bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of lymphocyte adhesion to cytokine‐activated synovial fibroblasts by glucocorticoids involves the attenuation of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 gene expression
Authors: Tessier Philippe A. , Cattaruzzi Paola , McColl Shaun R. 
Published: February 2007

AbstractObjective. The aim of this study was to evaluate the ability of glucocorticoids to inhibit lymphocyte adhesion to human synovial fibroblasts.Methods. Adhesion of lymphocytes to cultured synovial fibroblasts was measured by counting the number of cells bound to fibroblasts. Surface expression of intercellular adhesion molecule 1 (ICAM‐1) was measured by enzyme‐linked immunosorbent assay, while vascular cell adhesion molecule 1 (VCAM‐1) surface expression was measured by flow cytometry. ICAM‐1 and VCAM‐1 messenger RNA (mRNA) levels were assessed by Northern blot analysis.Results. Stimulation of synovial fibroblasts by the proinflammatory cytokines tumor necrosis factor α, interleukin‐1β, and interferon‐γ resulted in a dose‐dependent increase in lymphocyte adhesion to synovial fibroblasts. This response was inhibited by preincubation of the cells with the synthetic glucocorticoid dexa‐methasone. Since lymphocyte adhesion to synovial fibroblasts is known to be mediated by VCAM‐1 and ICAM‐1, we examined the modulation of VCAM‐1 and ICAM‐1 expression in these cells. All 3 cytokines stimulated VCAM‐1 and ICAM‐1 surface and mRNA expression. Dexamethasone inhibited both VCAM‐1 and ICAM‐1 surface and mRNA expression in a dose‐dependent manner, which correlated with the inhibition of lymphocyte adhesion.Conclusion. Taken together, these results suggest that glucocorticoids may reduce inflammatory responses at extravascular sites by inhibiting the expression of these adhesion molecules, thereby reducing the adhesion of lymphocytes to connective tissue cells.
The systemic effect of intraarticular administration of corticosteroid on markers of bone formation and bone resorption in patients with rheumatoid arthritis
Authors: Emkey Ronald D. , Lindsay Robert , Lyssy Jane , Weisberg Jerome S. , Dempster David W. , Shen Victor 
Published: February 2007

AbstractObjective. To assess the effects of intraarticular (IA) corticosteroid use on bone metabolism in patients with rheumatoid arthritis (RA).Methods. Levels of the bone turnover markers, serum osteocalcin (BGP) and urinary pyridinoline (PYD), were monitored in RA patients for 4 weeks following a single IA administration of xylocaine alone or in combination with triamcinolone acetonide.Results. Levels of the bone resorption marker, PYD, did not show any significant change, whereas BGP levels were drastically decreased 1 day after IA administration of corticosteroid, and then returned to pretreatment levels by day 14. The efficacy of IA corticosteroid treatment lasted for 4 weeks.Conclusion. Our results suggest that IA administration of corticosteroid has no net effects on bone resorption and only a transient systemic effect on bone formation. IA corticosteroid administration may be better for bone metabolism than continuous use of orally administered corticosteroid.
Evaluating systemic lupus erythematosus disease activity using molecular markers of hemostasis
Authors: Inoh Masayukiinoh , Tokuda Michiaki , Kiuchi Hiroyuki , Kurata Noriyuki , Takahara Jiro 
Published: February 2007

AbstractObjective. To determine the usefulness of measuring sensitive markers of the coagulation–fibrinolysis system (i.e., thrombin–antithrombin III complex [TAT], D dimer fragments [DD], and plasmin–α2‐plasmin inhibitor complex [PIC]) for evaluating disease activity in patients with systemic lupus erythematosus (SLE).Methods. We studied 57 SLE patients. Plasma concentrations of DD were measured by latex agglutination using monoclonal antibodies; TAT and PIC were determined by sandwich enzyme‐linked immunosorbent assay. Disease activity was determined by using the SLE Disease Activity Index (SLEDAI).Results. Levels of TAT, DD, and PIC were higher in SLE patients than in healthy controls (P < 0.05). Levels of TAT and DD showed good correlations with SLEDAI scores (for TAT r = 0.66, P < 0.001; for DD r = 0.50, P < 0.001). Elevated levels of TAT, DD, and PIC were decreased following treatment.Conclusion. These results strongly suggest that measurement of molecular markers of hemostasis is useful for evaluating disease activity in patients with SLE.
Interleukin‐10 inhibition of the progression of established collagen‐induced arthritis
Authors: Walmsley Marita , Katsikis Peter D. , Abney Erika , Parry Sarah , Williams Richard O. , Maini Ravinder N. , Feldmann Marc 
Published: February 2007

