bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predominant Role of Neutrophils in the Inactivation of α2‐Macroglobulin in Arthritic Joints
Authors: Abbink J. J. , Kamp A. M. , Nieuwenhuys E. J. , Nuijens J. H. , Swaak A. J. G. , Hack C. E. 
Published: February 2007

AbstractWe studied the state of α2‐macroglobulin (α2M), an important inhibitor of cartilage‐degrading proteinases, in relation to activation of neutrophils in 82 patients with several types of arthritis, including 52 with rheumatoid arthritis and 11 with osteoarthritis. Levels of total inactive α2M (iα2M), which comprises α2M complexed to proteinases and α2M inactivated by oxidation or hydrolysis, were measured with a monoclonal antibody specific for iα2M. In addition, levels of α2M complexed to proteinases were quantitated with specific assays. Neutrophil activation was assessed by measuring elastase–α1‐antitrypsin complexes and lactoferrin. In 83% of the 82 patients tested, the synovial fluid (SF) to plasma ratio of iα2M exceeded 1, indicating an intraarticular generation. Levels of iα2M significantly correlated with neutrophil numbers (P < 0.0005) and with levels of elastase–α1‐antitrypsin complexes and of lactoferrin (P < 0.00001 for both). Moreover, part of iα2M consisted of α2M complexed to elastase‐like and chymotrypsin‐like proteinases, presumably, neutrophil elastase and cathepsin G, respectively. However, the amount of iα2M was approximately 10‐fold larger than the amount complexed to these proteinases. In vitro inactivation of α2M by activated neutrophils was only partly inhibitable by eglin C, a specific inhibitor of both elastase and cathepsin G. Release of reactive oxygen species was presumably responsible for the additional inactivation of α2M, because eglin C completely abolished the inactivation of α2M by cell‐free supernatant of activated neutrophils. Thus, our results suggest a predominant role of neutrophils in the inactivation of α2M in the SF of patients with inflammatory joint diseases. However, this inactivation could be explained only in part by the release of neutrophilic proteinases. We propose that the inactivation of α2M in SF was due to the concerted action of both reactive oxygen species and lysosomal proteinases.
Isolation of YERSINIA‐Specific T Cell Clones from the Synovial Membrane and Synovial Fluid of a Patient with Reactive Arthritis
Authors: Viner N. J. , Bailey L. C. , Life P. F. , Bacon P. A. , Gaston J. S. H. 
Published: February 2007

AbstractSynovial fluid (SF) mononuclear cells from patients with reactive arthritis (ReA) proliferate in vitro when challenged with ReA‐associated bacteria, the maximal response being for the organism causing the triggering infection. We report the results of a study of the antigenic specificity of synovial T lymphocytes from an HLA–B27 positive ReA patient whose SF mononuclear cells responded preferentially to Yersinia antigens. This is the first report of the isolation of Yersinia‐specific T cell clones from synovial membrane (obtained by closed‐needle synovial biopsy). We present a detailed analysis of these clones, together with others obtained from the SF.
Retardation of Radiologic Progression in Rheumatoid Arthritis With Methotrexate Therapy. A Controlled Study
Authors: Rau R. , Herborn G. , Karger T. , Werdier D. 
Published: February 2007

AbstractWe evaluated the effects of methotrexate (MTX) on radiographic changes of rheumatoid arthritis (RA) in the hands, wrists, and feet of 31 patients who completed at least 24 months of treatment. Radiographs were obtained at baseline and every 1 or 2 years thereafter. MTX was administered for 2–6 years (mean 3.9 years); the total dose was 1,925 mg (range 970–3,810 mg). The mean duration of disease at baseline was 8.1 years (range 1–26 years). Radiographs taken over 1–5 years during previous, clinically ineffective, gold therapy (mean 2.2 years) were available for 24 patients, and the changes over time were compared. During MTX treatment, the mean number of swollen joints decreased from 22.5 to 8.3 (40 joints evaluated), and the mean erythrocyte sedimentation rate decreased from 61.6 mm/hour to 28.4 mm/hour. Thirty‐six (19%) of 190 joints with Larsen scores of 0 at baseline progressed to a score of 1 or 2 within 1 year of beginning MTX, whereas with gold, 37 (44%) of 89 joints progressed (P < 0.001). Of 419 joints with Larsen scores of 1, 12.5% deteriorated within 1 year with MTX treatment, compared with 14.7% of 183 joints during gold therapy (P not significant). There were no between‐treatment differences for joints with higher Larsen scores. During gold therapy, the mean Larsen index (score per joint) for the hand and wrist joints (18 joints counted) progressed from 1.45 to 1.82 over a mean of 22.1 months, and during MTX, from 1.82 to 1.97 over a mean of 48.0 months. The mean rate of progression during MTX therapy (0.005/month) was significantly lower (P = 0.01) than that during gold therapy (0.025/month). The mean rate of progression in the metatarsophalangeal joints (0.011/month versus 0.010/month, MTX versus gold) was not significantly different. There was a sharp decrease in the proportion of radiologically active joints during MTX treatment. Our findings thus indicate that MTX may retard the radiologic progression of RA in patients with disease that is unresponsive to gold.
T Lymphocyte Adhesion to Human Synovial Fibroblasts. Role of Cytokines and the Interaction Between Intercellular Adhesion Molecule 1 and CD11a/CD18
Authors: Krzesicki Raymond F. , Fleming William E. , Winterrowd Greg E. , Hatfield Cheryl A. , Sanders Martin E. , Chin Jia En 
Published: February 2007

