UMLS:C0003873 - FACTA Search

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Query: UMLS:C0003873 (rheumatoid arthritis)
53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At present only few biological data are available to indicate whether psoriatic arthritis (PsA) is part of the spondyloarthropathy (SpA) concept, whether it is a separate disease entity or a heterogeneous disease group with oligoarticular/axial forms belonging to SpA and polyarticular forms resembling rheumatoid arthritis (RA). To address this issue with regard to peripheral synovitis, we compared the synovial characteristics of PsA with those of ankylosing spondylitis (AS)/undifferentiated SpA (USpA) and RA, and compared the synovium of oligoarticular versus polyarticular PsA. Synovial biopsies were obtained from patients with RA, nonpsoriatic SpA (AS + USpA), and oligoarticular and polyarticular PsA. The histological analysis included examination(s) of the lining layer thickness, vascularity, cellular infiltration, lymphoid aggregates, plasma cells and neutrophils. Also, we performed immunohistochemical assessments of CD3, CD4, CD8, CD20, CD38, CD138, CD68, CD163, CD83, CD1a, CD146, alphaVbeta3, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, S100A12, intracellular citrullinated proteins and major histocompatibility complex (MHC)-human cartilage (HC) gp39 peptide complexes. Comparing SpA (PsA + AS + USpA) with RA, vascularity, and neutrophil and CD163+ macrophage counts were greater in SpA (P < 0.05), whereas lining layer thickness and the number of CD83+ dendritic cells were greater in RA (P < 0.05). In RA, 44% of samples exhibited positive staining for intracellular citrullinated proteins and 46% for MHC-HC gp39 peptide complexes, whereas no staining for these markers was observed in SpA samples. We excluded influences of disease-modifying antirheumatic drug and/or corticosteroid treatment by conducting systematic analyses of treated and untreated subgroups. Focusing on PsA, no significant differences were observed between PsA and nonpsoriatic SpA. In contrast, vascularity (P < 0.001) and neutrophils were increased in PsA as compared with RA (P = 0.010), whereas staining for intracellular citrullinated proteins and MHC-HC gp39 peptide complexes was exclusively observed in RA (both P = 0.001), indicating that the same discriminating features are found in PsA and other SpA subtypes compared with RA. Exploring synovial histopathology between oligoarticular and polyarticular PsA, no significant differences were noted. Moreover, intracellular citrullinated proteins and MHC-HC gp39 peptide complexes, which are specific markers for RA, were observed in neither oligoarticular nor polyarticular PsA. Taken together, these data indicate that the synovial histopathology of PsA, either oligoarticular or polyarticular, resembles that of other SpA subtypes, whereas both groups can be differentiated from RA on the basis of these same synovial features, suggesting that peripheral synovitis in PsA belongs to the SpA concept.
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PMID:Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis. 1589 64

Cardiovascular event rates are markedly increased in rheumatoid arthritis (RA), and RA atherogenesis remains poorly understood. The relative contributions of traditional and nontraditional risk factors to cardiovascular disease in RA await elucidation. The present study comprises three components. First, we compared biomarkers of endothelial dysfunction (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1 and endothelial leucocyte adhesion molecule [ELAM]-1) in 74 RA patients and 80 healthy control individuals before and after controlling for traditional and nontraditional cardiovascular risk factors, including high-sensitivity C-reactive protein (hs-CRP), IL-1, IL-6 and tumor necrosis factor-alpha. Second, we investigated the potential role of an extensive range of patient characteristics in endothelial dysfunction in the 74 RA patients. Finally, we assessed associations between biomarkers of endothelial dysfunction and ultrasonographically determined common carotid artery intima-media thickness and plaque in RA. The three biomarkers of endothelial dysfunction, as well as hs-CRP, IL-1, IL-6 and tumor necrosis factor-alpha, were higher in patients than in control individuals (P < 0.0001). Patients were also older, exercised less and had a greater waist circumference, blood pressure and triglyceride levels (P <or= 0.04). Five patients had diabetes. Differences in endothelial function were no longer significant between patients and controls (P = 0.08) only after both traditional and nontraditional cardiovascular risk factors were controlled for. In the 74 RA patients, IL-6 predicted levels of all three biomarkers (P <or= 0.03), and rheumatoid factor titres and low glomerular filtration rate (GFR) both predicted levels of VCAM-1 and ICAM-1, independent of traditional cardiovascular risk factors (P <or= 0.02). VCAM-1 was associated with common carotid artery intima-media thickness (P = 0.02) and plaque (P = 0.04) in RA. Patients had impaired endothelial function, less favourable traditional cardiovascular risk factor profiles, and higher circulating concentrations of hs-CRP and cytokines compared with healthy control individuals. Both traditional and nontraditional cardiovascular risk factors contributed to the differences in endothelial function between RA patients and healthy control individuals. IL-6, rheumatoid factor titres and low GFR were independently predictive of endothelial dysfunction in RA. Disease-modifying agents that effectively suppress both cytokine and rheumatoid factor production, and interventions aimed at preserving renal function may attenuate cardiovascular risk in RA.
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PMID:Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. 1589 50

