bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of articular cartilage degradation and loss of boundary‐lubricating ability of synovial fluid following injury and inflammatory arthritis
Authors: Elsaid K. A. , Jay G. D. , Warman M. L. , Rhee D. K. , Chichester C. O. 
Published: June 2005

AbstractObjectiveTo study the relationship between the boundary‐lubricating ability of synovial fluid (SF) and articular cartilage damage in a rabbit knee injury model, to correlate collagen markers of such damage with SF boundary‐lubricating ability and elastase activity, and to examine the lubricating ability of SF, together with collagen markers of articular cartilage damage, under the inflammatory conditions of knee joint synovitis (KJS) and rheumatoid arthritis (RA).MethodsSF was aspirated weekly from the affected knee joints of 10 adult rabbits following transection of the anterior and posterior cruciate ligaments. The boundary‐lubricating ability of SF was determined in vitro using a previously described friction apparatus. Lubricin concentrations and type II collagen (CII) peptides were quantified by sandwich enzyme‐linked immunosorbent assays (ELISAs). Levels of the C‐terminal neoepitope 9A4 (derived from collagenase degradation of CI, CII, and CIII) and of epitope 5‐D‐4 of keratan sulfate (a marker of proteoglycan depletion) were quantified by inhibition ELISAs. Elastase activity was measured spectrophotometrically. The sensitivity of purified human lubricin to digestion by neutrophil elastase (NE) was examined by Western blotting.ResultsThe lubricating ability of SF from injured rabbit knees was significantly decreased at weeks 2 and 3 compared with week 1 after injury. Lubricin concentrations were significantly higher at week 1 than at weeks 2 and 3. CII peptide concentrations increased significantly at weeks 2 and 3 compared with week 1, while 9A4 neoepitope concentrations increased significantly at week 3 compared with weeks 1 and 2. There were no significant differences in epitope 5‐D‐4 concentrations among the 3 weeks. Elastase activity in SF increased significantly at weeks 2 and 3 compared with week 1. Elastase activity correlated significantly with diminishing lubrication at weeks 1, 2, and 3. SF from patients with KJS or RA exhibited deficient lubrication and elevated levels of CII peptides compared with SF from normal controls. NE was shown to completely degrade purified human lubricin in vitro.ConclusionLoss of boundary‐lubricating ability of SF after injury is associated with damage to the articular cartilage matrix. This can be attributed to inflammatory processes resulting from the injury, particularly in the early phases. This association also exists in patients with acute knee injuries or progressive chronic inflammatory arthritis.
Angiotensin receptor blockers suppress antigen‐specific T cell responses and ameliorate collagen‐induced arthritis in mice
Authors: Sagawa Kayo , Nagatani Katsuya , Komagata Yoshinori , Yamamoto Kazuhiko 
Published: June 2005

AbstractObjectiveThe renin–angiotensin system plays an important role in the regulation of cardiovascular, renal, and endocrine functions. Recent studies have demonstrated that angiotensin II has proinflammatory effects that may contribute to the pathogenesis of immune‐mediated diseases. We used the collagen‐induced arthritis (CIA) model to investigate the influence of angiotensin II receptor blockers (ARBs) on antigen‐specific immune responses and determine whether ARBs have preventive or therapeutic effects on the development of arthritis.MethodsWe administered ARBs (olmesartan, candesartan, and telmisartan) to mice and evaluated antigen‐specific T cell proliferation and cytokine production following immunization with ovalbumin (OVA) or type II collagen in Freund's complete adjuvant (CFA) or aluminum hydroxide (alum). Next, we induced CIA in DBA/1 mice and administered olmesartan. The severity and incidence of arthritis were scored according to clinical manifestations, and joint tissue sections were examined histopathologically.ResultsARBs severely suppressed lymphocyte proliferation and interferon‐γ production in mice immunized with OVA or type II collagen in CFA. Olmesartan also suppressed lymphocyte proliferation in mice immunized with ovalbumin in alum. In the CIA model, olmesartan reduced the mean arthritis score and the incidence of severe arthritis, even when it was administered only after disease onset. Histopathologic findings for joint destruction were improved in olmesartan‐treated mice.ConclusionARBs suppressed antigen‐specific immune responses for Th1 and Th2 in vivo. Furthermore, olmesartan suppressed the development of severe arthritis and joint destruction in the CIA model. These findings suggest that ARBs may have therapeutic potential in rheumatoid arthritis.
Dermatologic manifestations of the antiphospholipid syndrome: Two hundred consecutive cases
Authors: Francès Camille , Niang Suzanne , Laffitte Emmanuel , Pelletier Francois le , Costedoat Nathalie , Piette Jean Charles 
Published: June 2005

