bluuebunny/crossref_metadata_2025_split huggingface dataset:
A broad analysis of IL1 polymorphism and rheumatoid arthritis
Authors: Johnsen Alyssa K. , Plenge Robert M. , Butty Vincent , Campbell Christopher , Dieguez‐Gonzalez Rebeca , Gomez‐Reino Juan J. , Shadick Nancy , Weinblatt Michael , Gonzalez Antonio , Gregersen Peter K. , Benoist Christophe , Mathis Diane 
Published: June 2008

AbstractObjectiveIt has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well‐powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA.MethodsKey coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single‐nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case–control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects.ResultsNo fully significant associations were observed. Analysis of the discovery case–control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case–control samples. No association with rheumatoid factor, anti–cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here.ConclusionIn spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA.
CXCR2‐specific chemokines mediate leukotriene B4–dependent recruitment of neutrophils to inflamed joints in mice with antigen‐induced arthritis
Authors: Grespan Renata , Fukada Sandra Y. , Lemos Henrique P. , Vieira Silvio M. , Napimoga Marcelo H. , Teixeira Mauro M. , Fraser Alasdair R. , Liew Foo Y. , McInnes Iain B. , Cunha Fernando Q. 
Published: June 2008

AbstractObjectiveTo investigate the mechanism underlying neutrophil migration into the articular cavity in experimental arthritis and, by extension, human inflammatory synovitis.MethodsAntigen‐induced arthritis (AIA) was generated in mice with methylated bovine serum albumin (mBSA). Migration assays and histologic analysis were used to evaluate neutrophil recruitment to knee joints. Levels of inflammatory mediators were measured by enzyme‐linked immunosorbent assay. Antibodies and pharmacologic inhibitors were used in vivo to determine the role of specific disease mediators. Samples of synovial tissue and synovial fluid from rheumatoid arthritis (RA) or osteoarthritis patients were evaluated for CXCL1 and CXCL5 expression.ResultsHigh levels of CXCL1, CXCL5, and leukotriene B4 (LTB4) were expressed in the joints of arthritic mice. Confirming their respective functional roles, repertaxin (a CXCR1/CXCR2 receptor antagonist), anti‐CXCL1 antibody, anti‐CXCL5 antibody, and MK886 (a leukotriene synthesis inhibitor) reduced mBSA‐induced neutrophil migration to knee joints. Repertaxin reduced LTB4 production in joint tissue, and neutrophil recruitment induced by CXCL1 or CXCL5 was inhibited by MK886, suggesting a sequential mechanism. Levels of both CXCL1 and CXCL5 were elevated in synovial fluid and were released in vitro by RA synovial tissues. Moreover, RA synovial fluid neutrophils stimulated with CXCL1 or CXCL5 released significant amounts of LTB4.ConclusionOur data implicate CXCL1, CXCL5, and LTB4, acting sequentially, in neutrophil migration in AIA. Elevated levels of CXCL1 and CXCL5 in the synovial compartment of RA patients provide robust comparative data indicating that this mechanism plays a role in inflammatory joint disease. Together, these results suggest that inhibition of CXCL1, CXCL5, or LTB4 may represent a potential therapeutic strategy in RA.
Failure of oral atorvastatin to modulate a murine model of systemic lupus erythematosus
Authors: Graham Kareem L. , Lee Lowen Y. , Higgins John P. , Steinman Lawrence , Utz Paul J. , Ho Peggy P. 
Published: June 2008

