bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantibodies that bind glomeruli: Cross‐reactivity with bacterial antigen
Authors: Chowdhry Iftikhar A. , Kowal Czeslawa , Hardin John , Zhou Zhijie , Diamond Betty 
Published: July 2005

AbstractObjectiveSystemic lupus erythematosus (SLE) is characterized by the production of multiple autoantibodies. Anti‐DNA antibodies are associated with glomerulonephritis in SLE. It has been shown that anti‐DNA antibodies cross‐react with bacterial polysaccharide and, thus, might be elicited by microbial exposure. Non–DNA‐binding antibodies also contribute significantly to the pathogenesis of lupus nephritis. The goal of this study was to characterize non–DNA‐binding, kidney‐binding antibodies.MethodsWe generated a combinatorial library derived from spleen cells of a patient with SLE who had just previously received pneumococcal vaccine. The phage library was used in an in vivo biopanning technique to identify non–DNA‐binding, kidney‐binding antibodies. Antibodies were then analyzed for binding to bacterial polysaccharide and to renal antigens.ResultsEight antibodies were characterized that bound glomeruli, but not DNA. All antibodies isolated by this protocol were IgG class, suggesting that there is affinity maturation for glomerular binding. Four of the antibodies cross‐reacted with pneumococcal polysaccharide. Six of the antibodies bound to renal antigens that have previously been reported to be cross‐reactive with DNA; the other 2 bound to histone.ConclusionThis study suggests that both DNA‐binding and non–DNA‐binding antibodies in SLE may be elicited by the same bacterial antigens.
Longitudinal patterns in the prevention of osteoporosis in glucocorticoid‐treated patients
Authors: Curtis Jeffrey R. , Westfall Andrew O. , Allison Jeroan J. , Becker Angela , Casebeer Linda , Freeman Allison , Spettell Claire M. , Weissman Norman W. , Wilke Scott , Saag Kenneth G. 
Published: July 2005

AbstractObjectiveTo evaluate patient and physician factors associated with prevention of glucocorticoid‐induced osteoporosis and to describe temporal trends in screening and prevention of glucocorticoid‐induced osteoporosis.MethodsUsing databases from a national managed care organization, enrollees who had been prescribed glucocorticoids (taken for at least 60 days) during an 18‐month period were identified. Administrative data from January 2001 through June 2003 and linked survey data from October 2003 were examined for measurement of bone mass, prescription of antiresorptive medication, and use of over‐the‐counter calcium and/or vitamin D treatment. Factors associated with screening and bone‐protective therapies were identified using multivariable logistic regression, focusing on physician specialty and survey respondent ethnicity. Trends in glucocorticoid‐induced osteoporosis prevention were assessed using administrative data from 2001–2003 versus 1995–1998.ResultsWe identified 6,281 patients who were prescribed glucocorticoids in 2001–2003 (mean ± SD prescribed prednisone‐equivalent dosage 16 ± 14 mg/day). Forty‐two percent underwent bone mass measurement and/or were prescribed bone‐protective medication; rates were lowest for men (25%). Compared with patients of internists, the odds of bone mass measurement were lowest among patients prescribed glucocorticoids by family physicians (odds ratio [OR] 0.56 [95% confidence interval] [95% CI] 0.30–1.04) and highest among patients prescribed glucocorticoids by rheumatologists (OR 1.48 [95% CI 1.06–2.08]). Patients prescribed glucocorticoids by gastroenterologists were less likely to be treated with antiresorptive agents (OR 0.49 [95% CI 0.28–0.86]). African American patients were less likely than white patients to be screened (OR 0.55 [95% CI 0.40–0.75]) or treated (OR 0.71 [95% CI 0.51–0.98]). The frequency of bone mass measurement among glucocorticoid‐treated patients in 2001–2003 increased 3‐fold compared with 1995–1998, and the use of prescription antiresorptive medication increased ∼2‐fold.ConclusionDespite significant temporal increases in the frequency of screening for and treatment of glucocorticoid‐induced osteoporosis, absolute rates remain low, especially among men, African Americans, and patients of certain physician specialties.
Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti–tumor necrosis factor agents infliximab and etanercept
Authors: Braun J. , Baraliakos X. , Listing J. , Sieper J. 
Published: July 2005

