bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular adhesion molecules in rat adjuvant arthritis
Authors: Halloran Margaret M. , Szekanecz Zoltan , Barquin Nora , Haines G. Kenneth , Koch Alisa E. 
Published: February 2007

AbstractObjective. To examine adhesion molecule expression during the progression of inflammation in a rheumatoid arthritis model of adjuvant‐induced arthritis (AIA) in rats.Methods. Immunohistochemical analysis was used to determine the distribution of the following adhesion molecules: lymphocyte function–associated antigen 1 (LFA‐1; CD11a/CD18), Mac‐1 and p150/95 (CD11bc/CD18), intercellular adhesion molecule 1 (ICAM‐1), and CD44 in tissue sections from the ankle joints of rats with AIA. Control animals and those with AIA were killed at intervals over a 54‐day period after injection with mineral oil and Mycobacterium butyricum, respectively.Results. CD44 and LFA‐1 were expressed on lymphocytes, macrophages, and synovial (ST) lining cells. CD44 expression on macrophages was found to be increased compared with control animals by day 18, and was significantly increased by day 41. CD44 expression on lymphocytes significantly increased earlier, on days 11–18. Increased LFA‐1 expression on macrophages occurred late, on day 41. LFA‐1 expression on lymphocytes was significantly increased on days 25, 47, and 54. ST lining cells exhibited two distinct periods of increased expression, one early, on days 11–25 and one later, on days 41–54. CD11b/c was expressed on macrophages and ST lining cells, showing a significant increase on AIA rat ST lining cells compared with control animals on day 4. No differences in ICAM‐1 expression on endothelial cells between rats with AIA and controls were found on any of the days examined.Conclusion. CD44 expression is up‐regulated on macrophages and lymphocytes during the early development of AIA, while LFA‐1 expression is up‐regulated later in the development of AIA. The up‐regulation of CD44 and LFA‐1 at different times in the development of AIA suggests an important role for these adhesion molecules in establishing and sustaining an inflammatory response in the AIA joint.
Prevention and reversal of cartilage degradation in rheumatoid arthritis by interleukin‐10 and interleukin‐4
Authors: van Roon Joel A. G. , van Roy Johanna L. A. M. , Gmelig‐Meyling Frits H. J. , Lafeber Floris P. J. G. , Bijlsma Johannes W. J. 
Published: February 2007

AbstractObjective. Inflammation‐induced articular cartilage degradation is a major problem in rheumatoid arthritis (RA). Type 1 T cell activity (characterized by interferon‐γ/interleukin‐2 [IL‐2] production), and consequently, the production of the proinflammatory cytokines IL‐1 and tumor necrosis factor α (TNFα), have been reported to play a major role in cartilage damage. IL‐10 and IL‐4, both produced by type 2 T cells, are cytokines with the capacity to down‐regulate proinflammatory responses. The present study was undertaken to investigate the way in which these cytokines affect activated mononuclear cells (MNC) of RA patients in relation to human articular cartilage degradation in vitro.Methods. MNC from synovial fluid and peripheral blood of RA patients were stimulated with bacterial antigen and treated with IL‐10 and/or IL‐4. Bacterial antigen is known to activate type 1 T cells and to induce proinflammatory IL‐1/TNFα–dependent cartilage damage. Cytokine production and effects of conditioned media, as well as effects of IL‐10 and IL‐4 on proteoglycan (PG) turnover (as a measure for cartilage damage), were determined.Results. IL‐10 and IL‐4 inhibited proinflammatory cytokine production of stimulated RA MNC and completely reversed inhibition of cartilage PG synthesis induced by these stimulated RA MNC. IL‐10 was more potent than IL‐4 in this respect, and the combination of IL‐10 and IL‐4 had an additive effect. In addition, IL‐10 directly stimulated cartilage PG synthesis.Conclusion. IL‐10 reverses the cartilage degradation induced by antigen‐stimulated MNC, and IL‐4 has an additive effect on this process. Furthermore, IL‐10 has a direct stimulatory effect on PG synthesis, and IL‐4, as a growth factor for type 2 T cells, can reduce the ratio of type 1 to type 2 T cell activity. These results provide evidence in favor of the use of a combination of the two cytokines in the treatment of RA.
Strong association of dermatomyositis‐specific Mi‐2 autoantibodies with a tryptophan at position 9 of the HLA‐DRβ chain
Authors: Mierau Rudolf , Dick Thomas , Bartz‐Bazzanella Peter , Keller Elisabeth , Albert Ekkehard D. , Genth Ekkehard 
Published: February 2007