AbstractObjectiveInhibitors of the 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase enzyme (statins) are cholesterol‐lowering drugs that have shown promise as therapeutic agents in various animal models of autoimmune disease. The results of initial clinical trials with statins in multiple sclerosis and rheumatoid arthritis have also been encouraging. In this study, we attempted to treat a widely studied murine model of spontaneous systemic lupus erythematosus (SLE) with atorvastatin.Methods(NZB × NZW)F1 (NZB/NZW) mice received daily oral doses of atorvastatin for 20 weeks. The mice were monitored weekly for survival and proteinuria. Anti–double‐stranded DNA (anti‐dsDNA) antibody levels in sera were determined by enzyme‐linked immunosorbent assay (ELISA). T lymphocyte cytokine production in vitro, as well as cytokine levels in vivo, were measured by ELISA. T cell proliferation was assessed by thymidine incorporation assay. Serum cholesterol levels were determined using a standard fluorometric assay. Kidney tissue was harvested and evaluated for pathologic changes.ResultsIn NZB/NZW mice, oral atorvastatin had significant effects on T cell proliferation and cytokine production in vitro. Atorvastatin also induced significant increases in serum levels of interleukin‐4. However, atorvastatin treatment in NZB/NZW mice had no significant impact on proteinuria, survival, serum anti‐dsDNA antibody and cholesterol levels, or extent of renal disease.ConclusionMonotherapy with oral atorvastatin has no protective effects in a murine model of spontaneous SLE. The efficacy of atorvastatin in human SLE remains to be determined.
Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: Results of a twelve‐week randomized, double‐blind, placebo‐controlled trial followed by an open‐label extension up to week fifty‐two
Authors: Haibel Hildrun , Rudwaleit Martin , Listing Joachim , Heldmann Frank , Wong Robert L. , Kupper Hartmut , Braun Jürgen , Sieper Joachim 
Published: June 2008

AbstractObjectiveTo evaluate the efficacy and safety of the tumor necrosis factor (TNF) antagonist adalimumab in patients with axial spondylarthritis (SpA) without radiographically defined sacroiliitis refractory to conventional treatment.MethodsPatients with active axial SpA (n = 46) were randomized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks, followed by an open‐label extension that continued up to week 52. The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria, including 2 of the following 3 criteria: inflammatory back pain, HLA–B27 positivity, or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging, in the absence of radiographic evidence of sacroiliitis. The primary end point was a 40% response according to the improvement criteria of the Assessment of SpondyloArthritis international Society (ASAS40).ResultsAll 46 patients (22 receiving adalimumab and 24 receiving placebo) completed the 12‐week trial; 38 patients completed the extension period to week 52. At week 12, an ASAS40 response was achieved by 54.5% of the adalimumab‐treated patients, as compared with 12.5% of the placebo‐treated patients (P = 0.004). After switching to adalimumab, a similar degree of efficacy was also achieved by the patients who were initially treated with placebo. Efficacy was maintained in all patients until week 52. Young age at study entry and an elevated C‐reactive protein concentration were the best predictors of achieving an ASAS40 response. Serious adverse events occurred in 5 patients, none of which was related to the study drug.ConclusionAdalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis.
Inhibition of β‐catenin signaling in articular chondrocytes results in articular cartilage destruction
Authors: Zhu Mei , Chen Mo , Zuscik Michael , Wu Qiuqian , Wang Yong‐Jun , Rosier Randy N. , O'Keefe Regis J. , Chen Di 
Published: June 2008

