bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiphospholipid antibodies in pediatric and adult patients with rheumatic disease are associated with parvovirus B19 infection
Authors: von Landenberg Philipp , Lehmann Hartwig W. , Knöll Antje , Dorsch Simone , Modrow Susanne 
Published: July 2003

AbstractObjectiveTo show a possible association between parvovirus B19 infection and the presence of antiphospholipid antibodies (aPL) in patients with rheumatic diseases.MethodsSerum samples obtained from 88 children with various forms of juvenile rheumatic disease and from 40 adults with systemic lupus erythematosus, the antiphospholipid syndrome, or other rheumatic disease, who had previously been tested and shown to be positive for IgG aPL, were analyzed for the presence of B19 DNA, for antibodies against the B19 viral proteins VP1, VP2, and NS1, and for IgG aPL (anticardiolipin, anti–β2‐glycoprotein I, and antiphosphatidylserine). As controls, serum samples obtained from 135 children with noninflammatory bone diseases or growth retardation were also analyzed.ResultsTwenty‐four (27%) of the 88 children with rheumatic diseases had detectable amounts of IgG aPL. Fourteen (58%) of these 24 IgG aPL–positive patients showed IgG against VP1/VP2 and viral genomes, indicating the presence of acute (2 patients) or persistent (12 patients) infection. Past parvovirus B19 infection was identified in 7 (29%) of 24 IgG aPL–positive children, as indicated by VP1/VP2‐specific IgG in the absence of viral DNA. Three (12%) of 24 IgG aPL–positive children had not been infected with B19. Sixty‐nine (51%) of 135 control children displayed VP1/VP2‐specific IgG. Three (2%) of these 135 children were IgG aPL positive (2 children had past parvovirus B19 infection, and 1 was negative for parvovirus B19). Analysis of the parvovirus B19 status of 40 adult IgG aPL–positive patients showed that 33 (83%) were anti–IgG VP1/VP2–positive, and viral DNA was detected in 11 patients (28%). Ten of these 11 viremic patients were in the subgroup of 28 IgG aPL–positive SLE patients.ConclusionAntiphospholipid antibodies are preferentially found in serum of children with juvenile idiopathic arthritis who have been previously infected with parvovirus B19 and have established, persistent infection. Adult patients with IgG aPL positivity have a high incidence of persistent parvovirus B19 infection. We conclude that parvovirus B19 might be directly involved in the elicitation of autoimmune reactions partly mediated by aPL.
Doppler sonographic findings in the long bicipital tendon sheath in patients with rheumatoid arthritis as compared with patients with degenerative diseases of the shoulder
Authors: Strunk Johannes , Lange Uwe , Kürten Bernhard , Schmidt Klaus Louis , Neeck Gunther 
Published: July 2003

AbstractObjectiveTo compare power Doppler sonography (PDS) findings inside the bicipital tendon sheath in patients with rheumatoid arthritis (RA) and degenerative disorders of the shoulder, in order to evaluate the diagnostic value of PDS in distinguishing between inflammatory and noninflammatory shoulder pain.MethodsThe glenohumeral joints of 41 consecutive patients with shoulder pain were examined by ultrasound. Using ventral transverse and longitudinal scanning, the vascularity near and/or inside the bicipital tendon sheath was visualized by PDS. One fully trained and experienced examiner performed the sonography. Representative images were digitally stored and were read, under blinded conditions, by 2 independent investigators, who categorized the Doppler signals as being either inside or outside the tendon sheath.ResultsBiceps tendon sheath effusion, represented by the typical hypoechoic rim, was found in 95.8% of the RA patients (23 of 24) and in 58.8% of the patients with degenerative disorders (10 of 17). PDS signals were localized to inside the tendon sheath in 22 of the RA patients (91.7%) and in none of the patients with degenerative disorders. Although no PDS signal was found inside the tendon sheath in patients with degenerative disorders, in 9 of these patients (52.9%), signals could be localized to the environment of the tendon sheath.ConclusionPDS demonstrates vascularity in the long bicipital tendon sheath of patients with RA, but not in those with degenerative shoulder disorders.
Heterogeneous requirement of IκB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: Implications for therapy
Authors: Andreakos Evangelos , Smith Clive , Kiriakidis Serafim , Monaco Claudia , de Martin Rainer , Brennan Fionula M. , Paleolog Ewa , Feldmann Marc , Foxwell Brian M. 
Published: July 2003

