Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 11125312 | Increased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio deline | 2000 Dec | The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different diseases. The aim of this work was to study the cytokine network occurring in inflammatory arthropathies and to identify a cytokine profile which is characteristic of an immune-mediated synovitis. Levels of IL-12, as well as IL-4, IL-8, IL-10, IFN-gamma, sCD25, TNF-alpha and its soluble receptors were measured in the SF of various arthropathies, i.e. non-inflammatory arthropathies: "control" meniscus pathology (n = 21), osteoarthritis (n = 22) and chronic crystal arthritis (n = 9); a non-immune inflammatory arthropathy: acute crystal arthritis (n = 11); 2 immune inflammatory arthropathies: reactive arthritis (ReA) (n = 23) and rheumatoid arthritis (RA) (n = 44). SF levels of IL-10, TNF-alpha and sTNF-RII were found to be increased in the three inflammatory arthropathies compared to the "control" meniscus group. Within the inflammatory group, acute crystal arthritis was characterized by a significantly higher sTNF-RI/TNF-alpha ratio and ReA by a significantly lower sTNF-RII/TNF-alpha ratio compared to the two other diseases. The two immune arthropathies, RA and ReA, were characterized by increased SF levels of IL-12, sCD25 and of the sTNF-RII/sTNF-RI ratio. ReA differed however from RA by showing lower IL-8 and IL-4 levels, higher IFN-gamma levels and a higher IL-12/IL-10 ratio, suggesting a more prevalent Th1 profile in ReA SF. Our data indicate that the measurement of SF cytokines and soluble receptors may discriminate between each inflammatory arthropathy and might be useful in clinical practice. | |
| 9353419 | Inhibition of NFkappaB-mediated interleukin-1beta-stimulated prostaglandin E2 formation by | 1997 Nov | Exposure of human rheumatoid synovial fibroblasts (RSF) to interleukin 1beta (IL-1beta) results in the coordinate up-regulation of 85-kDa phospholipase A2 (PLA2) and mitogen-inducible cyclooxygenase (COX II) and subsequent biosynthesis of prostaglandin E2 (PGE2). We have recently demonstrated, through the use of oligonucleotide decoys and antisense, the participation of the proinflammatory transcription factor, nuclear factor kappaB (NFkappaB), in the regulation of the prostanoid-metabolizing enzymes. Hymenialdisine, a marine natural product has recently been characterized as an inhibitor of NFkappaB activation and exposure of IL-1-stimulated RSF-inhibited PGE2 production in a concentration-dependent manner (IC50 approximately 1 microM). Alternatively, both an analog, aldisine, and the protein kinase C inhibitor, RO 32-0432, were without affect. Direct action of hymenialdisine on IL-1-induced NFkappaB activation was demonstrated by a significant reduction (approximately 80%) in NFkappaB binding to the classical kappaB consensus motif (as assessed by electrophoretic mobility shift assay) and inhibition of stimulated p65 migration from the cytosol of treated cells (as assessed by Western analysis). Consistent with the role of NFkappaB in the transcriptional regulation of COX II and 85-kDa PLA2, hymenialdisine-treated RSF did not transcribe the respective mRNAs in response to IL-1. This led to reductions in their respective protein levels and subsequent reductions in the ability to produce PGE2. Specificity of action is suggested as IL-1-stimulated interleukin-8 (IL-8) production, which is known to be an NFkappaB-regulated event, was also inhibited by hymenialdisine, whereas IL-1-induced production of vascular endothelial growth factor, a non-NFkappaB-regulated gene, was not affected by exposure to hymenialdisine. Taken together, hymenialdisine inhibits IL-1-stimulated-RSF PGE2 formation acting predominately through modulation of NFkappaB activation and offers an interesting novel tool to evaluate the role of NFkappaB in inflammatory disease. | |