AbstractObjectiveOsteoarthritis is a degenerative joint disease whose molecular mechanism is currently unknown. Wnt/β‐catenin signaling has been demonstrated to play a critical role in the development and function of articular chondrocytes. To determine the role of β‐catenin signaling in articular chondrocyte function, we generated Col2a1‐ICAT–transgenic mice to inhibit β‐catenin signaling in chondrocytes.MethodsThe expression of the ICAT transgene was determined by immunostaining and Western blot analysis. Histologic analyses were performed to determine changes in articular cartilage structure and morphology. Cell apoptosis was determined by TUNEL staining and the immunostaining of cleaved caspase 3 and poly(ADP‐ribose) polymerase (PARP) proteins. Expression of Bcl‐2, Bcl‐xL, and Bax proteins and caspase 9 and caspase 3/7 activities were examined in primary sternal chondrocytes isolated from 3‐day‐old neonatal Col2a1‐ICAT–transgenic mice and their wild‐type littermates and in primary chicken and porcine articular chondrocytes.ResultsExpression of the ICAT transgene was detected in articular chondrocytes of the transgenic mice. Associated with this, age‐dependent articular cartilage destruction was observed in Col2a1‐ICAT–transgenic mice. A significant increase in cell apoptosis in articular chondrocytes was identified by TUNEL staining and the immunostaining of cleaved caspase 3 and PARP proteins in these transgenic mice. Consistent with this, Bcl‐2 and Bcl‐xL expression were decreased and caspase 9 and caspase 3/7 activity were increased, suggesting that increased cell apoptosis may contribute significantly to the articular cartilage destruction observed in Col2a1‐ICAT–transgenic mice.ConclusionInhibition of β‐catenin signaling in articular chondrocytes causes increased cell apoptosis and articular cartilage destruction in Col2a1‐ICAT– transgenic mice.
Patient preference disability questionnaire in systemic sclerosis: A cross‐sectional survey
Authors: Mouthon Luc , Rannou François , Bérezné Alice , Pagnoux Christian , Guilpain Philippe , Goldwasser François , Revel Michel , Guillevin Loïc , Fermanian Jacques , Poiraudeau Serge 
Published: June 2008

AbstractObjectiveTo assess patient priorities concerning disability in systemic sclerosis (SSc).MethodsA total of 150 SSc patients (22 men) fulfilling the American College of Rheumatology and/or LeRoy and Medsger criteria for SSc were evaluated by the McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), Karnofsky performance status (KPS), Cochin Hand Function Scale, Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale, Mouth Handicap in SSc (MHISS) scale, and global perception regarding their health status. Correlations between scores were analyzed using Spearman's coefficient. Logistic regression analysis was used to determine factors associated with patients' global perception of their health.ResultsOf the patients investigated, 81 (54%) had limited cutaneous SSc, 65 (43.3%) diffuse SSc, and 4 (2.7%) limited SSc. The 3 disability domains most often cited were walking (82 patients [54.6%]), housekeeping (67 patients [44.6%]), and sport activities (59 patients [39.3%]). The MACTAR score correlated moderately with KPS (r = 0.58) but only weakly with the HAQ score (r = 0.38). In multivariate analysis, 2 factors were associated with patients' negative global perception of their health status: KPS (odds ratio [OR] 1.07, 95% confidence interval [95% CI] 1.00–1.15) and MHISS score (OR 0.93, 95% CI 0.88–0.99).ConclusionFor assessing SSc patient priorities concerning disability, the MACTAR has acceptable construct validity. Its weak correlation with the HAQ suggests that it adds useful information on disability.
Does knee malalignment mediate the effects of quadriceps strengthening on knee adduction moment, pain, and function in medial knee osteoarthritis? A randomized controlled trial
Authors: Lim Boon‐Whatt , Hinman Rana S. , Wrigley Tim V. , Sharma Leena , Bennell Kim L. 
Published: June 2008

AbstractObjectiveTo examine whether the effects of 12 weeks of quadriceps strengthening on the knee adduction moment, pain, and function in people with medial knee osteoarthritis (OA) differ in those with and without varus malalignment.MethodsA single‐blind, randomized controlled trial of 107 community volunteers with medial knee OA was conducted. Participants were stratified according to knee malalignment (more varus or more neutral) and then randomized into either a 12‐week supervised home‐based quadriceps strengthening group or a control group with no intervention. The primary outcome was the knee adduction moment, measured using 3‐dimensional gait analysis. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index scores (measuring pain and physical function), step test score, stair climb test score, and maximum quadriceps isometric strength. Analyses of covariance were carried out based on intent‐to‐treat principles.ResultsQuadriceps strengthening did not significantly alter the knee adduction moment in either the more malaligned or the more neutral group (unadjusted knee adduction moment 0.12 and 0.05% Nm/BW×HT, respectively). Function did not improve significantly following quadriceps strengthening in either alignment group, but there was a significant improvement in knee pain in the more neutrally aligned group (P < 0.001).ConclusionQuadriceps strengthening did not have any significant effect on the knee adduction moment in participants with either more varus or more neutral alignment. The benefits of quadriceps strengthening on pain were more evident in those with more neutral alignment. Knee alignment thus represents a local mechanical factor that can mediate symptomatic outcome from exercise interventions in knee OA.
A randomized, double‐blind, multicenter, controlled clinical trial of chicken type II collagen in patients with rheumatoid arthritis
Authors: Zhang Ling‐Ling , Wei Wei , Xiao Feng , Xu Jian‐Hua , Bao Chun‐De , Ni Li‐Qing , Li Xing‐Fu 
Published: June 2008

