bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice:pathogenetic role in experimental vasculitis
Authors: Tomer Yaron , Gilburd Boris , Blank Miri , Lider Ofer , Hershkoviz Rami , Fishman Perina , Zigelman Rosa , Meroni Piere‐Luigi , Wiik Alan , Shoenfeld Yehuda 
Published: February 2007

AbstractObjective. To investigate the pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG).Methods. BALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANCA and other autoantibodies were determined. Mouse ANCA were tested for their ability to induce adhesion and respiratory burst of neutrophils. The mouse lungs and kidneys were examined for the development of vasculitis.Results. Mice immunized with human ANCA developed anti‐human ANCA and anti–anti‐human ANCA (mouse ANCA), while the controls did not develop these antibodies. Mouse ANCA were capable of inducing adhesion of neutrophils to fibronectin and activating the respiratory burst in neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis.Conclusion. The results suggest a pathogenic role of ANCA in WG, and may imply that activation of neutrophils is the initiating event in the development of vasculitis in WG.
Monoclonal anticardiolipin autoantibodies established from the (new zealand white x bxsb)f1 mouse model of antiphospholipid syndrome cross‐react with oxidized low‐density lipoprotein
Authors: Mizutani Hajime , Kurata Yoshiyuki , Kosugi Satoru , Shiraga Masamichi , Kashiwagi Hirokazu , Tomiyama Yoshiaki , Kanakura Yuzuru , Good Robert A. , Matsuzawa Yuji 
Published: February 2007

AbstractObjective. Autoimmunity‐prone (New Zealand white X BXSB)F1 ([NZW X BXSB]F1) mice have been shown to be useful as a model of antiphospholipid syndrome with myocardial infarction. The aim of this study was to examine the cross‐reactivity of anticardiolipin antibody (aCL) derived from (NZW X BXSB)F1 mice with oxidized low‐density lipoprotein (ox‐LDL), which is closely associated with atherosclerosis.Methods. Six monoclonal antibodies (MAb) against CL were established from (NZW X BXSB)F1 mice, and reactivity of aCL with ox‐LDL was examined by micro–enzyme‐linked immunosorbent assay.Results. Higher titers of anti–ox‐LDL autoantibodies were found in adult (NZW X BXSB)F1 mice compared with other autoimmunity‐prone mouse strains (P < 0.01) or a control strain (P < 0.005). There was a significant positive correlation between titers of aCL and those of anti–ox‐LDL in (NZW X BXSB)F1 mice (r = 0.79, P < 0.001). Of the 6 MAb against CL, 2 clones that showed β‐glycoprotein 1–dependent reactivity also cross‐reacted with ox‐LDL. Binding of monoclonal aCL to solid‐phase cardiolipin was inhibited by ox‐LDL, but not by native LDL.Conclusion. We confirmed that aCL derived from (NZW X BXSB)F1 mice can cross‐react with ox‐LDL. This result suggests that aCL, which is closely associated with lupus‐assocaited thrombosis, may also play an important role in atherosclerotic complications in patients with systemic lupus erythematosus.
The major dermatomyositis‐specific mi‐2 autoantigen is a presumed helicase involved in transcriptional activation
Authors: Seelig Hans Peter , Moosbrugger Isabelle , Ehrfeld Hans , Fink Thomas , Renz Manfred , Genth Ekkehard 
Published: February 2007

