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)

A high frequency of glomerulonephritis (GN) in diabetics, or coexistence of GN with diabetic glomerulosclerosis, has been reported by previous authors, but the true prevalence of GN in diabetics remains to be established. In the Department of Pathology, Heidelberg, from 1.1.1987 to 31.12.1989 we examined all consecutive patients (89 male, 121 female, median age 74 years; 47-98) who came to autopsy with the diagnosis of "diabetes mellitus" to assess this issue in an unbiased sample. Five patients had known type I diabetes, the others type II diabetes or diabetes of unknown classification. In 61/159 patients, proteinuria had been present (no information in 51 patients) and in 99/169 patients renal failure, i.e. serum creatinine above 1.4 mg/dl (no information in 41 patients). Paraffin-embedded kidney specimens from the upper pole of the left kidney were examined by immunohistochemistry (PAP technique; rabbit antihuman IgG; IgM; IgAab). 166/210 of the patients had glomerulosclerosis by light microscopy (129 diffuse, 37 nodular GS). Concomitant glomerulonephritis, i.e. typical mesangial IgA (and IgG) deposits, with mesangial enlargement by light microscopy were detected in only one case. Membranous GN was not found. These findings must be interpreted against the observation of mesangial immune deposits in 6 of 250 consecutive non-diabetic patients who had come to autopsy [Waldherr et al. 1989]. The findings show that an excessive prevalence of undiagnosed glomerulonephritis in our cohort of elderly type II diabetics was not to be found.
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PMID:How frequent is glomerulonephritis in diabetes mellitus type II? 163 76

Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life. We quantified insulin-containing cells in deceased human fetuses with IUGR (<10th percentile, n = 21) or normal growth (control fetuses, n = 15). Paraffin-embedded pancreatic tissues from fetuses older than 32 weeks were obtained from two fetopathology departments. Mean gestational age was 36 weeks in both groups. Tissues with lysis and those fetuses with defects, aneuploidy, or genetic abnormalities were excluded. For each subject, six pancreatic sections spaced evenly throughout the organ were immunostained with anti-insulin antibody. Total tissue and insulin-positive areas were measured by computer-assisted quantitative morphometry. Results were expressed in percentages. To evaluate islet morphogenesis, the percentages of beta-cells inside and outside islets were determined. Islet density was similar in the two groups (P = 0.86). The percentage of pancreatic area occupied by beta-cells (beta-cell fraction) was not correlated with gestational age (r = 0.06 and P = 0.97 in IUGR fetuses; r = 0.12 and P = 0.67 in control fetuses) or body weight (r = 0.16 and P = 0.47 in IUGR fetuses; r = 0.24 and P = 0.39 in control fetuses). Mean beta-cell fraction was 2.53% in the IUGR fetuses and 2.86% in the control fetuses (P = 0.47). The percentage of beta-cells located within islets was identical in the two groups (mean 35%). Our data militate against a primary developmental pancreatic abnormality in human IUGR, leaving peripheral insulin resistance as the most likely mechanism of glucose intolerance in adults born with IUGR.
Diabetes 2002 Feb
PMID:Endocrine pancreas development in growth-retarded human fetuses. 1181 45

