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PMID:Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. 2018 7

Type 2 diabetes is associated with increased risk of cancer. This risk is related to HbA1 increase and this influence is present also in prediabetes and in nondiabetics with HbA1c in upper normal range. In last 2 years, it was concluded that that the specific antidiabetic therapy could influence the cancer risk. In this review we show that reduction of HbA1c does not change cancer risk. Most important is the risk reduction of cancer risk by metformin. Insulin therapy and the use ofsulphonylurea related drugs, increases the risk of cancer. This risk can be eliminated in the combination with metformin. Other published results including the suspected effect related to the use of glargine, pioglitazone, sitagliptine and exenatide are inconsistent and analysis of long term effects of these drugs is necessary. The large discussion in many publications shows the important role of FDA and EMA. This agencies do not suspend drugs without consistent evaluation of results.
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PMID:[Is there any relation between diabetes therapy and cancer risk?]. 2195 71


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