AbstractObjective. Interleukin‐10 (IL‐10) is a potent inhibitor of the proinflammatory cytokines, including tumor necrosis factor α and IL‐1, which are considered important in the pathogenesis of rheumatoid arthritis (RA). The study was undertaken to establish whether IL‐10 can ameliorate arthritis in the collagen‐induced arthritis (CIA) model of RA.Methods. DBA/1 mice were immunized with bovine type II collagen in adjuvant, and treated daily after disease onset with recombinant murine IL‐10 or with saline as a control. Mice were monitored for paw swelling and clinical score. Histologic analysis was also performed.Results. IL‐10 treatment of established CIA inhibited paw swelling (P < 0.0001), as well as disease progression as defined by clinical score (P < 0.0002). Cartilage destruction, as assessed histologically, was reduced in IL‐10–treated mice compared with controls (P < 0.01).Conclusion. IL‐10 suppresses established CIA, probably by inhibiting proinflammatory cytokine production. Our results, taken together with previously reported findings, indicate a potential therapeutic role for IL‐10 in RA.
Epstein‐Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis
Authors: van de Rijn Matthijs , Cleary Michael L. , Variakojis Daina , Warnke Roger A. , Chang Pearl P. , Kamel Onsi W. 
Published: February 2007

AbstractObjective. A causative role for Epstein‐Barr virus (EBV) in the development of lymphoma in patients with rheumatoid arthritis (RA) has been proposed. We investigated the molecular features of EBV‐positive diffuse large cell lymphomas in 2 patients with RA.Methods. Southern blot analysis for immunoglobulin gene rearrangements, terminal repeat analysis for clonality of the EBV genome, and double‐labeling of the lymphoma cells by in situ hybridization and immuno‐peroxidase staining were performed.Results. In both cases, double‐labeling studies localized the EBV genome to the malignant B cells. Both neoplasms contained clonal immunoglobulin gene rearrangements and clonal EBV genomes.Conclusion. Our data indicate that EBV infection was an early step in the development of these neoplasms. The findings further extend knowledge on the similarity of this subset of lymphomas to posttransplantation lymphomas and emphasize the role of immunosuppression in their genesis.
Enhancement of anti‐DNA topoisomerase I autoantibody response after lung cancer in patients with systemic sclerosis: A report of two cases
Authors: Kuwana Masataka , Fujii Takao , Mimori Tsuneyo , Kaburaki Junichi 
Published: February 2007

AbstractAnti‐DNA topoisomerase I (anti–topo I) antibody profiles were compared before and after lung cancer in 2 patients with systemic sclerosis (SSc). Both patients developed adenocarcinoma of the lung late in the course of SSc and died of the cancer. Anti–topo I antibody levels, determined by double immunodiffusion and enzyme‐linked immunosorbent assay, increased markedly at the time of diagnosis of lung cancer. Furthermore, patients' sera obtained after lung cancer reacted with multiple epitopes on the entire topo I molecule, some of which had not previously been recognized. These results further support the concept that anti–topo I antibody production in SSc patients is due to an antigen‐driven process.
Cigarette smoking increases the risk of rheumatoid arthritis: Results from a nationwide study of disease‐discordant twins
Authors: Silman Alan J. , Newman Jason , Macgregor Alexander J. 
Published: February 2007

AbstractObjective. To test the hypothesis that cigarette smoking is associated with susceptibility to rheumatoid arthritis (RA) by comparing smoking history between twins with RA and their unaffected co‐twins.Methods. Interview questionnaires on smoking history were administered to 79 identical (monozygotic [MZ]) and 71 same‐sex nonidentical (dizygotic, [DZ]) twin pairs who were discordant for RA, recruited from the Arthritis and Rheumatism Council Twin Study. Results were expressed as odds ratios (OR) with 95% confidence intervals (95% CI).Results. Although most twin pairs were concordant for smoking history, there was a strong association between ever smoking and RA in the MZ pairs (OR 12.0, 95% CI 1.78–513), with a similar trend observed in the DZ pairs (OR 2.5, 95% CI 0.92–7.87).Conclusion. The discordance in cigarette smoking history for individuals who are at presumed identical genetic risk for RA supports other data suggesting the role of smoking in disease susceptibility.
Direct gene delivery to synovium: An evaluation of potential vectors in vitro and in vivo
Authors: Nita I. , Ghivizzani S. C. , Galea‐Lauri J. , Bandara G. , Georgescu H. I. , Robbins P. D. , Evans C. H. 
Published: February 2007