AbstractObjective. To characterize the complementary DNA (cDNA) and protein sequences of autoantigens recognized by anti–Mi‐2 antibodies, using recombinant Mi‐2 proteins for improved autoantibody detection.Methods. A cDNA expression library was immunoscreened, and cDNA isolation, alignment, and sequence analysis were performed. Northern blotting and in situ hybridization techniques were used. A recombinant protein (rMi‐2) was synthesized. Immunoprecipitation of 35S‐methionine–labeled HEp‐2 cell proteins and immunoblotting of rMi‐2 and natural nuclear proteins were performed. Immunofluorescence studies were done with anti–Mi‐2 positive sera of dermatomyositis (DM) patients, and with human or rabbit antibodies specific for rMi‐2. Antibody screening of systemic lupus erythematosus, rheumatoid arthritis, DM, and antinuclear antibody–positive human sera was performed using an rMi‐2 protein enzyme‐linked immunosorbent assay (ELISA).Results. A major antigen recognized by anti–Mi‐2 positive sera of DM patients was found to constitute a 218‐kd nuclear protein (218‐kd Mi‐2) encoded on chromosome 12 and to belong to the SNF2/RAD 54 helicase family. Human and rabbit antibodies that were affinity purified using the recombinant protein reacted with and precipitated a nuclear protein of similar size, which was also recognized by anti–Mi‐2 sera. Anti–218‐kd Mi‐2 antibodies detected by rMi‐2 protein ELISA seemed to be mainly restricted to sera from patients with DM.Conclusion. The molecular characterization of the 218‐kd Mi‐2 antigen may contribute to our understanding of autoimmune phenomena in DM. The use of immunoreactive recombinant proteins allows structural and functional studies of the helicase and the development of sensitive and accurate antibody screening tests.
Alteration of chlamydia trachomatis biologic behavior in synovial membranes suppression of surface antigen production in reactive arthritis and reiter's syndrome
Authors: Nanagara Ratanavadee , Li Feng , Beutler Anna , Hudson Alan , Schumacher H. Ralph 
Published: February 2007

AbstractObjective. To investigate the biologic state of Chlamydia and its surface antigen expression in the synovial membranes of patients with Chlamydia‐associated reactive arthritis/Reiter's syndrome (ReA/RS).Methods. Expression of chlamydial lipopoly‐saccharide (LPS), major outer membrane protein (MOMP), and elementary body (EB) antigens was studied by gold labeling immunoelectron microscopy on 6 synovial membrane and 2 synovial fluid (SF) pellet samples from 6 patients with Chlamydia‐associated arthritis. The study findings were compared with 24‐hour cultures of HeLa cells infected with Chlamydia trachomatis EB.Results. Persistent C trachomatis infection was found in all 6 synovial membrane samples from patients who had either early or chronic arthritis. The infection persisted despite antibiotic treatment, including a 1‐month course of doxycycline therapy. Most persistent organisms were atypical reticulate bodies (RBs) found in both fibroblasts and macrophages. Specific, but weak, immunogold staining for all 3 antibodies was found on both intracellular RBs and extracellular EBs. In the SF samples, Chlamydia surface antigens were detected only in phagosomes containing degraded electron‐dense materials.Conclusion. The synovial membrane biopsies conducted in this study of Chlamydia‐associated ReA/RS revealed atypical RBs with diminished MOMP and LPS expression. Such altered organisms may escape immune surveillance and contribute to disease chronicity; moreover, these organisms may be difficult to detect and treat in some ReA/RS patients.
Antibodies to synovial antigens in recent‐onset rheumatoid arthritis
Authors: Mccol Geoffrey J. , Cram David S. , Harrison Leonard C. 
Published: February 2007

AbstractObjective. To identify synovial antigens that bind to serum antibodies from subjects with recent‐onset rheumatoid arthritis (RA) (<6 months of synovitis).Methods. Soluble and insoluble fractions of Triton X‐100 extracts of RA and normal synovial tissue, and normal spleen and placenta, were immunoblotted with sera from 27 patients with recent‐onset RA, 13 autoimmune disease control subjects, and 13 blood bank control donors. Bound immunoglobulin was probed with 125I‐labeled protein A.Results. Antibodies in the sera of 20 (74%) patients with recent‐onset RA recognized at least 1 of 5 antigens in both a disease‐ and tissue‐specific and nonspecific manner. Anti‐La antibodies, usually associated with primary Sjögren's syndrome, were detected in 2 sera. Eight sera had increased reactivity to an IgG heavy and light chain dimer. There was strong binding of 8 sera with a 35‐kd doublet and of 3 sera with a 55‐kd species in RA and normal synovial lysates (insoluble fractions). Two sera uniquely recognized a 45‐kd protein only in the RA synovial lysate (soluble fraction).Conclusion. IgG antibodies in the sera of patients with recent‐onset RA show positive immunoblots for 3 novel synovial antigens of 35‐kd, 55‐kd, and 45‐kd, as well as for 2 previously characterized antigens (La and IgG). Thus, a variety of synovial antigens appear to be recognized by B cells even early in the clinical course of RA.
Prediction of progression of radiologic damage in newly diagnosed rheumatoid arthritis
Authors: Heide Agnes Van Der , Remme Carol Ann , Hofman Dirk M. , Jacobs JOHANNES W. G. , Bijlsma JOHANNES W. J. 
Published: February 2007

