bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel autoantibodies against muscle‐cell membrane proteins in patients with myositis
Authors: Stuhlmüller Bruno , Jerez Ricardo , Hausdorf Gert , Barthel Hans‐R. , Meurer Michael , Genth Eckehard , Kalden Joachim R. , Burmester Gerd R. 
Published: February 2007

AbstractObjective. To search for autoantibodies against muscle cell‐specific surface membrane antigens in patients with inflammatory myopathies.Methods. A cell enzyme‐linked immunosorbent assay (cell ELISA) using a human rhabdomyosarcoma cell line (TE‐671) was developed and performed in serial dilutions with either nonfixed or fixed cells. A total of 141 different patient sera were tested: 90 from patients with various rheumatic diseases, 12 from patients with cardiomyopathies, 25 from patients with other muscular diseases, and 14 from patients who had undergone major surgery or who had other noninflammatory diseases. As controls, 20 sera were obtained from healthy donors. Results were correlated using immunofluorescence staining and flow cytometry.Results. Using the nonfixed cell ELISA, the proportions of positive sera from the patient groups with rheumatic diseases were 71% with polymyositis (PM), 15% with dermatomyositis (DM), 18% with systemic sclerosis (SSc), 15% with systemic lupus erythematosus (SLE), and 7% with rheumatoid arthritis. Sera from healthy donors, as well as sera from patients with nonrheumatic diseases, did not show significant reactivities. When other cell lines, including a chondrosarcoma, a bladder carcinoma, a pancreas carcinoma, and human foreskin fibroblasts, were used as substrates, positive sera did not react in the cell ELISA. Results obtained with the cell ELISA system using nonfixed cells were confirmed by flow cytometry and immunofluorescence staining. A strong protein band of 50 kd was detected on plasma membrane preparations from TE‐671 muscle cells in 33% of PM sera (n = 12).Conclusion. In most sera from patients with PM, DM, and some other rheumatic diseases (i.e., SSc and SLE), autoantibodies directed against muscle‐cell surface antigens can be detected. Since these molecules are localized in the muscle‐cell surface membrane, autoantibodies directed against these antigens could play a major role in the pathogenesis of PM.
Autoimmunity to RNA polymerase II is focused at the carboxyl terminal domain of the large subunit
Authors: Hirakata Michito , Kanungo Jyotshna , Suwa Akira , Takeda Yoshihiko , Craft Joe , Hardin John A. 
Published: February 2007

AbstractObjective. Previous studies have demonstrated antibodies to the large (220 kd) polypeptide subunit of RNA polymerase II (Pol II) in sera from certain patients with scleroderma. In the present study, we sought to identify the autoantigenic region on this polypeptide.Methods. A recombinant fusion protein, corresponding to the 52‐heptapeptide repeat found in the carboxyl terminal domain (CTD) of the large Pol II subunit, was used to identify 15 patient sera that contained autoantibodies. Synthetic peptides CTD7 (representing a single heptapeptide) and CTD18 (representing 2½ heptapeptide repeats) were used in a competitive inhibition assay to define the specificity of these sera and the importance of the CTD as an autoantigen.Results. All 15 sera immunoprecipitated the Pol II subunit from radiolabeled cell extracts, and 11 of them bound the CTD fusion protein in immunoblots. Immunoprecipitation of Pol II was completely inhibited by CTD18 in 5 sera and partially inhibited in 4 additional sera.Conclusion. These results indicate that the CTD heptapeptide repeat is a focal point for autoimmune responses in scleroderma. It is likely that the repetitive sequence and high content of charged residues of this structure contribute to its role as an autoantigen.
Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A department of veterans affairs cooperative study
Authors: Clegg Daniel O. , Reda Domenic J. , Mejias Edwin , Cannon Grant W. , Weisman Michael H. , Taylor Thomas , Budiman‐Mak Elly , Blackburn Warren D. , Vasey Frank B. , Mahowald Maren L. , Cush John J. , Schumacher H. Ralph , Silverman Stuart L. , Alepa F. Paul , Luggen Michael E. , Cohen Miriam R. , Makkena Rama , Haakenson Clair M. , Ward Richard H. , Manaster B. J. , Anderson Robert J. , Ward John R. , Henderson William G. 
Published: February 2007

