A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis.

Objective: We previously observed the association of the co-occurrence of the HLA-DRB1 shared epitope (SE) and RANKL single-nucleotide polymorphisms (SNPs) with younger age at the onset of rheumatoid arthritis (RA) in 182 rheumatoid factor (RF)-positive European American patients with early-onset RA. The aim of this study was to fine-map the 48-kb RANKL region in the extended cohort of 210 European American RF-positive patients with early RA, to seek replication of RA-associated SNPs in additional RA cohorts of 501 European Americans and 298 African Americans, and to explore the functional consequences of RA-associated SNPs.

Methods: SNP genotyping was conducted using pyrosequencing or TaqMan polymerase chain reaction (PCR) assays.

Stimulation with type I collagen induces changes in gene expression in peripheral blood mononuclear cells from patients with diffuse cutaneous systemic sclerosis (scleroderma).

An autoantigenic role for collagen type I (CI) has been suggested previously in diffuse cutaneous systemic sclerosis (dcSSc). Whether CI is indeed capable of affecting the immune system in dcSSc is not known. Patients with early (3 years or less) or late (>3 years) dcSSc and healthy controls donated blood.

Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT.

Background: Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited.

Objective: To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 2 years.

Methods: A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm).

Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis.

Objective: Endothelin is implicated as a participatory pathway in systemic sclerosis (SSc). We tested this hypothesis in a 12-month trial of bosentan, a nonselective endothelin receptor antagonist, as a therapy for SSc-related interstitial lung disease (ILD).

Method: Patients with SSc and significant ILD were recruited to this prospective, double-blind, randomized, placebo-controlled, parallel group study.

Validation of the 6 min walk test according to the OMERACT filter: a systematic literature review by the EPOSS-OMERACT group.

Objective: To assess the validity of the 6 min walk test (6MWT) in pulmonary arterial hypertension secondary to systemic sclerosis (PAH-SSc) according to the OMERACT filter.

Methods: A systematic literature search was conducted from 1966 through June 2009. The assessment of validation of the 6MWT was based on the OMERACT filter criteria with the domains 'truth', 'discrimination' and 'feasibility'.

Risk of elevated liver enzymes associated with TNF inhibitor utilisation in patients with rheumatoid arthritis.

Objective: Liver function test (LFT) elevations are reported with the use of tumour necrosis factor inhibitors (TNF-Is). The aim of this study was to compare LFT elevations in patients with rheumatoid arthritis receiving adalimumab (ADA), etanercept (ETN) or infliximab (INF) enrolled in the Consortium of Rheumatology Researchers of North America from October 2001 to March 2007.

Methods: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >1x upper limit of normal (ULN) were considered elevations and ALT/AST levels >2x ULN were considered abnormalities.

Systemic sclerosis and bilateral lung transplantation: a single centre experience.

Lung involvement is the leading cause of death in systemic sclerosis (SSc), but lung transplantation (LT) for systemic disease remains controversial. Our objective was to comprehensively evaluate post-LT outcomes for SSc compared to idiopathic pulmonary fibrosis (IPF). We retrospectively evaluated bilateral LT recipients (LTRs) with SSc or IPF at our centre between January 1, 2003 and December 31, 2007.

The frequency of DRB1*1454 in South German Caucasians.

Human leukocyte antigen (HLA)-DRB1*1454 differs from HLA-DRB1*1401 in only one position in exon 3. Before description of this polymorphism both alleles were routinely typed as HLA-DRB1*1401. This prompted our study on relative frequency of these alleles.

Description of the efficacy and safety of three new biologics in the treatment of rheumatoid arthritis.

English articles on abatacept, golimumab, and tocilizumab in rheumatoid arthritis published between 2002 and 2009 were reviewed systematically. All randomized clinical trials, open-label extensions, meta-analyses, and reviews were examined. There were thirteen articles on abatacept, four on golimumab, and seven on tocilizumab.

Tendon friction rubs in early diffuse systemic sclerosis: prevalence, characteristics and longitudinal changes in a randomized controlled trial.

Objectives: To characterize the baseline tendon friction rubs (TFRs) in early dcSSc and to evaluate the association of change in TFR over 6 and 12 months with changes in modified Rodnan skin score (MRSS) and HAQ-Disability Index (HAQ-DI) over 12 and 24 months, respectively.

Methods: We analysed data from the d-Pen study, a 2-year study in early dcSSc (< or =18 months from first non-Raynaud's symptom). TFR was scored as present/absent at seven anatomical sites at baseline and every 6 months thereafter.

High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study.

Objective: Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers.

Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.

Ponsin interacts with Nck adapter proteins: implications for a role in cytoskeletal remodelling during differentiation of skeletal muscle cells.

Skeletal muscle differentiation is a complex process: It is characterised by changes in gene expression and protein composition. Simultaneously, a dramatic remodelling of the cytoskeleton and associated cell-matrix contacts, the costameres, occurs. The expression and localisation of the protein ponsin at cell-matrix contacts marks the establishment of costameres.

Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials.

Objective: To evaluate the longterm safety of rituximab in clinical trials in patients with rheumatoid arthritis (RA).

Methods: Pooled analysis of safety data, including adverse events (AE) and infections, from patients treated with rituximab in combination with methotrexate in a global clinical trial program.

Results: A total of 2578 patients with RA received at least 1 course of rituximab.

