bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cadherin 11 promotes invasive behavior of fibroblast‐like synoviocytes
Authors: Kiener Hans P. , Niederreiter Birgit , Lee David M. , Jimenez‐Boj Esther , Smolen Josef S. , Brenner Michael B. 
Published: April 2009

AbstractObjectiveTo define the expression pattern of cadherin 11 in the destructive pannus tissue of patients with rheumatoid arthritis, and to determine whether cadherin 11 expression in fibroblast‐like synoviocytes controls their invasive capacity.MethodsCadherin 11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin 11 in regulating the invasive behavior of fibroblast‐like synoviocytes, we generated L cell clones expressing wild‐type cadherin 11, mutant cadherin 11, and empty vector–transfected controls. The invasive capacity of L cell transfectants and cultured fibroblast‐like synoviocytes treated with a blocking cadherin 11–Fc fusion protein or control immunoglobulin was determined in Matrigel invasion assays.ResultsImmunohistochemical analysis revealed that cadherin 11 is abundantly expressed in cells at the cartilage–pannus junction in rheumatoid synovitis. Assays to determine invasion demonstrated a 2‐fold increased invasive capacity of cadherin 11–transfected L cells compared with L cells transfected with E‐cadherin or control vector. The invasive behavior of L cells stably transfected with a cadherin 11 construct that lacked the juxtamembrane cytoplasmic domain was diminished to the level of vector control L cells. Furthermore, treatment with the cadherin 11–Fc fusion protein diminished the invasive capacity of fibroblast‐like synoviocytes.ConclusionThe results of these in vitro studies implicate a role for cadherin 11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast‐like synoviocytes in chronic synovitis and rheumatoid arthritis.
Comparison of drug retention rates and causes of drug discontinuation between anti–tumor necrosis factor agents in rheumatoid arthritis
Authors: Pan Sophie Martin Du , Dehler Silvia , Ciurea Adrian , Ziswiler Hans‐Rudolf , Gabay Cem , Finckh Axel 
Published: April 2009

AbstractObjectiveTumor necrosis factor (TNF) inhibitors have revolutionized the treatment of severe rheumatoid arthritis (RA), yet drug discontinuation is common. The aim of this study was to compare treatment retention rates and specific causes of anti‐TNF discontinuation in a population‐based RA cohort.MethodsAll patients treated with etanercept, infliximab, or adalimumab within the Swiss Clinical Quality Management RA cohort between 1997 and 2006 were included in the study. Causes of treatment discontinuation were broadly categorized as adverse events (AEs) or nontoxic causes, and further subdivided into specific categories. Specific causes of treatment interruption were analyzed using a Cox proportional hazards model and adjusted for potential confounders.ResultsA total of 2,364 anti‐TNF treatment courses met the inclusion criteria. Treatment discontinuation was reported 803 times: 309 with etanercept, 249 with infliximab, and 245 with adalimumab. Drug inefficacy represented the largest single cause of treatment discontinuation (55.8% of cases). The median time of receiving anti‐TNF therapy was 37 months, but discontinuation rates differed between the 3 anti‐TNF agents (P < 0.001), with shorter retention rates for infliximab (hazard ratio [HR] 1.24, 99% confidence interval [99% CI] 1.01–1.51). The specific causes of treatment discontinuation revealed an increased risk of AEs with infliximab (HR 1.4, 99% CI 1.003–1.96), mostly due to an increased risk of infusion or allergic reactions (HR 2.11, 99% CI 1.23–3.62). Other discontinuation causes were equally distributed between the anti‐TNF agents.ConclusionIn this population, infliximab was associated with higher overall discontinuation rates compared with etanercept and adalimumab, which is mainly due to an increased risk of infusion or allergic reactions.
Problems experienced by people with arthritis when using a computer
Authors: Baker Nancy A. , Rogers Joan C. , Rubinstein Elaine N. , Allaire Saralynn H. , Wasko Mary Chester 
Published: April 2009