AbstractWe studied the adhesion of human peripheral blood T lymphocytes to human synovial fibroblasts stimulated with interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), or combinations of these cytokines. T lymphocytes bound poorly to untreated human synovial fibroblasts. IFNγ treatment resulted in the largest increase in adhesion, followed by TNFα and IL‐1β. Combinations of IFNγ + TNFα and IFNγ + IL‐1β had a synergistic effect on intercellular adhesion molecule 1 (ICAM‐1) expression and adhesion. The increase in cellular adhesion induced by cytokines correlated with the up‐regulation of the number of cells expressing ICAM‐1 and the density of antigen/cell. There was no synergistic effect on leukocyte function–associated antigen 3 (LFA‐3) or on HLA class I or class II antigen expression. Adhesion was only partially inhibited by anti‐ICAM‐1, anti‐LFA‐1, or anti‐CD18. These findings suggest the existence of ICAM‐1‐independent and CD11/CD18‐independent adhesion mechanisms. Anti‐LFA‐3 was completely ineffective as an inhibitor of adhesion. There was no additive or synergistic advantage of using combinations of antibodies to increase the level of inhibition, i.e., anti–ICAM‐1 + anti–LFA‐3, anti–ICAM‐1 + anti‐CD18, or anti–ICAM‐1 + anti–LFA‐1 (CD11a). Our data indicate that proinflammatory cytokines may play a prominent role in the formation and exacerbation of synovial hyperplasia, by regulating the recruitment and retention of T lymphocytes via the up‐regulation of adhesion molecules on synovial fibroblasts.
Levels of Keratan Sulfate in the Serum and Synovial Fluid of Patients With Osteoarthritis of the Knee
Authors: Campion Giles V. , McCrae Fiona , Schnitzer Thomas J. , Lenz Mary Ellen , Dieppe Paul A. , J.‐M. A. Thonar Eugene 
Published: February 2007

AbstractWe examined the relationship between serum and synovial fluid (SF) levels of antigenic keratan sulfate (KS) and the clinical, laboratory, and radiologic features of disease in 125 well‐characterized patients with knee osteoarthritis (OA). KS was quantified by enzyme‐linked immunosorbent assay, using an antibody specific for a highly sulfated epitope on KS chains; the results were calculated as equivalents of an international standard of KS from human costal cartilage. The mean level of serum KS (393 ng/ml) was significantly higher than those previously reported for populations of adults without OA. There was a wide scatter of serum KS values (range 156–912 ng/ml), with little correlation with clinical or radiologic features. Men had significantly higher levels than women (456 ± 135 ng/ml versus 368 ± 110 ng/ml, mean ± SD), and there was a statistically significant but weak association with indicators of polyarticular involvement (number of symptomatic joints, Heberden's nodes, hip symptoms) in women. Despite the wide scatter of results in the population as a whole, individual levels of KS were stable for up to 4 consecutive years in the 9 patients studied. Levels of KS were much higher in SF (n = 25) than in serum, but the two were not correlated. There was an inverse correlation between radiographic evidence of cartilage loss and the level of KS in SF. The large variations in serum KS values suggest that this measure may not be of diagnostic significance among populations of patients. However, the stability of serum levels with time and the relationship between cartilage mass and SF levels may be useful for monitoring the individual patient's response to therapy, both systemically (serum KS) and in single joints (SF KS).
Human Basophil Releasability. VIII. Increased Basophil Releasability in Patients with Scleroderma
Authors: de Paulis Amato , Valentini Gabriele , Spadaro Giuseppe , Lupoli Salvatore , Tirri Giuseppe , Marone Gianni 
Published: February 2007