| 10090156 | Downregulation of intercellular adhesion molecule-1 expression on human synovial fibroblas | 1999 Mar | OBJECTIVE: To study the effect of endothelin-1 (ET-1) on the expression of intercellular adhesion molecule-1 (ICAM-1) by synovial fibroblasts derived from individuals with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: The expression of ICAM-1 protein and the abundance of ICAM-1 mRNA in synovial fibroblasts derived from individuals with RA or OA, or healthy controls, was assessed by flow cytometry and Northern blot analysis, respectively. mRNA expression of ET type A (ETA) and ET type B (ETB) receptors was assessed by reverse transcription polymerase chain reaction. RESULTS: Tumor necrosis factor-alpha (TNF-alpha) increased the expression of ICAM-1 by RA and OA fibroblasts. While ET-1 alone had no significant effect on ICAM-1 expression by either cell type, it inhibited the TNF-alpha induced increase in ICAM-1 expression, and this effect was more marked in RA fibroblasts. TNF-alpha also increased the amount of ICAM-1 mRNA in both cell types, and ET-1 inhibited this increase to a greater extent in RA fibroblasts than in OA fibroblasts. This inhibitory effect of ET-1 was reversed by addition of specific antagonist of ETA receptor. mRNA expression of ETA and ETB receptors was significantly greater in RA fibroblasts stimulated with TNF-alpha or even medium alone than in OA fibroblasts. CONCLUSION: These results suggest that ICAM-1 expression by fibroblasts is regulated not only by proinflammatory cytokines such as TNF-alpha and interleukin-1beta, but also by the vasoactive peptide ET-1, and that ET-1 may play an important role in inflammatory responses, especially in rheumatoid synovitis. | |
| 11258677 | Kallikrein and kinin receptor expression in inflammation and cancer. | 2001 Jan | The kallikrein family of serine proteases has been investigated in many inflammatory disorders as molecular mapping, gene characterisation and cloning of kinin receptor genes have unfolded experimentally. In the molecular events of the inflammatory response the kallikrein cascade plays a significant role, since it is considered to initiate and maintain systemic inflammatory responses and immune-modulated disorders. A primary event is the chemotactic attraction of neutrophils which deliver the kallikrein-kinin cascade to sites of cellular injury and carcinogenic transformation of cells. The present study establishes the casual involvement of the kallikrein cascade in infection, inflammatory joint disease, acute transplant rejection, renal glomerular diseases, angiogenesis and carcinoma. We provide strong evidence for new or enhanced expression of kinin B1 receptors in inflammation, and additionally the induction of kallikrein genes in angiogenesis and carcinoma. The results provide insights into possible roles of kallikrein inhibitors and kinin receptor antagonists. | |
| 11315916 | Blockade of Wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte activation. | 2001 Apr | OBJECTIVE: It is not understood why cultured fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) often display a persistently activated phenotype, despite removal from an inflammatory environment. Previously, we found that these FLS expressed high levels of both Wnt-5A and Frizzled 5 (Fz5), a receptor-ligand pair implicated in both limb bud and bone marrow stem cell development. The objective of the present experiments was to determine whether Wnt-5A/FzS signaling contributes to FLS activation. METHODS: Wnt-5A expression in FLS was inhibited by transfection with both antisense and dominant negative (dn) vectors. Fz5 signaling was blocked with an antibody to the extracellular domain of the receptor. The effects of these treatments on the expression of the proinflammatory cytokines interleukin-6 (IL-6) and IL-15 and on the expression of receptor activator of nuclear factor kappaB ligand (RANKL) were assessed by reverse transcriptase-polymerase chain reaction and immunoblotting. RESULTS: Both antisense Wnt-5A and dnWnt-5A vectors, but not empty vector, diminished IL-6 and IL-15 expression in RA FLS. Anti-Fz5 antibody exerted similar effects and also reduced RANKL expression. CONCLUSION: Wnt-5A/Fz5 signaling may contribute to the activated state of FLS in RA. Receptor antagonists of Fz5 should be considered for the treatment of refractory synovitis. | |
