bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of transforming growth factor β signaling in scleroderma: Overexpression of endoglin in cutaneous scleroderma fibroblasts
Authors: Leask A. , Abraham D. J. , Finlay D. R. , Holmes A. , Pennington D. , Shi‐Wen X. , Chen Y. , Venstrom K. , Dou X. , Ponticos M. , Black C. , Jackman J. K. , Findell P. R. , Connolly M. K. 
Published: September 2002

AbstractObjectiveAs an initial approach to understanding the basis of the systemic sclerosis (SSc; scleroderma) phenotype, we sought to identify genes in the transforming growth factor β (TGFβ) signaling pathway that are up‐regulated in lesional SSc fibroblasts relative to their normal counterparts.MethodsWe used gene chip, differential display, fluorescence‐activated cell sorter, and overexpression analyses to assess the potential role of TGFβ signaling components in fibrosis. Fibroblasts were obtained by punch biopsy from patients with diffuse cutaneous SSc of 2–14 months' duration (mean 8 months) and from age‐ and sex‐matched healthy control subjects.ResultsUnexpectedly, we found that fibroblasts from SSc patients showed elevated expression of the endothelial cell–enriched TGFβ receptor endoglin. Endoglin is a member of the nonsignaling high‐affinity TGFβ receptor type III family. The expression of endoglin increased with progression of disease. Transfection of endoglin in fibroblasts suppressed the TGFβ‐mediated induction of connective tissue growth factor promoter activity.ConclusionSSc is characterized by overproduction of matrix; that is, genes that are targets of TGFβ signaling in normal fibroblasts. Our findings suggest that lesional SSc fibroblasts may overexpress endoglin as a negative feedback mechanism in an attempt to block further induction of profibrotic genes by TGFβ.
Stromelysin 1 (matrix metalloproteinase 3) and HLA–DRB1 gene polymorphisms: Association with severity and progression of rheumatoid arthritis in a prospective study
Authors: Constantin Arnaud , Lauwers‐Cancès Valérie , Navaux Frédérique , Abbal Michel , Meerwijk Joost van , Mazières Bernard , Cambon‐Thomsen Anne , Cantagrel Alain 
Published: September 2002

AbstractObjectiveTo test the hypothesis of an association between a polymorphism in the matrix metalloproteinase 3 (MMP‐3) gene promoter and the susceptibility, severity, and progression of rheumatoid arthritis (RA), and to further document the association between HLA–DRB1 alleles encoding the shared epitope (SE) and the severity and progression of RA.MethodsPatients with early RA (n = 103) were included in this prospective study. A total radiographic damage score (TDS; by the Sharp/van der Heijde method) was used to quantify RA severity at baseline and after 4 years of followup. The 5A/6A biallelic polymorphism in the MMP‐3 gene promoter was analyzed using fluorescence‐based polymerase chain reaction (PCR). HLA–DRB1 genotyping was performed using PCR methods. Control subjects (n = 127) were unrelated healthy individuals.ResultsMMP‐3 allele carriage rates and allele and genotype frequencies did not differ between patients and controls. The MMP‐3 6A/6A genotype was associated with the highest TDS both at baseline and after a 4‐year followup and with the highest progression of the TDS over the 4 years of followup. The DRB1 SE+/+ genotype was associated with the highest TDS after a 4‐year followup and with the highest progression of the TDS over the 4 years of followup. Patients homozygous for MMP‐3 6A and DRB1 SE had the highest progression of the TDS.ConclusionThis study provides the first evidence of an association between a polymorphism in the MMP‐3 gene promoter and the severity and progression of RA, but not RA susceptibility. Investigation of this polymorphism could be combined with that of DRB1 gene polymorphism to improve the predictive accuracy and management strategy in early RA.
An epidemiologic study of trends in prevalence of rheumatoid factor seropositivity in Pima Indians: Evidence of a decline due to both secular and birth‐cohort influences
Authors: Enzer Ian , Dunn Graham , Jacobsson Lennart , Bennett Peter H. , Knowler William C. , Silman Alan 
Published: September 2002

