Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1832526 (PCC)
 5,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genotoxic stress caused by a variety of chemical and physical agents may lead to DNA breaks and genome instability. Response to DNA damage depends on ATM/ATR sensor kinases and their downstream proteins, which arrange cell cycle checkpoints. Activation of ATM (ataxia-telangiectasia-mutated)/ATR (ATM and Rad 3-related) signaling pathway triggers cell cycle arrest (by keeping cyclin-Cdk complexes inactive), combined with gamma-phosphorylation of histone H2A.X and induction of DNA repair processes. However, genotoxic stress activates also mitogen-activated protein kinases (MAPKs) which may control the functions of checkpoint proteins both directly, by post-translational modifications, or indirectly, by regulation of their expression. Our results indicate that in root meristem cells of Vicia faba, MAP kinase signaling pathway takes part in response to hydroxyurea-induced genotoxic stress. It is shown that SB202190, an inhibitor of p38 MAP kinase, triggers PCC (premature chromosome condensation) more rapidly, but only if cell cycle checkpoints are alleviated by caffeine. Since SB202190 and, independently, caffeine reduces HU-mediated histone H4 Lys5 acetylation, it may be that there is a cooperation of MAP kinase signaling pathways and ATM/ATR-dependent checkpoints during response to genotoxic stress.
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PMID:SB202190 affects cell response to hydroxyurea-induced genotoxic stress in root meristems of Vicia faba. 2292 76

ACPA (anti-citrullinated protein antibody) tests are today systematically added to clinical and radiological investigations when diagnosing rheumatoid arthritis (RA), and the inclusion of ACPA positivity in the new 2010 RA criteria underlines their importance. The aim of this study was to determine the sensitivity and specificity of different ACPA assays and IgA, IgG and IgM isotypes of rheumatoid factor (RF) in a cohort of patients with early RA in order to assess the value of combining the tests. The serum samples were obtained from 46 RA patients, 80 patients with systemic rheumatic disease, and 20 blood donors. ACPAs were measured using five different commercial kits. The receiver operating characteristic (ROC) curves of the anti-ACPA tests had area under the curve (AUC) values of 0.60-0.83. The diagnostic accuracy of the Bio-Rad multiplex flow immunoassay, a new technology for ACPA testing, was very similar to that of the other widely used commercial immunoassays. The EliA CCP-Phadia test was the most specific, and had the best positive likelihood ratio and positive predictive values, whereas the anti-CCP Inova 3.1 test was the most sensitive, and had the best negative likelihood ratio and negative predictive values. The best combination to use for early RA screening was an ACPA test together with IgM and IgA RF.
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PMID:Anti-citrullinated peptide antibodies and rheumatoid factor isotypes in the diagnosis of rheumatoid arthritis: an assessment of combined tests. 2489 12

Anti-cyclic citrullinated peptide antibodies (anti-CCPs) are important diagnostic markers for rheumatoid arthritis (RA). We evaluated the analytical and clinical performance of the QUANTA Flash CCP3 (INOVA Diagnostics, USA), a fully automated third-generation anti-CCP assay, in comparison with three second-generation anti-CCP (CCP2) assays. A total of 300 sera (67 from RA patients, 64 from other rheumatic diseases, 43 from osteoarthritis [OA], and 126 from other conditions) were tested with QUANTA Flash CCP3, Kallestad Anti-CCP II (Bio-Rad, USA), Elecsys Anti-CCP (Roche Diagnostics GmbH, Germany), and ARCHITECT Anti-CCP (Abbott Diagnostics, USA). Within-run and total imprecision (% coefficient of variation) of the QUANTA Flash CCP3 were <6%, and its linearity was acceptable over the claimed range (4.0-2,749.7 chemiluminescent units). The frequency of anti-CCP was similar between QUANTA Flash CCP3 and the other CCP2 assays in the RA (67.2% vs. 62.7-70.1%), other rheumatic diseases (7.8% vs. 6.3%), and OA (2.3% vs. 0-2.3%) groups. The concordance rate between QUANTA Flash CCP3 and the other assays ranged from 96.3% to 97.7% (kappa from 0.87 to 0.92). For the diagnosis of RA, the sensitivity/specificity was 67.2%/95.7%, 62.7%/98.3%, 70.2%/96.6%, and 67.2%/97.9%, and the areas under the receiver operating characteristic curves were 0.851, 0.791, 0.853, and 0.867 for QUANTA Flash CCP3, Kallestad, Elecsys, and ARCHITECT assays, respectively. The performance of the QUANTA Flash CCP3 was satisfactory and comparable to that of the three CCP2 assays. This fully automated assay would be a practical and reasonable option in clinical laboratories.
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PMID:Comparison of second- and third-generation immunoassays for detection of anti-cyclic citrullinated peptide antibodies. 3007 67