| 9743157 | Complement components and their activation products in pleural fluid. | 1998 Sep | STUDY OBJECTIVES: The aim of this study was to determine the role of complement components in pleural effusion measured with novel markers of complement activation, to assess which pathway of activation is predominant in different diseases, and to find out whether the analysis of complement components and their activation products could help in diagnostic procedure differentiating the etiologies of pleural effusion. PATIENTS: The study population consisted of 71 patients who had pleural effusion secondary to tuberculosis (n=23), rheumatic disease (n=10), or malignancy (n=38). MEASUREMENTS: Complement components and their activation products, including the soluble terminal complex SC5b-9, were measured in plasma and pleural fluid. RESULTS: In all patients with rheumatic pleurisy, pleural fluid SC5b-9 was higher than 2 AU/mL and in all patients with malignant pleural fluid it was lower than 2 AU/mL. The mean level of SC5b-9 in rheumatic pleural effusion was also significantly higher than in tuberculosis. In addition, the concentrations of pleural fluid C3 and C4 were significantly lower and the ratio C4d/C4 was significantly higher in rheumatic compared with tuberculous or malignant pleurisy. In plasma, both SC5b-9 and C1s-C1r-C1INH-complexes were significantly higher in rheumatic subjects than in other patients. In stepwise multinominal logistic regression analyses, the most significant predictors for rheumatic pleural fluid were high pleural fluid SC5b-9 and low C4. CONCLUSIONS: These observations indicate that the complement cascade is activated through both the classic and the alternative pathways in rheumatic pleurisy. Determinations of SC5b-9 and C4d/C4 in pleural fluid were the best variables differentiating rheumatic, tuberculous, and malignant effusions. | |
| 9519212 | Treatment of Felty's syndrome with the haemopoietic growth factor granulocyte colony-stimu | 1998 Jan | Felty's syndrome (FS) (rheumatoid arthritis with neutropenia and splenomegaly) has a poor prognosis, largely because of the high risk of severe infection. Granulocyte colony-stimulating factor (G-CSF) is an emerging treatment for chronic neutropenia. We prospectively monitored its use in eight patients with recurrent infections or who required joint surgery. Significant side-effects were documented in five, including nausea, malaise, generalized joint pains, and in one patient, a vasculitic skin rash. In two patients treatment had to be stopped, and in these cases G-CSF had been started at full vial dosage (300 micrograms/ml filgrastim or 263 micrograms/ml lenograstim) alternate days or daily. G-CSF treatment was continued in three patients by restarting at reduced dose, and changing the proprietary formulation. G-CSF raised the neutrophil count, reduced severe infection, and allowed surgery to be performed. A combined clinical and laboratory index suggested that long-term treatment (up to 3.5 years) did not exacerbate the arthritis. Once on established treatment, it may be possible to use smaller weekly doses of G-CSF to maintain the same clinical benefit. One of the three patients whose FS was associated with a large granular T-cell lymphocytosis showed a reduction in this subset of lymphocytes during G-CSF treatment. | |
| 11441986 | Factor V Leiden and prothrombin G20210A in relation to arterial and/or vein rethrombosis: | 2001 Jul | The factor V Leiden (FV Leiden) and prothrombin G20210A mutations, are the most common established genetic risk factors for deep vein thrombosis (DVT). However, the relationship between these mutations and arterial thrombotic syndromes (coronary heart disease, myocardial infarction, stroke) has not been established. Some studies have suggested a relationship between them, but other authors have considered it unlikely that these anomalies are a major risk factor for arterial thrombosis. From the clinical point of view, a question arises concerning the risk of repeated thrombosis in patients carrying one of these two mutations. The question is whether the recurrence is attributable to the mutations or to the presence of additional circumstantial risk factors. As the risk of repeated thrombosis varies considerably from one patient to another, decisions about long-term treatment require weighing the persistence of risk factors for vascular disease (venous and arterial), especially in selected cases such as young patients or patients with thrombosis of unusual localization. | |