AbstractObjectivePrevious population studies have suggested that both rheumatoid factor (RF) production and rheumatoid arthritis (RA) may be declining in occurrence, and both secular and birth‐cohort influences have been implicated. Since Pima Indians have a very high incidence of RA and also have shown recent evidence of a decline in RA, this study evaluated the relative contributions of age, secular, and birth‐cohort influences on RF seropositivity in the Pima Indian population.MethodsRF data, as assayed by both the bentonite flocculation test (BFT) and the sheep cell agglutination test (SCAT), were available on 5,345 Pima Indians born between 1886 and 1975, who were surveyed at biennial intervals between 1966 and 1995. An age–period–cohort analysis was conducted using data on 18,295 examinations undertaken during the period of study.ResultsThere was a decline in the proportion of positive test results for RF (titer ≥1:32) by both BFT and SCAT, in both male and female subjects from 1966–1975 to the later decades of the study (1976–1985 and 1986–1995). Across all periods, by both assays, the crude proportion of positive titers increased with increasing age of the subjects. There was a very clear birth‐cohort effect: the highest likelihood of seropositivity was in those individuals born around the end of the nineteenth century, with continuing decline in seropositivity up to the most recent birth cohort. A logistic regression analysis, adjusting for Pima heritage and sex, demonstrated a substantially greater influence of birth cohort than of calendar year on the frequency of RF positivity.ConclusionIn the Pima Indian population, environmental influences in early life are important predictors of the lifelong likelihood of RF positivity. This may have implications for understanding the epidemiology and etiology of RA.
Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: A population‐based, case–control study in the Southeastern United States
Authors: Parks Christine G. , Cooper Glinda S. , Nylander‐French Leena A. , Sanderson Wayne T. , Dement John M. , Cohen Philip L. , Dooley Mary Anne , Treadwell Edward L. , St.Clair E. William , Gilkeson Gary S. , Hoppin Jane A. , Savitz David A. 
Published: September 2002

AbstractObjectiveCrystalline silica may act as an immune adjuvant to increase inflammation and antibody production, and findings of occupational cohort studies suggest that silica exposure may be a risk factor for systemic lupus erythematosus (SLE). We undertook this population‐based study to examine the association between occupational silica exposure and SLE in the southeastern US.MethodsSLE patients (n = 265; diagnosed between January 1, 1995 and July 31, 1999) were recruited from 4 university rheumatology practices and 30 community‐based rheumatologists in 60 contiguous counties. Controls (n = 355), frequency‐matched to patients by age, sex, and state of residence, were randomly selected from driver's license registries. The mean age of the patients at diagnosis was 39 years; 91% were women and 60% were African American. Detailed occupational and farming histories were collected by in‐person interviews. Silica exposure was determined through blinded assessment of job histories by 3 industrial hygienists, and potential medium‐ or high‐level exposures were confirmed through followup telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression.ResultsMore patients (19%) than controls (8%) had a history of medium‐ or high‐level silica exposure from farming or trades. We observed an association between silica and SLE (medium exposure OR 2.1 [95% CI 1.1–4.0], high exposure OR 4.6 [95% CI 1.4–15.4]) that was seen in separate analyses by sex, race, and at different levels of education.ConclusionThese results suggest that crystalline silica exposure may promote the development of SLE in some individuals. Additional research is recommended in other populations, using study designs that minimize potential selection bias and maximize the quality of exposure assessment.
Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis
Authors: Prahalad Sampath , Shear Edith S. , Thompson Susan D. , Giannini Edward H. , Glass David N. 
Published: September 2002

