bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: A prospective cohort study
Authors: van Gaalen F. A. , Linn‐Rasker S. P. , van Venrooij W. J. , de Jong B. A. , Breedveld F. C. , Verweij C. L. , Toes R. E. M. , Huizinga T. W. J. 
Published: March 2004

AbstractObjectiveRheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an inception cohort of patients with recent‐onset arthritis, we undertook this study to assess the predictive value of RA‐specific autoantibodies to cyclic citrullinated peptides (CCPs) in patients with undifferentiated arthritis (UA).MethodsAnti‐CCP2 antibody tests were performed at baseline in 936 consecutive, newly referred patients with recent‐onset arthritis. Patients who could not be properly classified 2 weeks after inclusion were categorized as having UA. Patients with UA were followed up for 3 years and evaluated for progression of their disease to RA as defined by the American College of Rheumatology (ACR) 1987 revised criteria.ResultsThree hundred eighteen of 936 patients with recent‐onset arthritis were classified as having UA and were available for analysis. After 3 years of followup, 127 of 318 UA patients (40%) had been classified as having RA. RA had developed in 63 of 249 patients (25%) with a negative anti‐CCP test and in 64 of 69 patients (93%) with a positive anti‐CCP test (odds ratio 37.8 [95% confidence interval 13.8–111.9]). Multivariate analysis of the presence of anti‐CCP antibodies and parameters from the ACR criteria identified polyarthritis, symmetric arthritis, erosions on radiographs, and anti‐CCP antibodies as significant predictors of RA.ConclusionTesting for anti‐CCP antibodies in UA allows accurate prediction of a substantial number of patients who will fulfill the ACR criteria for RA.
Normative values for the Health Assessment Questionnaire Disability Index: Benchmarking disability in the general population
Authors: Krishnan Eswar , Sokka Tuulikki , Häkkinen Arja , Hubert Helen , Hannonen Pekka 
Published: March 2004

AbstractObjectiveThe Health Assessment Questionnaire (HAQ) disability index (DI) has been commonly used in rheumatology to quantify functional disability in patient groups, but current general population values of this index are not available. This study was undertaken to establish normative values for the HAQ DI in a general population and to analyze its correlates.MethodsThe HAQ DI (range of scores 0–3) was measured in a random sample of 1,530 adults in the Central Finland District. Prevalence rates of disability by strata of age, sex, education level, body mass index (BMI), and health behaviors (including smoking and exercise habits) were calculated. Pearson's product‐moment correlation coefficient and ordinary least squares regression were used to analyze the data.ResultsThe estimated population mean HAQ DI was 0.25 (95% confidence interval 0.22–0.28), and 32% of respondents had at least some disability. Both for men and for women, functional disability increased exponentially with age. The HAQ DI was correlated with pain (r = 0.58) and global self assessment (r = 0.61). The prevalence of disability decreased with increasing number of years of education, lower BMI, and increasing frequency of physical exercise.ConclusionAlmost one‐third of the general population has some functional disability. Functional disability is associated in part with lifestyle choices and increases with age in a nonlinear manner. The normative values of the HAQ DI that we have presented could be used as a reference benchmark for clinical and epidemiologic studies using this measure of disability.
A novel synthetic, nonpsychoactive cannabinoid acid (HU‐320) with antiinflammatory properties in murine collagen‐induced arthritis
Authors: Sumariwalla Percy F. , Gallily Ruth , Tchilibon Susanna , Fride Ester , Mechoulam Raphael , Feldmann Marc 
Published: March 2004