AbstractObjective. To investigate the extent to which early radiologic damage is predicted by joint inflammation in patients with newly diagnosed rheumatoid arthritis (RA).Methods. Regression analysis was performed on 1‐year progression of total radiologic damage for baseline characteristics and cumulative disease activity measures, and the effects of continued joint inflammation on the progression of damage in separate joint groups were investigated.Results. Odds ratios for progression of total damage were 12 for the presence of rheumatoid factor, 5 for the presence of damage at baseline, and 2 for cumulative joint inflammation. A positive association between continued joint inflammation and progression of damage was found to be statistically significant for most joint groups.Conclusion. Progression of radiologic damage in patients with newly diagnosed RA is independently associated with the presence of rheumatoid factor and damage at baseline and with cumulative joint inflammation.
Identification of patient subsets among those presumptively diagnosed with, referred, and/or followed up for systemic lupus erythematosus at a large tertiary care center
Authors: Calvo‐Alén Jaime , Bastian Holly M. , Straaton Karin V. , Burgard Sheila L. , Mikhail Isis S. , Alarcón Graciela S. 
Published: February 2007

AbstractObjective. To identify different subsets of patients from a large tertiary care center who were presumptively referred for and/or diagnosed with systemic lupus erythematosus (SLE) (or followed up).Methods. All patients who were referred, followed up, and/or diagnosed with SLE at our center, who had disease duration of ≤5 years, and who resided in Alabama, were identified and their charts reviewed and abstracted.Results. Abstracted data were reviewed by 3 rheumatologists, and patients were assigned to 1 of 3 categories: 1) SLE by the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) criteria, 2) clinical SLE but not meeting 4 of the ACR criteria, or 3) fibromyalgia‐like manifestations with antinuclear antibody (ANA) positivity. There were 90 patients in the first group (criteria), 22 in the second group (clinical), and 37 in the third group (fibromyalgia‐like). Patients in all 3 groups were predominantly women. Only 50% of the fibromyalgia‐like group were African‐American, compared with 55–65% for the other 2 groups. Organ system involvement occurred with comparable frequency in the first 2 groups, but mucocutaneous and hematologic abnormalities were more frequent in the criteria group; in contrast, the patients with fibromyalgia‐like symptoms primarily presented with arthralgias/myalgias, fatigue, depression, and sleep disturbances, as well as mucocutaneous manifestations.Conclusion. When the ACR criteria for SLE are used to determine eligibility for lupus studies, a group of patients with clinically unequivocal SLE are excluded. A group of patients with fibromyalgia‐like manifestations, who test positive for ANA and differ clinically and sociodemographically from the patients in the other 2 groups, very likely do not belong within the spectrum of SLE.
Presence of nucleosome‐restricted antibodies in patients with systemic lupus erythematosus
Authors: Chabre Henri , Amoura Zahir , Piette Jean‐Charles , Godeau Pierre , Bach Jean‐François , Koutouzov Sophie 
Published: February 2007

AbstractObjective. To assess whether nucleosome‐restricted antibodies, i.e., antibodies that react with the whole nucleosome particle but not with its individual components (double‐stranded DNA [dsDNA] and his‐tones), are present in the sera of patients with systemic lupus erythematosus (SLE).Methods. Antibodies were detected by enzyme‐linked immunosorbent assay using purified nucleo‐somes, dsDNA, or histones. These tests were applied to the sera of 40 patients with SLE. Protein G–purified IgGs of representative sera were sequentially adsorbed on dsDNA‐and histone‐conjugated solid‐phase supports and further assayed for their nucleosome, dsDNA, and histone reactivities.Results. Of the 40 sera tested, 16 displayed anti‐dsDNA and/or antihistone antibody activity, which was always associated with significant antinucleosome reactivity. In addition, 3 sera showed antinucleosome activity that was not associated with concomitant anti‐dsDNA or antihistone activity. The presence of true nucleosome‐restricted antibodies was demonstrated, after solid‐phase adsorption, in representative SLE sera that showed anti‐dsDNA or antihistone antibody activity, and also in sera that did not show these activities.Conclusion. Our results provide evidence for the presence of nucleosome‐restricted antibodies in patients with lupus. These nucleosome‐restricted antibodies, along with anti‐dsDNA and antihistone antibodies, appear to belong to a broad set of antinuclear antibodies, the antinucleosome family.
Lack of detection of enteroviral rna or bacterial dna in magnetic resonance imaging–directed muscle biopsies from twenty children with active untreated juvenile dermatomyositis
Authors: Pachman Lauren M. , Litt Deborah L. , Rowley Anne H. , Hayford Jennifer R. , Caliendo Janice , Heller Scott , Ticho Baruch S. , Christensen Mary , Patterson Bruce , Ytterberg Steven R. , Pallansch Mark 
Published: February 2007