AbstractObjectiveTo determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects.MethodsInterviews were used to obtain histories of the following disorders among living first‐ and second‐degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin‐dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi‐squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently.ResultsThere were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1–5.7], P < 0.000001). The prevalence of autoimmunity was increased in first‐degree and in second‐degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6–7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families.ConclusionThese data demonstrate that the prevalence of autoimmunity is significantly higher among first‐ and second‐degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.
Avoidance of activity and disability in patients with osteoarthritis of the knee: The mediating role of muscle strength
Authors: Steultjens M. P. M. , Dekker J. , Bijlsma J. W. J. 
Published: September 2002

AbstractObjectiveAvoidance of activity is hypothesized to lead to muscle weakness and consequently, to physical disability. This study was undertaken to validate the avoidance model by providing evidence for the mediating role of muscle weakness in the relationship between avoidance of activity and physical disability in patients with osteoarthritis (OA) of the knee.MethodsData on avoidance of activity, observed physical disability, and muscle strength of the knee in 107 patients with knee OA were analyzed. A series of regression analyses was performed to establish the mediating role of muscle weakness. First, the effect of avoidance of activity on the level of disability was assessed. Next, the relationship between avoidance of activity and muscle strength was established. Finally, the mediating role of muscle strength could be established if the effect of avoidance of activity on disability decreased when muscle strength was taken into account.ResultsInitially, avoidance of activity accounted for 21.5% of variance in disability. Avoidance of activity also accounted for 3.9% of variance in muscle strength. After muscle strength was taken into account, the variance in disability accounted for by avoidance of activity was reduced from 21.5% to 15.7%. Thus, the criteria for establishing the mediating role of muscle strength were met.ConclusionThe results of this study provide evidence for the mediating role of muscle weakness in the relationship between avoidance of activity and disability in patients with knee OA.
In vitro cytokine production and proliferation of T cells from patients with anti‐proteinase 3‐ and antimyeloperoxidase‐associated vasculitis, in response to proteinase 3 and myeloperoxidase
Authors: Popa E. R. , Franssen C. F. M. , Limburg P. C. , Huitema M. G. , Kallenberg C. G. M. , Cohen Tervaert J. W. 
Published: September 2002

AbstractObjectiveTo investigate in vitro proliferative responses of CD4+ T cells and generation of specific cytokines induced by stimulation of peripheral blood mononuclear cells (PBMCs) from patients with antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis with the autoantigens proteinase 3 (PR3) and myeloperoxidase (MPO).MethodsPBMCs from vasculitis patients with PR3 ANCA or MPO ANCA and from healthy controls were stimulated for 7 days with PR3, MPO, or control stimuli. Proliferation of CD4+ T cells was assessed by flow cytometry, using the proliferation marker Ki‐67. Levels of the pro‐proliferative cytokines interleukin‐2 (IL‐2) and IL‐6 and of the Th1 and Th2 cytokines interferon‐γ (IFNγ) and IL‐10 in culture supernatants were determined.ResultsPR3 and MPO induced proliferative responses in CD4+ T cells from individual patients with ANCA‐associated vasculitides and healthy controls in vitro. Neither PR3 nor MPO elicited significant IL‐2 production. Levels of IL‐6 were highest after stimulation with PR3 but low after stimulation with MPO, independent of study group. Stimulation with PR3, and to a lesser extent with MPO, induced a Th2 cytokine milieu, characterized by high production of IL‐6 and IL‐10 and low production of IFNγ in patients and controls.ConclusionPR3 and MPO promote proliferation of CD4+ T cells from patients with ANCA‐associated vasculitides, but also cross‐stimulate T cells from healthy individuals. Strong IL‐10 production elicited by PR3 in vitro may act as an inhibitory signal for T cell proliferation and may have an important immunoregulatory function in vivo.
A subset of natural killer cells is greatly expanded within inflamed joints
Authors: Dalbeth Nicola , Callan Margaret F. C. 
Published: September 2002