AbstractObjectiveTo describe dermatologic manifestations of the antiphospholipid syndrome (APS) and to investigate possible correlations between livedo reticularis and other APS manifestations.MethodsWe conducted a single‐center study of 200 consecutive patients with primary or systemic lupus erythematosus–related APS. To qualify for the study, patients had to fulfill clinical and laboratory criteria from the most recent international consensus statement on classification of definite APS. Dermatologic manifestations were systematically evaluated by a dermatologist. Only dermatologic lesions that may be related to APS were included in the analyses. Correlations between livedo reticularis and other APS manifestations were determined using Fisher's 2‐tailed, chi‐square, and nonparametric Mann‐Whitney tests.ResultsDermatologic manifestations were noted in 49% of the patients and were the presenting manifestations in 30.5%. Livedo reticularis was the most frequent manifestation, observed in 25.5% of the patients. Livedo reticularis was shown to be significantly associated with cerebral or ocular ischemic arterial events (odds ratio [OR] 10.8, 95% confidence interval [95% CI] 5.2–22.5), seizures (OR 6.5, 95% CI 2.6–16), all arterial events (OR 6, 95% CI 2.9–12.6), heart valve abnormalities detected on echocardiography (OR 7.3, 95% CI 3.6–14.7), and arterial systemic hypertension (≥160/90 mm Hg) (OR 2.9, 95% CI 1.5–5.7). Conversely, it was observed with decreased frequency in patients with only venous thrombosis (OR 0.2, 95% CI 0.1–0.5).ConclusionThe dermatologic manifestations of APS are frequently the presenting feature of the syndrome, and livedo reticularis is significantly associated with the arterial subset of APS.
Elevated levels of soluble fractalkine in active systemic lupus erythematosus: Potential involvement in neuropsychiatric manifestations
Authors: Yajima Nobuyuki , Kasama Tsuyoshi , Isozaki Takeo , Odai Tsuyoshi , Matsunawa Mizuho , Negishi Masao , Ide Hirotsugu , Kameoka Yosuke , Hirohata Shunsei , Adachi Mitsuru 
Published: June 2005

AbstractObjectiveTo determine levels of the soluble form of the chemokine fractalkine (sFkn) and its receptor, CX3CR1, in patients with systemic lupus erythematosus (SLE) with neuropsychiatric involvement (NPSLE) and in SLE patients without neuropsychiatric involvement, and to assess their relationship with disease activity and organ damage.MethodsLevels of sFkn in serum and cerebrospinal fluid (CSF) were measured by enzyme‐linked immunosorbent assay. Expression of Fkn and CX3CR1 was quantified using real‐time polymerase chain reaction. Surface expression of CX3CR1 on peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry. Disease activity and organ damage were assessed using the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index, respectively.ResultsSerum sFkn levels were significantly higher in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls. In addition, significant correlations between serum sFkn levels and the SLEDAI, the SLICC/ACR Damage Index, anti–double‐stranded DNA and anti‐Sm antibody titers, immune complex levels (C1q), and serum complement levels (CH50) were observed. Expression of CX3CR1 was significantly greater in PBMCs from patients with active SLE than in those from RA patients or healthy controls. Levels of sFkn were also significantly higher in CSF from untreated patients with newly diagnosed NPSLE than in SLE patients without neuropsychiatric involvement; treatment reduced both serum and CSF levels of sFkn in patients with SLE.ConclusionSoluble Fkn and CX3CR1 may play key roles in the pathogenesis of SLE, including the neuropsychiatric involvement. Soluble Fkn is also a serologic marker of disease activity and organ damage in patients with SLE, and its measurement in CSF may be useful for the diagnosis of NPSLE and followup of patients with NPSLE.
Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists
Authors: Carmona Loreto , Gómez‐Reino Juan J. , Rodríguez‐Valverde Vicente , Montero Dolores , Pascual‐Gómez Eliseo , Mola Emilio Martin , Carreño Luis , Figueroa Manuel ,   BIOBADASER Group
Published: June 2005

