Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunocytochemical assays (ICA) using monoclonal antiestrogen receptors (ER ICA), antiprogesterone receptors (PR ICA), and monoclonal antibody Ki67 (Ki67 ICA) were performed in 127 breast carcinomas. The immunostaining procedures were applied on frozen tissue sections, tumour imprints, and fine-needle aspirates in order to compare the variations in the distribution of the antigens detected in the three different types of preparations. Positive reactions detected with peroxidase-antiperoxidase and avidinbiotin-peroxidase, and alkaline phosphatase-antialkaline phosphatase complexes were evaluated through a computerized system of image analysis referred to as SAMBA 200 (SAMBA TITN, Grenoble, France). Application programs specifically developed for the analysis of tissue sections and of cytologic preparations were applied. This system allowed a multiparametric, accurate, reliable, reproducible and automatized evaluation of the heterogeneity of the antigenic sites in tumors. For each markers positive cell surface (PS), and integrated and mean optical densities (IOD, MOD) and IOD histograms were compared. It was shown that (1) there was no significant variation in optical densities in cell imprints and aspirates whereas PS significantly (P less than 0.01) differed in both preparations; (2) there were significant differences of the optical densities between tissue sections and cytological preparations, either imprints or aspirates, likely due to randomly cut nuclei in tissue sections; and (3) there was a significant difference between the PS of tissue sections and aspirates but no significant difference between tissue sections and imprints. It is concluded that fine-needle aspiration constitutes a convenient method for cell sampling, reliable for the diagnosis of malignancies. However, it may not reflect the heterogeneity of cell subpopulations in tissue.
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PMID:Immunodetection in fine-needle aspirates and multiparametric (SAMBA) image analysis. Receptors (monoclonal antiestrogen and antiprogesterone) and growth fraction (monoclonal Ki67) evaluation in breast carcinomas. 264 15

Autoimmune mechanisms may be involved in the pathogenesis of insulin dependent diabetes mellitus (IDDM). Multiple autoantibodies have been detected in patients with IDDM. Islet cell antibodies (ICA), complent-fixing islet cell antibodies (CF-ICA) and antibodies to an islet cell protein 64000 M(r) (64K antibodies) have been regarded as immunological markers in IDDM. ICA detection with immunohistochemistry requires fresh normal human pancreas (blood group O) which provides an antigen for measuring ICA in serum samples. In the present study ICA detection was first carried out by using avidin-biotin-peroxidase complex technique (ABC) method and paraffin sections of human pancreas (blood group O), Serum samples were obtained from 17 patients with IDDM, 20 with NIDDM and 20 without diabetes mellitus. In patients with IDDM, ICA were detected in 9 of the 17 (52.94%) while none of the patients with NIDDM and without diabetes mellitus were ICA positive. In comparison with other methods, the present one is more reliable, sensitive, specific and simple. Therefore, it may be widely used for ICA detection in clinical practice.
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PMID:[Detection of islet cell antibodies by using avidin-biotin-peroxidase complex technique]. 807 Feb 98

Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cultured aortic ECs. Our previous studies demonstrated that PSF is dominantly expressed by arterial smooth muscle cells (SMCs). In the present study, we found PSF to exist in the SMCs of human coronary arteries by means of immunohistochemical methods. Human coronary arteries obtained from autopsies were divided into four subgroups, with or without NIDDM and/or myocardial infarction. Immunostaining for PSF was performed by the avidin-biotin peroxidase complex method using a purified anti-PSF antibody, and the immunostaining for PSF was assessed semiquantitatively. PSF staining was markedly reduced in coronary arterial SMCs from patients with NIDDM and/or myocardial infarction. In addition, the effect of a high glucose culture on PSF mRNA expression and PSF production in bovine aortic SMCs was examined by immunocytochemical staining and both Western and Northern blot analyses. The immunostaining and immunoblot band for PSF also significantly decreased when bovine aortic SMCs were cultured with high concentrations of glucose. Furthermore, as compared with the SMCs cultured with a physiological glucose concentration, the density ratio of PSF mRNA to 28S rRNA expression significantly decreased when the SMCs were cultured with high concentrations of glucose. These results strongly suggest that the decreased PSF production may thus results in a decreased production of PGI2 in the coronary artery, thus leading to the development of both diabetic macroangiopathy and atherosclerosis.
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PMID:Immunohistochemical study of prostacyclin-stimulating factor (PSF) in the diabetic and atherosclerotic human coronary artery. 931 60

