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Tajvur P Saber CT Ng Guillaume Renard Bernadette M Lynch Eliza Pontifex Ceara AE Walsh Alexia Grier Marian Molloy Barry Bresnihan Oliver FitzGerald Ursula Fearon Douglas J Veale 《Arthritis research & therapy》2010,12(3):1-6
Introduction
Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.Methods
Analysis of a prospective patient cohort attending a biologic clinic, between November 2004 and March 2008, was performed prior to commencing therapy and at regular intervals. Baseline clinical characteristics including demographics, previous disease-modifying antirheumatic drug (DMARD) response, tender and swollen joint counts, early morning stiffness, pain visual analogue score, patient global assessment, C reactive protein (CRP) and health assessment questionnaire (HAQ) were collected.Results
A total of 473 patients (152 PsA; 321 rheumatoid arthritis (RA)) were analyzed. At 12 months remission, defined according to the disease activity score using 28 joint count and CRP (DAS28-CRP), was achieved in 58% of PsA patients compared to 44% of RA patients, significant improvement in outcome measures were noted in both groups (P < 0.05). Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission. Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients (P < 0.001).Conclusions
DAS28 remission is possible in PsA patients at one year following anti-TNF therapy, at higher rates than in RA patients and is predicted by baseline HAQ. 相似文献54.
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The West Nile virus: its recent emergence in North America 总被引:6,自引:0,他引:6
Garmendia AE Van Kruiningen HJ French RA 《Microbes and infection / Institut Pasteur》2001,3(3):223-229
West Nile fever emerged in New York in the summer of 1999 when seven people, several horses and thousands of wild birds died. It was soon established that the human disease and the mortality of birds were related. Continued surveillance detected West Nile virus in mosquitoes, birds, horses, small mammals, bats and humans, and has shown its spread to several northeastern states. These events confirm the establishment of West Nile virus endemically in the United States. 相似文献
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Cross validation (CV) was used to analyze the effects of different environments and different genotypic samples on estimates of the proportion of genotypic variance explained by QTL (p). Testcrosses of 344 F(3) maize lines grown in four environments were evaluated for a number of agronomic traits. In each of 200 replicated CV runs, this data set was subdivided into an estimation set (ES) and various test sets (TS). ES were used to map QTL and estimate p for each run (p(ES)) and its median (p(ES)) across all runs. The bias of these estimates was assessed by comparison with the median (p(TS.ES)) obtained from TS. We also used two independent validation samples derived from the same cross for further comparison. The median p(ES) showed a large upward bias compared to p(TS.ES). Environmental sampling generally had a smaller effect on the bias of p(ES) than genotypic sampling or both factors simultaneously. In independent validation, p(TS.ES) was on average only 50% of p(ES). A wide range among p(ES) reflected a large sampling error of these estimates. QTL frequency distributions and comparison of estimated QTL effects indicated a low precision of QTL localization and an upward bias in the absolute values of estimated QTL effects from ES. CV with data from three QTL studies reported in the literature yielded similar results as those obtained with maize testcrosses. We therefore recommend CV for obtaining asymptotically unbiased estimates of p and consequently a realistic assessment of the prospects of MAS. 相似文献
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A global view of antibiotic resistance 总被引:2,自引:0,他引:2
Jose Luis Martinez Alicia Fajardo Leonor Garmendia Alvaro Hernandez Juan Francisco Linares Laura Martínez-Solano & María Blanca Sánchez 《FEMS microbiology reviews》2009,33(1):44-65