AbstractObjective. To characterize the clinical and immunogenetic features of patients with Mi‐2 autoantibodies.Methods. Eighteen adult white patients with Mi‐2 antibodies were clinically characterized and compared with 41 Mi‐2–negative dermatomyositis (DM) patients. HLA class I and class II typing for DRB alleles was done by microcytotoxicity assay and for DQA and DQB alleles by polymerase chain reaction–based oligotyping.Results. Seventeen of the 18 Mi‐2–positive patients had DM. Symptoms of scleroderma, lung involvement, and arthritis were less common in this group than in the Mi‐2–negative DM patients; the V‐sign rash and nailfold involvement were found more frequently. Mi‐2 antibodies were strongly associated with HLA‐DR7 (88% versus 24% in healthy controls), HLA–DQA1*0201 (86% versus 23%), and DR7 “homozygosity” (31% versus 0%). A tryptophan residue at position 9 of the HLA–DRβ chain was present in all Mi‐2–positive patients (100% versus 62%; homozygous in 81% versus 15%).Conclusion. Our results reemphasize the specificity of Mi‐2 antibodies for DM, and extend previous reports that Mi‐2 antibody production is associated with certain HLA class II antigens. We propose β9‐Trp as a candidate epitope on the HLA–DRβ chain as a prerequisite for this type of autoimmune response.
Chronic intestinal pseudoobstruction associated with autoantibodies against proliferating cell nuclear antigen
Authors: Nojima Yoshihisa , Mimura Toshihide , Hamasaki Ken , Furuya Hiroko , Tanaka Go , Nakajima Atsushi , Matsuhashi Nobuyuki , Yazaki Yoshio 
Published: February 2007

AbstractAutoantibodies against proliferating cell nuclear antigen (PCNA) have been detected almost exclusively in sera from patients with systemic lupus erythematosus (SLE). Because of the extremely low prevalence of anti‐PCNA, however, it has been difficult to establish its disease specificity and clinical associations. We present 2 cases in which patients with anti‐PCNA developed severe gastrointestinal dysfunction that led to chronic intestinal pseudoobstruction. Neither patient had manifestations suggestive of SLE. Although sclerodermatous skin changes were minimal or absent in these patients, physical and radiographic findings indicated that systemic sclerosis was a likely cause of the gastrointestinal dysfunction. The similarity of the clinical features in these patients implies that the unusual detection of this unique autoantibody may not be a coincidence.
Synergy between T cell receptor β gene polymorphism and HLA–DR4 in susceptibility to rheumatoid arthritis
Authors: Mu Hua , Charmley Patrick , King Mary‐Claire , Criswell Lindsey A. 
Published: February 2007

AbstractObjective. To investigate the etiologic significance of germline polymorphisms in the T cell receptor β variable region 6S7 (TCRBV6S7) gene segment and adjacent loci in susceptibility to rheumatoid arthritis (RA).Methods. Ten TCRB allelic polymorphisms were analyzed from 3 groups of white women: 112 with RA, 72 with systemic lupus erythematosus, and 70 healthy controls. All participants were also HLA typed.Results. HLA–DR4+ RA patients showed significantly increased frequencies of TCRBV6S7*1, 13S5P*1 (an allelic variant of BV13S5 promoter), and 12S4*2, compared with healthy controls. The combination of DR4 with either BV6S7*1, 13S5P*1, or 12S4*2 conferred greater risk for RA than HLA–DR4 alone. Pairwise analyses showed a high degree of linkage disequilibrium (P = 10−5‐10−8) between these 3 TCRBV loci that span 47 kilobases (kb).Conclusion. Our data suggest that a TCR gene segment in or linked to this 47‐kb region may be involved in genetic susceptibility to RA through an interaction with HLA–DR4.
Molecular detection of bacterial DNA in venereal‐associated arthritis
Authors: Li Feng , Bulbul Rula , Schumacher H. Ralph , Kieber‐Emmons Thomas , Callegari Peter E. , von Feldt Joan M. , Norden Daniel , Freundh Bruce , Wang Bin , Imonitie Victor , Chang Cheng Pei , Nachamkin Irving , Weiner David B. , Williams William V. 
Published: February 2007