AbstractObjective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy.Methods. Two hundred twenty‐one patients with PsA were recruited from 15 clinics, randomized (double‐blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments.Results. Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea.Conclusion. SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.
Degradation of type II collagen, but not proteoglycan, correlates with matrix metalloproteinase activity in cartilage explant cultures
Authors: Kozaci L. Didem , Buttle David J. , Hollander Anthony P. 
Published: February 2007

AbstractObjective. To determine the contribution of certain matrix metalloproteinases (MMPs) to the degradation of proteoglycan and type II collagen in cartilage.Methods. Bovine nasal and articular cartilage explants were cultured with recombinant human interleukin‐1α (IL‐1α) for up to 4 weeks. Release of proteoglycan and type II collagen into the medium was determined by colorimetric assay and immunoassay, respectively. The activity of MMPs in the medium was assayed using a quenched fluorescent substrate, as well as with a collagen fibril assay, by zymography, and in Western immunoblots. In some experiments, the effects of specific MMP inhibitors on type II collagen degradation were studied.Results. In cultures of nasal cartilage with IL‐1α, almost all the proteoglycan was released within the first week, whereas there was no detectable release of type II collagen for the first 2 weeks of culture. A rapid period of almost complete dissolution of the collagen occurred in the third or fourth week. MMP activity measured using a quenched fluorescent substrate was negligible during the first 2 weeks of culture but was substantially increased in the third week of culture, at the time of collagen degradation. Similarly, there was a large increase in collagenolytic activity (by collagen fibril assay) and gelatinolytic activity (by zymography) during the third week of culture. Articular cartilage cultured with IL‐1α lost proteoglycan progressively during the 4‐week period; however, there was no loss of type II collagen from the matrix in that time and no significant increase in MMP activity. The loss of type II collagen from nasal cartilage stimulated with IL‐1α was inhibited by BB87, an inhibitor of both collagenases and gelatinases, and by BB3003, a selective inhibitor of gelatinase A. In Western immunoblots, procollagenase and active interstitial collagenase could be readily detected in nasal cartilage cultures. Some procollagenase 3 and active collagenase 3 was also shown to be present.Conclusion. MMP activity correlates with degradation of type II collagen, but not proteoglycan, in cartilage cultures. Interstitial collagenase, collagenase 3, and gelatinases are all likely to contribute to cleavage and removal of collagen from the cartilage matrix. The proteinase(s) responsible for aggrecan breakdown remains unclear.
Cd8high+ (CD57+) T cells in patients with rheumatoid arthritis
Authors: Wang Eddie C. Y. , Lawson Tom M. , Vedhara Kav , Moss Paul A. H. , Lehner Paul J. , Borysiewicz Leszek K. 
Published: February 2007

AbstractObjective. To investigate the development and T cell receptor (TCR) usage of CD8+, CD57+ T cells in rheumatoid arthritis (RA) patients.Methods. Three‐color flow cytometry using monoclonal antibodies (MAb) to CD8, CD57 and different TCR Vβ gene products.Results. The proportion of CD8+ T cells expressing CD57 (CD57/CD8) was significantly higher in RA patients compared with age‐matched controls. Expanded TCR Vβ populations were more frequent, and were found in both RA patient—derived CD8high+(CD57+) and CD8+, CD57– populations. TCR Vβ5+ and TCR Vβ13+ expansions were present at high frequency (5 of 26 and 7 of 26, respectively). TCR Vβ expansions in CD8high+(CD57+) lymphocytes from RA patients were significantly larger than those in age‐matched controls (expansion index 2.38 ± 0.28, n = 41 and 1.63 ± 0.09, n = 32, respectively), and were stable over time.Conclusion. RA leads to an increase in the frequency of expanded CD8+ T cell subsets expressing selected TCR, due to expansion of TCR Vβ+ populations in CD8high+(CD57+) T cells. Their restricted TCR usage suggests potential specificity for RA antigens and, therefore, a potential role in the pathogenesis of RA.
Nitric oxide production by superficial and deep articular chondrocytes
Authors: Hayashi Takeshi , Abe Etsuko , Yamate Tomoo , Taguchi Yasuto , Jasin Hugo E. 
Published: February 2007