AbstractObjectiveTo investigate the impact of official recommendations regarding the management of latent tuberculosis (TB) infection on the rate of active TB in patients receiving treatment with tumor necrosis factor (TNF) antagonists.MethodsData on active TB rates and on screening and treatment of latent TB infection were extracted from the BIOBADASER (Spanish Society of Rheumatology Database on Biologic Products), a registry of patients with rheumatic conditions treated with TNF antagonists. The rates of active TB among the BIOBADASER patients were compared with those in the background Spanish population, and BIOBADASER patients with rheumatoid arthritis (RA) were compared with a cohort of RA patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) study who were not treated with TNF antagonists and were followed up for 5 years.ResultsActive TB developed in 34 patients, of whom 32 started taking TNF antagonists prior to the official recommendations on latent TB infection (pre‐OR) and 2 began treatment after the recommendations were issued (post‐OR). All cases of TB occurred during treatment with infliximab, and 28 of these patients had RA. Pre‐OR, the active TB rate in BIOBADASER patients was 20.9‐fold higher than in the background Spanish population, while RA patients in the BIOBADASER had rates 22.6‐ and 6.2‐fold higher than the background and EMECAR populations, respectively. Post‐OR, 324 patients with a tuberculin skin test result ≥5 mm and/or chest radiograph findings suggestive of past TB were treated for 9 months with isoniazid (INH). Post‐OR, active TB rates among the BIOBADASER patients decreased by 78% (incidence risk ratio [IRR] 0.22, 95% confidence interval [95% CI] 0.03–0.88; P = 0.008), while among RA patients in the BIOBADASER, the rate dropped by 83% and reached the EMECAR rate (IRR 1.0, 95% CI 0.02–8.2). There were no INH treatment–related hospitalizations or deaths.ConclusionStrategies to treat latent TB infection that are tailored to the at‐risk population can effectively and safely lessen the likelihood of active TB in patients treated with TNF antagonists.
Increased intraarticular interleukin‐7 in rheumatoid arthritis patients stimulates cell contact–dependent activation of CD4+ T cells and macrophages
Authors: van Roon Joel A. G. , Verweij Marieke C. , Wijk Marion Wenting‐van , Jacobs Kim M. G. , Bijlsma Johannes W. J. , Lafeber Floris P. J. G. 
Published: June 2005

AbstractObjectiveTo determine the level of intraarticular expression of interleukin‐7 (IL‐7) in patients with rheumatoid arthritis (RA) and to investigate the mechanisms by which IL‐7 facilitates activation of CD4+ T cells and monocyte/macrophages in RA.MethodsIL‐7 levels were measured in synovial fluid obtained from patients with RA and patients with osteoarthritis (OA). Immunohistologic analysis was used to assess the expression of IL‐7 in synovial tissue from patients with RA. Proliferation and activation markers were determined in order to measure the effect of IL‐7 on mononuclear cells, isolated CD4+ T cells, and monocyte/macrophages from the peripheral blood and synovial fluid. Cocultures of CD4+ T cells and monocytic cells in the absence or presence of a semipermeable membrane were performed to assess the extent to which IL‐7 induces its effects, either contact dependently or via soluble mediators.ResultsIL‐7 levels were increased in synovial fluid from patients with RA compared with the levels in synovial fluid from patients with OA. Macrophages, fibroblasts, and endothelial cells in the joint lining tissue expressed abundant IL‐7. In vitro, synovial fluid CD4+ T cells and macrophages were hyperresponsive to IL‐7 when compared with peripheral blood cells. Furthermore, IL‐7 enhanced cell contact–dependent activation of CD4+ T cells and monocyte/macrophages.ConclusionThe abundant intraarticular expression of IL‐7 and the stimulation by IL‐7 of contact‐dependent activation of CD4+ T cells and monocytic cells indicate that this cytokine plays an important proinflammatory role in RA synovitis. Further identification of IL‐7–induced pathways may improve understanding of the important interactive role of CD4+ T cells and monocytic cells in RA.
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXI. Disease activity, damage accrual, and vascular events in pre‐ and postmenopausal women
Authors: Fernández Mónica , Calvo‐Alén Jaime , Alarcón Graciela S. , Roseman Jeffrey M. , Bastian Holly M. , Fessler Barri J. , McGwin Gerald , Vilá Luis M. , Sanchez Martha L. , Reveille John D. ,   for the LUMINA Study Group
Published: June 2005