AbstractObjectiveTo explore the antiarthritic potential of a novel synthetic cannabinoid acid, Hebrew University–320 (HU‐320), in the DBA/1 mouse model of arthritis, and to investigate in vitro antiinflammatory and immunosuppressive effects of HU‐320 on macrophages and lymphocytes.MethodsDBA/1 mice were immunized with bovine type II collagen (CII) to induce arthritis and then injected intraperitoneally daily with HU‐320. The effects of treatment on arthritic changes in hind feet were assessed clinically and histologically, and draining lymph node responses to CII were assayed. Murine splenic and human blood lymphocytes were cultured to study the effect of HU‐320 on polyclonal mitogenic stimulation. Macrophage cultures were set up to evaluate in vitro effects of HU‐320 on production of tumor necrosis factor α (TNFα) and reactive oxygen intermediates (ROIs). The effect of HU‐320 administration on lipopolysaccharide‐induced serum TNF levels was assayed using C57BL/6 mice. Bioactive TNF production was measured using BALB/c clone 7 target cells. Evaluation of HU‐320 psychoactivity was performed using established laboratory tests on Sabra mice.ResultsSystemic daily administration of 1 and 2 mg/kg HU‐320 ameliorated established CII‐induced arthritis. Hind foot joints of treated mice were protected from pathologic damage. CII‐specific and polyclonal responses of murine and human lymphocytes were down‐modulated. HU‐320 inhibited production of TNF from mouse macrophages and of ROIs from RAW 264.7 cells and suppressed the rise in serum TNF level following endotoxin challenge. HU‐320 administration yielded no adverse psychotropic effects in mice.ConclusionOur studies show that the novel synthetic cannabinoid acid HU‐320 has strong antiinflammatory and immunosuppressive properties while demonstrating no psychoactive effects. The profound suppressive effects on cellular immune responses and on the production of proinflammatory mediators all indicate its usefulness as a novel nonpsychoactive, synthetic antiinflammatory product.
Mutant fibrillin 1 from tight skin mice increases extracellular matrix incorporation of microfibril‐associated glycoprotein 2 and type I collagen
Authors: Lemaire Raphael , Farina Guiseppina , Kissin Eugene , Shipley J. Michael , Bona Constantine , Korn Joseph H. , Lafyatis Robert 
Published: March 2004

AbstractObjectiveSkin fibrosis in the TSK mouse, a model of skin fibrosis seen in systemic sclerosis (SSc), is caused by a large in‐frame duplication in the Fbn1 gene, tsk‐Fbn1. We investigated whether tsk‐Fbn1 might cause dermal fibrosis by affecting Fbn1 and associated extracellular matrices. We also studied whether deposition of microfibril‐associated glycoprotein 2 (MAGP‐2), a protein that is associated with fibrillin 1, was altered in the skin of patients with SSc.MethodsAn in vitro model of the TSK mouse was created by conditionally expressing tsk‐Fbn1 in mouse embryonic fibroblasts (MEFs). Cell cultures were examined by immunofluorescence and Western and Northern blotting to determine the effect of tsk‐Fbn1 on the structure, expression, and deposition of fibrillin 1 (Fbn‐1), type I collagen, and MAGP‐2. The skin of TSK mice and SSc patients was analyzed by immunohistochemistry for MAGP‐2 expression.ResultsExpression of tsk‐Fbn1 in cultured MEF cells altered the morphology of Fbn‐1 fibers and increased the deposition of type I collagen into the extracellular matrix (ECM) without concomitantly changing messenger RNA expression, secretion, or processing of type I procollagen. Moreover, MEF cells expressing tsk‐Fbn1 showed increased MAGP‐2 matrix. MAGP‐2 was increased in the dermis of TSK mice. Fibrotic SSc skin also showed higher levels of MAGP‐2 in the dermis than nonfibrotic SSc skin and normal skin.ConclusionTsk‐Fbn1 altered ECM organization and caused fibrosis by affecting the deposition of MAGP‐2 or other Fbn‐1–associated proteins. Alterations in microfibril structure or deposition might contribute to fibrosis in SSc.
MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M–stimulated CCL2 expression in human osteoblasts through a common transcription factor
Authors: Lin Sze‐Kwan , Kok Sang‐Heng , Yeh Flora Tzu‐Chin , Kuo Mark Yen‐Ping , Lin Ching‐Chuan , Wang Chih‐Chiang , Goldring Steven R. , Hong Chi‐Yuan 
Published: March 2004