AbstractObjectiveTo estimate the incidence of anterior uveitis in patients with ankylosing spondylitis (AS) who underwent anti–tumor necrosis factor (anti‐TNF) therapy, using data from recently performed trials.MethodsData from 4 placebo‐controlled studies with anti‐TNF agents in AS (2 with etanercept and 2 with infliximab) and 3 open‐label studies were analyzed for the prestudy prevalence and the incidence of reported flares of anterior uveitis.ResultsA total of 717 patients who received treatment for anterior uveitis during the course of published clinical studies were identified by a systematic literature search using Medline. Followup information on the course of anterior uveitis was available for 397 patients. Of these, 297 were exposed to etanercept and 90 were exposed to infliximab for a total of 430 and 146.4 years, respectively. Among 190 patients who received placebo, the overall exposure was 70.5 years. The frequency of flares of anterior uveitis in the placebo group was 15.6 per 100 patient‐years (95% confidence interval 7.8–27.9), while the patients treated with anti‐TNF agents had a mean of only 6.8 anterior uveitis flares per 100 patient‐years (P = 0.01). Flares of anterior uveitis occurred less frequently (although not significantly) in patients treated with infliximab than in patients treated with etanercept (3.4 per 100 patient‐years and 7.9 per 100 patient‐years, respectively).ConclusionTreatment of AS patients with biologic agents directed against TNFα is associated with a significant decrease in the number of anterior uveitis flares. This reduction was slightly more marked among patients treated with infliximab, but the difference was not significant.
Articular chondrocytes express the receptor for advanced glycation end products: Potential role in osteoarthritis
Authors: Loeser Richard F. , Yammani Raghunatha R. , Carlson Cathy S. , Chen Hong , Cole Ada , Im Hee‐Jeong , Bursch Laura S. , Yan Shi Du 
Published: July 2005

AbstractObjectiveThe receptor for advanced glycation end products (RAGE) binds multiple ligands, including S100 proteins, high mobility group box chromosomal protein 1 (HMGB‐1), and AGEs, all of which are present in articular cartilage. Stimulation of RAGE signaling can lead to MAP kinase activation and increased NF‐κB activity. The objective of the present study was to determine if chondrocytes express functional RAGE.MethodsThe presence of chondrocyte RAGE was analyzed by immunohistochemistry using normal and osteoarthritic (OA) cartilage from young and old monkeys and humans, immunoblotting of chondrocyte lysates and human cartilage extracts, and reverse transcription–polymerase chain reaction (RT‐PCR) analysis of RNA from chondrocytes treated with interleukin‐1 (IL‐1) and fibronectin fragments. RAGE signaling was evaluated by stimulating chondrocytes with S100B and HMGB‐1 and analyzing for activation of the ERK MAP kinase and NF‐κB. The ability of S100B and HMGB‐1 to stimulate matrix metalloproteinase 13 (MMP‐13) production was also assessed. A pull‐down assay using biotin‐labeled S100B was used to demonstrate binding to RAGE.ResultsRAGE was detected in sections of monkey knee cartilage and human knee and ankle cartilage. Increased immunostaining for RAGE was noted in cartilage from older adult monkeys and humans and was further increased in OA tissue. RAGE was also detected by immunoblotting and by RT‐PCR, where IL‐1β and fibronectin fragments were found to stimulate RAGE expression. Stimulation of chondrocytes with S100B or HMGB‐1 increased phosphorylation of the ERK MAP kinase and the p65 subunit of NF‐κB and increased the production of MMP‐13. This signaling was inhibited in cells pretreated with soluble RAGE, and S100B was shown to bind to chondrocyte RAGE.ConclusionArticular chondrocytes express functional RAGE. The increase in RAGE noted in OA cartilage and the ability of RAGE ligands to stimulate chondrocyte MAP kinase and NF‐κB activity and to stimulate MMP‐13 production suggests that chondrocyte RAGE signaling could play a role in OA.
The comparative effectiveness of tumor necrosis factor–blocking agents in patients with rheumatoid arthritis and patients with ankylosing spondylitis: A six‐month, longitudinal, observational, multicenter study
Authors: Heiberg Marte S. , Nordvåg Bjørn‐Yngvar , Mikkelsen Knut , Rødevand Erik , Kaufmann Cecilie , Mowinckel Petter , Kvien Tore K. 
Published: July 2005

