Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 12516573 | Lack of deleterious somatic mutations in the CD95 gene of plasmablasts from systemic lupus | 2002 Dec | The interaction of CD95 with its ligand CD95L is important for negative selection of B cells during the germinal center (GC) reaction. Recently, mutations conferring resistance to CD95-induced apoptosis have been described for human GC B cells. Hence, as has been demonstrated for CD95-deficient mice, also GC-derived autoreactive B cells carrying somatic CD95 gene mutations may potentially service negative selection and participate in the development of autoimmune diseases. Here, single plasmablasts (PB) which are implicated in the production of autoantibodies in systemic lupus erythematosus (SLE) patients as well as ten human B cell lines producing autoantibodies were analyzed for destructive somatic CD95 gene mutations. However, inactivating CD95 gene mutations were very rare in PB and not detected in the cell lines. Sequence analysis of V gene rearrangements amplified from single PB confirmed that the cells are (post) GC B cells and additionally demonstrated massive clonal expansion of these cells in two of four SLE patients. We conclude that CD95 gene mutations play little if any role in the generation of the pool of PB in SLE patients and that mutations in the CD95 gene are rare among autoantibody-producing B cells in SLE and rheumatoid arthritis. | |
| 12429870 | Homocysteine determinants and the evidence to what extent homocysteine determines the risk | 2002 Dec | Cardiovascular diseases (CVD), especially coronary heart disease (CHD), are the most important causes of death in industrialized countries. Increased concentrations of total plasma homocysteine (tHcy) have been associated with an increased risk of CHD. Assuming that this relation is causal, a lower tHcy concentration will reduce the occurrence and recurrence of CHD. Therefore, it is important to know which factors determine the tHcy concentration. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the tHcy concentration, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors. The most important nonmodifiable determinant is the 677 C>T polymorphism in the gene that encodes methylenetetrahydrofolate reductase (MTHFR), a regulating enzyme in homocysteine metabolism. Especially subjects with the homozygous form of this polymorphism (i.e., 677TT genotype) and a low folate status have elevated tHcy concentrations. Specific clinical conditions like the use of antiepileptic drugs or methotrexate, renal failure, cancer, rheumatoid arthritis, and hypothyroidism may lead to elevated tHcy concentrations. The available epidemiological evidence indicates that an increased tHcy concentration is not an important risk factor for CHD in healthy subjects. However, prospective studies, which included subjects at high risk of CHD, and secondary prevention trials with intermediary endpoints consistently show that elevations in the tHcy concentration may be an important risk factor in these subjects for a (recurrent) CHD event. The induction of vascular endothelial dysfunction by homocysteine may underlie this increased risk. Ongoing intervention trials will indicate whether homocysteine-lowering through vitamin supplementation, prevents CHD in the treatment groups. | |
| 12412200 | Gold sodium thiomalate suppresses the differentiation and function of human dendritic cell | 2002 Sep | OBJECTIVE: Gold sodium thiomalate (GST) is a drug commonly used for the treatment of rheumatoid arthritis (RA). To clarify the mechanism of therapeutic effects of GST on RA, we investigated if GST affects the differentiation of dendritic cells (DC), which are thought to play a pivotal role in RA pathogenesis. METHODS: We generated immature DC (iDC) in vitro from PB monocytes during the 5 to 7-day culture in the presence of IL-4 and GM-CSF. Mature DC (mDC) were induced by adding TNF alpha on day 5 of the 7-day culture with GM-CSF and IL-4. DC capacity of stimulating T cells was examined in allogenic MLR using generated DC as stimulators. IL-12 production from DC was assayed with ELISA. RESULTS: We found that: 1) mDC generated in the presence of GST showed lower expression of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR compared to control mDC on FACS analysis. 2) GST-treated mDC showed reduced capacity of stimulating allogenic T cells in mixed leukocyte reaction. 3) IL-12p70 production after stimulation with SAC or LPS plus IFN gamma was markedly reduced in GST-treated mDC. CONCLUSION: GST suppresses the differentiation and function of DC generated from peripheral blood monocytes. This previously unknown action may explain the in vivo effects of GST in the treatment of RA. | |