AbstractObjectiveTo analyze the effects of oncostatin M (OSM), a gp130‐type cytokine, on CCL2 expression in MG‐63 cells, a human osteosarcoma cell line with a characteristic osteoblastic phenotype, and to investigate the signaling pathway involved.MethodsThe expression of messenger RNA (mRNA) for CCL2 and c‐Fos was analyzed by Northern blotting. Amounts of CCL2 released into the supernatant were measured by enzyme‐linked immunosorbent assay. Western blotting was used to examine the activation of MAPK signaling pathways. Interactions between activator protein 1 (AP‐1) and DNA were evaluated by electrophoretic mobility shift assay.ResultsOSM stimulated CCL2 expression at both the mRNA and the protein levels. Cyclooxygenase 2 (COX‐2) was also induced by OSM. However, the up‐regulation of CCL2 mRNA was COX‐2–independent but required tyrosine kinase and protein kinase C (PKC). OSM stimulated the phosphorylation of MEK‐1/2 and ERK‐1/2 but not p38 and JNK. A transient elevation of c‐Fos mRNA was induced by OSM, but PD 98059 (MEK inhibitor), fludarabine (signal transducer and activator of transcription 1 [STAT‐1] inhibitor), and piceatannol (STAT‐3 and STAT‐5 inhibitor) abolished this effect. Electrophoretic mobility shift assay revealed that OSM stimulated AP‐1–DNA binding, which was also abolished by PD 98059, fludarabine, and piceatannol. Supershift study further confirmed the role of c‐Fos in the above interaction. PD 98059, fludarabine, piceatannol, and curcumin (AP‐1 inhibitor) inhibited the OSM‐induced expression of CCL2.ConclusionOSM induces CCL‐2 expression in osteoblasts. Activation of the MEK/ERK and STAT pathways, which leads to c‐Fos expression and AP‐1–DNA binding, is involved in the process. The signaling requires tyrosine kinase and PKC but not COX‐2.
Magnetic resonance imaging evaluation of the effects of juvenile rheumatoid arthritis on distal femoral weight‐bearing cartilage
Authors: Kight Amanda C. , Dardzinski Bernard J. , Laor Tal , Graham T. Brent 
Published: March 2004

AbstractObjectiveTo examine magnetic resonance imaging–derived T2 relaxation times in the weight‐bearing cartilage of the distal femur in healthy children and in children with juvenile rheumatoid arthritis (JRA).MethodsT2 relaxation time maps were created for 39 girls (ages 4.9–10.9 years), 21 of whom were considered healthy and 18 of whom had JRA. The spatial distribution of T2 relaxation times for the distal femoral weight‐bearing cartilage (including epiphyseal and articular cartilage) was mapped for each group as a whole. Average data sets for each group were then compared using paired t‐tests to detect differences between the 2 populations.ResultsThe spatial distribution of T2 relaxation time values was nearly identical in the 2 groups, with a concave curve that was highest near the subchondral bone and articular surfaces. The average T2 relaxation times were significantly higher in the girls with JRA than in the group of healthy girls (P < 0.05).ConclusionThe finding of an increased average T2 relaxation time in the children with JRA suggests that T2 relaxation time maps may reflect cartilage microstructure differences that occur in JRA. T2 relaxation time mapping may allow for early detection of cartilage changes and provide an objective, quantitative method of monitoring disease progression, with the long‐term potential to guide therapy.
Clustering of disease features within 512 multicase rheumatoid arthritis families
Authors: Jawaheer Damini , Lum Raymond F. , Amos Christopher I. , Gregersen Peter K. , Criswell Lindsey A. 
Published: March 2004

AbstractObjectiveTo determine whether specific rheumatoid arthritis (RA) disease features demonstrate the presence of significant familial clustering.MethodsWe studied 1,097 individuals with RA from 512 multicase families enrolled in the North American Rheumatoid Arthritis Consortium. All patients were interviewed and examined to collect standardized information about demographic and clinical characteristics. Affected individuals also underwent radiography of the hands and wrists and were genotyped for the HLA–DRB1 shared epitope. Familial clustering of disease features was assessed using contingency table analysis and Pearson correlation coefficients. Multivariate logistic and linear regression analyses were used to account for other characteristics that might influence familial clustering, such as disease duration, sex, and age at diagnosis.ResultsSeveral disease characteristics exhibited significant familial clustering, including seropositivity (multivariate odds ratio [OR] 4.3, P < 0.0001), nodules (OR 2.3, P < 0.0001), and age at RA diagnosis (multivariate regression coefficient [β] 0.44, P < 0.0001). Other characteristics demonstrated statistically significant but modest degrees of familial clustering (Joint Alignment and Motion score, Health Assessment Questionnaire score, and year of RA diagnosis) or modest but nonsignificant familial clustering (other extraarticular manifestations, other autoimmune diseases).ConclusionThe clustering of certain disease characteristics implicates specific genetic or nongenetic causes. These results highlight the importance of considering disease phenotype in future genetic and epidemiologic studies of RA.
Anti‐DFS70 antibodies in 597 healthy hospital workers
Authors: Watanabe Akihiro , Kodera Masanari , Sugiura Kazumitsu , Usuda Toshikazu , Tan Eng M. , Takasaki Yoshinari , Tomita Yasushi , Muro Yoshinao 
Published: March 2004