AbstractObjectiveTo compare the effectiveness of tumor necrosis factor (TNF)–blocking agents (etanercept and infliximab) in patients with rheumatoid arthritis (RA) and patients with ankylosing spondylitis (AS).MethodsData from an ongoing longitudinal, observational study in Norway were used to assess changes in health‐related quality of life (HRQOL) in patients with RA (n = 291) and AS (n = 62). Patients received anti‐TNF therapy, and changes in scores on the Short Form 36 (SF‐36), SF‐6D, modified Health Assessment Questionnaire, and visual analog scales for patients' assessments of pain, fatigue, and global status from baseline to followup examinations at 3 and 6 months were compared. Data were adjusted for age, sex, and baseline values and are presented as crude estimates as well as standardized response means.ResultsBoth groups had improvements in all measures at 3 and 6 months. At 3 months, the changes were significantly better in the AS group compared with the RA group for all measures except the SF‐36 social functioning scores. At 6 months, all changes were numerically greater in the AS group. Differences were significant for the SF‐36 role emotional scores and were borderline significant for the SF‐36 physical functioning, role physical, and vitality scores and for the SF‐6D scores.ConclusionIn this real‐life setting, patients with AS experienced improvement in HRQOL that was comparable to, and sometimes greater than, that observed in RA patients. These results support the idea that patients with AS should have the same access to TNF‐blocking agents as patients with RA.
High‐resolution magnetic resonance imaging for the assessment of hand osteoarthritis
Authors: Tan Ai Lyn , Grainger Andrew J. , Tanner Steven F. , Shelley David M. , Pease Colin , Emery Paul , McGonagle Dennis 
Published: July 2005

AbstractObjectiveTo investigate the use of a novel surface coil for clinically utilized magnetic resonance imaging (MRI) scanners, in order to describe the microanatomic basis for hand osteoarthritis (OA) at all stages of disease.MethodsMRI of proximal or distal interphalangeal joints was performed in 58 subjects: 16 patients with early OA (symptom duration ≤12 months), 14 patients with chronic OA, 10 patients with clinically normal asymptomatic joints adjacent to arthritic joints, and 18 normal controls. High‐resolution images were obtained with displayed pixel dimensions of 80–100 μm using a 1.5T scanner and a 23‐mm–diameter surface coil. All joint structures were evaluated.ResultsThe high‐resolution images of every joint structure showed comparable abnormalities in both early and chronic OA, including cartilage loss, bone edema, synovial enhancement, osteophytosis, and erosions. Heberden's and Bouchard's node formation occurred at regions where soft tissue bulged through the capsule between the dorsal tendons and collateral ligaments (CLs). Prominent CL thickening or disruption (100% of OA patients) was evident even in joints where cartilage was partially preserved. Clinically normal joints adjacent to OA hand joints showed thickening and enhancement of CLs which was the most common abnormality seen (80% of OA patients). Older normal subjects showed subtle changes within the CLs.ConclusionObtaining high‐resolution MR images from clinically utilized scanners represents a novel way for exploring the microanatomic basis of hand arthritis and may have considerable potential in the clinical setting. In the present evaluation in nodal OA, previously unappreciated CL abnormalities were especially common.
RANK and RANKL expression as markers of dendritic cell–t cell interactions in paired samples of rheumatoid synovium and lymph nodes
Authors: Page Guillaume , Miossec Pierre 
Published: July 2005

AbstractObjectiveThe RANK/RANKL pathway is critical in bone destruction in conditions such as rheumatoid arthritis (RA). Since RANK/RANKL‐deficient mice show major lymph node (LN) abnormalities, undertook this study to investigate the expression of RANK/RANKL in paired samples of synovium and LNs from RA patients.MethodsUsing immunohistochemistry, RANK/RANKL expression by dendritic cell (DC) and T cell subsets was studied in this unique set of samples and in RA synoviocytes stimulated with interleukin‐1β (IL‐1β), tumor necrosis factor α (TNFα), and IL‐17.ResultsIn RA synovium, RANKL+ cells were detected in the lining layer and the lymphocytic infiltrates, whereas RANK expression was restricted to the perivascular infiltrates. In LNs, RANK+ and RANKL+ cells were diffusely expressed in the T cell zone and in germinal centers. Double staining of paired RA synovium and LN sections showed that some immature CD1a+ DCs expressed RANK and RANKL, while some mature DC‐LAMP+ DCs expressed only RANK. Some CD3+, CD4+, interferon‐γ+, and IL‐17+ cells expressed RANKL, while none expressed RANK. Treatment of synoviocytes with TNFα or IL‐1β in combination with IL‐17 was particularly potent at inducing RANKL expression.ConclusionThis study shows the involvement of RANK/RANKL in DC–T cell interactions during an inflammatory process. RANK expression appears to be limited to the sites of immune reaction, both in the synovium and in LNs. Therapeutic control of these targets may have both positive and negative consequences for the immune system.
Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source
Authors: Sakaguchi Yusuke , Sekiya Ichiro , Yagishita Kazuyoshi , Muneta Takeshi 
Published: July 2005