| 10666820 | [Reducing pain by oral enzyme therapy in rheumatic diseases]. | 1999 | Proteolytic enzymes have analgesic, effects, besides the wellknown antiinflammatory and edema-reducing properties. These analgesic effects are based on the inhibition of inflammation and in addition to that on direct influences on the nociceptors. All that explains the therapeutical effects of such enzymes in degenerative-rheumatic and soft tissue rheumatic diseases in which inflammatory or immunologic processes are not in the forefront. In recent years a significant reduction of pain in various rheumatic diseases, concerning these aspects, was shown in several clinical studies. The clinical trial in patients with periarthritis of shoulder showed statistical equivalence of pain reduction, whether they were treated with phlogenzym or diclofenac. Likewise in the trial of patients suffering from painful osteoarthritis of the knee, there was a statistical equivalence of the pain-scores, comparing diclofenac and enzymes. The study of painful vertebral syndromes again resulted in equivalence of the treatment with NSAIDs compared to therapy with enzymes. | |
| 9512532 | Consensus-degenerate hybrid oligonucleotide primers for amplification of distantly related | 1998 Apr 1 | We describe a new primer design strategy for PCR amplification of unknown targets that are related to multiply-aligned protein sequences. Each primer consists of a short 3' degenerate core region and a longer 5' consensus clamp region. Only 3-4 highly conserved amino acid residues are necessary for design of the core, which is stabilized by the clamp during annealing to template molecules. During later rounds of amplification, the non-degenerate clamp permits stable annealing to product molecules. We demonstrate the practical utility of this hybrid primer method by detection of diverse reverse transcriptase-like genes in a human genome, and by detection of C5DNA methyltransferase homologs in various plant DNAs. In each case, amplified products were sufficiently pure to be cloned without gel fractionation. This COnsensus-DEgenerate Hybrid Oligonucleotide Primer (CODEHOP) strategy has been implemented as a computer program that is accessible over the World Wide Web (http://blocks.fhcrc.org/codehop.html) and is directly linked from the BlockMaker multiple sequence alignment site for hybrid primer prediction beginning with a set of related protein sequences. | |
| 11605685 | T-cell immunity in acute coronary syndromes. | 2001 Oct | Acute coronary syndromes (ACS) are complications of atherosclerotic vascular disease that are triggered by the sudden rupture of an atheroma. Atherosclerotic plaque stability is determined by multiple factors, of which immune and inflammatory pathways are critical. Unstable plaque is characterized by an infiltrate of T cells and macrophages, thereby resembling a delayed hypersensitivity reaction. On activation, T cells secrete cytokines that regulate the activity of macrophages, or the T cells may differentiate into effector cells with tissue-damaging potential. Constitutive stimulation of T cells and macrophages in ACS is not limited to the vascular lesion but also involves peripheral immune cells, suggesting fundamental abnormalities in homeostatic mechanisms that control the assembly, turnover, and diversity of the immune system as a whole. This review gives particular attention to the emergence of a specialized T-cell subset, natural killer T cells, in patients with ACS. Natural killer T cells have proinflammatory properties and the capability of directly contributing to vascular injury. | |
| 10979111 | Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteo | 2000 Sep 13 | CONTEXT: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown. OBJECTIVE: To determine whether celecoxib, a COX-2-specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs. DESIGN: The Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000. SETTING: Three hundred eighty-six clinical sites in the United States and Canada. PARTICIPANTS: A total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months. INTERVENTIONS: Patients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis ( | |