AbstractObjective. Chondrocytes have been shown to produce large amounts of nitric oxide (NO) when appropriately stimulated with proinflammatory cytokines or bacterial lipopolysaccharide (LPS). In view of recent observations underscoring profound phenotypic differences between superficial and deep articular chondrocytes, these studies investigated NO production, inducible NO synthase (iNOS) activity, and messenger RNA (mRNA) expression of superficial and deep cartilage explants and cells.Methods. Superficial and deep bovine and human articular cartilage explants and isolated bovine chondrocytes were cultured in the presence of stimulating cytokines or LPS. NO was measured by the Griess reagent. Inducible NOS activity was quantitated by conversion of L‐14C‐arginine to L‐14C‐citrulline. Inducible NOS mRNA expression was quantitated by reverse transcription‐polymerase chain reaction (RT‐PCR) and in situ hybridization.Results. Superficial bovine cartilage explants stimulated with interleukin‐1α, LPS, or tumor necrosis factor α for 24 and 48 hours produced significantly more NO than did deep explants with all stimulants and at both times. Similar results were obtained with stimulated isolated superficial and deep cells. NO synthase activity, measured by the conversion of L‐14C‐arginine to L‐14C‐citrulline, paralleled NO production. Comparable results were obtained using explants from a normal human donor. Semiquantitation of iNOS mRNA by RT‐PCR showed significantly larger amounts of PCR products in superficial cells and superficial explants. These results were confirmed by in situ hybridization of explants and isolated cells.Conclusion. Increased NO production at the cartilage surface‐synovial fluid interface may play an important role in the modulation of cartilage damage in inflammatory arthritis.
Patterns of uveitis as a guide in making rheumatologic and immunologic diagnoses
Authors: Bañares Antonio , Jover Juan A. , Fernández‐Gutiérrez Benjamín , Del Castillo Jose M. Benítez , García Javier , Vargas Emilio , Hernández‐García César 
Published: February 2007

AbstractObjective. To describe the patterns of clinical presentation in a series of 407 patients with uveitis and to establish the relationship between these patterns and the final diagnosis.Methods. Patients were referred to the Uveitis Clinic of a tertiary hospital from January 1992 to January 1996. All patients received a complete ophthalmologic examination, and a general clinical history was obtained. The current International Uveitis Study Group classification system was used for anatomic classification. To establish the final diagnosis of the most common entities causing uveitis, current diagnostic criteria were used. A discriminant analysis, with diagnostic grouping as the outcome variable and the clinical presentation features as discriminating variables, was performed.Results. With our classification system, 66.5% of the cases could be correctly classified according to the clinical pattern and morphologic findings. By diagnostic groups, discriminant analysis showed that 75% of patients with Behçet's disease, 77.1% of those with spondylarthropathy (including inflammatory bowel disease), 33.3% of those with sarcoidosis, 97.9% of those with toxoplasmosis, 85.7% of those with Vogt‐Koyanagi‐Harada syndrome, 100% of those with herpes, and 50.4% of those with idiopathic uveitis were correctly classified. In the miscellaneous group, which included disease entities with fewer than 5 cases, 42.9% were correctly classified.Conclusion. Rheumatologic evaluation of the patient with uveitis can be more cost‐effective if the referring ophthalmologist follows the classification system described herein, allowing a tailored approach in which only specific and necessary diagnostic tests are used.
Total lymphoid irradiation in rheumatoid arthritis. A ten‐year followup
Authors: Westhovens Rene , Verwilghen Jo , Dequeker Jan 
Published: February 2007