AbstractObjectiveTo compare the properties of human mesenchymal stem cells (MSCs) isolated from bone marrow, synovium, periosteum, skeletal muscle, and adipose tissue.MethodsHuman mesenchymal tissues were obtained from 8 donors during knee surgery for ligament injury. After collagenase digestion or gradient‐density separation, nucleated cells were plated at an appropriate density for expansion at the maximum rate without colony‐to‐colony contact. Yield, expandability, differentiation potential, and epitope profile were compared among MSCs from the 5 different tissue sources.ResultsColony number per 103 nucleated cells was lower, and cell number per colony was higher, in bone marrow than in other mesenchymal tissues. When the cells were replated at low density every 14 days, bone marrow–, synovium‐, and periosteum‐derived cells retained their proliferation ability even at passage 10. In chondrogenesis studies in which the cells were pelleted and cultured in vitro, pellets from bone marrow–, synovium‐, and periosteum‐derived cells were shown to be larger and stained more extensively for cartilage matrix. Synovium‐derived cells, in particular, had the greatest ability for chondrogenesis. In adipogenesis experiments, the frequency of oil red O–positive colonies was highest in synovium‐ and adipose tissue–derived cells. In studies of osteogenesis, the rate of alizarin red–positive colonies was highest in bone marrow–, synovium‐, and periosteum‐derived cells. For epitope profiling, 15 surface antigens were measured. Most appeared to have similar epitope profiles irrespective of cell source.ConclusionOur findings indicate that there are significant differences in MSC properties according to tissue source, beyond donor and experimental variation. Superiority of synovium as a potential source of MSCs for clinical applications was demonstrated.
“Pain elsewhere” and the impact of knee pain in older people
Authors: Croft Peter , Jordan Kelvin , Jinks Clare 
Published: July 2005

AbstractObjectiveTo investigate how often knee pain is accompanied by pain elsewhere and to determine whether the presence of “pain elsewhere” than the knee influences either knee‐related disability or the impact of knee pain on health and psychological status.MethodsA survey was mailed to 8,995 individuals (age ≥50 years) registered with 3 general practices in North Staffordshire in the UK. Patients recorded pain on a manikin and completed the Short‐Form 36 health survey, the Hospital Anxiety and Depression Scale, and the Western Ontario and McMaster Universities Osteoarthritis Index. Responders were categorized as having no pain, knee pain with or without pain elsewhere, or other pain (no knee pain, but pain elsewhere). Those with knee pain or other pain were subdivided by the extent of pain elsewhere.ResultsThe adjusted survey response rate was 70%. Fifty‐seven percent of responders with knee pain had pain in at least 2 other joint areas. Pain elsewhere was associated with lower physical function and with anxiety and depression both in the knee‐pain group and in the other‐pain group (associations were stronger in the knee‐pain group). Knee pain and disability were less severe in those with knee pain alone than in those with knee pain and pain elsewhere, even after adjusting for age, sex, obesity, laterality of pain, and depression.ConclusionMost people with knee pain have multiple joint site pain. The importance of this to clinicians and researchers is that the severity of knee pain and related disability is worse in the presence of pain elsewhere. This finding has implications for the management and treatment of older people with knee pain.
Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis–specific humoral autoimmunity
Authors: De Rycke Leen , Nicholas Anthony P. , Cantaert Tineke , Kruithof Elli , Echols Joshua D. , Vandekerckhove Bart , Veys Eric M. , De Keyser Filip , Baeten Dominique 
Published: July 2005