AbstractObjective. To evaluate the utility of polymerase chain reaction (PCR) amplification in detecting DNA from venereal‐associated microorganisms in the synovial fluid of patients with inflammatory arthritis.Methods. Oligonucleotide primers were developed for nested PCR based on Chlamydia, Ureaplasma, and Neisseria DNA sequences. PCR products were detected by gel electrophoresis and dot‐blot hybridization. Primers specific for the target bacterial DNA were used to search for bacterial DNA in 61 synovial fluid specimens from patients with inflammatory arthritis, including several clinically associated with venereal infection.Results. Five of the 61 synovial fluid specimens were positive for Neisseria gonorrhoeae DNA. Four of the 5 patients had clinical diagnoses of gonococcal arthritis; the other patient had an unexplained monarthritis. One specimen from a patient with a clinical diagnosis of gonococcal arthritis was negative for N gonorrhoeae. Three of the 61 specimens were positive for Chlamydia DNA. Two were derived from patients with clinical diagnoses of reactive arthritis or Reiter's syndrome, and 1 was from a patient with unexplained monarthritis. One of the 61 specimens was positive for Ureaplasma DNA; this sample was from a patient with a clinical diagnosis of Reiter's syndrome. In an additional patient with Reiter's syndrome, Ureaplasma DNA was also found in prostate biopsy tissue and a urine sample obtained after prostate massage (synovial fluid not available).Conclusion. These data support the classification of these 3 venereal‐associated arthritides as infectious processes, and suggest that PCR for bacterial DNA is a useful method for detecting infectious agents in synovial fluid.
Risk of osteoarthritis associated with long‐term weight‐bearing sports: A radiologic survey of the hips and knees in female ex‐athletes and population controls
Authors: Spector Tim D. , Harris Pat A. , Hart Deborah J. , Cicuttini Flavia M. , Nandra Dalbir , Etherington John , Wolman Roger L. , Doyle David V. 
Published: February 2007

AbstractObjective. To estimate the risk of osteoarthritis (OA) of the hip and knee due to long‐term weight‐bearing sports activity in ex–elite athletes and the general population.Methods. A retrospective cohort study was conducted of 81 female ex–elite athletes (67 middle‐ and long‐distance runners, and 14 tennis players), currently ages 40–65, recruited from original playing records, and 977 age‐matched female controls, taken from the age–sex register of the offices of a group general practice in Chingford, Northeast London, England. The definition of OA included radiologic changes (joint space narrowing and osteophytosis) in the hip joints, patellofemoral (PF) joints, and tibiofemoral (TF) joints.Results. Compared with controls of similar age, the ex‐athletes had greater rates of radiologic OA at all sites. This association increased further after adjustment for height and weight differences, and was strongest for the presence of osteophytes at the TF joints (odds ratio [OR] 3.57, 95% confidence interval [95% CI] 1.89–6.71), at the PF joints (OR 3.50, 95% CI 1.80–6.81), narrowing at the PF joints (OR 2.97, 95% CI 1.15–7.67), femoral osteophytes (OR 2.52, 95% CI 1.01–6.26), and hip joint narrowing (OR 1.60, 95% CI 0.73–3.48), and was weakest for narrowing at the TF joints (OR 1.17, 95% CI 0.71–1.94). No clear risk factors were seen within the ex‐athlete groups, although the tennis players tended to have more osteophytes at the TF joints and hip, but the runners had more PF joint disease. Within the control group, a small subgroup of 22 women who reported long‐term vigorous weight‐bearing exercise had risks of OA similar to those of the ex‐athletes. Ex‐athletes had similar rates of symptom reporting but higher pain thresholds than controls, as measured by calibrated dolorimeter.Conclusion. Weight‐bearing sports activity in women is associated with a 2–3‐fold increased risk of radiologic OA (particularly the presence of osteophytes) of the knees and hips. The risk was similar in ex–elite athletes and in a subgroup from the general population who reported long‐term sports activity, suggesting that duration rather than frequency of training is important.
Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin a
Authors: Pasero Giampiero , Priolo Francesco , Marubini Ettore , Fantini Flavio , Ferraccioli Gianfranco , Magaro Mario , Marcolongo Roberto , Oriente Pasquale , Pipitone Vincenzo , Portioli Italo , Tirri Giuseppe , Trotta Francesco , Casa‐Alberighi Ornella Della 
Published: February 2007

