bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of major histocompatibility complex/human cartilage gp‐39 complexes in rheumatoid arthritis synovitis as a specific and independent histologic marker
Authors: Baeten Dominique , Steenbakkers Peter G. A. , Rijnders Antonius M. W. , Boots Annemieke M. , Veys Eric M. , De Keyser Filip 
Published: February 2004

AbstractObjectivePeptide 263–275 is the immunodominant epitope of human cartilage (HC) gp‐39, a candidate autoantigen in rheumatoid arthritis (RA). We recently generated and characterized a monoclonal antibody (mAb) called 12A, which is directed against HLA–DR4/HC gp‐39263–275 complexes and inhibits specific T cell responses in vitro. The aim of the present study was to analyze whether presentation of the immunodominant epitope of HC gp‐39 by shared epitope–positive synovial dendritic cells is a specific event in the development of chronic synovial inflammation in RA.MethodsStaining with mAb 12A was performed on synovium obtained from clinically swollen joints in 65 patients with RA and 67 non‐RA controls and from joints without clinical effusion in 9 additional patients with RA.ResultsMonoclonal antibody 12A staining was observed in the synovium of 40 of the 65 patients with RA. Histologically, expression of HC gp‐39, lymphoid aggregates, CD3, and CD1a as well as the global inflammation score were higher in mAb 12A–positive RA synovium than in mAb 12A–negative synovium, indicating a follicular synovitis in these samples. Accordingly, mAb 12A stained dendritic cells in the close vicinity of lymphoid aggregates. No mAb 12A staining was detected in synovium obtained from RA joints without effusion. Clinically, there were no correlations between mAb 12A staining and clinical or biologic parameters in RA. However, positive staining was observed in 61.5% of the inflamed RA synovial samples compared with only 3.0% of the control samples (P < 0.001). This mAb 12A staining was not related to intracellular citrullinated peptides, which are another specific histologic marker for RA.ConclusionPresentation by synovial dendritic cells of the immunodominant epitope of HC gp‐39, in the context of the shared epitope, is associated with characteristic histologic features of follicular synovitis and is highly specific for RA. This suggests a contribution to the autoimmune‐related tissue inflammation and provides a new and independent tool for the immunopathologic diagnosis of RA.
Once‐weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: Results of a multicenter, randomized, double‐blind, placebo‐controlled trial
Authors: Keystone Edward C. , Schiff Michael H. , Kremer Joel M. , Kafka Shelly , Lovy Michael , DeVries Todd , Burge Daniel J. 
Published: February 2004

AbstractObjectiveTo evaluate the safety, efficacy, and pharmacokinetics of 50 mg etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA).MethodsFour hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg etanercept once weekly, 153 received 25 mg etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8.ResultsAn ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg etanercept once weekly, by 49% of the patients receiving 25 mg etanercept twice weekly, and by 19% of the patients in the placebo group (P ≤ 0.0001 for each etanercept group versus placebo). Similarly, achievement of the ACR50 response was attained by 18% of patients in each of the 2 etanercept groups, compared with 6% of patients in the placebo group (P < 0.03 for each comparison). Pharmacokinetics of the 2 etanercept regimens were similar at steady state. No clinically significant differences in efficacy or safety were observed between the 2 etanercept groups.ConclusionSafety, efficacy, and pharmacokinetics were comparable between the 2 etanercept dosing regimens. Thus, comparable clinical outcomes are to be expected when patients are treated with etanercept administered either as 50 mg once weekly or as 25 mg twice weekly.
Vβ‐restricted T cell adherence to endothelial cells: A mechanism for superantigen‐dependent vascular injury
Authors: Brogan P. A. , Shah V. , Klein N. , Dillon M. J. 
Published: February 2004