Effects of taurine supplementation on lipid peroxide formation and the activities of glutathione (GSH) dependent enzymes in diabetic model mice were investigated. Type I diabetes mellitus was induced by injecting alloxan to ICR mice while type II diabetes mellitus was produced by high calorie diet feeding to genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5% (w/v) for seven days. The malondialdehyde (MDA) levels of liver and the islets of type I diabetes were significantly increased compared to the control group but the levels were significantly decreased by taurine supplementation. In the type II diabetic model, the concentrations of MDA were not changed by taurine treatment. The activity of hepatic and islet GSH-peroxidase (GPX) was increased in the type I diabetic group, but in type II animals it was decreased. Hepatic GPX activity of both type I and II diabetics was not altered by taurine supplementation but was increased in the islets of the type II animals. No effect on the activity of GSH S-transferase (GST) was observed in both types of diabetes (I and II) following taurine supplementation. These results suggest that taurine supplementation protects type I diabetic mice from lipid peroxide formation.
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PMID:Effect of taurine supplementation on the lipid peroxide formation and the activities of glutathione-related enzymes in the liver and islet of type I and II diabetic model mice. 963 20

Free radical-mediated oxidative stress has been implicated in adverse tissue changes in a number of diseases. In view of the role of oxidative processes in non-insulin dependent diabetes mellitus (NIDDM), in this study, we investigated the oxidant and antioxidant status of plasma in patients with NIDDM and the effect of vitamin E (800 lU/day) supplementation on oxidative stress, antioxidant defense system, fructosamine levels and insulin action. Thirty controls and 40 NIDDM patients were studied. In controls and patients, plasma lipids, vitamin E, lipid peroxide, total thiols (t-SH), superoxide peroxidase (SOD) and glutathione peroxidase (GPx) were measured in the basal state and after vitamin E (800 IU/d) supplementation for a month. All lipids and lipid fractions in plasma were significantly decreased, whereas the HDL-C level was changed in diabetic patients supplemented with vitamin E when compared with baseline values. Vitamin E administration also significantly reduced fasting glucose and fructosamine levels, whereas increased significantly reduced fasting glucose and fructosamine levels, whereas increased significantly plasma C-peptide and insulin levels (p < 0.01, p < 0.001, respectively). Following vitamin E supplementation, TBARs levels were found to be significantly lower (p < 0.001) than the baseline value NIDDM patients are. On the other hand, activities of GPx and SOD were significantly higher (p < 0.001) than baseline values. A similar trend was observed for total thiols contents, but in this case, the increase was not significant. In conclusion, this study demonstrates that vitamin E improved beta-cell function and increased plasma insulin and C-peptide levels, possibly by inducing the antioxidant capacity of the organism and/or reducing the peripheral resistance in NIDDM. Long-term studies are needed to demonstrate the beneficial effects of vitamin E on treatment/prevention of NIDDM.
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PMID:Oxidant and antioxidant systems in niddm patients: influence of vitamin E supplementation. 1167 85

Autoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD(+) and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading > 3 s.d. higher than the mean value of control I, 10.4% of patients with thyroiditis and 7.7% of Graves' patients were anti-CD38 positive (P = 0.0009 versus 1.8% of control I). Similarly, 13.1% of patients with thyroiditis and 10.5% of Graves' patients had a standardized optical reading > 3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0.002 versus 1.2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0.03) and they were more frequent in Graves' patients with ophthalmopathy (P < 0.05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated.
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PMID:Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease. 1173 57

Glucose is the main physiological stimulus for insulin biosynthesis and secretion by pancreatic beta-cells. Glucose-6-phosphatase (G-6-Pase) catalyzes the dephosphorylation of glucose-6-phosphate to glucose, an opposite process to glucose utilization. G-6-Pase activity in pancreatic islets could therefore be an important factor in the control of glucose metabolism and, consequently, of glucose-dependent insulin secretion. While G-6-Pase activity has been shown to be present in pancreatic islets, the gene responsible for this activity has not been conclusively identified. A homolog of liver glucose-6-phosphatase (LG-6-Pase) specifically expressed in islets was described earlier; however, the authors could not demonstrate enzymatic activity for this protein. Here we present evidence that the previously identified islet-specific glucose-6-phosphatase-related protein (IGRP) is indeed the major islet glucose-6-phosphatase. IGRP overexpressed in insect cells possesses enzymatic activity comparable to the previously described G-6-Pase activity in islets. The K(m) and V(max) values determined using glucose-6-phosphate as the substrate were 0.45 mm and 32 nmol/mg/min by malachite green assay, and 0.29 mm and 77 nmol/mg/min by glucose oxidase/peroxidase coupling assay, respectively. High-throughput screening of a small molecule library led to the identification of an active compound that specifically inhibits IGRP enzymatic activity. Interestingly, this inhibitor did not affect LG-6-Pase activity, while conversely LG-6-Pase inhibitors did not affect IGRP activity. These data demonstrate that IGRP is likely the authentic islet-specific glucose-6-phosphatase catalytic subunit, and selective inhibitors to this molecule can be obtained. IGRP inhibitors may be an attractive new approach for the treatment of insulin secretion defects in type 2 diabetes.
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PMID:Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP). 1472 2