| 12394940 | Bilateral symptomatic synovial cysts of the lumbar spine caused by calcium pyrophosphate d | 2002 Oct 1 | STUDY DESIGN: A case of bilateral symptomatic facet joint synovial cysts arising in association with calcium pyrophosphate deposition disease is reported. OBJECTIVE: To present a previously unreported cause for symptomatic synovial cysts of the lumbar spine. SUMMARY OF BACKGROUND DATA: Synovial cysts of the facet joints occur most commonly in association with degenerative disease of the spine in older individuals. The association of these cysts with trauma, rheumatoid arthritis, spondylolysis, and kissing spinous processes also has been reported. These cysts can cause symptoms and signs from direct compression of the dura. Chondrocalcinosis has not been previously reported to cause symptomatic synovial cysts. METHODS: A 67-year-old woman presented with right lower limb sciatica caused by a right L4-L5 facet joint cyst, which resolved after surgical decompression. A year later, she presented with left lower limb sciatica caused by development of a new L4-L5 facet joint cyst, which also resolved after surgical decompression. RESULTS: Histopathologic examination of each cyst showed a cyst wall of fibrous tissue with synovial lining, inflammation, and granulation tissue. Examination of the tissue under polarized light showed positively birefringent, short blunt crystals of calcium pyrophosphate dihydrate. CONCLUSIONS: In patients with a history of gout or pseudogout, a rare possibility of a synovial cyst should be considered in the differential diagnosis during investigation for the cause of neural compression resulting in sciatic syndrome. | |
| 12367559 | Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI | 2002 Aug | To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls.Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sjögren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE. | |
| 12121400 | Stage IV CD30+ anaplastic large cell lymphoma: response to acitretin and interferon-alpha. | 2002 Aug | Retinoids and interferon (IFN)-alpha induce differentiation, affect cell proliferation and alter various immune parameters. In combination, their effects may be additive or even synergistic in the treatment of malignancy. We present a 53-year-old woman with stage IV CD30+ anaplastic large cell lymphoma with brain, lung and skin involvement. The patient had been on methotrexate for rheumatoid arthritis. After a combination of oral acitretin 50 mg daily and IFN-alpha 3 million units subcutaneously 3 times per week, the skin lesions cleared within 2 months, lung lesions by 5 months and brain lesions by 7 months. Although we cannot exclude that methotrexate played a role in the development of this lymphoma and that its withdrawal contributed to the clearance of lesions, we propose that the patient's disease responded to the combination of acitretin and IFN-alpha. | |
| 24383905 | Comparison of the inhibitory effects of two types (90 kDa and 190 kDa) of hyaluronic a | 2002 Jun | Abstract  Hyaluronic acid (HA) has been shown to be clinically effective, and is currently used for the treatment of arthropathy. We previously reported that HA of molecular weight 90 kDa (90-HA) inhibits the fibrinolytic factors in human synovial fibroblasts. In the present study, we investigated the effect of high molecular weight (190 kDa) HA (190-HA) compared with 90-HA on the pericellular fibrinolytic system of human synovial fibroblasts in osteoarthritis (OA) and rheumatoid arthritis (RA). Human synovial fibroblasts were obtained from synovial tissues of OA and RA, and were cultured in the presence and absence of 90-HA and 190-HA. Antigens of urokinase-type plasminogen activator (u-PA) and PA inhibitor-1 (PAI-1) were measured by ELISA, and the u-PA activity of the cell surface fraction was evaluated by electrophoretic enzymography. The binding assay of u-PA and the immunocytochemical analysis of u-PA were performed to detect u-PA receptor (u-PAR). HA inhibited the secretion of both u-PA and PAI-1 antigens from the synovial fibroblasts of OA to their conditioned medium, and the degree of inhibition was more effective in OA than in RA. The u-RA binding assay to these cells showed that both 90-HA and 190-HA slightly decreased the maximal number of binding sites (Bmax) in OA. However, in RA, stimulation with 90-HA and 190-HA decreased Bmax by a half and a quarter, respectively. Immunohistochemical analysis showed that u-PAR was constitutively expressed in both synovial fibroblasts, but if these cells were treated with HA, the decrease in the staining of u-PAR was more pronounced in RA than in OA. Furthermore, the degree was more effective with 190-HA than with 90-HA. HA inhibited the pericellular fibrinolytic activity mediated by the u-PA/u-PAR system in synovial fibroblasts of OA and RA, and 190-HA inhibited it more effectively than 90-HA. | |