AbstractObjectiveTo determine whether natural killer (NK) cells are present within inflamed joints and whether they might play a role in amplifying the inflammatory process.MethodsPaired samples of peripheral blood and synovial fluid were obtained from 22 patients with inflammatory arthritis. The frequency and phenotype of the peripheral and synovial NK cells were analyzed using a panel of monoclonal antibodies. Further experiments were performed to investigate the functional capacity of the synovial NK cells.ResultsThe study showed that the CD3−, CD56bright subset of NK cells was greatly expanded within inflamed joints. Our experiments suggested that this subset of cells was preferentially recruited from the periphery and that NK cells may be further activated by cytokines present within the joint. Furthermore, synovial NK cells responded to a combination of interleukin‐12 (IL‐12) and IL‐15, cytokines that are secreted by cells of the monocyte/macrophage lineage, by rapidly secreting interferon‐γ, a cytokine that can, in turn, activate macrophages.ConclusionA subset of NK cells was expanded within inflamed joints. The functional properties of these NK cells rendered them good candidates for a role in interacting with the macrophage/monocyte population within the joint, thus amplifying the production of proinflammatory cytokines.
Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: A double‐blind, placebo‐controlled study
Authors: Tao Xuelian , Younger Jean , Fan Fred Z. , Wang Betty , Lipsky Peter E. 
Published: September 2002

AbstractObjectiveTo examine the safety and efficacy of an extract of Tripterygium wilfordii Hook F (TWHF) in the treatment of patients with rheumatoid arthritis (RA).MethodsAn ethanol/ethyl acetate extract from the roots of TWHF was prepared and used in a prospective, double‐blind, placebo‐controlled study in patients with longstanding RA in whom conventional therapy had failed. Patients were randomly assigned to receive either placebo or low‐dose (180 mg/day) or high‐dose (360 mg/day) extract for 20 weeks, followed by an open‐label extension period. Clinical responses were defined as 20% improvement in disease activity according to the American College of Rheumatology criteria. Side effects were actively queried and recorded at each visit.ResultsA total of 35 patients were enrolled in the trial; 21 patients completed the 20‐week study. One patient from each group withdrew because of side effects. Twelve, 10, and 10 patients in the placebo, low‐dose, and high‐dose groups, respectively, completed at least 4 weeks of treatment. Of these patients, 8 and 4 in the high‐dose and low‐dose groups, but none in the placebo group, met criteria for clinical response. Four, 4, and 7 patients in the placebo, low‐dose, and high‐dose groups, respectively, were enrolled in the open‐label extension; of these, 2, 4, and 5 patients, respectively, met criteria for clinical response. The most common side effect was diarrhea, which caused 1 patient in the high‐dose group to withdraw from the trial. No patients withdrew because of adverse events during the open‐label extension.ConclusionThe ethanol/ethyl acetate extract of TWHF shows therapeutic benefit in patients with treatment‐refractory RA. At therapeutic dosages, the TWHF extract was well tolerated by most patients in this study.
Calibrating software reliability models when the test environment does not match the user environment
Authors: Zhang Xuemei , Jeske Daniel R. , Pham Hoang 
Published: September 2002

AbstractSoftware failures have become the major factor that brings the system down or causes a degradation in the quality of service. For many applications, estimating the software failure rate from a user's perspective helps the development team evaluate the reliability of the software and determine the release time properly. Traditionally, software reliability growth models are applied to system test data with the hope of estimating the software failure rate in the field. Given the aggressive nature by which the software is exercised during system test, as well as unavoidable differences between the test environment and the field environment, the resulting estimate of the failure rate will not typically reflect the user‐perceived failure rate in the field.The goal of this work is to quantify the mismatch between the system test environment and the field environment. A calibration factor is proposed to map the failure rate estimated from the system test data to the failure rate that will be observed in the field. Non‐homogeneous Poisson process models are utilized to estimate the software failure rate in both the system test phase and the field.For projects that have only system test data, use of the calibration factor provides an estimate of the field failure rate that would otherwise be unavailable. For projects that have both system test data and previous field data, the calibration factor can be explicitly evaluated and used to estimate the field failure rate of future releases as their system test data becomes available. Copyright © 2002 John Wiley & Sons, Ltd.
Teaching cooperative play to typical children utilizing a behavior modeling approach: a systematic replication
Authors: Jahr Erik , Eldevik Sigmund 
Published: September 2002