AbstractObjectiveAutoantibodies against DFS70 (dense fine speckles 70) antigen (also known as lens epithelium–derived growth factor) have been recently identified among the antinuclear antibodies (ANAs) in patients with atopic disorders. We undertook this study to examine the frequency of anti‐DFS70 antibodies in a large number of healthy people.MethodsSera of 597 healthy individuals working in a hospital (142 men, 455 women) were analyzed for ANAs and for anti‐DFS70 antibodies by indirect immunofluorescence (IIF) with HEp‐2 cells as a substrate and by immunoblotting using DFS70 recombinant protein and whole HeLa cell extract.ResultsANAs were present in 20% of all individuals by IIF. Nine percent of subjects were ANA positive at a serum dilution of 1:40, 4.0% at 1:80, 5.5% at 1:160, 1.0% at 1:320, and 0.3% at 1:640. There were 64 anti‐DFS70 antibody–positive individuals. Surprisingly, this was 11% of the whole population and 54% of the ANA‐positive population. The percentage of female anti‐DFS70 antibody–positive subjects (86%; 55 of 64 subjects) was higher than the percentage of female anti‐DFS70 antibody–negative subjects (75%; 398 of 533 subjects) (P < 0.05). The prevalence of anti‐DFS70 antibody–positive sera decreased with increasing age (P = 0.0017).ConclusionConsidering that anti‐DFS70 antibody positivity is rare in patients with systemic autoimmune diseases, introducing the anti‐DFS70 antibody examination as a screening test for ANA‐positive persons could be used to rule out systemic autoimmune diseases, resulting in considerable cost‐saving potential. In addition, this test defines a subpopulation of healthy people in whom long‐term followup might reveal health‐related implications of this finding, since anti‐DFS70 antibodies have been shown to be associated with some illnesses.
Mechanisms and kinetics of glycosaminoglycan release following in vitro cartilage injury
Authors: DiMicco Michael A. , Patwari Parth , Siparsky Patrick N. , Kumar Sanjay , Pratta Michael A. , Lark Michael W. , Kim Young‐Jo , Grodzinsky Alan J. 
Published: March 2004

AbstractObjectiveAcute joint injury leads to increased risk for osteoarthritis (OA). Although the mechanisms underlying this progression are unclear, early structural, metabolic, and compositional indicators of OA have been reproduced using in vitro models of cartilage injury. This study was undertaken to determine whether glycosaminoglycan (GAG) loss following in vitro cartilage injury is mediated by cellular biosynthesis, activation of enzymatic activity, or mechanical disruption of the cartilage extracellular matrix.MethodsImmature bovine cartilage was cultured for up to 10 days. After 3 days, groups of samples were subjected to injurious mechanical compression (single uniaxial unconfined compression to 50% thickness, strain rate 100% per second). GAG release to the medium was measured, and levels were compared with those in location‐matched, uninjured controls. The effects of medium supplementation with inhibitors of biosynthesis (cycloheximide), of matrix metalloproteinase (MMP) activity (CGS 27023A or GM 6001), and of aggrecanase activity (SB 703704) on GAG release after injury were assessed.ResultsGAG release from injured cartilage was highest during the first 4 hours after injury, but remained higher than that in controls during the first 24 hours postinjury, and was not affected by inhibitors of biosynthesis or degradative enzymes. GAG release during the period 24–72 hours postinjury was similar to that in uninjured controls, but the MMP inhibitor CGS 27023A reduced cumulative GAG loss from injured samples between 1 day and 7 days postinjury. Other inhibitors of enzymatic degradation or biosynthesis had no significant effect on GAG release.ConclusionInjurious compression of articular cartilage induces an initially high rate of GAG release from the tissue, which could not be inhibited, consistent with mechanical damage. However, the finding that MMP inhibition reduced GAG loss in the days following injury suggests a potential therapeutic intervention.
Quality of care indicators for gout management
Authors: Mikuls Ted R. , MacLean Catherine H. , Olivieri Jason , Patino Fausto , Allison Jeroan J. , Farrar John T. , Bilker Warren B. , Saag Kenneth G. 
Published: March 2004