AbstractObjectiveTo assess the efficacy and safety of chicken type II collagen (CCII) in rheumatoid arthritis (RA) compared with methotrexate (MTX).MethodsWe conducted a prospective, 24‐week, followup, multicenter, double‐blind, controlled study of CCII (0.1 mg/day) versus MTX (10 mg/week) in patients with active RA. Clinical assessments were performed at screening and at 12, 18, and 24 weeks of treatment.ResultsA total of 236 RA patients were included; 211 patients (89.4%) completed the 24‐week followup. In both groups there was a decrease in pain, morning stiffness, tender joint count, swollen joint count, Health Assessment Questionnaire score, and investigator and patient assessment of function; all differences were statistically significant. In the MTX group, erythrocyte sedimentation rate and C‐reactive protein level decreased. Rheumatoid factor did not change in either group. At 24 weeks, 68.57% of patients in the CCII group and 83.02% in the MTX group met the American College of Rheumatology 20% improvement criteria (ACR20), and 40.95% and 57.54%, respectively, met the ACR50 criteria. The ACR20 and ACR50 response rates in the CCII group were lower than those in the MTX group, and this difference was statistically significant (P < 0.05). Gastrointestinal symptoms were common in both groups. There were fewer and milder side effects in the CCII group than the MTX group. The difference in incidence of adverse events between the 2 groups was statistically significant (P < 0.05).ConclusionCCII is effective in the treatment of RA. CCII is well tolerated, and the incidence of adverse events of CCII is lower than that of MTX.
Sleep disturbances in fibromyalgia syndrome: Relationship to pain and depression
Authors: Bigatti Silvia M. , Hernandez Ann Marie , Cronan Terry A. , Rand Kevin L. 
Published: June 2008

AbstractObjectiveThis study is an examination of sleep, pain, depression, and physical functioning at baseline and 1‐year followup among patients with fibromyalgia syndrome (FMS). Although it is clear that these symptoms are prevalent among FMS patients and that they are related, the direction of the relationship is unclear. We sought to identify and report sleep problems in this population and to examine their relationship to pain, depression, and physical functioning.MethodsPatients diagnosed with fibromyalgia were recruited from a Southern California health maintenance organization and evaluated according to American College of Rheumatology criteria in the research laboratory. Six hundred patients completed the baseline assessment and 492 completed the 1‐year assessment. Measures included the Center for Epidemiologic Studies Depression Scale, the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index, and the Fibromyalgia Impact Questionnaire.ResultsThe majority of the sample (96% at baseline and 94.7% at 1 year) scored within the range of problem sleepers. Path analyses examined the impact of baseline values on 1‐year values for each of the 4 variables. No variable of interest predicted sleep, sleep predicted pain (β = 0.13), pain predicted physical functioning (β = −0.13), and physical functioning predicted depression (β = −0.10).ConclusionThese findings highlight the high prevalence of sleep problems in this population and suggest that they play a critical role in exacerbating FMS symptoms. Furthermore, they support limited existing findings that sleep predicts subsequent pain in this population, but also extend the literature, suggesting that sleep may be related to depression through pain and physical functioning.
Ability of epistatic interactions of cytokine single‐nucleotide polymorphisms to predict susceptibility to disease subsets in systemic sclerosis patients
Authors: Beretta Lorenzo , Cappiello Francesca , Moore Jason H. , Barili Morena , Greene Casey S. , Scorza Raffaella 
Published: June 2008