AbstractObjectiveTo investigate the potential for endothelial cells to operate as superantigen‐presenting cells for T cells and the potential for such an interaction to cause endothelial cell activation and injury.MethodsClass II major histocompatibility complex (MHC)–positive human umbilical vein endothelial cells (HUVECs) were cocultured for 4 hours with purified T cells and the superantigens staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST‐1). After staining with fluorescence‐conjugated monoclonal antibodies, flow cytometric analysis was performed on the HUVECs and T cells to examine Vβ‐restricted T cell adherence to the endothelial cell monolayer, Vβ‐restricted T cell activation (CD69 up‐regulation), surface expression of endothelial cell activation markers, and generation of endothelial microparticles (EMPs).ResultsCoculture of purified T cells with class II MHC–positive HUVECs and either TSST‐1 or SEB resulted in Vβ‐restricted CD69 up‐regulation by CD4 and CD8 cells (Vβ2 activation for TSST‐1; Vβ3, Vβ5.1, and Vβ12 activation for SEB). Additionally, there was CD4 and CD8 T cell Vβ‐restricted adherence to the HUVEC monolayer at 4 hours. Expression of intercellular adhesion molecule 1, E‐selectin, and vascular cell adhesion molecule 1 was up‐regulated on the class II MHC–positive HUVECs following exposure to superantigen in the presence of T cells, and there was increased EMP release from activated HUVECs, which occurred earlier and was of greater magnitude than that observed in response to tumor necrosis factor α.ConclusionClass II MHC–positive endothelial cells operate as competent superantigen‐presenting cells for CD4 and CD8 lymphocytes in vitro. Dual signaling between endothelial cells and T cells results in Vβ‐restricted activation and adherence to endothelial monolayers and endothelial cell activation and release of EMPs expressing inducible cell adhesion molecules. It is proposed that this mechanism could account in part for the vascular injury associated with superantigen‐mediated diseases including Kawasaki disease.
Ameliorative effects of follistatin‐related protein/TSC‐36/FSTL1 on joint inflammation in a mouse model of arthritis
Authors: Kawabata Daisuke , Tanaka Masao , Fujii Takao , Umehara Hisanori , Fujita Yoshimasa , Yoshifuji Hajime , Mimori Tsuneyo , Ozaki Shoichi 
Published: February 2004

AbstractObjectiveTo clarify the in vivo function of follistatin‐related protein (FRP)/TSC‐36/FSTL1 in rheumatoid arthritis (RA), we investigated the roles of FRP in a mouse model of arthritis.MethodsArthritis was induced in BALB/c mice by injecting anti–type II collagen monoclonal antibody and lipopolysaccharide. Mice were treated with daily intraperitoneal injections of 20 μg of recombinant FRP. Development of arthritis was assessed by the clinical score and footpad swelling. Histologic examination of affected paws was performed on day 21 after the onset of arthritis. The gene expression profiles of affected paws in FRP‐treated and untreated mice were compared using commercially available complementary DNA (cDNA) arrays. The difference in gene expression was confirmed by real‐time quantitative reverse transcription–polymerase chain reaction.ResultsTreatment with recombinant FRP showed significant amelioration of the arthritis severity. Histologic analyses confirmed this finding and revealed the alleviation of cellular infiltration into the synovium as well as cartilage damage. The significant decrease in the amount of urinary deoxypyridinoline also indicated the ameliorative effect of FRP on joint destruction. Moreover, cDNA array analysis of the gene expression profile in FRP‐treated arthritic lesions revealed a reduced expression of the c‐fos, ets‐2, IL6, MMP3, and MMP9 genes, some of which are thought to be associated with synovial inflammation and joint destruction.ConclusionThese findings from in vivo experiments suggest that FRP could be one of the key molecules in the treatment of inflammatory joint diseases such as RA.
Reliability of the knee examination in osteoarthritis: Effect of standardization
Authors: Cibere Jolanda , Bellamy Nicholas , Thorne Anona , Esdaile John M. , McGorm Kelly J. , Chalmers Andrew , Huang Simon , Peloso Paul , Shojania Kam , Singer Joel , Wong Hubert , Kopec Jacek 
Published: February 2004

