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971.
972.
Cristiano S. Moura Michal Abrahamowicz Marie-Eve Beauchamp Diane Lacaille Yishu Wang Gilles Boire Paul R. Fortin Louis Bessette Claire Bombardier Jessica Widdifield John G. Hanly Debbie Feldman Walter Maksymowych Christine Peschken Cheryl Barnabe Steve Edworthy Sasha Bernatsky CAN-AIM 《Arthritis research & therapy》2015,17(1)
IntroductionUse of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada.MethodsA cohort of new-onset RA patients was identified from Quebec’s physician billing and hospitalization databases from 2002–2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity.ResultsDuring follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95 % confidence interval, 95 % CI 0.93-0.97) or other DMARDs (HR = 0.97, 95 % CI 0.95-0.99) was associated with longer time to joint replacement.ConclusionsOur results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0713-3) contains supplementary material, which is available to authorized users. 相似文献973.
974.
Makhijani K Alexander B Tanaka T Rulifson E Brückner K 《Development (Cambridge, England)》2011,138(24):5379-5391
Interactions of hematopoietic cells with their microenvironment control blood cell colonization, homing and hematopoiesis. Here, we introduce larval hematopoiesis as the first Drosophila model for hematopoietic colonization and the role of the peripheral nervous system (PNS) as a microenvironment in hematopoiesis. The Drosophila larval hematopoietic system is founded by differentiated hemocytes of the embryo, which colonize segmentally repeated epidermal-muscular pockets and proliferate in these locations. Importantly, we show that these resident hemocytes tightly colocalize with peripheral neurons and we demonstrate that larval hemocytes depend on the PNS as an attractive and trophic microenvironment. atonal (ato) mutant or genetically ablated larvae, which are deficient for subsets of peripheral neurons, show a progressive apoptotic decline in hemocytes and an incomplete resident hemocyte pattern, whereas supernumerary peripheral neurons induced by ectopic expression of the proneural gene scute (sc) misdirect hemocytes to these ectopic locations. This PNS-hematopoietic connection in Drosophila parallels the emerging role of the PNS in hematopoiesis and immune functions in vertebrates, and provides the basis for the systematic genetic dissection of the PNS-hematopoietic axis in the future. 相似文献
975.
An electrochemical impedance spectroscopy (EIS) assay measuring the calcification inhibition capacity in biological fluids 总被引:1,自引:0,他引:1
Ismail AH Schäfer C Heiss A Walter M Jahnen-Dechent W Leonhardt S 《Biosensors & bioelectronics》2011,26(12):4702-4707
Pathological calcification of the cardiovascular system is one of the major causes of high mortality and morbidity in dialysis patients. The inhibition of ectopic calcification relies (I) on the formation of calciprotein particles (CPPs), nanospherical complexes of calcium phosphate mineral, fetuin-A and other acidic serum proteins, and (II) on the stabilization of calcium phosphate prenucleation clusters by fetuin-A monomers. In supersaturated serum, mineral ion aggregation leads to a change in the electrical impedance. In this work, we present a method based on electrochemical impedance spectroscopy (EIS) to establish an impedance trace of mineral ion clustering in vitro. In the presence of 20 μM of serum protein fetuin-A, a prototypic calcification inhibitor, we measured a change in impedance (Δ(R)) of 195.52 ± 27.78%Ω compared to 430.41 ± 11.36%Ω in inhibitor-free samples. We also identified a CPP-formation dependency on the actual content of ions and protein in the samples under investigation. Two-step ripening of CPP was also observed. The presented method may form the basis of a simple label-free bedside or online test to be used in routine clinical practice for estimating the calcification risk in serum. 相似文献
976.
977.
978.
Hoffmann TJ Kvale MN Hesselson SE Zhan Y Aquino C Cao Y Cawley S Chung E Connell S Eshragh J Ewing M Gollub J Henderson M Hubbell E Iribarren C Kaufman J Lao RZ Lu Y Ludwig D Mathauda GK McGuire W Mei G Miles S Purdy MM Quesenberry C Ranatunga D Rowell S Sadler M Shapero MH Shen L Shenoy TR Smethurst D Van den Eeden SK Walter L Wan E Wearley R Webster T Wen CC Weng L Whitmer RA Williams A Wong SC Zau C Finn A Schaefer C Kwok PY Risch N 《Genomics》2011,98(2):79-89
The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies. 相似文献
979.
Wenglowsky S Ahrendt KA Buckmelter AJ Feng B Gloor SL Gradl S Grina J Hansen JD Laird ER Lunghofer P Mathieu S Moreno D Newhouse B Ren L Risom T Rudolph J Seo J Sturgis HL Voegtli WC Wen Z 《Bioorganic & medicinal chemistry letters》2011,21(18):5533-5537
Structure-activity relationships around a novel series of B-Raf(V600E) inhibitors are reported. The enzymatic and cellular potencies of inhibitors derived from two related hinge-binding groups were compared and3-methoxypyrazolopyridine proved to be superior. The 3-alkoxy group of lead B-Raf(V600E) inhibitor 1 was extended and minimally affected potency. The propyl sulfonamide tail of compound 1, which occupies the small lipophilic pocket formed by an outward shift of the αC-helix, was expanded to a series of arylsulfonamides. X-ray crystallography revealed that this lipophilic pocket unexpectedly enlarges to accommodate the bulkier aryl group. 相似文献
980.
Schmiedl A Behrens J Zscheppang K Purevdorj E von Mayersbach D Liese A Dammann CE 《American journal of physiology. Lung cellular and molecular physiology》2011,301(4):L490-L499
Pulmonary ErbB4 deletion leads to a delay in fetal lung development, alveolar simplification, and lung function disturbances in adult mice. We generated a model of intrauterine infection in ErbB4 transgenic mice to study the additive effects of antenatal LPS administration and ErbB4 deletion during fetal lung development. Pregnant mice were treated intra-amniotically with an LPS dose of 4 μg at E17 of gestation. Lungs were analyzed 24 h later. A significant influx of inflammatory cells was seen in all LPS-treated lungs. In heterozygote control lungs, LPS treatment resulted in a delay of lung morphogenesis characterized by a significant increase in the fraction of mesenchyme, a decrease in gas exchange area, and disorganization of elastic fibers. Surfactant protein (Sftp)b and Sftpc were upregulated, but mRNA of Sftpb and Sftpc was downregulated compared with non-LPS-treated controls. The mRNA of Sftpa1 and Sftpd was upregulated. In ErbB4-deleted lungs, the LPS effects were more pronounced, resulting in a further delay in morphological development, a more pronounced inflammation in the parenchyma, and a significant higher increase in all Sftp. The effect on Sftpb and Sftpc mRNA was somewhat different, resulting in a significant increase. These results imply a major role of ErbB4 in LPS-induced signaling in structural and functional lung development. 相似文献