AbstractObjective. To evaluate the ability of low‐dose cyclosporin A (CsA) to control radiologic disease progression, and to assess the clinical efficacy and tolerability of CsA, compared with conventional disease‐modifying antirheumatic drugs (DMARDs), in patients with early active rheumatoid arthritis (RA).Methods. In this long‐term, multicenter, prospective, open, blinded end point, randomized trial, 361 consenting patients with early (< 4 years since diagnosis) active RA were enrolled. Of the eligible patients, 167 were treated with CsA at 3 mg/kg/day, and 173 with DMARDs. The decision to use conventional antirheumatic drugs as controls was based on the fact that joint erosion could be expected to occur after 1 year regardless of the type of DMARD being used. The possibility of switching therapies in both groups was intended to keep the largest possible number of patients in the study.Results. Blinded evaluation of hand and foot radiographs after 12 months of treatment showed that CsA led to a significant (P < 0.001) delay in the mean ± SD progression in the eroded joint count (1.3 ± 3.1 versus 2.4 ± 3.0 for the control group) and in the joint damage score (3.6 ± 8.9 versus 6.9 ± 9.1 for the control group), both measured by the Larsen‐Dale method. When only the patients without erosion at baseline were considered (37 in the CsA‐treated group and 54 in the control group), erosion appeared in only 10.8% of the CsA‐treated patients, but in 51.8% of the controls (P = 0.00005). Low‐dose CsA was as effective as traditional DMARDs in controlling clinical symptoms. Maintenance on the initially prescribed treatment regimen (“survival on treatment”) was also better at 12 months with CsA than with DMARDs (89.2% versus 77.5%; P = 0.002). The tolerability of CsA was acceptable.Conclusion. These 12‐month results suggest that low‐dose CsA decreases the rate of further joint damage in previously involved joints as well as the rate of new joint involvement in previously uninvolved joints, in patients with early RA.
Acute febrile toxic reaction in patients with refractory rheumatoid arthritis who are receiving combined therapy with methotrexate and azathioprine
Authors: Blanco Ricardo , Martínez‐Taboada Victor M. , González‐Gay Miguel A. , Armona Jose , Fernández‐Sueiro Jose L. , Gonzaléz‐Vela M. Carmen , Rodríguez‐Valverde Vicente 
Published: February 2007

AbstractObjective. To assess the frequency and clinical features of an acute febrile toxic reaction (AFTR) in patients with refractory rheumatoid arthritis (RA) receiving combined therapy with methotrexate (MTX) and azathioprine (AZA).Methods. A cohort of 43 RA patients being treated with MTX/AZA combination therapy were studied. In all of them, RA had been refractory to single‐therapy disease‐modifying antirheumatic drugs. We analyzed the frequency and clinical features of AFTR, which consisted mainly of the development of fever, leukocytosis, and cutaneous leukocytoclastic vasculitis when AZA was added to the MTX regimen.Results. Four of the 43 patients (9.3%) who had been receiving long‐term, well‐tolerated treatment with MTX (mean ± SD 375.5 ± 159.5 days, range 227–561 days) developed AFTR shortly (mean ± SD 25.7 ± 13.6 days, range 17–46 days) after the addition of AZA to the regimen. The AFTR resolved rapidly (3 ± 1.4 days) after discontinuation of AZA and MTX. In 2 cases, rechallenge with AZA and MTX was linked to a new flare of AFTR.Conclusion. The knowledge of this side effect is particularly important because it mimics a severe infectious complication related to immunosuppressive therapy, and because rechallenge can produce severe toxicity. Most of the new combined therapies for RA do not seem to be more toxic than single‐drug treatment. Nevertheless, clinicians should be aware of a possible increase in side effects due to drug interactions or some other unidentified mechanism.
Depressive symptoms associated with scleroderma
Authors: Roca Robert P. , Wigley Fredrick M. , White Barbara 
Published: February 2007

AbstractObjective. To examine the prevalence and correlates of depressive symptoms among patients with systemic sclerosis (SSc; scleroderma).Method. Fifty‐four outpatients with scleroderma were administered the Beck Depression Inventory, the Neuroticism‐Extraversion‐Openness Personality Inventory, the Health Assessment Questionnaire, and the Psychosocial Adjustment to Illness Scale. In addition, patients underwent a comprehensive clinical assessment, and pulmonary function tests were obtained.Results. Nearly half of the patients had mild depressive symptoms, and an additional 17% had symptoms in the moderate‐to‐severe range. Younger patients, those with digital ulceration, and those with more self‐rated functional impairment had more depressive symptoms, but there were few other relationships between depressive symptoms and either demographic or physician‐rated medical variables. In contrast, there were highly significant relationships between depression and aspects of personality, psychosocial adjustment to illness, and social support.Conclusion. Depressive symptoms in patients with SSc are more strongly related to personality, self‐rated disability, and adequacy of emotional support than to objective medical indices of illness severity. Depression in scleroderma is a debilitating comorbid condition that should be recognized and treated in its own right.
Malignancy in systemic lupus erythematosus
Authors: Abu‐Shakra Mahmoud , Gladman Dafna D. , Urowitz Murray B. 
Published: February 2007