AbstractObjectiveTo investigate the potential role of IκB kinase 1 (IKK‐1) and IKK‐2 in the regulation of nuclear factor κB (NF‐κB) activation and the expression of tumor necrosis factor α (TNFα), as well as interleukin‐1β (IL‐1β), IL‐6, IL‐8, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), in rheumatoid arthritis (RA).MethodsRecombinant adenoviruses expressing β‐galactosidase, dominant‐negative IKK‐1 and IKK‐2, or IκBα were used to infect ex vivo RA synovial membrane cultures and synovial fibroblasts obtained from patients with RA undergoing joint replacement surgery, or human dermal fibroblasts, human umbilical vein endothelial cells (HUVECs), and monocyte‐derived macrophages from healthy volunteers. Then, their effect on the spontaneous or stimulus‐induced release of inflammatory cytokines, VEGF, and MMPs from RA synovial membrane cells was examined.ResultsIKK‐2 was not required for lipopolysaccharide (LPS)–induced NF‐κB activation or TNFα, IL‐6, or IL‐8 production in macrophages, but was essential for this process in response to CD40 ligand, TNFα, and IL‐1. In synovial fibroblasts, dermal fibroblasts, and HUVECs, IKK‐2 was also required for LPS‐induced NF‐κB activation and IL‐6 or IL‐8 production. In RA synovial membrane cells, IKK‐2 inhibition had no effect on spontaneous TNFα production but significantly reduced IL‐1β, IL‐6, IL‐8, VEGF, and MMPs 1, 2, 3, and 13.ConclusionOur study demonstrates that IKK‐2 is not essential for TNFα production in RA. However, because IKK‐2 regulates the expression of other inflammatory cytokines (IL‐1β, IL‐6, and IL‐8), VEGF, and MMPs 1, 2, 3, and 13, which are involved in the inflammatory, angiogenic, and destructive processes in the RA joint, it may still be a good therapeutic target.
Estrogen receptor α gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women
Authors: Bergink Arjan P. , van Meurs Joyce B. , Loughlin John , Arp Pascal P. , Fang Yue , Hofman Albert , van Leeuwen Johannes P. T. M. , van Duijn Cornelia M. , Uitterlinden André G. , Pols Huibert A. P. 
Published: July 2003

AbstractObjectiveGenetic influences have been shown to play an important role in the etiology of osteoarthritis (OA), but the genes involved are ill‐defined. We studied the association between polymorphisms in the estrogen receptor α (ERα) gene and the prevalence of radiographic OA of the knee.MethodsThe study group comprised 1,483 men and women from the Rotterdam Study. Direct molecular haplotyping was used to determine the relationship between 2 polymorphisms in the ERα gene (the Pvu II and Xba I restriction fragment–length polymorphisms). Radiographs of the knee were evaluated according to the Kellgren/Lawrence (K/L) score, along with separate scores for osteophytosis and joint space narrowing.ResultsThree different haplotype alleles were identified: px (54%), PX (34%), and Px (12%). Allele PX was associated with an increased prevalence of radiographic knee OA (K/L score ≥2). The prevalence of radiographic OA was 22% among subjects without allele PX, 24% among those carrying 1 copy, and 35% among subjects carrying 2 copies. The corresponding odds ratios, after adjustment for confounding factors, were 1.3 (95% confidence interval [95% CI] 0.9–1.7) for heterozygotes and 2.2 (95% CI 1.5–3.4) for homozygotes. Separate analyses for men and women showed similar risk estimates. The association appeared to be driven by osteophytosis and is somewhat consistent with the association observed in previous studies of these polymorphisms in relation to OA.ConclusionThis study shows that polymorphisms in the ERα gene are associated with radiographic OA of the knee, and in particular with osteophytosis, in both elderly men and elderly women.
Role of Crk‐associated substrate lymphocyte type in the pathophysiology of rheumatoid arthritis in tax transgenic mice and in humans
Authors: Miyake‐Nishijima Rikako , Iwata Satoshi , Saijo Shinobu , Kobayashi Hiroshi , Kobayashi Seiji , Souta‐Kuribara Akiko , Hosono Osamu , Kawasaki Hiroshi , Tanaka Hirotoshi , Ikeda Eiji , Okada Yasunori , Iwakura Yoichiro , Morimoto Chikao 
Published: July 2003