| 12040173 | TNF-R1 signaling: a beautiful pathway. | 2002 May 31 | Tumor necrosis factor (TNF) is a major mediator of apoptosis as well as inflammation and immunity, and it has been implicated in the pathogenesis of a wide spectrum of human diseases, including sepsis, diabetes, cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases. The interaction of TNF with TNF receptor-1 (TNF-R1) activates several signal transduction pathways. A common feature of each pathway is the TNF-induced formation of a multiprotein signaling complex at the cell membrane. Over the past decade, many of the components and mechanisms of these signaling pathways have been elucidated. We provide an overview of current knowledge of TNF signaling and introduce an STKE Connections Map that depicts a canonical view of this process. | |
| 11790996 | Central nervous system mechanisms of pain in fibromyalgia and other musculoskeletal disord | 2002 Jan | Pain is one of the most important and challenging consequences of musculoskeletal disorders. This article examines the role of central nervous system structures in the physiology of pain. It also describes the neuromatrix, a construct that provides a framework for understanding the interaction between physiologic mechanisms and psychosocial factors in the development and maintenance of chronic pain. This construct suggests that behavioral and psychologic interventions may alter the pain experience primarily through their effects on emotional states and cognitive processes. The literature on cognitive-behavioral interventions for patients with rheumatoid arthritis and osteoarthritis indicates that they are well-established treatments for these disorders. However, the efficacy of these interventions for patients with fibromyalgia has not been established. It is anticipated that the development of valid measures of readiness for behavioral change may allow investigators to identify the patients with musculoskeletal disorders who are most likely to benefit from cognitive-behavioral intervention. | |
| 11711546 | Interstitial collagens I, III, and VI sequester and modulate the multifunctional cytokine | 2002 Feb 1 | The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that oncostatin M (OSM), a profibrogenic cytokine and modulator of cancer cell proliferation, specifically binds to collagen types I, III, IV, and VI, immobilized on polystyrene or nitrocellulose. Single collagen chains inhibit these interactions in a dose-dependent manner. Cross-inhibition experiments of collagen-derived peptides point to a limited set of OSM-binding collagenous consensus sequences. Furthermore, this interaction is found for OSM but not for other interleukin-6 type cytokines. OSM binding to collagens is saturable, with dissociation constants around 10(-8) m and estimated molar ratios of 1-3 molecules of OSM bound to one molecule of triple helical collagen. Furthermore, collagen-bound OSM is biologically active and able to inhibit proliferation of A375 melanoma cells. We conclude that abundant interstitial collagens dictate the spatial pattern of bioavailable OSM. This interaction could be exploited for devising collagenous peptide-antagonists that modulate OSM bioactivity in tumor growth and fibrotic disorders like rheumatoid arthritis and hepatic fibrosis. | |
| 20641599 | Cyclo(-Arg-Gly-Asp-d-Phe-Lys(([(18)F]Fluoropropionyl)galacto-amino acid)-). | 2004 | Integrins are a family of heterodimeric cell surface glycoproteins consisting of an α and a β subunit. Integrins mediate diverse biological events involving cell-cell and cell-matrix interactions (1) and are important for cell adhesion and signal transduction. Integrin α(v)β(3) is the most prominent receptor class, affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). It is strongly expressed on tumor cells and activated endothelial cells, whereas it is weakly expressed on resting endothelial cells and most normal tissues. Antagonists to integrin α(v)β(3) are being studied as antitumor and antiangiogenic agents (4, 8, 9), and agonists are being studied as angiogenic agents for coronary angiogenesis (10, 11). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (12); however, these RGD analogs are lipophilic and concentrate in the liver. To reduce the lipophilicity of the peptide, Haubner et al. (13, 14) conjugated a sugar molecule to a cyclic RGD peptide to produce cyclo(-Arg-Gly-Asp-d-Phe-Lys(([(18)F]fluoropropionyl)galacto-amino acid)-) ([(18)F]Galacto-RGD) for use in positron emission tomography (PET) imaging studies. | |