AbstractObjectiveTo determine the differences in clinical manifestations, disease activity, damage accrual, and medication use in systemic lupus erythematosus (SLE) patients as a function of menopausal status at disease onset.MethodsWomen with SLE as per the criteria of the American College of Rheumatology, with disease duration of ≤5 years and of Hispanic (Texas and Puerto Rico ancestries), African American, and Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal cohort, were studied. Menopause at the time of disease onset was defined as self‐report of climacteric symptoms, and/or amenorrhea lasting >6 months, and/or oophorectomy, and/or increased follicle‐stimulating hormone values for reproductive‐age women, and/or treatment with hormone replacement therapy. Patients were divided into premenopausal and postmenopausal categories. Socioeconomic status, cumulative clinical manifestations, disease activity (at study entry or time 0, last visit, and over time), as measured by the Systemic Lupus Activity Measure, and damage accrual, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (at time 0 and at last visit) were compared between the 2 groups of women. Multivariable models were then examined making adjustments for all possible known confounders. Dependent variables in the models were renal involvement, damage accrual, arterial vascular events, and venous thrombosis.ResultsFive hundred eighteen women from the LUMINA cohort were included; 436 (84.2%) were premenopausal and 82 (15.8%) were postmenopausal. Disease onset after menopause was more common among Caucasians. Renal involvement was more common in premenopausal women, whereas vascular arterial events were more frequent in postmenopausal women. All other disease manifestations, as well as disease activity, were comparable between both groups. The presence of damage accrual at time 0 and study end was more frequent in postmenopausal women. Age, rather than menopausal status, independently contributed to damage accrual, renal involvement, and vascular arterial events in these women.ConclusionA hypoestrogenemic state secondary to menopause appears not to be protective against disease activity and damage accrual. Age rather than menopausal status is a strong independent predictor of damage accrual and of vascular events in women with lupus.
Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: Further support that PTPN22 is an autoimmunity gene
Authors: Hinks Anne , Barton Anne , John Sally , Bruce Ian , Hawkins Clive , Griffiths Christopher E. M. , Donn Rachelle , Thomson Wendy , Silman Alan , Worthington Jane 
Published: June 2005

AbstractObjectiveThe protein tyrosine phosphatase N22 (PTPN22) gene exhibits regulatory activities for both T cells and B cells. A missense single‐nucleotide polymorphism (SNP) within this gene (rs2476601) has recently been associated with 4 autoimmune diseases: rheumatoid arthritis (RA), systemic lupus erythematosus, autoimmune thyroid disease, and type 1 diabetes mellitus, all of which are T cell–mediated and associated with the elaboration of autoantibody. The aim of this study was to investigate associations of the missense SNP of PTPN22 in a number of autoimmune diseases in the UK population, including RA, juvenile idiopathic arthritis (JIA), psoriasis, psoriatic arthritis (PsA), and multiple sclerosis (MS), some of which have not been examined previously.MethodsThe PTPN22 missense SNP was genotyped in 886 RA, 661 JIA, 279 psoriasis, 455 PsA, and 379 MS patients and in 595 healthy controls. Association with the PTPN22 SNP was analyzed by chi‐square test as implemented in Stata software.ResultsThere was a significant association between the PTPN22 SNP and RA (P = 1.8 × 10–8) and JIA (P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected.ConclusionWe replicated the findings of a previous association with RA and identified a novel association with JIA. Together with previous data showing associations with other autoimmune diseases, our findings provide further evidence that the PTPN22 gene plays a role in the pathogenesis of a subgroup of autoimmune diseases.
Association between physician volume and in‐hospital mortality in patients with systemic lupus erythematosus
Authors: Ward Michael M. 
Published: June 2005