Troglitazone (TGZ) was the first glitazone used for the treatment of type II diabetes mellitus. TGZ undergoes an oxidative chroman ring-opening reaction to form a quinone product. Recently, cytochrome P450 (P450) was shown to be able to catalyze the formation of TGZ quinone. TGZ quinone was the major metabolite formed by dexamethasone-induced rat liver microsomes or myeloperoxidase (MPO) incubated with TGZ. The ultimate source for the quinone carbonyl oxygen atom of TGZ quinone was investigated using (18)O water in both enzyme reaction systems followed by liquid chromatography/tandem mass spectometry analysis of the TGZ quinone product. The resultant TGZ quinone formed by either liver microsomes or MPO contained a single atom of (18)O. The (18)O atom was determined to be the quinone carbonyl oxygen by collision-induced dissociation fragmentation of the (18)O-labeled TGZ quinone. The formation of TGZ quinone was inhibited approximately 90% by coincubation with ascorbic acid or cysteine in the MPO reaction system but only 10 to 20% in liver microsomes, which might reflect the difference in the mechanism by which TGZ quinone is formed by P450 and peroxidase. These results suggest that P450 catalyze an atypical reaction to form TGZ quinone, involving the incorporation of an oxygen from water into the quinone carbonyl position.
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PMID:Incorporation of an oxygen from water into troglitazone quinone by cytochrome P450 and myeloperoxidase. 1503 98

Increased oxidative stress and impaired anti-oxidant defense have been suggested as contributory factors for initiation and progression of complications in diabetes mellitus. Aging itself has been shown to be along with increased oxidative stress and lower anti-oxidant defense. We aimed at investigating oxidative stress and anti-oxidant enzymes in 61 elderly subjects. Fifteen healthy individuals (group 1, mean age 72.2 +/- 5.13), 13 glucose intolerant patients (group 2, mean age 71.7 +/- 4.9), 19 patients with type 2 diabetes mellitus (T2DM) without any complication (group 3, mean age 70.0 +/- 6.0), and 14 patients with T2DM with at least one complication (group 4, mean age 69.8 +/- 4.7) were included in the study. Whilst plasma levels for malondialdehyde (MDAP) and erythrocyte malondialdehyde (MDAE) were measured as markers of oxidative stress, activity of erythrocyte superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) were taken as markers of oxidative defense system. MDAP level was significantly elevated in group 4 (P = 0.001). MDAE was elevated in patients with T2DM, particularly in group 4, however, the difference between the groups was of borderline significance (P = 0.07). Whilst CAT was elevated in groups 3 and 4 compared to control subjects (P = 0.025 and 0.002, respectively), no difference was found for SOD between the groups. GSH-Px activity was found to be increased in groups 2, 3 and 4, it did not reach statistical significance (P = 0.106). There were significant correlations between CAT and MDAE (P < 0.0001, r = 0.056) and MDAP (P = 0.016, r = 0.306). These results suggest that there was an increased oxidative stress in elderly diabetics, however, this is not due to reduced erythrocyte antioxidant defense potential but, rather, increased free radical production possibly due to hyperglycemia.
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PMID:Oxidative stress and antioxidant status in elderly diabetes mellitus and glucose intolerance patients. 1538 45

An ELISA for urine microalbumin using microtiter plates has been developed. The assay uses polyclonal anti-human albumin antibody for coating the microtiter plates and the same antibody conjugated with horseradish peroxidase for detection. The assay sensitivity is 1.6 microg/ml. Results by this in-house ELISA show good correlation (r = 0.99) with those obtained by a commercial assay using the Behring BNII autoanalyzer. Within-day and between-day CVs are 10%. Reference values for microalbumin in 769 urine specimens from healthy Chinese subjects were higher in women than men and higher in subjects 50 yr than in those <50 yr of age. Elevated mean concentrations of urine microalbumin were observed in patients with type 2 diabetes and CVD. This in-house ELISA is simple, sensitive, precise, and especially suited for laboratories without expensive autoanalyzers.
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PMID:Microplate ELISA for urine microalbumin: reference values and results in patients with type 2 diabetes and cardiovascular disease. 1594 78


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