| 15498056 | Paediatric uveitis: a Sydney clinic experience. | 2004 Oct | PURPOSE: The aim of this study was to retrospectively review uveitis cases at The Children's Hospital at Westmead, Sydney, since its inception in 1997 to 2001, including patients presenting at the Camperdown, Sydney, campus between 1989 and 1997 attending Westmead for further care. Comparison is made with international centres. METHODS: Information was obtained from medical records. RESULTS: Forty patients (53 eyes) presented, of whom 23 (57.5%) were female and 17 (42.5%) were male (mean age 6.7 years). Of 53 eyes, 35 (66%) had anterior uveitis, three (5.7%) intermediate uveitis, seven (13.2%) posterior uveitis and eight (15.1%) panuveitis. Twenty-seven (67.5%) patients had disease unilaterally and 13 (32.5%) bilaterally. Twenty-four (60%) cases were idiopathic. Seven (17.5%) cases were associated with juvenile rheumatoid arthritis, three (7.5%) with herpes zoster, two (5%) with herpes simplex, two (5%) with toxocara, one (2.5%) with toxoplasma, and one (2.5%) with ulcerative colitis. Complications included cataract in 14 (26.4%) eyes; band keratopathy in four (7.5%) eyes; macular scarring in three (5.7%) eyes; and glaucoma in four (7.5%) eyes. Last measured acuity was 6/6 for 19 (35.8%) eyes, < or =6/18 for 15 (28.3%) eyes and <6/60 for eight (15.1%) eyes. CONCLUSIONS: Despite small numbers, the comparisons of this study with some international studies, and its contrasts with other studies, are due to similarities and differences amongst these studies with respect to factors of referral bias, and the aetiological basis of disease. | |
| 15259027 | Secretory phospholipase A2 induces dendritic cell maturation. | 2004 Aug | High level of phospholipase A(2) (PLA(2)) activity is found in serum and biological fluids during the acute-phase response (APR). Extracellular PLA(2) in fluids of patients with inflammatory diseases such as sepsis, acute pancreatitis or rheumatoid arthritis is also associated with propagation of inflammation. PLA(2) activity is involved in the release of both pro- and anti-inflammatory lipid mediators from phospholipids of cellular membranes or circulating lipoproteins. PLA(2) may thus generate signals that influence immune responses. Here, group III secretory PLA(2) were tested for their ability to promote generation of functionally mature human dendritic cells (DC). PLA(2) treatment of differentiating monocytes in the presence of granulocyte/macrophage colony-stimulating factor and IL-4 yielded cells with phenotypical and functional characteristics of mature DC. This maturation was dependent on the dose of PLA(2), and PLA(2)-generated DC stimulated IFN-gamma secretion by allogeneic T cells. The effects of PLA(2) on DC maturation was mainly dependent on enzyme activity and correlated with the activation of NF-kappaB, AP-1 and NFAT. The data suggest that transient increase in PLA(2) activity generates signals that promote transition of innate to adaptive immunity during the APR. | |
| 20641496 | N-4-[(18)F]Fluorobenzoyl-c[(RGDyK)](2). | 2004 | Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell-cell and cell-matrix interactions (1). They consist of an α and a β subunit and are important for cell adhesion and signal transduction. α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. α(v)β(3) antagonists are being studied as antitumor and antiangiogenic agents and the agonists as angiogenic agents for coronary angiogenesis (6, 8, 9). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10). Most of the cyclic RGD peptides are monomeric and are composed of five amino acids. [(18)F]FB-c(RGDyK) was synthesized to study in vivo biodistribution of the tracer in tumor-bearing mice. [(18)F]FB-c(RGDyK) was found to have high accumulation in tumors, but it also had high tumor washout and biliary excretion into the gallbladder and intestines (11). A dimeric analog was synthesized as [(18)F]FB-E[c(RGDyK)](2), which was shown to have higher tumor uptake (~1-fold) than the monomer and predominantly renal excretion (12). | |