AbstractObjectiveGene–gene interaction, or epistasis, is considered a ubiquitous component of complex human diseases such as systemic sclerosis (SSc). Epistasis is difficult to model by traditional parametric approaches; therefore, nonparametric computational algorithms, such as multifactor dimensionality reduction (MDR), have been developed.MethodsA total of 242 consecutive unrelated Italian SSc patients and an equal number of well‐matched healthy controls were genotyped for 22 cytokine single‐nucleotide polymorphisms (SNPs; 13 cytokine genes). The distribution of the SNPs between controls and SSc patients, controls and limited cutaneous SSc (lcSSc) patients, and controls and diffuse cutaneous SSc (dcSSc) patients was tested by the MDR constructive induction algorithm and by focused interaction testing framework (FITF), a logistic regression–based approach.ResultsNone of the studied SNPs had main independent effects on SSc or disease subset susceptibility, therefore no epistatic interaction was detectable by FITF. The MDR analysis showed a significant epistatic interaction among the interleukin‐2 (IL‐2) G‐330T, IL‐6 C‐174G, and interferon‐γ AUTR5644T SNPs and the IL‐1 receptor Cpst1970T, IL‐6 Ant565G, and IL‐10 C‐819T SNPs in lcSSc and dcSSc susceptibility, respectively. The relevance of the single multilocus attributes constructed by the MDR inductive algorithm was then confirmed by the parametric approach (P < 0.001 for both controls versus lcSSc patients and controls versus dcSSc patients).ConclusionWe provide evidence for gene–gene interaction among cytokine SNPs in the context of SSc. The interaction among cytokine SNPs with a profibrotic or a regulatory function on profibrotic interleukins is relevant to the susceptibility to SSc subsets and it appears to be more important than the contribution of any single cytokine SNP.
Tartardiamide‐Functionalized Chiral Organosilicas with Highly Ordered Mesoporous Structure
Authors: Zhang Lei , Liu Jian , Yang Jie , Yang Qihua , Li Can 
Published: June 2008

AbstractA novel chiral mesoporous organosilica with L‐tartardiamide moieties integrated in the backbone has been synthesized for the first time by a mild synthetic approach with block copolymer P123 as a template. The materials have highly ordered 2D hexagonal mesostructure and uniform pore size in the range of 7.6 to 5.5 nm. NMR, IR, and TG analyses confirm that the tartardiamide group was successfully incorporated into the framework. The intrinsic chirality of L‐tartardiamide endows the materials with unique optical activities and chiral‐recognition properties. By dissolving the materials into NaOH, the solutions show rotation of polarized light by +8.42° to +15.53°, depending on the amount of the chiral moieties in the materials. Owing to the chirality of L‐tartardiamide, the materials exhibited chiral‐induction ability in the epoxidation of allyl alcohol, thus further demonstrating the chirality of the materials.
Catalyzed Oxidative Corrosion of Porous Silicon Used as an Optical Transducer for Ligand–Receptor Interactions
Authors: Voelcker Nicolas H. , Alfonso Ignacio , Ghadiri M. Reza 
Published: June 2008

AbstractBiosensors fabricated on the nanoscale offer exciting new avenues in the quest for better understanding and characterization of biological systems. Porous silicon is an ideal nanostructured material for the construction of optical transducer matrices because it is easily functionalized with biomolecular probes and displays strong optical interferences. Here, we show that certain transition metal complexes, including nickel(II)cyclam, are able to induce corrosion in porous silicon films rapidly, generating a strong optical interferometric signal that originates from the porous layer. We subsequently exploit this effect to design a transducer for ligand–receptor recognition. With a nickel(II)cyclam derivative as a catalytic label, DNA‐ and avidin‐binding events are detected by time‐lapse interferometric reflectance spectroscopy in a fast, simple, and inexpensive fashion.