AbstractObjective. To assess the abilities of various vectors to transfer genes to the synovial lining of joints.Methods. Vectors derived from retrovirus, adenovirus, and herpes simplex virus as well as cationic liposomes and naked plasmid DNA were evaluated. Each construct contained the lac Z marker gene; and one retroviral construct, and one plasmid also contained a gene encoding human interleukin‐1 receptor antagonist. Gene expression was under the control of the human cytomegalovirus promoter in all vectors except the retrovirus, where the endogenous 5′ long terminal repeat was retained as the promoter. Cultures of rabbit synovial fibroblasts were exposed to these vectors and stained with X‐gal to identify lac Z+ cells. Vectors were then injected directly into rabbits' knee joints, and gene transfer and expression were assessed by X‐gal staining and polymerase chain reaction (PCR).Results. Adenovirus was a highly effective vector both in vitro and in vivo, with lac Z gene expression persisting for at least 28 days. However, an inflammatory response was noted in vivo. Cells infected in vitro and in vivo with herpes simplex virus also expressed the lac Z gene at high levels, but expression was limited by cytotoxicity. Retroviruses, in contrast, were effective only under in vitro conditions, permitting cell division. Liposomes gave variable in vitro results; when injected into joints in vivo, gene expression was low and was detectable for only a few days, even though a PCR signal persisted for at least 28 days. Unexpectedly, plasmid DNA was captured by the synoviocytes and expressed transiently following intraarticular injection.Conclusion. None of the vectors was ideal for in vivo gene delivery to synovium, although adenovirus was clearly the most effective of those tested. Retroviruses, although poor vectors for in vivo gene delivery, are well suited for ex vivo gene transfer to the synovial lining of joints.
Enrichment of differentiated CD45RBdim, CD27 – memory T cells in the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis
Authors: Kohem Charles L. , Brezinschek Ruth I. , Wisbey Heather , Tortorella Cosimo , Lipsky Peter E. , Oppenheimer‐Marks Nancy 
Published: February 2007

AbstractObjective. To delineate in greater detail the phenotype of T cells that reside in the synovial tissue (ST) and synovial fluid (SF) of patients with rheumatoid arthritis (RA), in order to determine their precise differentiation status, and to determine whether the accumulation of these specific T cell subsets in these synovial compartments could be related to their capacity for transendothelial migration.Methods. Lymphocytes from normal subjects or from the peripheral blood (PB), ST, and/or SF of RA patients were phenotypically analyzed by flow cytometry. Normal PB CD4+ T cells were also characterized using an in vitro assay of transendothelial migration.Results. ST and SF were found to be enriched with memory (CD45RA‐, CD45RO+, CD11abright, CD44bright) and activated (CD69+) T cells. Moreover, ST and SF cells from RA patients were enriched in differentiated CD4+, CD45RBdim, CD27‐ T cells, a subset of mature memory T cells that develops after prolonged antigenic stimulation. In addition, PB of some RA patients contained an increased number of CD4+, CD45RBdim, CD27‐ T cells. The CD4+, CD11abright, CD44bright memory T cells, which included the CD45RBdim, CD27‐ more mature memory cells, exhibited an enhanced capacity for transendothelial migration that is likely to contribute to their enrichment in the rheumatoid synovium.Conclusion. RA patients manifest an increased number of mature memory T cells in the SF and ST, and some also have an increased number of these cells in PB that is likely to reflect chronic antigenic stimulation. The enrichment of these cells in the SF and ST reflects, in part, an enhanced capacity to migrate from the vascular space into inflamed tissue.
A comparative study of HLA genes in HLA–B27 positive ankylosing spondylitis and HLA–B27 positive peripheral reactive arthritis
Authors: Westman Pia , Leirisalo‐Repo Marjatta , Partanen Jukka , Koskimies Saija 
Published: February 2007

AbstractObjective. To determine whether HLA–B27 positive patients with ankylosing spondylitis (AS) and reactive arthritis (ReA) share additional HLA factors that confer disease susceptibility.Methods. HLA class I antigens were typed serologically, and class II antigens molecularly, in samples taken from 33 patients with AS, 30 patients with ReA, and 55 healthy HLA–B27 positive controls.Results. There was no major difference between the HLA alleles in AS and ReA patients, but deviations were observed when compared with healthy controls, especially between the antigens that were probably encoded by genes in the non‐B27 chromosome.Conclusion. These results suggest that both HLA class I and class II genes may influence the pathogenesis of HLA–B27 positive ReA, whereas class I antigens seem to be the major additional genetic factors in HLA–B27 positive AS.
Why health care costs more in the US: Comparing health care expenditures between systemic lupus erythematosus patients in Stanford and Montreal
Authors: Gironimi Gail , Clarke Ann E. , Hamilton Vivian H. , Danoff Deborah S. , Bloch Daniel A. , Fries James F. , Esdaile John M. 
Published: February 2007