Endothelial cells play an important role in inflammatory diseases like rheumatoid arthritis by recruitment of inflammatory cells. The cytokines TNF-alpha and IL-1beta are major inducers of endothelial cell activation and are stimulators of inflammatory signal transduction pathway involving p38 MAPK (mitogen-activated protein kinase). The present study investigated the effects of p38 MAPK inhibition on cell adhesion molecule (CAM) expression and chemokine production by endothelial cells both on mRNA and protein level. Pre-treatment of endothelial cells with the pharmacologically relevant concentration of 1 microM of the p38 MAPK inhibitor RWJ 67657 reduced TNF-alpha and IL-1beta induced mRNA and membrane expression of E-selectin. Moderate inhibitory effects on ICAM-1 and VCAM-1 expression were found. Significant reduction of mRNA expression and protein production of the inflammatory cytokine IL-6 and the chemokines IL-8 and MCP-1 was demonstrated. Treatment with RWJ 67657 could lead to reduced leukocyte infiltration by the reduction of E-selectin expression and chemokine production.
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PMID:Chemokine production and E-selectin expression in activated endothelial cells are inhibited by p38 MAPK (mitogen activated protein kinase) inhibitor RWJ 67657. 1591 30

A small cell-permeable compound, dehydroxymethylepoxyquinomicin (DHMEQ), does not inhibit phosphorylation and degradation of IkappaB (inhibitor of nuclear factor-kappaB [NF-kappaB]) but selectively inhibits nuclear translocation of activated NF-kappaB. This study aimed to demonstrate the antiarthritic effect of this novel inhibitor of the NF-kappaB pathway in vivo in a murine arthritis model and in vitro in human synovial cells. Collagen-induced arthritis was induced in mice, and after onset of arthritis the mice were treated with DHMEQ (5 mg/kg body weight per day). Using fibroblast-like synoviocyte (FLS) cell lines established from patients with rheumatoid arthritis (RA), NF-kappaB activity was examined by electrophoretic mobility shift assays. The expression of molecules involved in RA pathogenesis was determined by RT-PCR, ELISA, and flow cytometry. The proliferative activity of the cells was estimated with tritiated thymidine incorporation. After 14 days of treatment with DHMEQ, mice with collagen-induced arthritis exhibited decreased severity of arthritis, based on the degree of paw swelling, the number of swollen joints, and radiographic and histopathologic scores, compared with the control mice treated with vehicle alone. In RA FLS stimulated with tumor necrosis factor-alpha, activities of NF-kappaB components p65 and p50 were inhibited by DHMEQ, leading to suppressed expression of the key inflammatory cytokine IL-6, CC chemokine ligand-2 and -5, matrix metalloproteinase-3, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. The proliferative activity of the cells was also suppressed. This is the first demonstration of an inhibitor of NF-kappaB nuclear translocation exhibiting a therapeutic effect on established murine arthritis, and suppression of inflammatory mediators in FLS was thought to be among the mechanisms underlying such an effect.
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PMID:Effect of a small molecule inhibitor of nuclear factor-kappaB nuclear translocation in a murine model of arthritis and cultured human synovial cells. 1627 88

In order to selectively block nuclear factor kappaB (NF-kappaB)-dependent signal transduction in angiogenic endothelial cells, we constructed an alphavbeta3 integrin specific adenovirus encoding dominant negative IkappaB (dnIkappaB) as a therapeutic gene. By virtue of RGD modification of the PEGylated virus, the specificity of the cell entry pathway of adenovirus shifted from coxsacki-adenovirus receptor dependent to alphavbeta3 integrin dependent entry. The therapeutic outcome of delivery of the transgene into endothelial cells was determined by analysis of cellular responsiveness to tumor necrosis factor (TNF)-alpha. Using real time reverse transcription PCR, mRNA levels of the cell adhesion molecules E-selectin, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, the cytokines/growth factors IL-6, IL-8 and vascular endothelial growth factor (VEGF)-A, and the receptor tyrosine kinase Tie-2 were assessed. Furthermore, levels of ICAM-1 protein were determined by flow cytometric analysis. RGD-targeted adenovirus delivered the dnIkappaB via alphavbeta3 to become functionally expressed, leading to complete abolishment of TNF-alpha-induced up-regulation of E-selectin, ICAM-1, VCAM-1, IL-6, IL-8, VEGF-A and Tie-2. The approach of targeted delivery of dnIkappaB into endothelial cells presented here can be employed for diseases such as rheumatoid arthritis and inflammatory bowel disease where activation of NF-kappaB activity should be locally restored to basal levels in the endothelium.
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PMID:Functional inhibition of NF-kappaB signal transduction in alphavbeta3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant IkappaB gene. 1680 39