AbstractWe evaluated basophil releasability in 16 female patients with scleroderma (systemic sclerosis) and in 16 normal age‐ and sex‐matched donors. Basophils from patients with scleroderma released significantly more histamine „spontaneously”︁ than did those from normal donors (12.9 ± 2.1% versus 4.5 ± 0.7%; P < 0.0005). Basophil reactivity (maximal percentage histamine release) to anti‐IgE was higher in patients with scleroderma than in controls (57.0 ± 7.5% versus 35.4 ± 7.8%; P < 0.05). Basophil sensitivity (the concentration of anti‐IgE that causes 40% of maximal percentage histamine release) to anti‐IgE in scleroderma patients was similar to that found in controls (4.6 ± 2.8 × 10−2 μg/ml versus 2.3 ± 1.0 × 10−1 μg/ml; P not significant). Scleroderma patients also showed enhanced releasability compared with that of the controls when challenged in vitro with interleukin‐3 (8.3 ± 1.7% versus 3.2 ± 0.6% P < 0.01). Releasability induced by the formylcontaining tripeptide, f‐met peptide, was significantly higher in the scleroderma patients than in the controls at the 2 lower concentrations used. No differences in basophil reactivity and sensitivity to f‐met peptide and calcium ionophore A23187 were found between patients and normal donors. These results show that spontaneous basophil releasability and releasability in response to IgE cross‐linking and activation of interleukin‐3 receptors are increased in patients with scleroderma.
Secular Changes in Published Clinical Trials of Second‐Line Agents in Rheumatoid Arthritis
Authors: Anderson Jennifer J. , Felson David T. , Meenan Robert F. 
Published: February 2007

AbstractThe present investigation was undertaken to explore changes over time in the design and reporting of trials of second‐line drugs in rheumatoid arthritis, in the characteristics of patients included in the trials, and in the sources of funding. We studied 105 trials of second‐line agents for the treatment of rheumatoid arthritis, including placebo‐controlled and comparative trials involving 8 different agents. Three time periods, 1945–1969, 1970–1979, and 1980–1989, were compared. We found little change in the standards for reporting on the design of trials or for reporting information on patient dropout and drug side effects, some increase in the complexity of the statistical methods used, but no increase in the use of power analysis (reported in only 13% of trials). The average age of patients in clinical trials has increased. In recent years, there has been a substantial shift from placebo‐controlled to comparative trials, and it is increasingly common for trials to be financially supported by pharmaceutical companies. The possible effects of secular trends should be considered when combining or comparing results of trials conducted in different years.
HLA–DPB1*0301 is a Major Risk Factor for Rheumatoid Factor–Negative Adult Rheumatoid Arthritis
Authors: Gao Xiaojiang , Fernandez‐Vina Marcelo , Olsen Nancy J. , Pincus Theodore , Stastny Peter 
Published: February 2007

AbstractHLA–DPB1 alleles were determined using the polymerase chain reaction and allele‐specific oligonucleotide probes in Caucasoid patients with rheumatoid arthritis (RA) and in healthy controls. DPB1*0301 was found to be increased in seronegative patients (50.0% versus 10.8% in controls; relative risk = 8.3, P < 0.0001). With our previous finding that DPB1*0301 is increased in seronegative children with polyarticularonset arthritis, the results suggest a relationship between this disease and seronegative RA in adults.
Antibodies to Retroviral Proteins and Reverse Transcriptase Activity in Patients With Essential Cryoglobulinemia
Authors: Perl Andras , Gorevic Peter D. , Condemi John J. , Papsidero Lawrence , Poiesz Bernard J. , Abraham George N. 
Published: February 2007

AbstractHuman T cell lymphotropic virus type I (HTLV‐I) gag and env protein–specific antibodies were identified in 6 of 13 patients with essential cryoglobulinemia (EC), by Western blot and radioimmunoprecipitation analysis. Supernatants of cells from 2 of the 5 EC patients tested showed reverse transcriptase activity. DNA sequences homologous to HTLV‐I could not be detected by polymerase chain reaction, thus excluding the presence of prototype HTLV‐I in each patient with EC. The data suggest that retroviral proteins distinct from but related to HTLV‐I may be involved in the pathogenesis of EC in some patients.
AIMS2. The Content and Properties of a Revised and Expanded Arthritis Impact Measurement Scales Health Status Questionnaire
Authors: Meenan Robert F. , Mason John H. , Anderson Jennifer J. , Guccione Andrew A. , Kazis Lewis E. 
Published: February 2007