Diabetic cardiomyopathy is responsible for substantial morbidity and mortality in the diabetic population. Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. Multiple biochemical mechanisms have been proposed to increase oxidative stress in diabetes. The present study was aimed at elucidating the role of a potent oxidative and cellular stress-responsive system, the heme oxygenase (HO) system, in the heart in diabetes. Streptozotocin-induced diabetic rats were treated with a potent inhibitor of HO system, tin protoporphyrin IX (SnPPIX, 50 micromol/kg/d), and were compared with untreated diabetic and non-diabetic animals. All treatments began at the onset of diabetes, 48 h after injection of streptozotocin along with the confirmation of hyperglycemia. Animals were euthanized after 1 week and 1 month of treatment, and heart tissues were harvested. Frozen tissues were subjected to HO-1 and HO-2 mRNA expression by real-time RT-PCR and HO activity determination. Paraffin-embedded tissue sections were used for immunohistochemical analysis of HO-1 and HO-2. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) stain, a sensitive and specific marker of DNA damage, was preformed to assess damage induced by oxidative stress. In addition, tissue sections were subjected to histochemical analysis for iron. We further examined non-diabetic animals treated with a direct HO agonist, hemin (50 mg/kg/d). A possible relationship between the HO and the nitric oxide (NO) pathways was also considered by studying the mRNA levels of endothelial nitric oxide synthase (NOS) and inducible NOS, and by measuring the amount of NOS products. Our results demonstrate no significant alterations of the HO system following 1 week of diabetes. However, 1 month of diabetes caused increased oxidative stress as demonstrated by higher levels of 8-OHdG-positive cardiomyocytes (80% positive as compared to 11.25% in controls), in association with increased HO isozyme mRNA (2.7-fold increase as compared to controls) and protein expression, and augmented HO activity (759.3 as compared to 312.3 pmol BR/h/mg protein in controls). Diabetic rats further demonstrated increased number of cardiomyocytes with stainable iron. SnPPIX treatment resulted in reduced number of 8-OHdG-positive cardiomyocytes (19.5% as compared to 80% in diabetics) in parallel with reduced HO activity (569.7 as compared to 759.3 pmol BR/h/mg protein in diabetics). Non-diabetic rats treated with HO-agonist hemin exhibited abnormalities similar to diabetic rats. Our results provide the first direct demonstration that diabetes-induced oxidative stress in the heart is, in part, due to upregulated HO expression and activity. These results provide evidence of pro-oxidant activity of HO in the heart in diabetes, which could be mediated by increased redox-active iron.
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PMID:Heme oxygenase in diabetes-induced oxidative stress in the heart. 1465 70

Type 1 diabetes (T1DM) results from a failure of central and peripheral tolerance to islet cell antigens. ICA69 belongs to a group of molecules expressed predominantly in neuroendocrine tissues (including pancreatic islets), which are targets of autoimmune responses in T1DM. These molecules are also expressed in the thymus and peripheral lymphoid organs by dendritic cells. The aim of the present study was to evaluate possible variation in thymic ICA69 expression, comparing diabetes-resistant controls to T1DM-prone NOD mice. Thymic tissue was retrieved from 3- to 6-week-old female B6, NOD-H2(b), and NOD mice. Paraffin-embedded sections were stained with an ICA69-specific antibody in an immunoperoxidase assay. ICA69 staining of thymic sections from B6 and NOD.H2(b) showed strong and continual staining, yet the sections from the NOD mice showed significantly reduced staining for ICA69. Corroboration of the reduced level of ICA69 in the thymus of NOD mice has been obtained via analysis for the expression of ICA69 versus other candidate autoantigens (glutamic acid decarboxylase 65, glutamic acid decarboxylase 67, and insulin 2) in the thymus. Real-time PCR analysis, using cDNA generated from the thymus, displayed that the expression of GAD65, GAD67, and INS2 were equivalent when comparing NOD at any age to B6, BALB/cJ, and ALR/LtJ. In marked contrast, the level of ICA69 in the thymus of the NOD mice examined was significantly reduced when compared to the controls. In fact, the real-time PCR analysis strongly suggested that ICA69 was not expressed in the thymus of NOD mice. These findings support the hypothesis that the level of thymic ICA69 expression may be of importance in regulating self-tolerance in T1DM.
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PMID:Reduced thymic expression of islet antigen contributes to loss of self-tolerance. 1467 3

Wolfram syndrome (WFS1, OMIM 222300) is a rare genetic disorder associated with multiple organ abnormalities, most prominently optic nerve atrophy and diabetes. Mutations in the WFS1 gene coding for wolframin have been identified. The pathogenesis for optic nerve atrophy remains elusive. We here tested the hypothesis that wolframin is expressed in glial cells of the optic nerve and in retinal ganglion cells in the cynomolgus monkey. Paraffin sections through the retina and optic nerve were examined with immunohistochemistry using affinity-purified antibodies to wolframin. Retinal ganglion cells and optic nerve glial cells were found to be strongly labeled. Dual dysfunction of wolframin in optic nerve glial cells and retinal ganglion cells may explain the progressive optic nerve atrophy in Wolfram syndrome.
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PMID:Wolfram syndrome 1 (WFS1) protein expression in retinal ganglion cells and optic nerve glia of the cynomolgus monkey. 1692 72

