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ID PMID Title PublicationDate abstract
9182923 Soluble Fas (APO-1, CD95) and soluble Fas ligand in rheumatic diseases. 1997 Jun OBJECTIVE: To assess levels of soluble Fas (sFas) and soluble Fas ligand (sFas-L) in sera from patients with various rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), mixed connective tissue disease (MCTD), and Sjogren's syndrome (SS). METHODS: Levels of sFas and sFas-L were determined by a sandwich enzyme-linked immunosorbent assay. RESULTS: In SLE, PM/DM, MCTD, and SS, sFas levels were significantly higher compared with normal controls. Levels of sFas in the SLE patients were significantly higher than in patients with other rheumatic diseases. Levels of sFas-L were significantly increased in SS patients. SLE and RA patients with high levels sFas-L tended to have high levels of sFas, while sFas and sFasL levels did not correlate in patients with other diseases. In some of the SLE patients, sFas and sFas-L levels decreased following steroid therapy. CONCLUSION: Serum sFas and sFas-L levels were significantly higher in some rheumatic disease patients. Since these changes are complex in these rheumatic diseases, it may be difficult to directly relate sFas and sFasL to their pathogenesis.
10422515 [Caplan's syndrome]. 1998 Dec The authors describe two cases suffering from Caplan s syndrome, i.e. a combination of pneumoconiosis and rheumatoid arthritis, in miners of deep coal mines in southern Moravia. The finding on the lungs preceded the manifestation of articular symptoms. The disease progressed even after the risk of fibrogenic dust was eliminated. In both patients occupational diseases were involved.
10378712 Type IX collagen immunoreactive peptides in synovial fluids from arthritis patients. 1999 Apr OBJECTIVES: To determine whether type IX collagen-related peptides can be detected in the synovial fluids of arthritis patients and to assess their potential as molecular markers of arthritis. PATIENTS/METHODS: Synovial fluids from a set of carefully diagnosed arthritis patients and from healthy volunteers were used. Hydroxyproline assays were carried out to determine the content and concentration of collagen. Collagen cross-link determinations were conducted by reversed-phase HPLC. SDS PAGE and immunoblotting were used to identify the collagenous components, and N-terminal sequencing was performed to confirm these identities. RESULTS: All the synovial fluids were found to contain measurable amounts of collagen at similar concentrations. This appeared to be mainly high-molecular-weight material consisting of type I and type IX collagens, but not type II collagen. However, other smaller molecular weight type IX immunoreactive peptides were detected which were more apparent in the synovial fluids from arthritis patients. These peptides were also found to contain non-collagenous material. Collagen cross-links were also present in the arthritis synovial fluids. CONCLUSION: Collagenous material can be detected in all synovial fluids and the presence of pyridinoline cross-links indicates that at least some of this is derived from a mature collagen matrix. Type IX immunoreactive peptides were identified, but were found to contain significant amounts of non-collagenous material, and their presence, even at lower levels, in synovial fluids from normal subjects limits their potential for use as molecular markers of disease. Nevertheless, this is the first report of type IX collagen-related fragments in synovial fluids.
11149553 Rapidly progressive glomerulonephritis with D-penicillamine. 2000 Dec We present 3 cases of anti-myeloperoxidase, anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive rapidly progressive glomerulonephritis developed during the treatment with D-penicillamine (D-PC) for rheumatoid arthritis. Rheumatoid arthritis was diagnosed in these patients, and D-PC was administered to them at doses of 100, 200, and 300 mg per day for 32, 42, and 39 months, respectively. They developed proteinuria, hematuria, renal insufficiency, and anemia, and D-PC was stopped. On admission, MPO-ANCA was strongly positive in their sera. Renal biopsy showed glomerulonephritis with cellular crescents. Immunofluorescence examination revealed deposits of granular IgG, IgM, IgA, C1q, and C3 in the mesangium. The 3 patients were treated with steroid pulse therapy along with administration of anticoagulants, and cyclophosphamide was also used in 2 patients. Their renal function improved gradually and MPO-ANCA disappeared after immunosuppressive treatment.