AbstractObjectiveSystemic lupus erythematosus (SLE) is an uncommon, clinically complex disease for which prior experience treating similar patients may be particularly important. This study was undertaken to determine if physician volume is associated with the outcome of hospitalization of patients with SLE.MethodsData on in‐hospital mortality in a population‐based sample of 15,509 patients with SLE ages 18 years or older who were hospitalized in 2000, 2001, or 2002 in New York or Pennsylvania were obtained from state health planning agencies. Risks of in‐hospital mortality were examined in relation to the average annual number of patients with SLE hospitalized by the admitting physician.ResultsPhysician volume was inversely associated with mortality. Mortality was 4.1% among patients of physicians who treated <1 hospitalized patient with SLE per year, 3.5% among patients of physicians who treated 1–3 patients per year, and 2.5% among patients of physicians who treated >3 patients per year. After adjustment for demographic characteristics, severity of illness, and hospital characteristics, the mortality risk was 20% lower among patients in the middle category of physician volume (odds ratio 0.80, 95% confidence interval 0.66–0.96, P =0.02), and 42% lower among patients in the highest category of physician volume (odds ratio 0.58, 95% confidence interval 0.42–0.82, P = 0.002), compared with patients in the lowest category. The association was stronger among patients with nephritis (n = 2,673), for whom the adjusted odds of mortality were ∼60% lower among those in the highest category of physician volume.ConclusionOur findings indicate that higher disease‐specific physician volume is associated with lower risks of in‐hospital mortality in patients with SLE.
Association of a PDCD1 polymorphism with renal manifestations in systemic lupus erythematosus
Authors: Johansson Martin , ärlestig Lisbeth , Möller Bozena , Rantapää‐Dahlqvist Solbritt 
Published: June 2005

AbstractObjectiveTo analyze the association of the PD‐1.3 polymorphism within the PDCD1 gene in patients with systemic lupus erythematosus (SLE) from the homogeneous population in northern Sweden. The PD‐1.3A allele was analyzed in relation to disease manifestations and severity representing various phenotypes of SLE.MethodsThe study group comprised 260 patients fulfilling at least 4 of the American College of Rheumatology (ACR) criteria for SLE during 1 year. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/ACR damage index scores were recorded. Population‐based, randomly selected individuals (n = 670) from the same geographic area served as controls. DNA was extracted from blood samples from both patients and controls and was genotyped for the PD‐1.3 A/G polymorphism, using an ABI Prism 7900HT Sequence Detection System.ResultsThe frequency distribution of alleles, carriers, or genotypes did not differ between patients and controls. The PD‐1.3A allele and carriage of the A allele were highly associated with renal disorder (ACR criterion 7) (P = 0.005, odds ratio [OR] 2.71 [95% confidence interval (95% CI) 1.32–5.55] and P = 0.012, OR 2.62 [95% CI 1.28–5.35], respectively). In regression analysis adjusted for sex and age at disease onset, carriage of the A allele remained significantly associated with renal disorder (P = 0.002, OR 3.54 [95% CI 1.56–8.01]). The presence of proteinuria, as measured by the SLEDAI score, and the presence of renal damage were also significantly associated with carriage of the A allele (P = 0.007, OR 3.88 [95% CI 1.44–10.47] and P = 0.021, OR 2.98 [95% CI 1.18–7.54], respectively).ConclusionThe PD‐1.3A allele is associated with renal manifestations in SLE patients from northern Sweden but not with susceptibility to SLE per se.