AbstractObjectiveTo describe the prevalence of computer use problems experienced by a sample of people with arthritis, and to determine differences in the magnitude of these problems among people with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM).MethodsSubjects were recruited from the Arthritis Network Disease Registry and asked to complete a survey, the Computer Problems Survey, which was developed for this study. Descriptive statistics were calculated for the total sample and the 3 diagnostic subgroups. Ordinal regressions were used to determine differences between the diagnostic subgroups with respect to each equipment item while controlling for confounding demographic variables.ResultsA total of 359 respondents completed a survey. Of the 315 respondents who reported using a computer, 84% reported a problem with computer use attributed to their underlying disorder, and ∼77% reported some discomfort related to computer use. Equipment items most likely to account for problems and discomfort were the chair, keyboard, mouse, and monitor. Of the 3 subgroups, significantly more respondents with FM reported more severe discomfort, more problems, and greater limitations related to computer use than those with RA or OA for all 4 equipment items.ConclusionComputer use is significantly affected by arthritis. This could limit the ability of a person with arthritis to participate in work and home activities. Further study is warranted to delineate disease‐related limitations and develop interventions to reduce them.
Association of biomarkers with pre–radiographically defined and radiographically defined knee osteoarthritis in a population‐based study
Authors: Cibere Jolanda , Zhang Hongbin , Garnero Patrick , Poole A. Robin , Lobanok Tatiana , Saxne Tore , Kraus Virginia B. , Way Amanda , Thorne Anona , Wong Hubert , Singer Joel , Kopec Jacek , Guermazi Ali , Peterfy Charles , Nicolaou Savvakis , Munk Peter L. , Esdaile John M. 
Published: April 2009

AbstractObjectiveTo evaluate 10 biomarkers in magnetic resonance imaging (MRI)–determined, pre–radiographically defined osteoarthritis (pre‐ROA) and radiographically defined OA (ROA) in a population‐based cohort of subjects with symptomatic knee pain.MethodsTwo hundred one white subjects with knee pain, ages 40–79 years, were classified into OA subgroups according to MRI‐based cartilage (MRC) scores (range 0–4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0–4): no OA (MRC score 0, K/L grade <2), pre‐ROA (MRC score ≥1, K/L grade <2), or ROA (MRC score ≥1, K/L grade ≥2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C‐telopeptide of type II collagen (uCTX‐II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N‐telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C‐propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index.ResultsThe risk of ROA versus no OA increased with increasing levels of uCTX‐II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35–7.21), uC2C (OR 2.13, 95% CI 1.04–4.37), and uC1,2C (OR 2.07, 95% CI 1.06–4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30–0.94). The risk of pre‐ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05–4.01) and uC1,2C (OR 2.06, 95% CI 1.12–3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX‐II][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34–9.03) and a risk of pre‐ROA versus no OA of 2.56 (95% CI 1.03–6.40).ConclusionDifferent cartilage degradation markers are associated with pre‐ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.
Efficacy, pharmacodynamics, and safety of VX‐702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: Results of two randomized, double‐blind, placebo‐controlled clinical studies
Authors: Damjanov Nemanja , Kauffman Robert S. , Spencer‐Green George T. 
Published: April 2009