AbstractObjective. Recent studies to identify the causes of higher health care expenditure in the US versus Canada have relied on population‐based measures of health care utilization and have restricted their analysis to one sector, such as physician or hospital expenditures. We present a detailed comparative analysis of the direct costs (health services utilized) of treating systemic lupus erythematosus (SLE) patients in Stanford, CA and Montreal, Quebec.Methods. Using the self‐report Stanford Health Assessment Questionnaire, we assessed 6‐month direct costs incurred by 174 American and 164 Canadian SLE patients. We explored 3 potential reasons for the differential expenditure. These were 1) higher prices for health care inputs, 2) more severe disease in the patient case mix, and 3) greater resource utilization.Results. The direct health care costs for the American SLE patients exceeded those for the Canadian patients by almost 2‐fold ($10,530 versus $5,271, expressed in 1991 US dollars). The higher direct costs were explained by the higher price of health services in the US and the more severe disease mix. In fact, for all health resource categories studied, Canadians utilized at least as many services as their American counterparts. Canadians had longer hospital stays, made more emergency room visits, and used more medications.Conclusion. Despite significantly greater per capita health care expenditure in the US, our data show that Canadian SLE patients actually receive more medical services.
N‐[4‐hydroxyphenyl] retinamide in rheumatoid arthritis: A pilot study
Authors: Gravallese Ellen M. , Handel Malcolm L. , Coblyn Jonathan , Anderson Ronald J. , Sperling Richard I. , Karlson Elizabeth W. , Maier Agnes , Ruderman Eric M. , Formel Franca , Weinblatt Michael E. 
Published: February 2007

AbstractObjective. To evaluate the efficacy and tolerability of N‐[4 hydroxyphenyl] retinamide (4‐HPR), a synthetic retinoid, in the treatment of rheumatoid arthritis (RA).Methods. An uncontrolled, open clinical trial with synovial biopsy pre‐ and postmedication to evaluate the clinical effects of 4‐HPR as well as its effects on metalloproteinase gene expression.Results. Twelve patients with severe, longstanding RA were enrolled in this study. Six patients withdrew before study completion, 2 because of drug toxicity, 2 because of a flare of RA, and 2 because of intercurrent medical problems. No patient met predetermined Paulus criteria for treatment response, and there was no improvement in the laboratory parameters, except for a modest decrease in C‐reactive protein. No decrease in messenger RNA for the metalloproteinases collagenase and stromelysin was seen in the 2 patients in whom paired synovial biopsies were obtained.Conclusion. No beneficial clinical effect was observed with the retinoid 4‐HPR in the treatment of severe, longstanding RA at the 300 mg/day dosage studied. The use of higher dosages is precluded by the observed toxicities. The effect of this drug in patients with early or mild disease was not studied. Although this particular retinoid was not effective in this pilot study, the use of other retinoids in RA should still be considered.
Human synovial mast cells. I. Ultrastructural in situ and in vitro immunologic characterization
Authors: De Paulis Amato , Marinò Isabella , Ciccarelli Anna , De Crescenzo Gennaro , Concardi Monica , Verga Laura , Arbustini Eloisa , Marone Gianni 
Published: February 2007

AbstractObjective. To examine the ultrastructure of human synovial mast cells in situ, to identify immunologic and nonimmunologic stimuli that activate these cells in vitro, and to quantify a number of preformed and de novo–synthesized mediators.Methods. We conducted an ultrastructural study of synovial mast cells in situ and performed immunoelectron microscopy localization of tryptase and chymase. Isolated synovial mast cells were analyzed biochemically, immunologically, and functionally in vitro and compared with cells from human lung, heart, and skin.Results. Ultrastructural study of synovial tissue revealed mast cells with homogeneously dense, scrolled, crystal, and mixed granules, and lipid bodies in the cytoplasm. A small percentage of mast cells showed evidence of degranulation. Immunoelectron microscopy demonstrated the subcellular localization of tryptase and chymase over granules of >90% of the mast cells, which were of the MCTC subtype. Isolated synovial mast cells released histamine in response to immunologic (anti‐IgE and anti‐Fcε receptor I [anti‐FcεRI]) and nonimmunologic (substance P, recombinant human stem cell factor, and 48/80) stimuli, but did not respond to recombinant human C5a in vitro. Synovial mast cells differed from those isolated from other human tissues, in a variety of immunologic and biochemical features. There was a linear correlation between the percentage of histamine secretion and tryptase release (r = 0.79, P < 0.001) induced by cross‐linking of FcεRI. Cross‐linking of IgE with anti‐IgE on synovial mast cells induced de novo synthesis of prostaglandin D2 (mean ± SEM 87.5 ± 4.9 ng/106 cells) and of leukotriene C4 (57.6 ± 17.8 ng/106 cells).Conclusion. Mast cells ultrastructurally characterized in situ in synovial tissue were seen to differ from mast cells previously isolated from other human tissues. This raises the possibility that the local microenviroment influences their phenotype. Isolation of mast cells from human synovia can be useful for studying their role and their mediatrors in patients with arthritis.
Expression and function of CD80 and CD86 costimulator molecules on synovial dendritic cells in chronic arthritis
Authors: Summers Kelly L. , O'Donnell John L. , Williams Lisa A. , Hart Derek N. J. 
Published: February 2007