AbstractObjective. The goal of this project was to develop a more comprehensive and sensitive version of the Arthritis Impact Measurement Scales (AIMS).Methods. AIMS scale items were revised, and 3 new scales were added to evaluate arm function, work, and social support. Sections were also added to assess satisfaction with function, attribution of problems to arthritis, and self‐designation of priority areas for improvement. The new instrument was designated the AIMS2. A pilot test of format and content and a performance test of reliability and validity were carried out.Results. Questionnaire completion times in a pilot study of 24 subjects averaged 23 minutes, and evaluations were positive regarding the instrument's length and ease of completion, and the subjects' willingness to complete serial forms and return them by mail. Measurement performance was tested in 408 subjects: 299 with rheumatoid arthritis (RA) and 109 with osteoarthritis (OA); 45 of these subjects completed a second AIMS2 within 3 weeks. Internal consistency coefficients for the 12 scales were 0.72—0.91 in the RA group and 0.74—0.96 in the OA group. Test‐retest reliability was 0.78—0.94. All within‐scale factor analyses produced single factors, except for mobility level in OA. Validity analyses in both the RA and the OA groups showed that patient designation of an area as a problem or as a priority for improvement was significantly associated with a poorer AIMS2 scale score in that area. Reliability, factor analysis, and validity results were consistent in age, sex, and education subgroups. Satisfaction was moderately correlated with level of function in the same health status area, and the satisfaction items formed a reliable scale. Responses to the arthritis attribution items showed that most dysfunction in this sample was due to arthritis.Conclusion. The AIMS2 is a revised and expanded health status questionnaire with excellent measurement properties that should be useful in arthritis clinical trials and in outcomes research.
Variable‐Constant Segment Genotype of Immunoglobulin Kappa is Associated with Increased Risk for Rheumatoid Arthritis
Authors: Moxley George 
Published: February 2007

AbstractObjective. To further investigate the association of rheumatoid arthritis (RA) with a particular genotype identified by a restriction site polymorphism near the constant segment of immunoglobulin kappa (Ck).Methods. The frequencies of genomic DNA polymorphisms detected within or near Ck (the most Ck‐proximal variable segment [Vk] B3 and a T lymphocyte marker [CD8A]) were determined by Southern blotting and hybridization. The frequencies of coding‐region polymorphisms of Ck (Km allotypes) were determined by amplification by polymerase chain reaction followed by restriction enzyme digestion.Results. Although the frequencies of B3, Km, and CD8A genotypes were not different between RA and normal control populations, more individuals were homozygous for both Ck and B3 in the RA group (relative risk 2.2, P < 0.01), especially in the DR4‐negative RA subgroup (relative risk 3.9, P < 0.001).Conclusion. The homozygous genotype of an approximately 30,000‐base region including the Ck segment confers an elevated risk for RA, particularly in the DR4‐negative subgroup.
Detection of Stromelysin and Collagenase in Synovial Fluid From Patients with Rheumatoid Arthritis and Posttraumatic Knee Injury
Authors: Walakovits Lori A. , Moore Vernon L. , Bhardwaj Nina , Gallick Gregory S. , Lark Michael W. 
Published: February 2007

AbstractObjective. To quantify stromelysin and collagenase in synovial fluid (SF) from patients with rheumatoid arthritis (RA) or traumatic knee injury.Methods. Stromelysin and collagenase were measured in the SF of 33 patients with RA or posttraumatic knee injury, using specific double‐antibody sandwich enzyme‐linked immunosorbent assays. Stromelysin was fractionated from representative SF, and the molecular form was identified by immunoblot analysis.Results. The stromelysin concentration was ˜20‐fold higher than the collagenase concentration in the fluids from patients with RA and ˜8‐fold higher in the fluids from patients with traumatic injury. For both metalloproteinases, there was a higher enzyme concentration in RA SF than in the SF from patients with trauma (stromelysin 40.1 ± 26 μ/ml [mean ± SD] in RA SF, 8.5 ± 15 μ/ml in trauma SF; collagenase 2.2 ± 3.3 μ/ml in RA SF, 1.1 ± 2.3 μ/ml in trauma SF). The majority of the stromelysin within the SF bound to reactive red—agarose and was identified as prostromelysin based on electrophoretic mobility and immunoblotting with monospecific antibodies.Conclusion. The finding of high levels of stromelysin in SF from patients with RA supports the proposal that this enzyme may play a role in the connective tissue degradation observed in this disease.
Long‐Term Prospective Study of Methotrexate in the Treatment of Rheumatoid Arthritis
Authors: Weinblatt Michael E. , Weissman Barbara N. , Holdsworth Donald E. , Fraser Patricia A. , Maier Agnes L. , Falchuk Kenneth R. , Cobly Jonathan S. 
Published: February 2007