AbstractObjectiveTo assess the efficacy and safety of VX‐702, a p38 MAPK inhibitor, in patients with active, moderate‐to‐severe rheumatoid arthritis (RA).MethodsTwo 12‐week, double‐blind, placebo‐controlled studies of VX‐702 were conducted in patients with active, moderate‐to‐severe RA. In the VeRA study, 313 patients received placebo or 2 daily doses of VX‐702. In Study 304, 117 patients received placebo, daily VX‐702, or twice weekly VX‐702 in addition to concomitant methotrexate (MTX). Study end points included the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (an ACR20 response), ACR50 and ACR70 responses, changes in the serum levels of biomarkers of inflammation, and safety assessments.ResultsThe numerically superior ACR20 response rates among patients receiving VX‐702 compared with those receiving placebo in both studies did not reach pairwise statistical significance at the highest doses in either study. At week 12 in the VeRA study, ACR20 response rates were 40%, 36%, and 28% among patients receiving 10 mg of VX‐702, 5 mg of VX‐702, and placebo, respectively. In Study 304, the response rates were 40%, 44%, and 22% for patients receiving 10 mg VX‐702 daily plus MTX, 10 mg VX‐702 twice weekly plus MTX, and placebo, respectively. Reductions in the levels of C‐reactive protein, soluble tumor necrosis factor receptor p55, and serum amyloid A were observed as early as week 1 in both studies, but these levels rapidly returned to baseline values by week 4. The overall frequency of adverse events was similar between the VX‐702 and placebo groups. In the VeRA study, serious infections were more frequent in the VX‐702 groups compared with the placebo group (2.4% versus 0%) but not in Study 304 (2.6% versus 4.9%).ConclusionThe modest clinical efficacy plus the transient suppression of biomarkers of inflammation observed in this study suggest that p38 MAPK inhibition may not provide meaningful, sustained suppression of the chronic inflammation seen in RA.
Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis
Authors: Hemmatazad Hossein , Rodrigues Hanna Maciejewska , Maurer Britta , Brentano Fabia , Pileckyte Margarita , Distler Jörg H. W. , Gay Renate E. , Michel Beat A. , Gay Steffen , Huber Lars C. , Distler Oliver , Jüngel Astrid 
Published: April 2009

AbstractObjectiveWe have recently shown a significant reduction in cytokine‐induced transcription of type I collagen and fibronectin in systemic sclerosis (SSc) skin fibroblasts upon treatment with trichostatin A (TSA). Moreover, in a mouse model of fibrosis, TSA prevented the dermal accumulation of extracellular matrix. The purpose of this study was to analyze the silencing of histone deacetylase 7 (HDAC‐7) as a possible mechanism by which TSA exerts its antifibrotic function.MethodsSkin fibroblasts from patients with SSc were treated with TSA and/or transforming growth factor β. Expression of HDACs 1–11, extracellular matrix proteins, connective tissue growth factor (CTGF), and intercellular adhesion molecule 1 (ICAM‐1) was analyzed by real‐time polymerase chain reaction, Western blotting, and the Sircol collagen assay. HDAC‐7 was silenced using small interfering RNA.ResultsSSc fibroblasts did not show a specific pattern of expression of HDACs. TSA significantly inhibited the expression of HDAC‐7, whereas HDAC‐3 was up‐regulated. Silencing of HDAC‐7 decreased the constitutive and cytokine‐induced production of type I and type III collagen, but not fibronectin, as TSA had done. Most interestingly, TSA induced the expression of CTGF and ICAM‐1, while silencing of HDAC‐7 had no effect on their expression.ConclusionSilencing of HDAC‐7 appears to be not only as effective as TSA, but also a more specific target for the treatment of SSc, because it does not up‐regulate the expression of profibrotic molecules such as ICAM‐1 and CTGF. This observation may lead to the development of more specific and less toxic targeted therapies for SSc.
Transmembrane BAFF from rheumatoid synoviocytes requires interleukin‐6 to induce the expression of recombination‐activating gene in B lymphocytes
Authors: Rochas Caroline , Hillion Sophie , Saraux Alain , Mageed Rizgar A. , Youinou Pierre , Jamin Christophe , Devauchelle Valérie 
Published: April 2009