AbstractObjective. To investigate for the presence of increased titers of circulating antibody to putative infectious agents and for detectable viral RNA or bacterial DNA in children with active recent‐onset juvenile der‐ matomyositis (DM).Methods. Magnetic resonance imaging–directed muscle biopsies were performed in 20 children with active, untreated, recent‐onset juvenile DM and in age‐matched children with neurologic disease. Sera were tested for complement‐fixing antibody to Coxsack‐ievirus B (CVB), influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae, mumps, respiratory syncytial virus, and Reovirus; and by immunofluorescence for IgG antibody to Toxoplasma gondii cytomegalovirus and IgM antibody to Epstein‐Barr virus. Muscle from juvenile DM patients and control children, CD‐1 Swiss mice with and without CVB1 infection, and viral stock positive for CVB1–6 were tested using reverse‐transcriptase polymerase chain reaction with 5 primer sets, 4 probes (1 Coxsackievirus, 3 Enterovirus), and universal primers for DNA.Results. No increased antibody, viral RNA, or bacterial DNA was present in the juvenile DM patients or the control children.Conclusion. Juvenile DM may be triggered by unidentified agent(s) in the genetically susceptible host.
The elusive search for geographic clusters of systemic lupus erythematosus.
Authors: Wallace Daniel J. , Quismorio Francisco P. 
Published: February 2007

AbstractObjective. To ascertain whether there are any geographic clusters of systemic lupus erythematosus (SLE), and critically review 2 previous reports of these clusters.Methods. A literature review of all epidemiologic surveys relevant to SLE published since 1966 was undertaken. This included a search of abstracts and reports, in addition to peer‐reviewed publications.Results. Two geographic clusters were identified in the literature. A report purporting that contaminated ground water in southwest Tucson, Arizona was associated with significantly increased symptoms of SLE was flawed since no patients were examined, discarded criteria were used, and incorrect definitions were employed by the nonrheumatologist authors. Another study, which identified a cluster in Nogales, Arizona, used generally valid methodology. However, the authors' conclusion that a 94/100,000 prevalence of SLE was evidence of an excessive increase in this 92% Hispanic/Native American community is not consistent with published surveys among Hispanic and Native American populations.Conclusion. No valid claims of SLE geographic clusters have been published.
Double‐blind, placebo‐controlled multicenter trial using chimeric monoclonal anti‐cd4 antibody, cm‐t412, in rheumatoid arthritis patients receiving concomitant methotrexate
Authors: Moreland Larry W. , Pratt Parks W. , Mayes Maureen D. , Postlethwaite Arnold , Weisman Michael H. , Schnitzer Thomas , Lightfoot Robert , Calabrese Leonard , Zelinger David J. , Woody James N. , Koopman William J. 
Published: February 2007