| 11060789 | Sjögren's syndrome: current therapies remain inadequate for a common disease. | 2000 Sep | Sjögren's syndrome (SS) is a systematic autoimmune disease characterised by dysfunction of the lacrimal and salivary glands. This dryness leads to the symptoms of dry eyes and keratoconjunctivitis sicca, which is painful and may predispose patients to ocular infections. Also, SS patients develop dry mouth, which is uncomfortable and associated with progressive dental disease. SS is divided into secondary SS (where the dryness symptoms are associated with another well defined autoimmune disorder such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma) and primary SS (where the patients do not fulfil criteria for another well defined associated autoimmune disease). Primary SS has extra glandular organ involvement including lung (interstitial pneumonitis), renal (interstitial nephritis), peripheral and central nervous system manifestations, vasculitis of skin and other organs and increased frequency of lymphoma. This review will concentrate on primary SS. Therapies are divided into agents for topical replacement of deficient secretions (artificial tears, artificial salivas), stimulation of muscarinic M3 receptors (pilocarpine, cevimeline) to increase aqueous secretions, reduction of topical inflammation (topical cyclosporin or corticosteroids for the eye and fluorides or antibacterial varnishes for the mouth) and modification of the immune response in a manner similar to treatment of systemic lupus (antimalarial drugs, methotrexate, cyclophosphamide and perhaps newer agents such as leflunomide or TNF inhibitors). | |
| 10342717 | The BH1 idiotype defines a population of anticardiolipin antibodies closely associated wit | 1999 | BACKGROUND: A human IgM monoclonal anticardiolipin antibody - BH1 - has previously been described, which has characteristics typical of antiphospholipid antibodies in the serum of patients with antiphospholipid syndrome (APS). It appears to be idiotypically distinct from other human monoclonal autoantibodies of different or overlapping ligand-binding specificities derived from patients with related conditions. AIM: To determine whether the idiotype of BH1 is expressed on particular populations of antibodies (antiphospholipid and anti-beta2-glucoprotein I) in the serum of patients with APS and other conditions. METHODS: Sera from patients with APS (9), systemic lupus erythematosus without APS ('uncomplicated SLE' -9), and rheumatoid arthritis (RA 15), and from normal controls (15) were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with cardiolipin, beta2 glycoprotein I (beta2GPI), and a polyclonal anti-idiotype raised against BH1 (RIdBH1). Absorption experiments were subsequently performed on selected sera using micelles of cardiolipin or phosphatidyl choline. RESULTS: Eight out of nine patients with APS were positive for binding to RIdBH1 (IgG and/or IgM), while only one patient with uncomplicated SLE and none of the patients with RA or the healthy controls were positive. Although all of the patients with APS were positive for binding to beta2GPI, there was poor correlation between these results and levels of binding to cardiolipin and RIdBH1. Absorption of sera from patients with APS by cardolipin micelles resulted in a median reduction in IgG anticardiolipin and anti-beta2GPI activity of 81.6% and 6.3% respectively. For those sera positive for IgG reactivity with RIdBH1 the median reduction in this activity was 79.4%. Antibodies eluted from selected micelles showed activity against cardiolipin, beta2GPI and RIdBH1. Three anticardiolipin-positive sera from patients with RA were similarly absorbed; however the eluted antibodies failed to bind to RIdBH1. Absorption of all these sera with phosphatidyl choline resulted in no significant reduction in any of these activities. CONCLUSIONS: The BH1 idiotype defines a population of serum antibodies associated with features of APS. The antibody response in this condition, though diverse, may include the expression of a restricted group of variable region genes. | |
| 11561866 | Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in human blood. | 2001 Jul | Therapy with oral proteolytic enzymes (OET) with combination drug products containing papain, bromelain, trypsin, and chymotrypsin has been shown to be beneficial in clinical settings such as radiotherapy-induced fibrosis, bleomycin pneumotoxicity and immunosuppression in cancer, all of which are nowadays known to be accompanied by excessive transforming growth factor-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) from the "slow" form into the "fast" form, whereby the "fast" form binds and inactivates TGF-beta irreversibly. In this study we have investigated the effect of OET on the concentration of TGF-beta1 in serum of patients with rheumatoid arthritis (RA) (n = 38), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta1 levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and latent TGF-beta1 in serum (r=0.8021; P<0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or patients with a normal level of TGF-beta1. In patients with elevated TGF-beta1 concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P < 0.005), in OMF (P < 0.05) and in HZ (P < 0.05). CONCLUSION: These results support the concept that OET is beneficial in diseases characterized in part by TGF-beta1 overproduction. | |