| 23741767 | [(18)F]Fluoroethyl-recombinant human interlukin-1 receptor antagonist. | 2004 | The interleukin-1 family consists of two proinflammatory cytokines, IL-1α and IL-1β, which bind to two IL-1 receptors (IL-1R1 and IL-1R2), and an IL-1R antagonist (IL-1ra), which is mainly produced by activated macrophages and tissue macrophages (1). IL-1α and IL-1β are important mediators of the inflammatory response and hematopoiesis, and they are involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. IL-1 is involved in chronic inflammatory diseases and in neuropathological conditions (2, 3). The balancing act of IL-1 and IL-1ra plays an important role in regulation of inflammation and immune responses (4). IL-1ra has been shown to be effective as an anti-inflammatory treatment in several chronic inflammatory diseases and stroke (5, 6). A human recombinant, non-glycosylated form of the human IL-1ra (rhIL-1ra, Anakinra) has been approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis (7). Cawthorne et al. (8) used positron emission tomography (PET) imaging to evaluate the biodistribution of [(18)F]fluoroethyl-recombinant human interleukin-1 receptor antagonist ([(18)F]IL-1ra) in rats. | |
| 15630152 | Metabolic syndrome, a cardiovascular disease risk factor: role of adipocytokines and impac | 2004 Dec | The metabolic syndrome comprises an array of cardiovascular disease (CVD) risk factors such as abdominal obesity, dyslipidemia, hypertension, and glucose intolerance. Insulin resistance and/or increased abdominal (visceral) obesity have been suggested as potential etiological factors. More recently, increasing evidence has associated insulin resistance and subclinical inflammation involving cytokines derived from adipose tissue, or adipocytokines. Despite the fact that precise mechanisms have yet to be established, there is a significant role for both diet and physical activity to improve the many factors associated with the metabolic syndrome, including modulation of various adipocytokines. Although both diet and physical activity have been studied for their ability to modify cytokines in more traditional inflammatory conditions, such as rheumatoid arthritis, they have been less studied in relation to inflammation as an underlying cause of the metabolic syndrome and/or CVD. A more thorough understanding of the clustering of metabolic abnormalities and their underlying etiology will help to define diet and physical activity guidelines for preventing and treating the metabolic syndrome, an important aspect of CVD prevention. This paper will address potential underlying causes of the metabolic syndrome, with a focus on the putative mechanistic role of adipocytokines, and will discuss the impact of diet and physical activity on the metabolic syndrome. | |
| 15541497 | Effects of chronic treatment with sodium tetrachloroaurate(III) in mice and membrane model | 2004 Dec | Gold is a nonessential element with a variety of applications in medicine. A few gold(I) compounds are used in the clinics for treatment of rheumatoid arthritis and of discoid lupus. Some novel gold(III) compounds are under evaluation as anticancer agents. It is known that gold compounds generally produce toxic effects on the kidneys and characteristic lesions in the brain. However, information concerning the neurotoxicity of gold derivatives in humans as well as in experimental toxicology is rather scarce. For this reason we tried to shed some further light on this aspect of gold neurotoxicity by chronic treatment of mice with sodium tetrachloroaurate(III) in order to observe possible biophysical and morphological alterations that may occur in the brain. Chronic gold treatment resulted in a markedly decreased expression of metallothioneins and of glial fibrillary acidic protein in astrocytes of different brain areas. To examine its effects on cell membranes, interactions of sodium tetrachloroaurate(III) with molecular models were also evaluated. The models consisted in bilayers built-up of classes of phospholipids located in the outer and inner monolayers of biological membranes. Structural perturbation of cell membrane models was observed only at concentrations 10(5) times higher than those detected in the brains of animals after three months' treatment. These results show that toxic effects on animal brain upon treatment with sodium tetrachloroaurate develop with difficulty and may be observed only at high doses. | |