AbstractObjectiveTo assess the reliability of physical examination of the osteoarthritic (OA) knee by rheumatologists, and to evaluate the benefits of standardization.MethodsForty‐two physical signs and techniques were evaluated using a 6 × 6 Latin square design. Patients with mild to severe knee OA, based on physical and radiographic signs, were examined in random order prior to and following standardization of techniques. For those signs with dichotomous scales, agreement among the rheumatologists was calculated as the prevalence‐adjusted bias‐adjusted kappa (PABAK), while for the signs with continuous and ordinal scales, a reliability coefficient (Rc) was calculated using analysis of variance. A PABAK of >0.60 and an Rc of >0.80 were considered to indicate adequate reliability.ResultsAdequate poststandardization reliability was achieved for 30 of 42 physical signs/techniques (71%). The most highly reliable signs identified by physical examination of the OA knee included alignment by goniometer (Rc = 0.99), bony swelling (Rc = 0.97), general passive crepitus (Rc = 0.96), gait by inspection (PABAK = 0.78), effusion bulge sign (Rc = 0.97), quadriceps atrophy (Rc = 0.97), medial tibiofemoral tenderness (Rc = 0.94), lateral tibiofemoral tenderness (Rc = 0.85), patellofemoral tenderness by grind test (Rc = 0.94), and flexion contracture (Rc = 0.95). The standardization process resulted in substantial improvements in reliability for evaluation of a number of physical signs, although for some signs, minimal or no effect of standardization was noted. After standardization, warmth (PABAK = 0.14), medial instability at 30° flexion (PABAK = 0.02), and lateral instability at 30° flexion (PABAK = 0.34) were the only 3 signs that were highly unreliable.ConclusionWith the exception of physical examinations for instability, a comprehensive knee examination can be performed with adequate reliability. Standardization further improves the reliability for some physical signs and techniques. The application of these findings to future OA studies will contribute to improved outcome assessments in OA.
Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis
Authors: Matyas John R. , Atley Lynne , Ionescu Mirela , Eyre David R. , Poole A. Robin 
Published: February 2004

AbstractObjectiveTo study 3 body fluids for changes in the levels of 5 biomarkers of cartilage metabolism during the early phases of experimental osteoarthritis (OA).MethodsTwenty skeletally mature mixed‐breed canines underwent unilateral surgical transection of the anterior cruciate ligament. Samples of joint fluid, serum, and urine were obtained preoperatively and just before necropsy (3 weeks or 12 weeks postoperatively). Biomarkers included 2 markers of cartilage matrix synthesis/turnover (aggrecan 846 epitope and C‐propeptide of type II collagen) and 3 markers of cartilage degradation (keratan sulfate proteoglycan epitope, the collagenase‐generated cleavage epitope of type II collagen [Col2‐3/4Clong mono, or CIIC], and crosslinked peptides from the C‐telopeptide domain of type II collagen [Col2CTx]). Significant changes in the levels of these biomarkers were determined by paired analyses.ResultsJoint pathology was more severe in the 12‐week group compared with the 3‐week group. In joint fluid, due to limited volume, only Col2‐3/4Clong mono and Col2CTx were measured. Significant elevations in the levels of both of these markers were observed in experimental joints in both the 3‐week group and the 12‐week group. In serum, the level of aggrecan 846 epitope was elevated at both 3 weeks and 12 weeks, the level of Col2‐3/4Clong mono was elevated at 12 weeks, and the level of Col2CTx was elevated at both 3 weeks and 12 weeks. In urine, the level of Col2‐3/4Clong mono was elevated at 12 weeks after surgery.ConclusionLevels of biomarkers of intact aggrecan proteoglycan (aggrecan 846 epitope) and type II collagen degradation (Col2‐3/4Clong mono and Col2CTx) were elevated early after unilateral stifle joint injury, suggesting that these markers are sensitive and specific for early cartilage changes associated with isolated joint injury in this established model of experimental OA.
Spectrum of clinical features in Muckle‐Wells syndrome and response to anakinra
Authors: Hawkins Philip N. , Lachmann Helen J. , Aganna Ebun , McDermott Michael F. 
Published: February 2004