| 11407686 | Regulation of synoviocyte phospholipase A2 and cyclooxygenase 2 by macrophage migration in | 2001 Jun | OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with known actions in macrophage and T cell activation. MIF also has the unique capacity to reverse the inhibitory effects of glucocorticoids on these cells. We have recently demonstrated MIF expression in human rheumatoid arthritis (RA) synovium and cultured fibroblast-like synoviocytes (FLS), as well as the ability of FLS-derived MIF to induce monocyte release of tumor necrosis factor alpha. We investigated the effects of MIF on aspects of RA FLS activation, including the induction of phospholipase A2 (PLA2) and cyclooxygenase (COX). METHODS: PLA2 activity was measured by 3H-arachidonic acid released from treated FLS supernatants. COX activity was measured by prostaglandin E2 enzyme-linked immunosorbent assay. Cytosolic PLA2 (cPLA2) and COX-2 messenger RNA (mRNA) were determined using semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: Constitutive PLA2 activity was detected in RA FLS. Recombinant human MIF up-regulated PLA2 activity (P < 0.01) and cPLA2 mRNA expression, but had no effect on secretory PLA2. Recombinant human MIF up-regulated COX activity (P < 0.05) and COX-2 mRNA, but had no observable effect on COX-1. Interleukin-1beta (IL-1beta) significantly up-regulated PLA2 activity (P < 0.005) and cPLA2 mRNA expression while anti-MIF monoclonal antibody (mAb) significantly inhibited this IL-1beta-induced PLA2 activity (P < 0.02). Anti-MIF mAb significantly reduced IL-1beta-induced COX activity (P < 0.05) and COX-2 mRNA expression. CONCLUSION: MIF exerts a proinflammatory effect on key aspects of RA FLS activation. That anti-MIF mAb inhibited IL-1beta up-regulation of FLS indicates an additional cofactor role for MIF in IL-1beta-induced FLS activation. These data suggest that MIF antagonism has important therapeutic potential in RA. | |
| 10772371 | Prevalence of osteoporosis risk factors and treatment among women aged 50 years and older. | 2000 Apr | We conducted a cross-sectional, retrospective review to evaluate screening, diagnosis, and treatment of 389 women aged 50 years or older at risk for osteoporosis in a large primary care practice. Records randomly selected from a computerized database were reviewed for drug history, age, height, weight, and osteoporosis-related diagnoses, symptoms, and risk factors. Among the 389 women, 255 (65.5%) were receiving bone-preserving treatment (247 estrogen replacement exclusively). Most (70.4%) were white, with an average age of 61 years, and an average of 3.3 risk factors for osteoporosis. Risk factors were postmenopausal status 94%, age 65 years or older 53%, hysterectomy 39%, cigarette smoking 33%, and physical inactivity 30%. By logistic regression, the only positive predictor of antiresorptive therapy was hysterectomy (adjusted odds ratio [AOR] 2.52, 95% confidence interval [CI] 1.54-4.14). Negative predictors were physical inactivity (AOR 0.44, 95% CI 0.25-0.71), rheumatoid arthritis (AOR 0.31, 95% CI 0.12-0.79), and age 65 years and older (AOR 0.54, 95% CI 0.34-0.86). Controlling for age, women with four or more risk factors were 62% less likely to be receiving antiresorptive treatment (AOR 0.38, 95% CI 0.23-0.64) than those with fewer risk factors. | |