AbstractThis study investigated the acquisition of cooperative play in three typical children. The differential effectiveness of two different modeling conditions was compared, where in the first condition the children were trained to observe and imitate modeled cooperative play. In the second condition the children observed and described the modeled play prior to imitation. During training, modeled play episodes varied across play topics. The criterion for mastery in training was correct responding on first trial with new modeled play episodes. The results showed that the children became able to take turns in novel episodes of cooperative play and to show play variability only after including verbal description as part of the modeling procedure. Copyright © 2002 John Wiley & Sons, Ltd.
Solution structure of a pentasaccharide representing the repeating unit of the O‐antigen polysaccharide from Escherichia coli O142: NMR spectroscopy and molecular simulation studies
Authors: Landersjö Clas , Widmalm Göran 
Published: September 2002

AbstractConformational studies have been performed of a pentasaccharide derived from the O‐polysaccharide from Escherichia coli O142. The polymer was selectively degraded by anhydrous hydrogen fluoride and reduced to yield an oligosaccharide model of its repeating unit, which in the branching region consists of four aminosugars. A comparison of 1H and 13C chemical shifts between the pentasaccharide and the polymer showed only minor differences, except where the cleavage had taken place, indicating that the oligomer is a good model of the repeating unit. Langevin dynamics and molecular dynamics simulations with explicit water molecules were carried out to sample the conformational space of the pentasaccharide. For the glycosidic linkages between the hexopyranoside residues, small but significant changes were observed between the simulation techniques. One‐dimensional (1D) 1H,1H double pulsed field gradient spin echo (DPFGSE) transverse rotating‐frame Overhauser effect spectroscopy (T‐ROESY) experiments were performed, and homonuclear cross‐relaxation rates were obtained. Subsequently, a comparison of interproton distances from NMR experiment and the two simulation approaches showed that in all cases the use of explicit water in the simulations resulted in better agreement. Hydrogen‐bond analysis of the trajectories from the molecular dynamics simulation revealed interresidue interactions to be important as a cluster of different hydrogen bonds and as a distinct highly populated hydrogen bond. NMR data are consistent with the presence of hydrogen bonding within the model of the repeating unit. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 283–291, 2002
In vitro protein–polysaccharide conjugation: Tyrosinase‐catalyzed conjugation of gelatin and chitosan
Authors: Chen Tianhong , Embree Heather D. , Wu Li‐Qun , Payne Gregory F. 
Published: September 2002

AbstractThe enzyme tyrosinase was used for the in vitro conjugation of the protein gelatin to the polysaccharide chitosan. Tyrosinases are oxidative enzymes that convert accessible tyrosine residues of proteins into reactive o‐quinone moieties. Spectrophotometric and dissolved oxygen studies indicate that tyrosinase can oxidize gelatin and we estimate that 1 in 5 gelatin chains undergo reaction. Oxidized tyrosyl residues (i.e., quinone residues) can undergo nonenzymatic reactions with available nucleophiles such as the nucleophilic amino groups of chitosan. Ultraviolet/visible, 1H‐NMR, and ir provided chemical evidence for the conjugation of oxidized gelatin with chitosan. Physical evidence for conjugation was provided by dynamic viscometry, which indicated that tyrosinase catalyzes the sol‐to‐gel conversion of gelatin/chitosan mixtures. The gels formed from tyrosinase‐catalyzed reactions were observed to differ from gels formed by cooling gelatin. In contrast to gelatin gels, tyrosinase‐generated gels had different thermal behavior and were broken by the chitosan‐hydrolyzing enzyme chitosanase. These results demonstrate that tyrosinase can be exploited for the in vitro formation of protein–polysaccharide conjugates that offer interesting mechanical properties. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 292–302, 2002