AbstractObjectiveTo investigate the role of Crk‐associated substrate lymphocyte type (Cas‐L), a downstream signaling molecule of β1 integrins, in the pathophysiology of rheumatoid arthritis (RA).MethodsWe analyzed human T lymphotropic virus type I (HTLV‐I) tax transgenic mice as well as samples from human RA patients. Splenocytes from tax transgenic mice were cultured on mouse endothelial cell–covered Transwell inserts, and cells migrating through the endothelial monolayer were counted. Biochemical studies were performed to analyze the protein expression and tyrosine phosphorylation of Cas‐L. Immunohistochemical analysis was performed to detect Cas‐L–positive cells that had infiltrated into the joints.ResultsMigratory activity of splenocytes from tax transgenic mice with arthritis (ATg) was much higher than that of tax transgenic mice without arthritis (NTg) and littermate control mice. The expression of Cas‐L protein and its tyrosine phosphorylation were increased in ATg mice compared with NTg and control mice, and this was accompanied by enhanced autophosphorylation of Fyn and Lck. Immunohistochemical analysis demonstrated a large number of Cas‐L–positive lymphocytes migrating into the affected joints. Furthermore, in human RA, Cas‐L–positive lymphocytes were shown to infiltrate to the inflammatory lesions.ConclusionThese results strongly suggest that Cas‐L plays an important role in the pathophysiology of RA.
Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman
Authors: García‐Pavía Pablo , Torres Rosa J. , Rivero Manuel , Ahmed Maqbool , García‐Puig Juan , Becker Michael A. 
Published: July 2003

AbstractOveractivity of phosphoribosylpyrophosphate synthetase (PRS) is an X chromosome–linked disorder of purine metabolism that is characterized by gout with uric acid overproduction and, in some families, neurodevelopmental impairment. We present the case of a 24‐year‐old Spanish woman with renal colic and hyperuricemia, which first manifested at age 11 years. Results of enzymatic and genetic studies supported the view that accelerated purine nucleotide and uric acid production in this woman resulted from defective allosteric regulation of PRS activity, which is, in turn, a consequence of a mutation in one of the patient's PRPS1 genes: an A‐to‐T substitution at nucleotide 578, encoding leucine for histidine at amino acid residue 192 of the mature PRS1 isoform. A previous example of disordered regulation of PRS1 activity in a family with a different substitution at the same amino acid residue strengthens this proposed mechanism. This is the first reported instance of PRS overactivity in which the propositus and sole affected family member is a woman.
Role of the Fcγ receptor IIA polymorphism in the antiphospholipid syndrome: An international meta‐analysis
Authors: Karassa Fotini B. , Bijl Marc , Davies Kevin A. , Kallenberg Cees G. M. , Khamashta Munther A. , Manger Karin , Michel Marc , Piette Jean‐Charles , Salmon Jane E. , Song Yeong Wook , Tsuchiya Naoyuki , Yoo Dae‐Hyun , Ioannidis John P. A. 
Published: July 2003

AbstractObjectiveTo assess the impact of the FcγRIIA‐R/H131 polymorphism on the risk for antiphospholipid syndrome (APS), both primary and secondary to systemic lupus erythematosus (SLE).MethodsThis international meta‐analysis combined data from 9 research teams. FcγRIIA‐R/H131 genotypes were determined in 481 APS cases (206 with primary APS), 1,420 SLE controls, and 1,655 disease‐free controls. Data were combined using fixed‐effects and random‐effects models.ResultsCompared with disease‐free controls, the RR genotype was enriched in the entire group of APS cases (odds ratio [OR] 1.65, 95% confidence interval [95% CI] 1.28–2.14); this was driven mostly by patients with secondary APS (OR 1.95, 95% CI 1.45–2.63). The excess of RR homozygotes but not heterozygotes among APS patients suggested a recessive mode of inheritance, rather than the additive model seen for SLE susceptibility, where RR conferred greatest risk, and RH intermediate risk, for SLE. This probably reflected the additional influence of another opposing genetic effect of HH homozygosity on APS predisposition (OR 0.72 for RH versus HH, 95% CI 0.55–0.96). Among SLE patients, those with APS were more frequently HH homozygotes than heterozygotes (OR 0.56 for RH versus HH, 95% CI 0.39–0.81). HH homozygosity also tended to predominate in primary APS compared with secondary APS (OR 0.50 for RR versus HH, 95% CI 0.25–0.99 by fixed‐effects model). There was no significant between‐study heterogeneity for any of these effects.ConclusionThe FcγRIIA‐R/H131 polymorphism is an important determinant of predisposition to APS, with different influences on SLE and APS susceptibility per se.
Increased asymmetric dimethylarginine and endothelin 1 levels in secondary Raynaud's phenomenon: Implications for vascular dysfunction and progression of disease
Authors: Rajagopalan Sanjay , Pfenninger Dana , Kehrer Christine , Chakrabarti Anjan , Somers Emily , Pavlic Robert , Mukherjee Debabrata , Brook Robert , D'Alecy Louis G. , Kaplan Mariana J. 
Published: July 2003