AbstractObjectiveB cells that accumulate in the synovial tissue of rheumatoid arthritis (RA) patients revise their receptors due to coordinate expression of recombination‐activating gene 1 (RAG‐1) and RAG‐2 genes. The aim of this study was to determine the mechanisms that control this re‐expression.MethodsB cells from healthy control subjects were cocultured with fibroblast‐like synoviocytes (FLS) from patients with RA and osteoarthritis (OA). Re‐expression of RAG messenger RNA (mRNA) and proteins was analyzed by reverse transcription–polymerase chain reaction (RT‐PCR) and indirect immunofluorescence. Activity of RAG enzymes was evaluated by flow cytometry to measure variations in immunoglobulin κ and λ light chain expression and by ligation‐mediated–PCR to assess specific DNA breaks. Blocking antibodies, short hairpin RNA, and recombinant cytokine were used to identify the molecules involved in RAG re‐expression.ResultsRA FLS, but not OA FLS, induced B cells to re‐express RAG mRNA and proteins. Enzymes were functional, since the κ‐to‐λ ratios decreased and specific DNA breaks were detectable after coculture with RA FLS. Transmembrane BAFF provided the first signal of RAG re‐expression, since its down‐regulation in RA FLS prevented RAG gene transcription in B cells. The failure of transmembrane BAFF from OA FLS to induce RAG suggests that a second signal was provided by RA FLS. Interleukin‐6 (IL‐6) is a candidate, since blockade of its receptors precluded transcription of RAG genes by RA FLS. Unless supplemented with IL‐6, OA FLS were unable to induce RAG gene expression in normal B cells.ConclusionTwo independent signals are required for the induction of RAG gene expression in B cells that infiltrate the synovium of patients with RA.
Th17 and natural Treg cell population dynamics in systemic lupus erythematosus
Authors: Yang Ji , Chu Yiwei , Yang Xue , Gao Di , Zhu Lubing , Yang Xinrong , Wan Linlin , Li Ming 
Published: April 2009

AbstractObjectiveTo investigate the relative abundance and activities of Th17 cells and natural Treg cells in systemic lupus erythematosus (SLE).MethodsBlood samples were collected from 50 adult patients with SLE. Samples were processed to detect Th17 cells and natural Treg cells by flow cytometry, and related gene expression was assessed by real‐time reverse transcription–polymerase chain reaction. Skin biopsy specimens were collected for histologic assessment. The function of Th17 cells in relation to human umbilical vein endothelial cells (HUVECs) was studied in vitro. Th17 cells were also examined in lupus‐prone MRL/Mp‐lpr/lpr (MRL/lpr) mice.ResultsWe demonstrated the presence of Th17 cells among the peripheral blood mononuclear cells (PBMCs) and in the involved organs of patients with active SLE. Both the percentage of circulating Th17 cells and the ability to produce interleukin‐17A (IL‐17A) were increased in samples derived from patients with active SLE. The number of Th17 cells increased during SLE flare, especially in patients with vasculitis, and decreased following certain treatments. We observed that IL‐17A from patients with SLE could induce adhesion molecule messenger RNA expression in HUVECs and adhesion of T cells to HUVECs. An increase in the percentage of Th17 cells was correlated with natural Treg cell depletion during disease flare. Finally, expansion of the Th17 cell population was detected in MRL/lpr mice.ConclusionSLE flare might be linked to the expansion of the Th17 cell population and the depletion of natural Treg cell subpopulations. Expansion of the Th17 cell population might be related to a distinct cytokine environment in active SLE. Th17 cells and microenvironmental IL‐17A are involved in vascular inflammation in SLE. Antagonism of Th17 cells by IL‐17A–blocking antibodies should be explored as a treatment of SLE.
Development and validation of a composite disease activity score for juvenile idiopathic arthritis
Authors: Consolaro Alessandro , Ruperto Nicolino , Bazso Anna , Pistorio Angela , Magni‐Manzoni Silvia , Filocamo Giovanni , Malattia Clara , Viola Stefania , Martini Alberto , Ravelli Angelo 
Published: April 2009

AbstractObjectiveTo develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS).MethodsThe JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well‐being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71‐joint (range 0–101), 27‐joint (range 0–57), or 10‐joint (range 0–40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI).ResultsThe JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long‐term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change.ConclusionThe JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.
An adaptable search engine for multimodal information retrieval
Authors: Hubert Gilles , Mothe Josiane 
Published: April 2009