AbstractObjectiveDespite the significant health impact of gout, there is no consensus on management standards. To guide physician practice, we sought to develop quality of care indicators for gout management.MethodsA systematic literature review of gout therapy was performed using the Medline database. Two abstractors independently reviewed each of the articles for relevance and satisfaction of minimal inclusion criteria. Based on the review of the literature, 11 preliminary quality indicators were developed and then reviewed and refined by an initial feasibility panel of community and academic rheumatologists. A twelfth indicator was added at the request of the first panel. Using a modification of the RAND/University of California at Los Angeles appropriateness method (bridging teleconference and white‐board Internet technology were added), a second expert panel rated each of the proposed indicators for validity using a 9‐point scale, in which ratings of 1–3, 4–6, and 7–9 were considered “invalid,” “indeterminate,” and “highly valid,” respectively. Indicators were considered valid if the median panel rating was ≥7 and there was no evidence of panel disagreement (defined to occur when 2 of 6 panelists provided a validity rating of 1–3 and 2 panelists provided a validity rating of 7–9).ResultsTen of the 12 draft indicators were rated to be valid by our second expert panel. Validated indicators pertained to 1) the use of urate‐lowering medications in chronic gout, 2) the use of antiinflammatory drugs, and 3) counseling on lifestyle modifications.ConclusionUsing a combination of evidence and expert opinion, 10 indicators for quality of gout care were developed. These indicators represent an important initial step in quality improvement initiatives for gout care.
Effector function of type II collagen–stimulated T cells from rheumatoid arthritis patients: Cross‐talk between T cells and synovial fibroblasts
Authors: Cho Mi‐La , Yoon Chong‐Hyeon , Hwang Sue‐Yun , Park Mi‐Kyung , Min So‐Youn , Lee Sang‐Heon , Park Sung‐Hwan , Kim Ho‐Youn 
Published: March 2004

AbstractObjectiveTo investigate the effector function exerted by type II collagen (CII)–stimulated T cells on rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS), and to determine their contribution to RA pathogenesis.MethodsWe used enzyme‐linked immunosorbent assays to measure the levels of interleukin‐15 (IL‐15), tumor necrosis factor α (TNFα), and IL‐18 production by FLS that were cocultured with antigen‐activated T cells. Likewise, we analyzed the levels of interferon‐γ (IFNγ) and IL‐17 production by RA T cells coincubated with FLS. To investigate the cross‐talk between CII‐stimulated T cells and RA FLS, we examined the effect of using a transwell membrane to separate T cells and FLS in a culture chamber, as well as the effect of adding an antibody to block CD40 ligation.ResultsThe levels of IL‐15, TNFα, IFNγ, and IL‐17 were all significantly increased in the serum of RA patients compared with normal control serum. Among the patients, the group with a stronger T cell proliferation response to CII showed higher levels of these inflammatory mediators. When coincubated with RA FLS, these T cells induced the production of IL‐15, TNFα, and IL‐18 by FLS with an intensity that increased in proportion to the duration of CII stimulation. T cells, in turn, responded to FLS stimulation by secreting higher amounts of IL‐17 and IFNγ in coculture. Interestingly, T cells that were activated by CII for longer periods of time showed stronger induction of these cytokines. The cross‐talk between T cells and FLS appeared to require direct cell–cell contact as well as CD40 ligation, at least in part.ConclusionThrough repeated stimulation by CII, RA synovial T cells became trained effector cells that induced the production of proinflammatory mediators by FLS, while in the process the T cells becoming more sensitized to the activation signal from FLS.
Plasmid encoding interleukin‐4 in the amelioration of murine collagen‐induced arthritis
Authors: Kageyama Yasunori , Koide Yukio , Uchijima Masashi , Nagata Toshi , Yoshida Atsushi , Taiki Aoshi , Miura Tomohiko , Nagafusa Tetsuyuki , Nagano Akira 
Published: March 2004

AbstractObjectiveTo evaluate the therapeutic effect of the administration of plasmid encoding interleukin‐4 (IL‐4) via gene‐gun delivery and via intradermal injection on collagen‐induced arthritis (CIA).MethodsIL‐4 plasmid was administered by gene‐gun delivery and intradermal injection to DBA/1 mice immunized with type II collagen (CII). The therapeutic effect on the development of CIA was evaluated clinically with a visual scoring method for arthritis and serologically by enzyme‐linked immunosorbent assays and polymerase chain reaction.ResultsTreatment with IL‐4–expressing plasmid significantly reduced the incidence and severity of CIA, including a reduction in the anti‐CII antibody level. In particular, gene‐gun delivery had a higher immunosuppressive effect on CIA compared with intradermal injection. As shown by in vitro stimulation assay, the spleen cells from mice immunized with CII and treated with IL‐4 plasmid via gene gun exhibited higher Th2 cytokine responses compared with cells treated with control plasmid after in vitro stimulation with CII.ConclusionThe results of this study suggest that treatment with IL‐4 plasmid may constitute a new clinical use of cytokine gene therapy for rheumatoid arthritis.