AbstractObjective. To determine the long‐term efficacy and safety of low‐dose methotrexate (MTX) in rheumatoid arthritis (RA).Methods. Eighty‐four—month open prospective trial at a single academic rheumatology center.Results. Twenty‐six patients were enrolled in a prospective study of the long‐term efficacy of MTX in RA; a significant improvement had been demonstrated after 36 months of therapy. Twelve patients remained in the study at the 84‐month visit; the mean weekly dosage of MTX was 10.2 mg. A significant improvement was still noted at 84 months in the number of painful joints, number of swollen joints, joint pain index, joint swelling index, and physician and patient global assessments. A 50% improvement in the joint pain index and joint swelling index was observed in more than 80% of the 12 patients still enrolled. A significant reduction in prednisone dosage was achieved; of 14 patients taking prednisone at entry, 7 had discontinued prednisone completely. Fourteen patients withdrew from the study: 10 between 0 and 36 months, and 4 between 36 and 84 months. Toxicity in 3 patients and visit noncompliance in 1 patient were the reasons for withdrawal between 36 and 84 months. At 84 months, 46% of the patients remained in the study; 11.5% had discontinued due to MTX toxicity.Conclusion. The effectiveness of MTX in the treatment of RA continues to be demonstrated in this prospective study, after 84 months of treatment.
Long‐Term Prospective Study of the Use of Methotrexate in the Treatment of Rheumatoid Arthritis
Authors: Kremer Joel M. , Phelps Carlton T. 
Published: February 2007

AbstractObjective. To determine and describe the clinical, radiographic, and toxicity profile in a cohort of rheumatoid arthritis patients receiving weekly oral methotrexate (MTX) over a mean period of 90 months, and to compare and contrast these data with our previous data on this cohort, reported after 53 months.Methods. Prospective, open observational study over a mean treatment period of 90 months (range 79—107 months). Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, 1 month, 3 months, and every 3 months thereafter.Results. A significant improvement from baseline was maintained in all clinical parameters but the number of tender joints. Toxic reactions were as common in months 54—90 as during the first 53 months. The mean dosage of MTX decreased from 14.6 mg/week at the time of the last report to 11.7 mg/week, while the mean prednisone dosage increased from 1.9 mg/day to 2.1 mg/day. Radiographic scores for erosive disease became statistically significantly different from baseline at year 8, and scores for joint space narrowing differed significantly from baseline at years 5 and 8. Since study entry, 2 patients (6.9%) have experienced MTX pneumonitis.Conclusion. We conclude that a majority of rheumatoid arthritis patients are able to continue MTX treatment with generally sustained efficacy, for intervals that meaningfully exceed those reported previously.
Timing of Pregnancy in Relation to the Onset of Rheumatoid Arthritis
Authors: Silman Alan , Kay April , Brennan Paul 
Published: February 2007

AbstractThe interval between the onset of rheumatoid arthritis (RA) and the most recent pregnancy prior to RA onset in 88 women was determined. These data were compared with data obtained from a group of 144 age‐matched normal women (controls) who had been assigned a “dummy date for RA onset” for the purposes of analysis. The frequency of disease onset during 3 time intervals within the period from conception to 1 year postpartum was compared with the frequency of disease onset outside this period. There was a reduction in the incidence of disease onset during pregnancy (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.04—2.6) and a numerically greater increased risk of RA onset during the first 3 months postpartum (OR 5.6, 95% CI 1.8—17.6), which persisted for the subsequent 9 months (OR 2.6, 95% CI 0.8—7.9). A reduction in the incidence of disease onset was seen during all pregnancies; in contrast, the postpartum increase was greater in those with RA onset after the first pregnancy. The reduced incidence of RA onset during pregnancy, with the increased risk postpartum, mirrors the previously described suppression of disease activity during pregnancy and the subsequent flare postpartum in women with established RA. In addition, the increased postpartum risk after the first pregnancy might suggest that in susceptible women, either the hormonal changes or the exposure to the fetus's paternal HLA might represent a risk factor for disease causation.