| 11099305 | Lack of correlation between chemokine receptor and T(h)1/T(h)2 cytokine expression by indi | 2000 Dec | Chemokine and chemokine receptor interactions may have important roles in leukocyte migration to specific immune reaction sites. Recently, it has been reported that CXC chemokine receptor (CXCR) 3 and CC chemokine receptor (CCR) 5 were preferentially expressed on T(h)1 cells, and CCR3 and CCR4 were preferentially expressed on T(h)2 cells. To investigate chemokine receptor expression by T(h) subsets in vivo, we analyzed cytokine (IL-2, IL-4 and IFN-gamma) and chemokine receptor (CXCR3, CXCR4, CCR3, CCR4 and CCR5) mRNA expression by individual peripheral CD4(+) memory T cells after short-term stimulation, employing a single-cell RT-PCR method. This ex vivo analysis shows that the frequencies of cells expressing chemokine receptor mRNA were not significantly different between T(h)1 and T(h)2 cells in normal peripheral blood. To assess a potential role of in vivo stimulation, we also analyzed unstimulated rheumatoid arthritis synovial CD4(+) memory T cells. CXCR3, CXCR4, CCR3 and CCR5 expression was detected by individual synovial T cells, but the frequencies of chemokine receptor mRNA were not clearly different between T(h)1 and non-T(h)1 cells defined by expression of IFN-gamma or lymphotoxin-alpha mRNA in all RA patients. These data suggest that chemokine receptor expression does not identify individual memory T cells producing T(h)-defining cytokines and therefore chemokine receptor expression cannot be a marker for T(h)1 or T(h)2 cells in vivo. | |
| 11544310 | Down-regulation of CD28 expression by TNF-alpha. | 2001 Sep 15 | Aging and chronic inflammatory syndromes, such as rheumatoid arthritis, are associated with high frequencies of CD4(+)CD28(null) T cells, which are rarely seen in healthy individuals younger than 40 years. Inasmuch as rheumatoid arthritis and aging are also associated with elevated levels of TNF-alpha, we examined whether this proinflammatory cytokine influences CD28 expression. Incubation of T cell lines and clones as well as Jurkat cells with TNF-alpha induced a reduction in the levels of cell surface expression of CD28. This effect of TNF-alpha was reversible; however, continuous culture of CD4(+)CD28(+) T cell clones in TNF-alpha resulted in the appearance of a CD28(null) subset. In reporter gene bioassays, TNF-alpha was found to inhibit the activity of the CD28 minimal promoter. Inactivation of the promoter was accompanied by a marked reduction in DNA-protein complex formation by two DNA sequence motifs corresponding to the transcriptional initiator of the CD28 gene. Indeed, in vitro transcription assays showed that nuclear extracts from TNF-alpha-treated cells failed to activate transcription of DNA templates under the control of a consensus TATA box and the CD28 initiator sequences. In contrast, similar extracts from unstimulated T cells supported transcription. These results demonstrate that TNF-alpha directly influences CD28 gene transcription. We propose that the emergence of CD4(+)CD28(null) T cells in vivo is facilitated by increased production of TNF-alpha. | |
| 9492564 | [Long-term follow-up of 43 patients with Sjögren's syndrome]. | 1997 Dec | OBJECTIVE: To study the long-term outcome in patients with Sjögren's syndrome (SS). METHODS: We retrospectively studied a cohort of 43 patients with SS; 31 patients with primary SS and 12 patients with secondary SS (6 patients with rheumatoid arthritis, 3 patients with mixed connective tissue disease, 2 patients with systemic lupus erythematosus and 1 patient with systemic sclerosis). Follow-up assessments were performed for 10-20 years following the initial diagnosis. RESULTS: During follow-up, 29 patients (67%) with SS developed new extraglandular manifestations including: a small amount of monoclonal gammopathy (10 patients), interstitial pulmonary disease (8 patients), malignancy (4 patients developed cancer, 1 patient developed malignant lymphoma), Raynaud's phenomenon (4 patient), peripheral neuropathy (3 patients), renal disease (2 patients), myopathy (2 patients) and others. Statistically significant differences in the salivary gland scintigraphy existed between the progressed group and the stable group at both the initial diagnosis and ten years later. Patients with anti-Ro (SS-A) antibody had a high incidence of salivary gland enlargement, hypocomplementemia, rheumatoid factor and anti-nuclear antibody. The focus scores of the labial salivary biopsy in anti-La (SS-B) antibody positive patients were significantly higher than in patients without this antibody. No statistically significant differences were noted in symptoms and signs between study entry and follow-up. CONCLUSIONS: Although sicca symptoms involving the eyes and the mouth did not progress in most of SS patients, 67.4% of SS patients developed new extraglandular manifestations during the 10-20 years follow-up period. |