AbstractObjectiveTo address the ongoing debate concerning the specificity of synovial citrullinated proteins for rheumatoid arthritis (RA) and to analyze their pathophysiologic relevance to the induction or perpetuation of the RA‐specific anti–citrullinated protein antibodies (ACPAs).MethodsSynovium of 19 RA patients and 19 non‐RA controls was immunostained for the presence of citrullinated proteins with a mouse monoclonal antibody (F95), for the citrullinating enzyme peptidyl arginine deiminase type 2 (PAD‐2), and for the free citrulline–producing enzyme inducible nitric oxide synthase (iNOS). Extending the RA cohort to 61 patients, the findings of anticitrulline staining in synovium were related to serum and synovial fluid ACPA levels, as measured by enzyme‐linked immunosorbent assay.ResultsF95 staining indicated the presence of synovial intracellular citrullinated proteins in 53% of RA samples versus 5% of control samples, whereas extracellular staining was not RA specific. Immunoblotting and inhibition experiments confirmed that the antibody recognized citrullinated proteins but not free citrulline. Accordingly, iNOS was equally found in RA and control synovium and in intracellular citrullinated protein–positive and intracellular citrullinated protein–negative samples. In contrast, intracellular citrullinated proteins colocalized with PAD‐2, which was found in 59% of RA samples versus 17% of control samples. Independent of local disease activity, the presence of the RA‐specific synovial intracellular citrullinated proteins was associated with significantly higher systemic and local ACPA levels and with local ACPA production in the joint.ConclusionThese data confirm the presence of RA‐specific intracellular citrullinated proteins in synovium. The link with PAD‐2 and local and systemic ACPA levels emphasizes their pathophysiologic relevance for RA‐specific humoral autoimmunity.
Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium
Authors: Patterson Angela M. , Gardner Lucy , Shaw Jennifer , David Guido , Loreau Emilie , Aguilar Luc , Ashton Brian A. , Jim Middleton  
Published: July 2005

AbstractObjectiveTo identify and characterize which endothelial heparan sulfate proteoglycans (HSPGs) bind the chemokine CXCL8 (interleukin‐8) in human rheumatoid arthritis (RA) and nonrheumatoid synovia.MethodCXCL8 binding to endothelial HSPGs in RA and nonrheumatoid synovia was determined by heparinase treatment followed by an in situ binding assay and autoradiography. Endothelial HSPGs were characterized by immunohistochemical analysis and quantitative reverse transcriptase–polymerase chain reaction (RT‐PCR). Phosphatidyinositol‐specific phospholipase C (PI‐PLC) and antibodies to HSPGs were used in in situ binding experiments to identify which HSPGs bound CXCL8.ResultsThe expression of heparan sulfate on microvascular endothelial cells was demonstrated in RA and nonrheumatoid synovia. Using antibodies to syndecan‐1–4 and glypican‐1, ‐3, and ‐4, the selective expression of syndecan‐3 by endothelial cells was detected in RA and nonrheumatoid synovia. In addition, RT‐PCR showed the presence of syndecan‐3 messenger RNA in endothelial cells extracted from RA and nonrheumatoid synovia. 125I‐CXCL8 bound to venular endothelial cells; treatment with heparinases I and III significantly reduced this binding in RA but not nonrheumatoid synovia. 125I‐CXCL8 binding was not reduced after treatment with PI‐PLC, which cleaves glycosyl phosphatidylinositol linkages, suggesting that CXCL8 did not bind to glypicans. Treatment of synovia with a syndecan‐3 antibody reduced CXCL8 binding to RA but not nonrheumatoid endothelial cells; however, no reduction in binding was observed with syndecan‐2 or glypican‐4 antibodies.ConclusionOur results show the selective induction of a CXCL8 binding site on endothelial syndecan‐3 in RA synovium. This site may be involved in leukocyte trafficking into RA synovial tissue.
Risk of malignancy in scleroderma: A population‐based cohort study
Authors: Chatterjee Soumya , Dombi George W. , Severson Richard K. , Mayes Maureen D. 
Published: July 2005

AbstractObjectiveTo determine the incidence of cancer in patients with scleroderma (systemic sclerosis) and to compare those rates with cancer rates in the local population.MethodsCancer risk in scleroderma patients in the Detroit metropolitan area was assessed by linking patient identification codes of the Michigan Scleroderma Registry to the Metropolitan Detroit Cancer Surveillance System database. Patients were screened between the years 1973 and 2002, with additional followup to 2004. Standardized incidence ratios (SIRs) were calculated for selected malignancies (lung, liver, colon, breast, cervical, and prostate cancers, and non‐Hodgkin's lymphomas), with stratification by sex and race.ResultsOf 934 patients in the Scleroderma Registry, 538 were included in the study based on tri‐county residency (436 females and 102 males). Of these, 45 first malignancies were noted (37 females and 8 males). Lung cancer (10 cases) was found to be the most common cancer in scleroderma patients. However, its incidence was not significantly different from that in the general population of metropolitan Detroit (SIR 1.23). Other types of cancer were examined, and no significant differences were found as compared with the rates in the local population, with 1 exception: black females with scleroderma had significantly higher rates of liver cancer (SIR 45.8).ConclusionContrary to previous studies, this study did not find statistical evidence of an increased incidence of cancer in scleroderma patients, except for liver cancer. One possible reason is the high background rates of certain cancers in the metropolitan Detroit area. It may be necessary to consider local cancer rates when comparing different scleroderma cohorts.