AbstractObjective. To report the findings of a 10‐year followup of patients enrolled in a randomized trial of total lymphoid irradiation (TLI) versus chemotherapy for rheumatoid arthritis (RA).Methods. A retrospective analysis of the charts of 19 patients who had been included in a randomized trial comparing TLI and chemotherapy for the treatment of RA.Results. Ten years after the start of the trial, a higher number of TLI‐treated patients had died (7 of 10), compared with patients who had received chemotherapy (2 of 9). In addition, 3 of the TLI‐treated patients developed B cell—related malignancies, whereas no such malignancies developed in the control group.Conclusion. TLI was associated with a less‐favorable long‐term outcome than chemotherapy. These data stress the importance of careful long‐term followup in experimental trials of immunosuppressive agents.
Characteristic epitope recognition pattern of autoantibodies against eukaryotic ribosomal protein L7 in systemic autoimmune diseases
Authors: Neu Elli , Hemmerich Peter H. , Peter Hans‐Hartmut , Krawinkel Ulrich , von Mikecz Anna H. 
Published: February 2007

AbstractObjective. To define the epitope‐recognition pattern and the fine specificity of the autoantibody response to protein L7 in patients with rheumatic diseases.Methods. The epitope‐recognition pattern was studied by enzyme‐linked immunosorbent assay utilizing overlapping fragments of L7. The fine specificity was examined by binding inhibition and isoelectric focusing.Results. We observed a disease‐specific epitope‐recognition pattern of anti‐L7 autoantibodies. There was one immunodominant epitope that was recognized by all anti‐L7‐positive sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc). Additional recognition of minor epitopes was observed; it arises by intramolecular epitope spreading and was correlated with disease activity in SLE patients. SSc patients differed from SLE and RA patients in that their sera did not recognize certain minor epitopes. The major epitope was recognized by high‐affinity autoantibodies of limited heterogeneity. Minor epitopes were recognized by heterogeneous low‐affinity autoantibodies.Conclusion. The anti‐L7 autoantibody response is oligoclonal. Additional B cell clones are activated by antigen during active phases of disease.
Risk factors for incident radiographic knee osteoarthritis in the elderly. The framingham study
Authors: Felson David T. , Zhang Yuqing , Hannan Marian T. , Naimark Allan , Weissman Barbara , Aliabadi Piran , Levy Daniel 
Published: February 2007

AbstractObjective. Knee osteoarthritis (OA) is highly prevalent, especially in the elderly. Preventive strategies require a knowledge of risk factors that precede disease onset. The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population.Methods. A longitudinal study of knee OA involving members of the Framingham Study cohort was performed. Weight‐bearing knee radiographs were obtained in 1983–1985 (baseline) and again in 1992–1993. Incident disease was defined as the occurrence of new radiographic OA (Kellgren and Lawrence grade ⩾2 on a 0–4 scale) in those without radiographic OA at baseline. Risk factors assessed at baseline and in the interim were tested in univariate and multivariate equations to evaluate their association with incident knee OA.Results. Of 598 patients without knee OA at baseline (mean age 70.5 years, 63.7% women), 93 (15.6%) developed OA. After adjustment for multiple risk factors, women had a higher risk of OA than did men (adjusted odds ratio [OR] = 1.8, 95% confidence interval [95% CI] 1.1–3.1). Higher baseline body mass index increased the risk of OA (OR = 1.6 per 5‐unit increase, 95% CI 1.2–2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10‐lb change in weight, 95% CI 1.1–1.8). Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4–7.5). Smokers had a lower risk than did nonsmokers (for those who smoked an average of ⩾10 cigarettes/day, OR = 0.4, 95% CI 0.2–0.8). Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA. Weight‐related factors affected the risk of OA only in women.Conclusion. Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA.
Cytokine concentrations in bronchoalveolar lavage fluid of patients with systemic sclerosis
Authors: Bolster Marcy B. , Ludwicka Anna , Sutherland Susan E. , Strange Charlie , Silver Richard M. 
Published: February 2007