AbstractObjectiveTo compare microvascular and macrovascular functions in a cohort of patients with primary and secondary Raynaud's phenomenon (RP) who were matched for demographic, risk factor, and severity profiles.MethodsForty patients with primary or secondary RP matched for vascular risk factors and severity scores underwent testing of endothelial function and cold pressor responsiveness of the brachial artery. Microvascular perfusion of the digital vasculature was assessed using laser Doppler fluxmetry in response to reactive hyperemia. Plasma was assayed for endothelin 1 (ET‐1), asymmetric dimethylarginine (ADMA), intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM‐1), and monocyte chemoattractant protein 1 (MCP‐1).ResultsPatients with RP had abnormal vasoconstrictor responses to cold pressor tests (CPT) that were similar in primary and secondary RP. There were no differences in median flow‐mediated and nitroglycerin‐mediated dilation or CPT of the brachial artery in the 2 populations. Patients with secondary RP were characterized by abnormalities in microvascular responses to reactive hyperemia, with a reduction in area under the curve adjusted for baseline perfusion, but not in time to peak response or peak perfusion ratio. Plasma ET‐1, ADMA, VCAM‐1, and MCP‐1 levels were significantly elevated in secondary RP compared with primary RP. There was a significant negative correlation between ET‐1 and ADMA values and measures of microvascular perfusion but not macrovascular endothelial function.ConclusionSecondary RP is characterized by elevations in plasma ET‐1 and ADMA levels that may contribute to alterations in cutaneous microvascular function.
Reconstitution of deficient T cell receptor ζ chain restores T cell signaling and augments T cell receptor/CD3–induced interleukin‐2 production in patients with systemic lupus erythematosus
Authors: Nambiar Madhusoodana P. , Fisher Carolyn U. , Warke Vishal G. , Krishnan Sandeep , Mitchell Jeanne P. , Delaney Nancy , Tsokos George C. 
Published: July 2003

AbstractObjectiveT cells from a majority of patients with systemic lupus erythematosus (SLE) display antigen receptor–mediated signaling aberrations associated with defective T cell receptor (TCR) ζ chain, a subunit of the TCR/CD3 complex. This study was undertaken to explore the possibility that forced expression of TCR ζ chain may reverse the known signaling abnormalities and defective interleukin‐2 (IL‐2) production in SLE T cells.MethodsFreshly isolated SLE T cells were transfected with TCR ζ chain construct in a eukaryotic expression vector at high efficiency, by a recently developed nucleoporation technique. Restoration of TCR/CD3‐mediated signaling was studied in the ζ chain–transfected cells.ResultsIn SLE T cells transfected with TCR ζ chain, surface expression of TCR chain was increased and the TCR/CD3‐induced increased free intracytoplasmic calcium concentration response was normalized, as was hyperphosphorylation of cellular substrates. Simultaneously, the previously noted increased expression of the Fc receptor γ chain was diminished in SLE T cells transfected with the ζ chain expression vector, and the surface membrane clusters of cell signaling molecules were redistributed to a more continuous pattern. TCR ζ chain replacement also augmented the expression of diminished TCR/CD3‐mediated IL‐2 production in SLE T cells, associated with increased expression of the p65 subunit of nuclear factor κB in the nuclear fractions of these T cells.ConclusionThese results suggest that reconstitution of deficient TCR ζ chain can reverse the TCR/CD3‐mediated signaling abnormalities as well as the defective IL‐2 production in T cells of patients with SLE.
Human α‐enolase from endothelial cells as a target antigen of anti–endothelial cell antibody in Behçet's disease
Authors: Lee Kwang Hoon , Chung Hae‐Shin , Kim Hyoung Sup , Oh Sang‐Ho , Ha Moon‐Kyung , Baik Ja‐Hyun , Lee Sungnack , Bang Dongsik 
Published: July 2003