AbstractObjectiveMutations in the NALP3/CIAS1/PYPAF1 gene are associated with the autoinflammatory diseases Muckle‐Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal‐onset multisystem inflammatory disease (NOMID), which is also known as chronic infantile neurologic, cutaneous, articular (CINCA) syndrome. Molecular studies suggest that NALP3 is involved in the processing of interleukin‐1β (IL‐1β), prompting us to investigate whether IL‐1 blockade may be therapeutic in patients with MWS.MethodsWe reviewed the clinical features of 3 members of a family, all of whom had MWS associated with the NALP3 variant V200M (also designated V198M), and evaluated the response of their inflammatory disease to treatment with the recombinant human IL‐1 receptor antagonist anakinra. The subjects kept a diary of symptoms and underwent fortnightly clinical and laboratory assessments, including measurement of the serum amyloid A protein concentration.ResultsEach subject had fever, rashes, arthralgia, conjunctivitis, sensorineural deafness, and an intense acute‐phase response characteristic of MWS. However, additional features were identified, including exacerbation of their disease by cold and neurologic manifestations, that have hitherto been described only in FCAS and NOMID, respectively. Clinical and serologic evidence of active inflammatory disease resolved rapidly and completely during treatment with anakinra.ConclusionThe remarkable response of MWS to anakinra suggests that IL‐1β has a fundamental role in the pathogenesis of inflammation associated with mutations in the NALP3 gene, and supports study of IL‐1 inhibition in patients with NOMID/CINCA syndrome or FCAS. The clinical features of the various syndromes associated with mutations in the NALP3 gene may overlap to a greater extent than has previously been recognized.
Association of radiographic hand osteoarthritis with radiographic knee osteoarthritis after meniscectomy
Authors: Englund M. , Paradowski P. T. , Lohmander L. S. 
Published: February 2004

AbstractObjectiveTo evaluate the association between radiographic hand osteoarthritis (OA), a disease with marked heredity, and radiographic knee OA in patients treated with meniscectomy.MethodsWe retrospectively identified 170 patients (mean age 54 years [range 33–87 years], 23% women) who had undergone isolated meniscectomy an average of 20 years earlier (range 17–22 years). Patients with cruciate ligament injury were excluded. All subjects were examined by standardized knee and hand radiography. Individual joints were considered to have OA when displaying radiographic features corresponding to a Kellgren/Lawrence (K/L) grade ≥2. Hand OA was considered present if at least 1 of the following criteria was fulfilled: the presence of radiographic OA (K/L grade ≥2) in at least 1 interphalangeal joint in each hand symmetrically, or in at least 2 distal or proximal interphalangeal joints in the same hand in a pattern consistent with primary OA (in the same row or ray), or in the first carpometacarpal joint bilaterally. The association between radiographic hand OA and radiographic knee OA was evaluated using logistic regression.ResultsRadiographic hand OA was present in 57 patients (34%) and radiographic knee OA was identified in 105 patients (62%), within 94 index knees (55%) and 47 contralateral knees (28%). In a multivariate model, radiographic hand OA was associated with an increased likelihood of radiographic OA in the index knee (odds ratio [OR] 3.0, 95% confidence interval [95% CI] 1.2–7.5) and in the nonoperated contralateral knee (OR 3.5, 95% CI 1.0–12.2).ConclusionThe presence of radiographic hand OA is associated with an increased frequency of radiographic knee OA after meniscectomy. This finding confirms and extends that of a single previous study showing an interaction between hereditary and environmental risk factors for OA, a common and genetically complex disease. Accordingly, the development of OA following a meniscal tear and the resulting meniscal surgery should not be regarded to be of secondary origin only.
Induction of costimulation of human CD4 T cells by tumor necrosis factor–related apoptosis‐inducing ligand: Possible role in T cell activation in systemic lupus erythematosus
Authors: Tsai Hwei‐Fang , Lai Jiann‐Jyh , Chou Ai‐Hsiang , Wang Ting‐Fang , Wu Chien‐Sheng , Hsu Ping‐Ning 
Published: February 2004

AbstractObjectiveTumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) has recently been shown to induce costimulation of mouse T cells in conjunction with signals from the T cell receptor. This study was undertaken to investigate TRAIL‐induced costimulation of human T cells in order to determine the role of TRAIL‐induced T cell activation in human systemic lupus erythematosus (SLE).MethodsAn in vitro T cell stimulation system with immobilized anti‐CD3 and recombinant TRAIL receptor DR4‐Fc proteins was used to activate human T cells purified from healthy individuals and from patients with SLE. The T cells were stimulated in vitro to assay their proliferation response by 3H‐thymidine incorporation, and their cytokine production by enzyme‐linked immunosorbent assay. Activation of p38 MAPK after TRAIL stimulation was detected with specific anti–phospho‐p38 MAPK monoclonal antibodies in Western blots.ResultsEnhanced T cell proliferation and increased interleukin‐2 and interferon‐γ (IFNγ) production were demonstrated in human T cells after stimulation with immobilized DR4‐Fc and anti‐CD3 in vitro. TRAIL engagement selectively activated human CD4, rather than CD8, T cells and augmented IFNγ production. Activation of p38 MAPK was detected after TRAIL‐induced T cell activation. T cells isolated from patients with SLE demonstrated a stronger response to TRAIL‐induced costimulation, in terms of proliferation and increased up‐regulation of CD25 after activation, when compared with T cells from healthy subjects.ConclusionTRAIL engagement induces costimulation of human CD4 T cells via a p38 MAPK–dependent pathway. The results suggest that enhanced reactivity of T cells to autoantigens as a result of TRAIL‐induced costimulation may play a role in the development of human autoimmune diseases.
A TNFR1 genotype with a protective role in familial rheumatoid arthritis
Authors: Dieudé Philippe , Osorio José , Petit‐Teixeira Elisabeth , Moreno Sarah , Garnier Sophie , Cailleau‐Moindrault Séverine , Stalens Caroline , Lasbleiz Sandra , Bardin Thomas , Prum Bernard , Cornélis François 
Published: February 2004