AbstractObjective. The pathophysiology of pulmonary fibrosis in patients with systemic sclerosis (SSc) is poorly understood, but a number of recent studies have demonstrated an inflammatory process involving the lower respiratory tract. The objective of the present study was to determine the concentrations of several cytokines in the bronchoalveolar lavage (BAL) fluid of patients with SSc and to assess whether the enhanced expression of certain cytokines is associated with the presence of alveolitis.Methods. BAL was performed on patients with SSc (with or without alveolitis) and on normal control subjects. Lyophilized BAL fluid samples were assayed by enzyme‐linked immunosorbent assay for tumor necrosis factor α (TNFα), interleukin‐1α (IL‐1α), IL‐4, IL‐6, IL‐8, macrophage inflammatory protein 1α (MIP‐1α), and RANTES.Results. There were significant differences between groups in the BAL fluid concentrations of TNFα (P = 0.0005, with levels in SSc patients with alveolitis higher than those in normal controls), IL‐8 (P = 0.006, with levels in both SSc groups higher than those in normal controls), MIP‐1α (P = 0.009, with levels in SSc patients with alveolitis higher than those in SSc patients without alveolitis and than those in normal controls), and RANTES (P = 0.03, with levels in SSc patients without alveolitis higher than those in normal controls). With the exception of RANTES, the highest levels were detected in SSc patients with alveolitis.Conclusion. Each of these cytokines, either alone or in combination, may play an important role in the pathogenesis of pulmonary fibrosis in SSc.
An unusual case of carcinoma polyarthritis with associated vasculitis
Authors: Madiedo Jose M. Acosta , Murthy Anant , Cortese Denis A. , Cohen Marc D. 
Published: February 2007

AbstractThis report describes a patient who presented with an unusual polyarthritis syndrome. After extensive evaluation, squamous cell carcinoma of the lung was diagnosed. During the course of the illness, the patient developed vasculitic features and “rheumatoid‐like” nodules. Two months after the administration of combined‐modality therapy for stage IIIA non‐small cell lung carcinoma, the signs and symptoms of polyarthritis and vasculitis had disappeared completely. Ten months later, the patient remains in clinical remission. This is the first published report of simultaneous vasculitic and polyarticular manifestations in a patient with carcinoma polyarthritis.
The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in patients with Systemic Lupus Erythematosus
Authors: Gladman Dafna D. , Urowitz Murray B. , Goldsmith Charles H. , Fortin Paul , Ginzler Ellen , Gordon Caroline , Hanly John G. , Isenberg David A. , Kalunian Kenneth , Nived Ola , Petri Michelle , Sanchez‐Guerrero Jorge , Snaith Michael , Sturfelt Gunnar 
Published: February 2007

AbstractObjective. To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE.Methods. Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design.Results. The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI.Conclusion. Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.
Selective activation of the JNK/AP‐1 pathway in FAS‐mediated apoptosis of rheumatoid arthritis synoviocytes
Authors: Okamoto Kazuyoshi , Fujisawa Koushi , Hasunuma Tomoko , Kobata Tetsuji , Sumida Takayuki , Nishioka Kusuki 
Published: February 2007

AbstractObjective. To evaluate the Fas‐dependent signaling pathway, we examined the involvement of protein tyrosine phosphorylation and the DNA binding activity of AP‐1 in rheumatoid arthritis (RA) cultured synovial cells.Methods. The number of dead cells was counted after treatment with anti‐Fas antibody in the presence of protein tyrosine kinase or phosphatase inhibitor. Protein tyrosine phosphorylation in synoviocytes after Fas ligation was examined by immunoblot and immunoprecipitation analyses. The DNA binding activity of AP‐1 was examined by electrophoretic mobility shift assay.Results. Treatment with the protein tyrosine phosphatase inhibitor, orthovanadate, significantly enhanced the apoptosis of RA synoviocytes after Fas ligation. Ligation of the Fas molecule on RA synoviocytes induced a rapid tyrosine phosphorylation of JNK (c‐Jun amino‐terminal kinase) and formation of the AP‐1 transcription factor.Conclusion. Our results strongly suggest that the JNK/AP‐1 signaling pathway is activated during the process of Fas‐mediated apoptosis of RA synovial cells.