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- den Broeder, A A, et al.
(författare)
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Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation.
- 2002
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 61:4, s. 311-318
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the effect of prolonged neutralisation of tumour necrosis factor alpha (TNFalpha) on the radiological course in rheumatoid arthritis (RA). To assess whether the radiological course can be predicted by clinical variables or biological markers of cartilage and synovium turnover and of endothelial activation. Patients and methods: Forty seven patients with active RA enrolled at our centre in monotherapy trials with adalimumab (D2E7), a fully human anti-TNFalpha monoclonal antibody, were studied for two years. Radiographs of hands and feet obtained at baseline and after one and two years were scored in chronological order by a single, blinded observer using the modified Sharp method. Radiological course was classified as stable or progressive using the smallest detectable difference as cut off point. The relation between radiological course and serum markers of cartilage and synovium turnover (metalloproteinases (MMP-1 and MMP-3), cartilage oligomeric matrix protein (COMP), human cartilage glycoprotein-39 (HC gp-39)), endothelial activation (soluble E-selectin and intercellular adhesion molecule (ICAM-1)), and integrated measures of disease activity were assessed using univariate and multivariate analysis. Results: Radiological evaluation was performed in 36 patients with paired sets of radiographs at baseline and two years. After two years a total of 15/36 (42%) presented no radiological progression. More patients with stable radiological course were still receiving anti-TNFalpha treatment after two years (13/15 (87%) v 11/21 (52%); p=0.03) and had lower baseline COMP and sICAM-1 levels (p=0.01 and 0.04, respectively) than those in the group with progressive disease. In a logistic regression model the combination of sustained TNF neutralisation and baseline COMP and sICAM-1 levels was predictive for radiological outcome (p=0.03). C reactive protein and disease activity score area under the curve were significantly correlated with changes in radiological scores after two years (r=0.40 and 0.37, p<0.05). Long term TNFalpha neutralisation decreased the levels of COMP, sICAM, MMPs, and HC gp-39, but not sE-selectin. Conclusion: The results suggest that long term monotherapy with anti-TNFalpha has a positive effect on radiological outcome and modulates cartilage and synovium turnover as measured by biological markers. Baseline serum sICAM-1 levels and COMP levels may be helpful to identify patients with progressive or non-progressive radiological outcome.
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- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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- Flores, H., et al.
(författare)
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Impact of climate change on Antarctic krill
- 2012
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Ingår i: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 458, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Antarctic krill Euphausia superba (hereafter 'krill') occur in regions undergoing rapid environmental change, particularly loss of winter sea ice. During recent years, harvesting of krill has in creased, possibly enhancing stress on krill and Antarctic ecosystems. Here we review the overall impact of climate change on krill and Antarctic ecosystems, discuss implications for an ecosystem-based fisheries management approach and identify critical knowledge gaps. Sea ice decline, ocean warming and other environmental stressors act in concert to modify the abundance, distribution and life cycle of krill. Although some of these changes can have positive effects on krill, their cumulative impact is most likely negative. Recruitment, driven largely by the winter survival of larval krill, is probably the population parameter most susceptible to climate change. Predicting changes to krill populations is urgent, because they will seriously impact Antarctic ecosystems. Such predictions, however, are complicated by an intense inter-annual variability in recruitment success and krill abundance. To improve the responsiveness of the ecosystem-based management approach adopted by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), critical knowledge gaps need to be filled. In addition to a better understanding of the factors influencing recruitment, management will require a better understanding of the resilience and the genetic plasticity of krill life stages, and a quantitative understanding of under-ice and benthic habitat use. Current precautionary management measures of CCAMLR should be maintained until a better understanding of these processes has been achieved. [GRAPHICS] .
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