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81.
Nicoline BM Voet Gijs Bleijenberg George W Padberg Baziel GM van Engelen Alexander CH Geurts 《BMC neurology》2010,10(1):56
Background
In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated.Methods/Design
A multi-centre, assessor-blinded, randomized controlled trial is conducted. A sample of 75 FSHD patients with severe chronic fatigue (CIS-fatigue ≥ 35) will be recruited and randomized to one of three groups: (1) AET + usual care, (2) CBT + usual care or (3) usual care alone, which consists of no therapy at all or occasional (conventional) physical therapy. After an intervention period of 16 weeks and a follow-up of 3 months, the third (control) group will as yet be randomized to either AET or CBT (approximately 7 months after inclusion). Outcomes will be assessed at baseline, immediately post intervention and at 3 and 6 months follow up.Discussion
The FACTS-2-FSHD study is the first theory-based randomized clinical trial which evaluates the effect and the maintenance of effects of AET and CBT on the reduction of chronic fatigue in patients with FSHD. The interventions are based on a theoretical model of chronic fatigue in patients with FSHD. The study will provide a unique set of data with which the relationships between outcome measures at all levels of the ICF could be assessed.Trial registration
Dutch Trial Register, NTR1447.82.
A cross-regulation between type I IFN and TNFα has been proposed recently, where both cytokines are hypothesized to counteract
each other. According to this model, different autoimmune diseases can be viewed as disequilibrium between both cytokines.
As this model may have important clinical implications, the present review summarizes and discusses the currently available
clinical evidence arguing for or against the proposed cross-regulation between TNFα and type I IFN. In addition, we review
how this cross-regulation works at the cellular and molecular levels. Finally, we discuss the clinical relevance of this proposed
cross-regulation for biological therapies such as type I IFN or anti-TNFα treatment. 相似文献
83.
Lisa GM van Baarsen Carla A Wijbrandts François Rustenburg Tineke Cantaert Tineke CTM van der Pouw Kraan Dominique L Baeten Ben AC Dijkmans Paul P Tak Cornelis L Verweij 《Arthritis research & therapy》2010,12(1):R11
Introduction
Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response. 相似文献84.
Seo Young Kim Sebastian Schneeweiss Jun Liu Gregory W Daniel Chun-Lan Chang Katie Garneau Daniel H Solomon 《Arthritis research & therapy》2010,12(4):R154
Introduction
Although osteoporosis has been reported to be more common in patients with rheumatoid arthritis (RA), little is known whether the risk of osteoporotic fractures in these patients differs by age, sex, and anatomic site. 相似文献85.
Weiss-Schneeweiss H Blöch C Turner B Villaseñor JL Stuessy TF Schneeweiss GM 《Evolution; international journal of organic evolution》2012,66(1):211-228
Polyploidy, an important factor in eukaryotic evolution, is especially abundant in angiosperms, where it often acts in concert with hybridization to produce allopolyploids. The application of molecular phylogenetic techniques has identified the origins of numerous allopolyploids, but little is known on genomic and chromosomal consequences of allopolyploidization, despite their important role in conferring divergence of allopolyploids from their parental species. Here, using several plastid and nuclear sequence markers, we clarify the origin of tetra- and hexaploids in a group of American daisies, allowing characterization of genome dynamics in polyploids compared to their diploid ancestors. All polyploid species are allopolyploids. Among the four diploid gene pools, the propensity for allopolyploidization is unevenly distributed phylogenetically with a few species apparently more prone to participate, but the underlying causes remain unclear. Polyploid genomes are characterized by differential loss of ribosomal DNA loci (5S and 35S rDNA), known hotspots of chromosomal evolution, but show genome size additivity, suggesting limited changes beyond those affecting rDNA loci or the presence of processes counterbalancing genome reduction. Patterns of rDNA sequence conversion and provenance of the lost loci are highly idiosyncratic and differ even between allopolyploids of identical parentage, indicating that allopolyploids deriving from the same lower-ploid parental species can follow different evolutionary trajectories. 相似文献
86.