Equivalent responses to disease-modifying antirheumatic drugs initiated at any time during the first 15 months after symptom onset in patients with seropositive rheumatoid arthritis.

Objective: To evaluate responses by time to initiation of nonbiologic disease-modifying antirheumatic drugs (DMARD) in a DMARD-naive cohort of patients with early seropositive rheumatoid arthritis (RA).

Methods: Subjects were categorized by the time from symptom onset to the first DMARD use (median 5.7 months, range 0.

Chaperone-assisted selective autophagy is essential for muscle maintenance.

How are biological structures maintained in a cellular environment that constantly threatens protein integrity? Here we elucidate proteostasis mechanisms affecting the Z disk, a protein assembly essential for actin anchoring in striated muscles, which is subjected to mechanical, thermal, and oxidative stress during contraction [1]. Based on the characterization of the Drosophila melanogaster cochaperone Starvin (Stv), we define a conserved chaperone machinery required for Z disk maintenance. Instead of keeping Z disk proteins in a folded conformation, this machinery facilitates the degradation of damaged components, such as filamin, through chaperone-assisted selective autophagy (CASA).

Echocardiography as an outcome measure in scleroderma-related pulmonary arterial hypertension: a systematic literature analysis by the EPOSS group.

Objective: To assess the validation status of echocardiography with continuous Doppler (echo-Doppler) as an outcome measure in pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc).

Methods: Structured literature review on full-text English articles was performed using the PubMed and Cochrane databases. Assessment of validation of echo-Doppler was based on the OMERACT filter criteria with the domains truth (face, content, construct, and criterion validity), discrimination, and feasibility.

Rapamycin versus methotrexate in early diffuse systemic sclerosis: results from a randomized, single-blind pilot study.

Objective: To assess the safety and efficacy of rapamycin in the treatment of diffuse systemic sclerosis (SSc; scleroderma).

Methods: Eighteen patients with diffuse SSc of View Article and Find Full Text PDF

Treatment of scleroderma-interstitial lung disease with cyclophosphamide is associated with less progressive fibrosis on serial thoracic high-resolution CT scan than placebo: findings from the scleroderma lung study.

Background: The Scleroderma Lung Study (SLS) demonstrated significant treatment-associated improvements in pulmonary function and symptoms when patients with scleroderma-related interstitial lung disease (SSc-ILD) were treated with a 1-year course of cyclophosphamide (CYC) in a randomized, double-blinded, placebo-controlled clinical trial. This study examined thoracic high-resolution CT (HRCT) scans obtained during the SLS for treatment-associated changes over time.

Methods: Ninety-eight of the 158 subjects (CYC group, 49 subjects; placebo group, 49 subjects) participating in the SLS underwent thoracic HRCT scans both at baseline and after 12 months of treatment, which were available for analysis.

A longitudinal analysis of humor coping and quality of life in systemic sclerosis.

A connection between humor and health outcomes is widely assumed but has been understudied, particularly in clinical populations. The use of humor as a coping mechanism has been suggested as a potential predictor of quality of life (QOL) outcomes in chronic disease. This study assessed the relationship between humor and physical/mental health variables in a longitudinal study of individuals with systemic sclerosis (SSc), a progressive rheumatic disease that can be fatal in severe cases.

Complete loss of murine Xin results in a mild cardiac phenotype with altered distribution of intercalated discs.

Aims: Xin is a striated muscle-specific F-actin binding protein that has been implicated in cardiomyopathies. In cardiomyocytes, Xin is localized at intercalated discs (IDs). Mice lacking only two of the three Xin isoforms (XinAB(-/-) mice) develop severe cardiac hypertrophy.

Measures of response in clinical trials of systemic sclerosis: the Combined Response Index for Systemic Sclerosis (CRISS) and Outcome Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS).

There have been steady efforts to develop a combined response index for systemic sclerosis (CRISS). A parallel and equally successful effort has been made by an Expert Panel on Outcome Measures in PAH related to Systemic Sclerosis (EPOSS) to measure effect in treatment of pulmonary arterial hypertension of systemic sclerosis (PAH-SSc). CRISS conducted a Delphi process combined with expert review to identify 11 candidate domains for inclusion in a core set of outcomes for SSc clinical trials: soluble biomarkers, cardiac, digital ulcers, gastrointestinal, global health, health related quality of life (HRQOL) and function, musculoskeletal, pulmonary, Raynaud's, renal, and skin.

Multipurpose modular lentiviral vectors for RNA interference and transgene expression.

We have created a multipurpose modular lentiviral vector system for expressing both transgenes and miRNA 30-based short hairpins (shRNAmirs) for RNAi. The core of the resulting vector system, pLVmir, allows a simple two step cloning procedure for expressing shRNAmirs under the control of a Pol II promoter in both a constitutive and conditional manner. The adapted cloning method includes a PCR-free method for transferring shRNAmir based RNAi clones from a publicly available library (Open Biosystems).

Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis.

Objective: To characterize the antiinflammatory function of high-density lipoprotein (HDL) in patients with rheumatoid arthritis (RA) and to identify specific differences in HDL-associated proteins and enzymes that distinguish proinflammatory HDL from normal, antiinflammatory HDL.

Methods: We studied 132 RA patients. The antiinflammatory function of HDL was assessed by a cell-free assay, and proinflammatory HDL was defined by an HDL inflammatory index > or =1.