AbstractObjective. To estimate the risk of cancer in patients with systemic lupus erythematosus (SLE).Methods. Patients with SLE (n = 724) have been followed prospectively, for 24 years, at the University of Toronto Lupus Clinic. The diagnosis of cancer was confirmed by histologic or autopsy reports. Standardized rates of cancer and standardized incidence rates (SIR) (ratio of observed‐to‐expected cancers) were used to estimate the risk for cancers.Results. Twenty‐four cancers were identified in 23 SLE patients (3.2%) during 7,233 patient‐years of followup. Compared with the Ontario population, the overall estimated risk for all cancers was not increased in the lupus cohort (SIR 1.08, 95% confidence interval 0.70–1.62). A 4.1‐fold increased risk for hematologic cancers was observed, due mainly to an increased risk of non‐Hodgkin's lymphoma. The risk for cancer was significantly lower in the SLE cohort compared with patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc).Conclusion. SLE is associated with a lower risk of all cancers compared with RA and SSc, but an increased risk for non‐Hodgkin's lymphoma compared with the general population.
Decrease in cellularity and expression of adhesion molecules by anti–tumor necrosis factor α monoclonal antibody treatment in patients with rheumatoid arthritis
Authors: Tak Paul P. , Taylor Peter C. , Breedveld Ferdinand C. , Smeets Tom J. M. , Daha Mohamed R. , Kluin Philip M. , Meinders A. Edo , Maini Ravinder N. 
Published: February 2007

AbstractObjective. The effect of chimeric anti–tumor necrosis factor α (TNFα) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti‐TNFα therapy leads to down‐regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST).Methods. The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti‐TNFα MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA). The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mg/kg (n = 7).Results. A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E‐selectin, was observed after therapy with 10 mg/kg or 20 mg/kg of cA2 in RA patients.Conclusion. The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis the antiinflammatory effect of anti‐TNFα therapy might be partly explained by down‐regulation of cytokine‐inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.
Dose‐range and dose‐frequency study of recombinant human interleukin‐1 receptor antagonist in patients with rheumatoid arthritis
Authors: Campion G. V. , Lebsack M. E. , Lookabaugh J. , Gordon G. 
Published: February 2007

AbstractObjective. To preliminarily evaluate the safety and efficacy of different dose levels and dosing frequencies of recombinant human interleukin‐1 receptor antagonist (rHuIL‐1Ra) in the treatment of patients with rheumatoid arthritis (RA).Methods. One hundred seventy‐five patients with active RA were enrolled in a randomized, double‐blind trial of rHuIL‐1Ra administered by subcutaneous injection. There were 9 treatment groups in the trial. During the initial 3‐week treatment phase, patients were treated with 20, 70, or 200 mg rHuIL‐1Ra, administered either once, 3 times, or 7 times per week, followed by a 4‐week maintenance phase, during which all patients received the treatment‐phase dose once per week. To maintain the blindness of the study, patients received daily injections of either rHuIL‐1Ra or placebo on the days rHuIL‐1Ra was not administered.Results. Recombinant HuIL‐1Ra was well tolerated. The most frequent adverse event was injection‐site reactions, which were reported in 62% of patients and caused 8 patients (5%) to withdraw prematurely from the study. Five patients (3%) developed serious adverse reactions unrelated to dose or dosing frequency. Due to the lack of a placebo arm and to the multiple small treatment groups, a definitive statement regarding efficacy could not be made. However, by the end of the 3‐week treatment phase, daily dosing appeared more effective than weekly dosing when assessed by the number of swollen joints, the investigator and patient assessments of disease activity, pain score, and C‐reactive protein levels.Conclusion. These preliminary data suggest that rHuIL‐1Ra may be safely administered by subcutaneous injection to RA patients. The frequency of dosing appears to be important in determining clinical response, with daily administration providing the most benefit. A placebo‐controlled trial is in progress to further assess the clinical usefulness and to better define appropriate doses of rHuIL‐1Ra in patients with RA.