AbstractObjective. To examine CD86 expression on dendritic cells isolated from the synovial fluid (SFDC) of patients with chronic arthritis, and to determine the importance of both CD80 and CD86 molecules in SFDC‐T lymphocyte interactions.Methods. CD86 messenger RNA (mRNA) and surface expression were analyzed in SFDC using reverse transcriptase‐polymerase chain reaction and flow cytometry, respectively. The costimulator activity of the SFDC CD80 and CD86 molecules was determined by allogeneic mixed lymphocyte reaction (MLR). CD80 and CD86 induction on SFDC during in vitro culture was also examined.Results. Fresh SFDC either lacked or showed very weak surface expression of CD86 molecules (as shown previously for CD80), yet contained CD86 mRNA. CD80 antibodies minimally inhibited an allogeneic MLR, whereas CD86 antibodies and CTLA‐4 Ig showed significant inhibition. Both CD80 and CD86 molecules were inconsistently induced on SFDC following culture in either media, interferon‐γ, or granulocyte‐macrophage colony‐stimulating factor.Conclusion. SFDC may be defective antigen‐presenting cells in vivo. The ability of CD80 and CD86 molecules to be induced and become functional on SFDC in vitro implies the presence of a negative regulatory compound(s) in the synovial environment.
The effects of the phospholipase a2 inhibitor, manoalide, on cartilage degradation, stromelysin expression, and synovial fluid cell count induced by intraarticular injection of human recombinant interleukin‐1α in the rabbit
Authors: Schrier Denis J. , Flory Craig M. , Finkel Martin , Kuchera Susan L. , Lesch Mark E. , Jacobson Peer B. 
Published: February 2007

AbstractObjective. To evaluate the effects of the phospho‐lipase A2 (PLA2) inhibitor manoalide on cartilage degradation, stromelysin expression, and inflammatory cell accumulation in rabbits treated intraarticularly with recombinant human interleukin‐1α (rHuIL‐1α).Methods. Rabbits were given an intraarticular injection of rHuIL‐1α. At various time points over a 24‐hour period, the rabbits were euthanized and the articular space was lavaged with sterile PBS. The proteoglycan content of the lavage fluid was measured using a dimethylmethylene blue assay. PLA2 activity and differential cell counts were also measured. The femur was removed and cartilage proteoglycan content determined. In some experiments, levels of synovial stromelysin messenger RNA (mRNA) were assessed. Manoalide or vehicle was administered 30 minutes before the rHuIL‐1α injection.Results. The rHuIL‐1α‐induced arthritic response is characterized by significant accumulation of inflammatory cells, loss of proteoglycan from the condylar cartilage, and induction of mRNA for stromelysin. PLA2 activity was also elevated in synovial fluids from rHuIL‐1α‐injected joints. Pretreatment with manoalide (0.3 mg/joint) significantly inhibited PLA2 activity in the synovial fluid, prevented the loss of proteoglycan from the condylar cartilage, and reduced proteoglycan levels in lavage fluids. However, manoalide either had no effect on, or stimulated, cell accumulation. To assess the relationship between the induction of PLA2 and stromelysin, levels of stromelysin mRNA were measured in synovial tissue from manoalide‐ and vehicle‐treated joints. Stromelysin message levels were significantly suppressed in a dose‐dependent manner.Conclusion. These studies demonstrate that manoalide is a potent inhibitor of inflammation and cartilage catabolism, and suggest that PLA2 is involved in the pathophysiology of rHuIL‐1α‐induced arthritis in rabbits.