AbstractThis article describes an information retrieval approach according to the two different search modes that exist: browsing an ontology (via categories) or defining a query in free language (via keywords). Various proposals offer approaches adapted to one of these two modes. We present a proposal leading to a system allowing the integration of both modes using the same search engine. This engine is adapted according to each possible search mode.
Image‐based hysteresis modeling and compensation for an AFM piezo‐scanner
Authors: Zhang Yudong , Fang Yongchun , Zhou Xianwei , Dong Xiaokun 
Published: April 2009

AbstractAs an important component of Atomic Force Microscopes (AFM), a piezo‐scanner exhibits some undesired nonlinear characteristics, among which the inherent hysteresis largely decreases positioning accuracy during scanning and nano‐manipulation process. To alleviate this problem, an image‐based approach is proposed in this paper to model and then compensate for the hysteresis behavior of the piezo‐scanner. Specifically, some scanning images over standard samples are utilized to identify the parameters of the classical Preisach model (CPM) of hysteresis. On the basis of the obtained model, an inversion‐based technique is adopted to design a compensator for the hysteresis of the piezo‐scanner. The proposed algorithm presents such advantages as low cost and little complexity since no nanoscale position sensor is required to collect identification data. Some scanning and nano‐imprinting results are included to demonstrate the performance of the proposed strategy. Copyright © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Inhibitory effects of a gradient static magnetic field on normal angiogenesis
Authors: Wang Zhe , Yang Pengfei , Xu Huiyun , Qian Airong , Hu Lifang , Shang Peng 
Published: April 2009

AbstractAngiogenesis, the formation of new blood vessels, is critical in many normal and pathological processes such as development, reproduction, tumor growth, and metastasis. Recently, exposure to moderate‐intensity static magnetic fields (1 mT to 1 T) has attracted much attention for its potential therapeutic value as a noninvasive intervening method. Nevertheless, the effects of moderate‐intensity and spatial gradient static magnetic fields (GSMF) on angiogenesis have not received enough attention. In this study, the effects of GSMF (0.2–0.4 T, 2.09 T/m, 1–11 days) on angiogenesis were investigated both in vitro and in vivo. An MTT assay was used as an in vitro method to detect the proliferation ability of human umbilical veins endothelial cells (HUVECs). Two kinds of in vivo models, a chick chorioallantoic membrane (CAM) and a matrigel plug, were used to detect the effects of GSMF on angiogenesis. The results showed that the proliferation ability of HUVECs was significantly inhibited 24 h after the onset of exposure. With regard to the CAM model, vascular numbers in the CAM that was continuously exposed to the GSMF were all less than those in normal condition. In accordance with the gross appearance, the contents of hemoglobin in the models exposed to GSMF for 7–9 days were also less. In addition, similar to the CAM model, the results of vascular density and hemoglobin contents in the matrigel plug also demonstrated that the GSMF exposure for 7 or 11 days inhibited vascularization. These findings indicate that GSMF might inhibit or prevent new blood vessels formation and could be helpful for the treatment of some diseases relevant to pathological angiogenesis. Bioelectromagnetics 30:446–453, 2009. © 2009 Wiley‐Liss, Inc.
Partition of thermodynamic energies of drug–DNA complexation
Authors: Kostjukov V. V. , Khomytova N. M. , Evstigneev M. P. 
Published: April 2009

AbstractWe report a computation methodology, which leads to the ability to partition the Gibb's free energy for the complexation reaction of aromatic drug molecules with DNA. Using this approach, it is now possible to calculate the absolute values of the energy contributions of various physical factors to the DNA binding process, whose summation gives a value that is reasonably close to the experimentally measured Gibb's free energy of binding. Application of the methodology to binding of various aromatic drugs with DNA provides an answer to the question “What forces are the main contributors to the stabilization of aromatic ligand–DNA complexes?” © 2009 Wiley Periodicals, Inc. Biopolymers 91: 773–790, 2009.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com