Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple factors interact during the evolution of renal diseases. In the present study, we examined the expression of DNA topoisomerases type I and IIalpha, which reflect gene transcription and DNA replication, respectively. Enzyme content was assessed by immunohistochemistry using two specific monoclonal antibodies, C21 and Ki-S4, on 81 archival punch-biopsy specimens from patients with renal diseases, including minimal change disease (MCD; n = 10), focal segmental glomerular sclerosis (FSGS; n = 6), mesangial proliferative glomerulonephritis (MPGN; n = 11), membranous glomerulonephritis (MGN; n = 10), mesangial capillary glomerulonephritis (MCGN; n = 7), rapidly progressive glomerulonephritis (RPGN; n = 12), lupus nephritis (LN; n = 15), and tubulointerstitial nephritis (TIN; n = 10). Both enzymes were strongly expressed in diseases tending to rapid progression, notably RPGN and LN, whereas MCD and MGN showed low protein levels in both the glomerular and tubular compartments. Moreover, topoisomerase expression was significantly associated with the density of monocytogenic infiltrates (monitored by means of the monoclonal antibody Ki-M1p), such pathogenesis-associated factors as antinuclear antibodies and paranuclear antineutrophilic antibodies, and serum immunoglobulin levels. There also was a positive correlation with serum creatinine levels and an inverse association with proteinuria and nephrotic syndrome. We conclude that the expression of DNA topoisomerases may be linked to pathogenetic mechanisms and may provide prognostic information. Because of their comparatively low nephrotoxicity, topoisomerase inhibitors might prove to be useful therapeutic agents in the treatment of renal diseases.
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PMID:Correlation between the expression of DNA topoisomerases I and IIalpha and clinical parameters in kidney disease. 1168 56

The performance of immunoassays for the detection of autoantibodies is of critical importance to the diagnosis and assessment of patients with systemic lupus erythematosus (SLE). Our objective was to compare 3 multiplexed assays for measurement of multiple autoantibodies and their association with global disease activity, active nephritis and cumulative organ damage in systemic lupus erythematosus (SLE). Stored sera, clinical and laboratory data from the enrollment visit of a long-term lupus registry were used. Autoantibodies were measured using the BioPlex 2200 ANA screen (Bio-Rad), QuantaPlex ENA8 (INOVA Diagnostics) and recomLine ANA/ENA (Mikrogen). The analytes included dsDNA, chromatin, ribosomal P protein, SS-A/Ro60, Ro52, SS-B/La, Sm, U1-RNP, centromere B, topoisomerase 1 and Jo-1 (histidyl tRNA synthetase). Global SLE disease activity was measured by the SLE disease activity index (SLEDAI) and cumulative organ damage by the SLICC/ACR damage index (SDI). One hundred ninety two patients (87% female; 91% Caucasian; mean disease duration 8.8years) were studied. Agreement between the 3 assays varied from 70% to 99% (Cohen's kappa: 0.04-0.88). There were significant associations between SLEDAI scores (excluding anti-dsDNA) and ANA (INOVA, Mikrogen), anti-dsDNA (Bio-Rad, Mikrogen), anti-chromatin (Bio-Rad, INOVA), anti-Ro (Mikrogen), anti-Sm and anti-U1-RNP (all 3 immunoassays) (p=0.002-0.05). Concurrent lupus nephritis was associated with anti-dsDNA (Bio-Rad (p=0.017) or Bio-Rad and Mikrogen together (p=0.015)). There was no significant association between autoantibodies and SDI scores. The overall agreement between assays for the detection of autoantibodies was reasonable. The greatest discordance (70-83%) occurred with those autoantibodies most strongly associated with global SLE disease activity (ANA, anti-dsDNA, anti-chromatin and anti-Sm). Furthermore, there were differences between assays in their associations with global SLE disease activity and lupus nephritis.
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PMID:Comparison between multiplex assays for autoantibody detection in systemic lupus erythematosus. 2043 30