AbstractObjectiveResults of genome scans in rheumatoid arthritis (RA) have suggested that the tumor necrosis factor receptor I (TNFRI) and TNFRII loci (TNFR1 and TNFR2) are susceptibility loci. A TNFR2 polymorphism was found to be associated with familial RA. TNFR1 is mutated in TNFR‐associated periodic syndrome (TRAPS). We undertook this study to test the TNFR1 exonic polymorphism closest to the TRAPS mutations site (+36 A/G) for association with RA.MethodsDNA samples were available from two groups of the French Caucasian population: 1) 100 families with 1 RA patient and both parents and 2) 86 RA index patients from families with at least 2 siblings with RA (affected sibpairs [ASPs]). The +36 A/G polymorphism of TNFR1 was genotyped by polymerase chain reaction–restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, the genotype relative risk, and a linkage‐based test previously described.ResultsA negative association between RA and the +36 A/A genotype, suggested in the first sample (P = 0.084), was demonstrated in the second (ASP RA) sample (odds ratio [OR] 0.465; P = 0.012) and confirmed by the linkage‐based test (OR 0.17; P = 0.008). The protective genotype, present in 41% of controls, was less frequent in RA patients: 33% in the first sample, 24% in the ASP RA sample, and 11% in the linkage‐derived subgroup. Distribution of both TNFR2 196 R/R and TNFR1 +36 A/A genotypes in the ASP RA sample showed that both suspected genotypes were exclusive.ConclusionWe found evidence for an association between RA and a TNFR1 protective genotype, restricted to familial RA. Distribution of the TNFR2 196 R/R and TNFR1 +36 A/A genotypes in familial RA could suggest an interaction between TNFR1 and TNFR2 in the genetic susceptibility for RA.
Are US adults with arthritis meeting public health recommendations for physical activity?
Authors: Fontaine Kevin R. , Heo Moonseong , Bathon Joan 
Published: February 2004

AbstractObjectiveTo estimate the prevalence of US adults with self‐reported, doctor‐diagnosed arthritis (without specifying the type of rheumatic disease) who are meeting the US Surgeon General's recommendations for physical activity.MethodsUsing population‐based survey data from the 2001 Behavioral Risk Factor Surveillance Survey, we classified respondents according to their arthritis status and their level of physical activity (i.e., physically inactive, insufficiently active, or meeting recommendations). Prevalence data were weighted to take account of the complex sampling design, and were broken down by a variety of demographic characteristics such as race, education, and body weight.ResultsNearly one‐quarter (23%) of US adults reported having doctor‐diagnosed arthritis. Among adults with arthritis, 23.8% were physically inactive, 38% reported insufficient levels of physical activity, and 38.3% reported meeting the recommendations for physical activity. The highest prevalence of inactivity in adults with arthritis was found among those subjects with fewer than 8 years of formal education (47.6%), those with 9–11 years of education (35.5%), those who were African American (35.4%), those whose age was ≥65 years (31.1%), and those who were Hispanic (30.4%).ConclusionDespite the benefits of physical activity, more than 60% of adults with arthritis do not meet the physical activity recommendations. Efforts should be made to ensure that adults with arthritis are made aware of the benefits of physical activity, and that interventions are prescribed to assist these individuals in becoming more physically active.