In a recent paper written by Hilbe et al (BMC vet res, 2009), the nature and specificity of the prion protein deposition in
the kidney of feline species affected with feline spongiform encephalopathy (FSE) were clearly considered doubtful. This article
was brought to our attention because we published several years ago an immunodetection of abnormal prion protein in the kidney
of a cheetah affected with FSE. At this time we were convinced of its specificity but without having all the possibilities
to demonstrate it. As previously published by another group, the presence of abnormal prion protein in some renal glomeruli
in domestic cats affected with FSE is indeed generally considered as doubtful mainly because of low intensity detected in
this organ and because control kidneys from safe animals present also a weak prion immunolabelling. Here we come back on these
studies and thought it would be helpful to relay our last data to the readers of BMC Vet res for future reference on this
subject. 相似文献
87.
在研究转基因香石竹品系月之霓裳(Moonshade)、月之伊人(Moonlite)中外源基因F3’5’H的表达中,本文克隆了F3’5’H全长基因1.5kb,构建获得工程菌株Escherichia coli BL21(DE3)(+F3'5'H)。SDS-PAGE分析的结果显示,该菌株高效表达出F3’5’H重组蛋白,约占菌体总蛋白的30%。用经纯化的F3’5’H重组蛋白作为抗原,制备F3’5’H重组蛋白的抗血清,经ELISA免疫学分析表明,该抗血清的效价为1:25600。Western blot结果表明F3’5’H重组蛋白具有良好的IgG结合活性,且抗血清与转基因香石竹品系月之霓裳和月之伊人中的外源基因F3’5’H所表达的蛋白发生明显的抗原抗体反应。这样,月之霓裳和月之伊人用于评价转基因香石竹品系的环境安全性在我国也得到了验证。 相似文献
88.
Alexandre Wagner Silva de Souza Johanna Westra Johan Bijzet Pieter C Limburg Coen A Stegeman Marc Bijl Cees GM Kallenberg 《Arthritis research & therapy》2013,15(5):R104
Background
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are systemic inflammatory disorders that include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), Churg-Strauss syndrome and renal limited vasculitis (RLV). Extracellular high-mobility group box 1 (HMGB1) acts as an alarmin and has been shown to be a biomarker of disease activity as well as an autoantigen in systemic lupus erythematosus (SLE) and, possibly, in AAV. This study aims to assess antibodies against HMGB1 and HMGB1 levels as biomarkers for AAV disease activity and predictors of relapsing disease.Methods
AAV patients with active disease and healthy controls (HC) were evaluated for anti-HMGB1 antibodies while serum HMGB1 levels were measured longitudinally in AAV patients at presentation, during remission, prior to and at relapses.Results
HMGB1 levels were similar between AAV patients at presentation (n = 52) and HC (n = 35) (2.64 ± 1.80 ng/ml vs. 2.39 ± 1.09 ng/ml; P = 0.422) and no difference regarding HMGB1 levels could be found among AAV disease subsets (GPA: 2.66 ± 1.83 ng/ml vs. MPA: 3.11 ± 1.91 ng/ml vs. RLV: 1.92 ± 1.48 ng/ml; P = 0.369). AAV patients with renal involvement had lower HMGB1 levels than patients without renal involvement at presentation (2.35 ± 1.48 ng/ml vs. 3.52 ± 2.41 ng/ml; P = 0.042). A negative correlation was observed between HMGB1 levels and 24-hour proteinuria (ρ = -0.361, P = 0.028). Forty-nine AAV patients were evaluated for HMGB1 levels during follow-up and no differences were observed between relapsing and nonrelapsing patients (P = 0.350). No significant increase in HMGB1 levels was observed prior to a relapse compared with the remission period and changes in HMGB1 levels were not associated with an increased risk for relapse in AAV. Positivity for anti-HMGB1 antibodies was low in patients with active AAV (three out of 24 patients).Conclusions
Serum HMGB1 levels at presentation are not increased and are lower in patients with renal involvement. Relapses are not preceded or accompanied by significant rises in HMGB1 levels and changes in HMGB1 levels are not related to ensuing relapses. Anti-HMGB1 antibodies are present in only a few patients in AAV. In contrast to SLE, HMGB1 is not a useful biomarker in AAV. 相似文献89.