Nerve microvasculitis and ischemic injury appear to be the primary and important pathogenic alterations in lumbosacral radiculoplexus neuropathy of patients with (DLRPN) and without (LRPN) diabetes mellitus (DM). Here, we examine the involvement of inflammatory mediators in DLRPN and LRPN. Paraffin sections of sural nerves from 19 patients with DLRPN, 13 patients with LRPN, and 20 disease control patients were immunostained for intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor kappaB (NF-kappaB). The findings were correlated with histopathology. The pathologic and immunohistochemical alterations of DLRPN and LRPN nerves were indistinguishable. The nerves of both types of LRPN had a significantly greater number of ICAM-1 positive vessels than did the controls (P < 0.01). TNF-alpha expression was seen in Schwann cells and some macrophages of DLRPN and LRPN nerves, whereas IL-6 expression was minimal. There was greater NF-kappaB immunoreactivity in vessels and endoneurial cells of DLRPN and LRPN nerves than of the controls (P < 0.001). NF-kappaB expression correlated with the number of empty nerve strands (P < 0.01) and the frequency of axonal degeneration (P < 0.05), whereas TNF-alpha expression correlated inversely with the number of empty nerve strands of teased fibers (P < 0.05). Our findings suggest that up-regulation of inflammatory mediators target different cells at different disease stages and that these mediators may be sequentially involved in an immune-mediated inflammatory process that is shared by both DLRPN and LRPN. Up-regulated inflammatory mediators may be immunotherapeutic targets in these two conditions.
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PMID:Inflammatory mediators in diabetic and non-diabetic lumbosacral radiculoplexus neuropathy. 1806 75

The Active Peptide from Shark Liver (APSL) was expressed in E. coli BL21 cells. The cDNA encoding APSL protein was obtained from shark regenerated hepatic tissue by RT-PCR, then it was cloned in the pET-28a expression vector. The expressed fusion protein was purified by Ni-IDA affinity chromatography. SDS-PAGE and HPLC analysis showed the purity of the purified fusion protein was more than 98%. The recombinant APSL (rAPSL) was tested for its biological activity both in vitro, by its ability to improve the proliferation of SMMC7721 cells, and in vivo, by its significant protective effects against acute hepatic injury induced by CCl(4) and AAP (acetaminophen) in mice. In addition, the rAPSL could decrease the blood glucose concentration of mice with diabetes mellitus induced by alloxan. Paraffin sections of mouse pancreas tissues showed that rAPSL (3 mg/kg) could effectively protect mouse islets from lesions induced by alloxan, which indicated its potential application in theoretical research and industry.
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PMID:Expression, purification and bioactivities analysis of recombinant active peptide from shark liver. 1959 84

Renal cell carcinoma (RCC) comprises 2%-3% of all visceral and 80%-85% of all adult kidney malignancies. Nephrectomy is the treatment of choice for renal tumors. The accurate pathological evaluation of nonneoplastic renal parenchyma in nephrectomy specimens is important for subsequent management. Eighty-two patients with RCC who underwent surgery at Imam Khomeini Hospital, Urmia, Iran, from April 2006 to February 2015 were studied. Paraffin blocks of the hospital archives were stained by hematoxylin and eosin (H and E) and periodic acid-Schiff staining. Microscopic examination was performed on nontumoral portions that were in the farthest possible distance from the tumor. Out of total 82 cases, 24 (29.3%) had normal renal parenchyma and 58 (70.7%) had pathological changes in renal parenchyma. The most frequent pathological findings were vascular sclerosis with parenchymal scarring and pyelonephritis. Other findings include focal and diffuse mesangial hypercellularity, eight; focal segmental glome-rulonephritis, five; membranoproliferative glomerulonephritis, three; and membranous glome-rulonephritis, two. Parenchymal scarring and vascular change included 36% of clear cell type, 41% of papillary type, and 53.8% of chromophobe type. Although there is not any statistical relation between the gender of patients and pathological findings, there was an obvious correlation between age and pathological findings. Before the age of 55 years, vascular sclerosis with parenchymal scarring and glomerular diseases and then chronic pyelonephritis are more prevalent.Evaluation of pathological changes in nonneo-plastic renal parenchyma is an essential step in recognizing patients at risk of accelerated functional failure of the single remaining kidney, particularly in patients with a background of chronic vascular injury associated with diabetes or hypertension.
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PMID:The pathological evaluation of nonneoplastic kidney disorder in tumor nephrectomy specimens. 2997 Jul 34