Antibiotic resistance is one of the few examples of evolution that can be addressed experimentally. The present review analyses this resistance, focusing on the networks that regulate its acquisition and its effect on bacterial physiology. It is widely accepted that antibiotics and antibiotic resistance genes play fundamental ecological roles – as weapons and shields, respectively – in shaping the structures of microbial communities. Although this Darwinian view of the role of antibiotics is still valid, recent work indicates that antibiotics and resistance mechanisms may play other ecological roles and strongly influence bacterial physiology. The expression of antibiotic resistance determinants must therefore be tightly regulated and their activity forms part of global metabolic networks. In addition, certain bacterial modes of life can trigger transient phenotypic antibiotic resistance under some circumstances. Understanding resistance thus requires the analysis of the regulatory networks controlling bacterial evolvability, the physiological webs affected and the metabolic rewiring it incurs. 相似文献
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Federico M Lauro Matthew Z DeMaere Sheree Yau Mark V Brown Charmaine Ng David Wilkins Mark J Raftery John AE Gibson Cynthia Andrews-Pfannkoch Matthew Lewis Jeffrey M Hoffman Torsten Thomas Ricardo Cavicchioli 《The ISME journal》2011,5(5):879-895
In nature, the complexity and structure of microbial communities varies widely, ranging from a few species to thousands of species, and from highly structured to highly unstructured communities. Here, we describe the identity and functional capacity of microbial populations within distinct layers of a pristine, marine-derived, meromictic (stratified) lake (Ace Lake) in Antarctica. Nine million open reading frames were analyzed, representing microbial samples taken from six depths of the lake size fractionated on sequential 3.0, 0.8 and 0.1 μm filters, and including metaproteome data from matching 0.1 μm filters. We determine how the interactions of members of this highly structured and moderately complex community define the biogeochemical fluxes throughout the entire lake. Our view is that the health of this delicate ecosystem is dictated by the effects of the polar light cycle on the dominant role of green sulfur bacteria in primary production and nutrient cycling, and the influence of viruses/phage and phage resistance on the cooperation between members of the microbial community right throughout the lake. To test our assertions, and develop a framework applicable to other microbially driven ecosystems, we developed a mathematical model that describes how cooperation within a microbial system is impacted by periodic fluctuations in environmental parameters on key populations of microorganisms. Our study reveals a mutualistic structure within the microbial community throughout the lake that has arisen as the result of mechanistic interactions between the physico-chemical parameters and the selection of individual members of the community. By exhaustively describing and modelling interactions in Ace Lake, we have developed an approach that may be applicable to learning how environmental perturbations affect the microbial dynamics in more complex aquatic systems. 相似文献
60.
Eider Larrarte Javier Margareto Catalina March Junkal Garmendia José A. Bengoechea 《Cellular microbiology》2011,13(1):135-153
Klebsiella pneumoniae is an important cause of community‐acquired and nosocomial pneumonia. Subversion of inflammation is essential for pathogen survival during infection. Evidence indicates that K. pneumoniae infections are characterized by lacking an early inflammatory response although the molecular bases are currently unknown. Here we unveil a novel strategy employed by a pathogen to counteract the activation of inflammatory responses. K. pneumoniae attenuates pro‐inflammatory mediators‐induced IL‐8 secretion. Klebsiella antagonizes the activation of NF‐κB via the deubiquitinase CYLD and blocks the phosphorylation of mitogen‐activated protein kinases (MAPKs) via the MAPK phosphatase MKP‐1. Our studies demonstrate that K. pneumoniae has evolved the capacity to manipulate host systems dedicated to control the immune balance. To exert this anti‐inflammatory effect, Klebsiella engages NOD1. In NOD1 knock‐down cells, Klebsiella neither induces the expression of CYLD and MKP‐1 nor blocks the activation of NF‐κB and MAPKs. Klebsiella inhibits Rac1 activation; and inhibition of Rac1 activity triggers a NOD1‐mediated CYLD and MKP‐1 expression which in turn attenuates IL‐1β‐induced IL‐8 secretion. A capsule (CPS) mutant does not attenuate the inflammatory response. However, purified CPS neither reduces IL‐1β‐induced IL‐8 secretion nor induces the expression of CYLD and MKP‐1 thereby indicating that CPS is necessary but not sufficient to attenuate inflammation. 相似文献