| 15485309 | Celecoxib: a novel treatment for lung cancer. | 2004 Oct | Lung cancer is by far the leading cause of cancer-related deaths. Overall survival is poor and has not improved substantially over the last 50 years. Therefore, it is clear that novel and more effective treatments are needed to improve the outcome of therapy. Recent attention has been drawn to the role of cyclooxygenase (COX)-2 in the pathogenesis of cancer, and it has been considered as an attractive target for therapeutic and chemopreventive strategies in lung cancer patients. Celecoxib (Celebrex), Pfizer), a selective COX-2 inhibitor and potent anti-inflammatory agent, has been approved for the treatment of osteoarthritis and rheumatoid arthritis. This orally administered agent is generally well tolerated and has almost no gastrointestinal or renal toxicity. Phase II clinical trials suggest that COX-2 inhibition by celecoxib would enhance response to cytotoxic chemotherapy or radiation therapy through interference with cellular proliferation and tumor angiogenic processes, promotion of apoptosis and immune surveillance, or other possible mechanisms. Celecoxib has shown promising antitumor efficacy in lung cancer and a large variety of solid tumors that rely on COX-2-related mechanisms for growth and survival. This article reviews the profile of celecoxib and evidence supporting its role in the therapy of lung cancer. | |
| 15307186 | Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. | 2004 Sep | Toll-like receptors (TLR) recognize bacterial and viral components, but direct interaction of receptor and ligand is unclear. Here, we demonstrate that TLR9 binds directly and sequence-specifically to single-stranded unmethylated CpG-DNA containing a phosphodiester backbone. TLR9-CpG-DNA interaction occurs at the acidic pH (6.5-5.0) found in endosomes and lysosomes. By sequence comparison we identified a potential CpG-DNA binding domain homologous to that described for methyl-CpG-DNA binding proteins. Amino acid substitutions in this region abrogated CpG-DNA binding and led to loss of NF-kappaB activation. Furthermore, chloroquine and quinacrine, therapeutic agents for autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus, directly blocked TLR9-CpG-DNA interaction but not TLR2-Pam3Cys binding. Our results demonstrate direct binding of TLR9 to CpG-DNA and suggest that the therapeutic activity of chloroquine and quinacrine in autoimmune diseases may be due to its activity as a TLR9 antagonist and inhibitor of endosomal acidification. | |
| 15301243 | Further clues to recognition of patients with fibromyalgia from a simple 2-page patient mu | 2004 Jul | OBJECTIVE: To analyze quantitative scores for pain, fatigue, functional disability, and the number of symptoms on a review of systems on a multidimensional health assessment questionnaire (MDHAQ), including the ratios of scores for pain to physical function and fatigue to physical function, and to further study how these scores can help to identify patients with fibromyalgia. METHODS: All consecutive patients seen at a rheumatology clinic completed a 2-sided, 1-page MDHAQ at each visit to assess physical function, pain, fatigue, global status, helplessness and review of systems, and had their erythrocyte sedimentation rate (ESR) measured. Scores for these variables were analyzed in 78 consecutive patients with fibromyalgia over a two-year period, and in 149 patients with rheumatoid arthritis (RA) as a "control" group. A subset analysis was conducted in patients with RA who were classified independently according to clinical criteria as having or not having coexistent fibromyalgia. Descriptive statistics, logistic regression, and receiver-operating-characteristic curves were computed for patients with fibromyalgia and compared to patients with RA. RESULTS: Patients with fibromyalgia had high ratios of pain:physical function and fatigue:physical function scores, and a high number of reported symptoms. These quantitative data differed significantly from patients with RA. Patients with fibromyalgia also had a lower ESR than patients with RA, whose scores were similar whether or not there was coexistent fibromyalgia. Patients with fibromyalgia were distinguished equally well from patients with RA by patient questionnaire data as by the ESR. CONCLUSION: A simple 1-page, 2-sided patient questionnaire provides quantitative information which may contribute to identify patients with fibromyalgia, including patients with RA who may also have coexistent fibromyalgia. |