AbstractObjectiveTo identify and recombine a protein of the human dermal microvascular endothelial cell (HDMEC) that specifically reacts with anti–endothelial cell antibody (AECA) in the serum of patients with Behçet's disease (BD), and to evaluate the usefulness of this protein in BD.MethodsThe proteomics technique, with 2‐dimensional gel electrophoresis and matrix‐assisted laser desorption ionization−time‐of‐flight (MALDI‐TOF) mass spectrometry, was used to identify and recombine HDMEC antigen. Western blotting and enzyme‐linked immunosorbent assay (ELISA) of recombinant protein isolated by gene cloning were performed on serum from healthy controls, patients with BD, and patients with other rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, and Wegener's granulomatosis).ResultsEighteen of 40 BD patients had serum IgM antibody to HDMEC antigen. The purified protein that reacted with AECA in BD patient sera was found to be α‐enolase by 2‐dimensional gel electrophoresis followed by immunoblotting and MALDI‐TOF mass spectrometry. Recombinant α‐enolase protein was isolated and refined by gene cloning. On Western blots, AECA‐positive IgM from the sera of patients with active BD reacted strongly with recombinant human α‐enolase. BD patient sera positive for anti–α‐enolase did not react with human γ‐enolase. On dot‐blotting, reactivity to human α‐enolase was detected only in the IgM‐positive group. Fifteen of the 18 AECA‐positive sera that were positive for the HDMEC antigen showed reactivity to recombinant α‐enolase IgM antibody by ELISA.ConclusionThe α‐enolase protein is the target protein of serum AECA in BD patients. This is the first report of the presence of IgM antibodies to α‐enolase in endothelial cells from the serum of BD patients. Although further studies relating this protein to the pathogenesis of BD will be necessary, α‐enolase and its antibody may prove useful in the development of new diagnostic and treatment modalities in BD.
Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects
Authors: del Rincón Inmaculada , Williams Ken , Stern Michael P. , Freeman Gregory L. , O'Leary Daniel H. , Escalante Agustín 
Published: July 2003

AbstractObjectiveTo examine the relationship between markers of systemic inflammation and carotid atherosclerosis in patients with rheumatoid arthritis (RA) and healthy controls.MethodsCarotid artery intima‐media thickness (IMT) and carotid plaque were measured using high‐resolution B‐mode ultrasound in 204 patients with RA, ages 40–85, and 102 age‐ and sex‐matched healthy persons. No subject in either group had ever smoked cigarettes. Erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) were used to measure systemic inflammation. The relationship of the carotid artery IMT and carotid plaque to inflammation markers was examined, adjusting for age, sex, RA versus control status, and the cardiovascular (CV) risk factors hypercholesterolemia, systolic blood pressure, diabetes mellitus, and body mass index (BMI).ResultsA significant linear trend for increased carotid artery IMT was associated with increasing ESR and CRP categories (r = 0.16, P = 0.004 for ESR, and r = 0.13, P = 0.02 for CRP). These trends did not differ among RA cases and controls, and were independent of age, sex, and CV risk factors. The difference in carotid artery IMT between the lowest and highest categories of ESR was 0.221 mm (95% confidence interval [95% CI] 0.767–1.020, P = 0.02). The difference between extreme CRP categories was 0.275 mm (95% CI 0.039–0.509, P = 0.02). Both remained significant after CV risk factor adjustment. Carotid plaque displayed a similar relationship to markers of inflammation.ConclusionIncreased carotid artery IMT and the presence of carotid plaque are associated with markers of systemic inflammation in patients with RA and in healthy subjects. This observation is consistent with hypotheses that assign a role to systemic inflammation in atherosclerosis, and may have implications regarding RA and other chronic inflammatory diseases.
Early and extensive erosiveness in peripheral joints predicts atlantoaxial subluxations in patients with rheumatoid arthritis
Authors: Neva Marko Henrik , Isomäki Pia , Hannonen Pekka , Kauppi Markku , Krishnan Eswar , Sokka Tuulikki 
Published: July 2003

AbstractObjectiveTo study the prevalence of cervical spine subluxations and predictive factors for atlantoaxial subluxations (including anterior atlantoaxial subluxation and atlantoaxial impaction, i.e., vertical subluxation) in patients with rheumatoid arthritis (RA) who were treated early and continuously with disease‐modifying antirheumatic drugs for 8–13 years.MethodsRadiographs of the cervical spine were obtained in 103 of 110 patients (the 110 surviving patients of the original 135‐patient cohort) at their 8–13‐year followup visits. The prevalence of cervical spine subluxations was determined. Demographic variables and the first 5‐year serial data concerning disease course were analyzed in a logistic regression model to find predictive factors for atlantoaxial subluxations.ResultsAtlantoaxial subluxations were found in 14 patients (14%), and 5 patients (5%) had subaxial subluxations. Older age at baseline, greater disease activity during the first 5 years, and early erosiveness in peripheral joints predicted the development of atlantoaxial subluxations. Patients who had ≥10% of the maximum possible radiographic damage (by Larsen score) in peripheral joints at 5 years were 15.9 times more likely to develop atlantoaxial subluxations at 8–13 years than patients whose peripheral joint damage remained <10% of the maximum.ConclusionCompared with historical control RA cohorts, a lower prevalence of cervical spine destruction was found in the present group of patients. Rapid erosiveness in peripheral joints was the best predictor for atlantoaxial subluxations. Extensive erosiveness in peripheral joints should alert rheumatologists to the possible development of atlantoaxial subluxations in patients with RA.