Conventional anti-inflammatory strategies induce multiple side effects, highlighting the need for novel targeted therapies. Here we show that knockdown of the basic-region leucine zipper protein, c-Jun, by a catalytic DNA molecule, Dz13, suppresses vascular permeability and transendothelial emigration of leukocytes in murine models of vascular permeability, inflammation, acute inflammation and rheumatoid arthritis. Treatment with Dz13 reduced vascular permeability due to cutaneous anaphylactic challenge or VEGF administration in mice. Dz13 also abrogated monocyte-endothelial cell adhesion in vitro and abolished leukocyte rolling, adhesion and extravasation in a rat model of inflammation. Dz13 suppressed neutrophil infiltration in the lungs of mice challenged with endotoxin, a model of acute inflammation. Finally, Dz13 reduced joint swelling, inflammatory cell infiltration and bone erosion in a mouse model of rheumatoid arthritis. Mechanistic studies showed that Dz13 blocks cytokine-inducible endothelial c-Jun, E-selectin, ICAM-1, VCAM-1 and VE-cadherin expression but has no effect on JAM-1, PECAM-1, p-JNK-1 or c-Fos. These findings implicate c-Jun as a useful target for anti-inflammatory therapies.
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PMID:Suppression of vascular permeability and inflammation by targeting of the transcription factor c-Jun. 2625 46

An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS(28)). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS(28) decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients.
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PMID:Keishibukuryogan (gui-zhi-fu-ling-wan), a Kampo formula, decreases disease activity and soluble vascular adhesion molecule-1 in patients with rheumatoid arthritis. 1695 20

Fibroblast-like synoviocytes (FLS) play a key role in the genesis of rheumatoid arthritis (RA). FLS are among the most versatile cells with the potential to activate an array of genes that are able to initiate and propagate inflammation in RA-affected joints. Controlling activation of FLS might hold the key to restraining inflammation in RA-affected joints. In this study, we investigate the effect and mechanisms of short-term hyperthermia on a series of proinflammatory genes in FLS. In vitro experiments demonstrate that exposure of FLS to elevated temperatures for the duration of 30 min prevents activation of a series of genes with proinflammatory properties. Exposure to hyperthermia reduces IL-1beta-induced prostaglandin E2 release, suppresses activation of the adhesion molecules VCAM-1, ICAM-1, the cytokines TNFalpha, IL-1alpha, IL-1beta, IL-8 as well as COX-2 protein synthesis. Real time reverse transcriptase-polymerase chain reaction showed that hyperthermia altered gene expression at the transcriptional level. The amount and the duration of inhibition is gene-specific and lasts for up to 25 h. As to the mechanism of inhibition, electrophoretic mobility shift assay experiments demonstrated that exposure of FLS to hyperthermia prevents IL-1beta-induced NF-kappaB translocation and subsequent DNA binding. Many mechanisms have been shown to be involved in hyperthermia-mediated effects on NF-kappaB-DNA interactions. We demonstrate by Western blot experiments that in FLS, hyperthermia prevents the phosphorylation and subsequent degradation of IkappaBalpha, therefore retaining the NF-kappaB complex in the cytoplasm. Carefully controlled in vivo tests are certainly needed before one can take full advantage of those phenomena; however, the ease by which the temperature in joints can be modulated might offer an opportunity for manipulating inflammatory processes in joints by simple balneological means.
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PMID:Short-term hyperthermia prevents activation of proinflammatory genes in fibroblast-like synoviocytes by blocking the activation of the transcription factor NF-kappaB. 1698 13

C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), implicating oxLDL/beta2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/beta2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/beta2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/beta2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.
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PMID:The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis. 1726 75

In search of a noninvasive diagnostic test for rheumatoid vasculitis (RV), this study addressed the questions whether changes in capillary blood cell velocity (CBV) detected by laser Doppler anemometry in patients with rheumatoid arthritis (RA) were correlated with the levels of soluble adhesion molecules and whether cutaneous flow abnormalities may reflect extraarticular manifestations in RA. In 31 RA patients and 20 patients with osteoarthritis (OA), CBV was measured in the skin above the left ring finger at rest and after 3-min arterial occlusion. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin) were assessed by enzyme linked immunosorbent assay. Peak CBV was reduced in RA patients compared to OA patients (0.42 +/- 0.07 mm/s vs. 0.70 +/- 0.13 mm/s; P = 0.013). Both CBV during rest and reactive hyperemia were not correlated with the levels of soluble adhesion molecules. There were no significant differences in resting or peak CBV between RA patients with or without extraarticular manifestations. The lack of an inverse correlation between the levels of soluble adhesion molecules and CBV during rest and reactive hyperemia contradicts the assumption that inflammatory vascular damage indicated by increased levels of soluble adhesion molecules was the main reason for the impairment of microcirculation. The present results do not suggest that cutaneous flow abnormalities may reflect extraarticular manifestations in RA.
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PMID:Microvascular dysfunction in rheumatoid arthritis assessed by laser Doppler anemometry: relationship to soluble adhesion molecules and extraarticular manifestations. 1760 11

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