A long standing and at times fervid debate in biogeography revolves around the question whether arctic and high alpine organisms survived Pleistocene ice ages on small island-like areas protruding above the ice-sheet, socalled nunataks, or whether they did so in peripheral nonglaciated refugial areas. A common picture emerging from a plethora of molecular phylogeographic studies in the last decade is that both in the Arctic and in temperate mountain ranges such as the European Alps nunatak survival needs to be only rarely invoked to explain observed genetic patterns (for a rare example see Stehlik et al. 2002). As two studies in this issue show, depreciation of the nunatak hypothesis is, however, not warranted. In this issue of Molecular Ecology Westergaard et al. (2011) investigate genetic patterns of two arctic-alpine plant species distributed on both sides of the Atlantic exclusively in areas that were mostly covered by ice-sheets during Pleistocene glacial advances. In both species, amplified fragment length polymorphism (AFLP) data identified divergent and partly genetically diverse groups east and west of the Atlantic. This suggests, for the first time in Arctic plants, in situ survival on nunataks. In an entirely different geographic setting and on a different geographic scale, Lohse et al. (2011, this issue) study the colonization of high alpine areas in the Orobian Alps, situated within and adjacent to a prominent peripheral refugial area (massif de refuge) in the Southern Alps of northern Italy, by dispersal-limited carabid ground beetles. Using explicit hypothesis testing and inference of ancestral locations in a Bayesian framework, stepwise colonization from two separate southern refugia is found to shape the genetic pattern of these beetles, but at the northern edge, populations survived at least parts of the last glaciation in situ on nunataks. 相似文献
90.
Sofieke E Klamer Carlijn GM Kuijk Peter L Hordijk C Ellen van der Schoot Marieke von Lindern Paula B van Hennik Carlijn Voermans 《Cell Adhesion & Migration》2013,7(5):434-449
Cell adhesion and migration are important determinants of homing and development of hematopoietic stem and progenitor cells (HSPCs) in bone marrow (BM) niches. The extracellular matrix protein transforming growth factor-β (TGF-β) inducible gene H3 (BIGH3) is involved in adhesion and migration, although the effect of BIGH3 is highly cell type-dependent. BIGH3 is abundantly expressed by mesenchymal stromal cells, while its expression in HSPCs is relatively low unless induced by certain BM stressors. Here, we set out to determine how BIGH3 modulates HSPC adhesion and migration. We show that primary HSPCs adhere to BIGH3-coated substrates, which is, in part, integrin-dependent. Overexpression of BIGH3 in HSPCs and HL60 cells reduced the adhesion to the substrate fibronectin in adhesion assays, which was even more profound in electrical cell-substrate impedance sensing (ECIS) assays. Accordingly, the CXCL12 induced migration over fibronectin-coated surface was reduced in BIGH3-expressing HSPCs. The integrin expression profile of HSPCs was not altered upon BIGH3 expression. Although expression of BIGH3 did not alter actin polymerization in response to CXCL12, it inhibited the PMA-induced activation of the small GTPase RAC1 as well as the phosphorylation and activation of extracellular-regulated kinases (ERKs). Reduced activation of ERK and RAC1 may be responsible for the inhibition of cell adhesion and migration by BIGH3 in HSPCs. Induced BIGH3 expression upon BM stress may contribute to the regulation of BM homeostasis. 相似文献