AbstractObjective. To evaluate the clinical response to and safety of single and repeat doses of a chimeric anti‐CD4 monoclonal antibody, cM‐T412, in patients with rheumatoid arthritis (RA) concomitantly treated with a stable regimen of low‐dose methotrexate.Methods. Sixty‐four patients with refractory RA, who were already receiving stable doses of methotrexate, were randomized into a multicenter, double‐blind, placebo‐controlled trial to receive 3 monthly treatments with either a placebo, or 5, 10, or 50 mg cM‐T412, given intravenously.Results. Using ≥50% improvement in swollen joint counts as a criterion for clinical response, 13%, 13%, 18%, and 13% of patients receiving 50, 10, or 5 mg cM‐T412, or the placebo, respectively, exhibited a clinical response at 3 months of therapy. Using ≥50% improvement in tender joint counts as a measure of clinical efficacy at 3 months, 19%, 13%, 12%, and 6% of patients receiving 50, 10, or 5 mg cM‐T412, or the placebo, respectively, exhibited a clinical response. “Flu‐like” symptoms (fever, chills, rigor) within 24 hours of the infusion occurred more frequently in the groups receiving 50‐mg (29%) and 10‐mg (31%) doses of cM‐T412 than those receiving 5 mg cM‐T412 (12%) or the placebo (13%). Significant CD4+ T cell depletion occurred in the 50‐mg group (mean of 353 CD4+ T cells/mm3 at 6 months versus 856 CD4+ T cells/mm3 at baseline). All patients were followed up for 12 months after the final treatment; no opportunistic infectious complications occurred.Conclusion. Treatment with cM‐T412 in this cohort of RA patients who were also taking methotrexate was not associated with clinical efficacy or enhanced toxicity from infectious complications, despite significant peripheral CD4+ T cell depletion.
Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis
Authors: Mladenovic Vlastimir , Domljan Zlatko , Rozman Blaz , Jajic Ivo , Mihajlovic Dimitrije , Dordevic Jovan , Popovic Milan , Dimitrijevic Miroslava , Zivkovic Milutin , Campion Giles , Musikic Predrag , Löw‐Friedrich Iris , Oed Christine , Seifert Hildegard , Strand Vibeke 
Published: February 2007

AbstractObjective. To assess the safety and effectiveness of leflunomide versus placebo in patients with active rheumatoid arthritis (RA) treated for 6 months.Methods. Four hundred two patients were randomly assigned to receive placebo or leflunomide at 5 mg, 10 mg, or 25 mg daily. A washout period of 6–12 weeks from prior second‐line therapy was required.Results. Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10‐mg and 25‐mg dosage groups compared to placebo. Twenty‐one patients (7.0%) in the active treatment groups withdrew due to adverse events (AEs). The incidence of AEs was higher with leflunomide than with placebo. Gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia were more common in the 10‐mg and 25‐mg dosage groups. The incidence of infections was similar between the treatment and placebo groupsno opportunistic infections were seen. Transient elevations in liver function studies were noted in a small number of patients.Conclusion. Leflunomide is effective in daily doses of 10 mg and 25‐mg in patients with active RA. Improved efficacy at the 25‐mg dose was associated with a higher incidence of AEs. Randomized, placebocontrolled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.
Quantification of rheumatoid synovitis by magnetic resonance imaging
Authors: Gaffney Karl , Cookson John , Blake David , Coumbe Adam , Blades Selina 
Published: February 2007

AbstractObjective. To develop a method for quantifying acute synovial inflammation in rheumatoid arthritis (RA), utilizing magnetic resonance imaging (MRI).Methods. Gadolinium–diethylenetriamine pentaacetic acid‐enhanced MRI was performed in 21 patients with knee synovitis. Changes in synovial membrane signal intensity were identified and quantified by line profile analysis. Multiple synovial biopsies were obtained by a blind biopsy technique, and standard clinical and laboratory measurements of disease activity were recorded.Conclusion. Dynamic MRI is a valuable technique for assessing acute synovial inflammation in RA.Results. The rate of synovial membrane enhancement correlated with histologic features of acute inflammation (r = 0.63, P < 0.01), but not with clinical or laboratory assessments.
Predictors of work disability in rheumatoid arthritis patients
Authors: Reisine Susan , Mcquillan Julia , Fifield Judith 
Published: February 2007

AbstractObjective. To evaluate regression models that include social, attitudinal, work structure, health status, and family characteristics, with regard to their prediction of work disability in a national sample of patients with rheumatoid arthritis (RA).Methods. Four hundred ninety‐eight employed RA patients were recruited from a national sample of private rheumatology practices. Three hundred ninety‐two remained in the study after 5 years. Data were collected from patients by telephone interview, and patients' physicians provided written clinical assessments. Only variables on which information was obtained in year 1 were used to predict work status in year 5, using hierarchical multiple logistic regression analysis.Results. The significant predictors of work disability were age (odds ratio [OR] 1.04), number of deformed joints (OR 1.26), number of joints with flare (OR 1.23), the complexity of working with things at work (OR 0.88), and the desire to remain employed (OR 2.3). The risk of work disability increased with increasing age, more severe disease, greater complexity of involvement with things at work, reduced work hours, and desire to not be working outside the home.Conclusion. The risk of becoming work disabled in 5 years was predicted more by clinical status at entry into the study than by work structure. These results, which contradict previous research on work disability in arthritis, prompt a rethinking of future studies of work disability in RA.