9263141 Limited bone loss due to corticosteroids; a systematic review of prospective studies in rh 1997 Aug OBJECTIVE: To clarify the relation between changes in bone density, the treated disease, and dose of corticosteroids prescribed. METHODS: MEDLINE database (1966-95) and bibliographic searches selected cohorts of patients with rheumatoid arthritis (RA) and non-RA patients, studied by reliable serial bone density measurements. RESULTS: Two randomized controlled trials in early RA found greater lumbar bone loss after corticosteroid treatment (pooled effect size at 6 mo 3.9%; 95% CI: 1.9, 6.0%). The other studies included 66 patients with RA taking mean 7 mg prednisone/day; 371 "untreated" RA patients; and 216 non-RA patients taking mean 20 mg prednisone/day. Lumbar bone mass changed (weighted mean) 0.0% (-0.6, 0.7%) per year in steroid treated RA, -0.6% (-0.9, -0.2%) in untreated RA, and -4.7% (-5.2, -4.3%) in non-RA. Femoral neck changed -3.0% (-4.2, -1.8%), -0.7% (-1.0, -0.3%), and -1.5% (-2.5, -0.4%), respectively. In RA, most bone was lost in the first half year, and in early or uncontrolled disease. CONCLUSION: In patients with RA bone loss is limited, influenced by the interaction of disease characteristics and low dose corticosteroid therapy. In contrast, non-RA patients taking higher doses of corticosteriods may loss clinically relevant amounts of bone (i.e., > 5%) within one year.
11257155 Non-steroidal anti-oestrogens inhibit the differentiation of synovial macrophages into den 2001 Feb BACKGROUND: Dendritic cells (DC) have been suggested to play an important role in the pathogenesis of rheumatoid arthritis (RA). Agents that inhibit DC differentiation and function may have a therapeutic value in the treatment of RA. OBJECTIVE: To examine the effect of the non-steroidal anti-oestrogens toremifene and tamoxifen on the differentiation of synovial fluid (SF) macrophages into DC. METHODS: SF macrophages from patients with RA were cultured with interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) in the presence or absence of anti-oestrogens. The expression of cell surface markers on SF antigen-presenting cells (APC) was studied by flow cytometry. The capacity of SF APC to stimulate allogeneic T cells was studied using the mixed lymphocyte reaction. The production of tumour necrosis factor-alpha, IL-10 and transforming growth factor-beta1 was studied using ELISA. RESULTS: Anti-oestrogens inhibited the differentiation of SF macrophages into DC and the capacity of SF macrophage-derived DC to stimulate allogeneic T cells. CONCLUSIONS: By inhibiting the differentiation of SF macrophages into DC, non-steroidal anti-oestrogens may have beneficial effects in RA.
9330930 Total and free methotrexate pharmacokinetics in elderly patients with rheumatoid arthritis 1997 Oct OBJECTIVE: To determine the pharmacokinetics of methotrexate (MTX) in a group of patients 65 to 83 years of age and to compare the pharmacokinetic data to those in patients 21 to 45 years of age. METHODS: Thirty-eight elderly patients (8 men, 30 women) and 24 young patients (6 men, 18 women) underwent this pharmacokinetic study. They received intramuscular administration of MTX each week, at a dose varying from 7.5 to 15 mg depending on the patient. MTX concentrations in plasma and ultrafiltrate samples were assayed by a fluorescence polarization immunoassay. Pharmacokinetic variables were estimated using a Bayesian approach with population parameters as a priori information together with 2 plasma MTX concentrations (2 and 8 h after injection). RESULTS: The extent of unbound fraction and the volume of distribution were not statistically significantly different between the 2 age groups. The elimination half-life measures of the free and total MTX were greatest in the elderly group (p < 0.001). The total clearances of free and total MTX were inversely proportional to age (p < 0.001). CONCLUSION: MTX clearance decreases with decreasing creatinine clearance and smaller doses may be chosen in this group. Thus, a dosage regimen should be adjusted in elderly patients or in those with renal impairment.
11156551 Effect of interleukin 2 on killer cell inhibitory receptors in patients with rheumatoid ar 2001 Feb OBJECTIVE: The genes for killer cell inhibitory receptors (KIRs) have been cloned and their functions and responses to other molecules, including cytokines, have been partially clarified. However, the expression of KIRs has not been analysed in patients with autoimmune diseases, such as rheumatoid arthritis (RA), who are highly susceptible to microbial infection. Therefore, KIR expression on lymphocytes in patients with RA, and the regulation of KIR expression by interleukin 2 (IL2) in RA was investigated. METHODS: CD158a/b expression on peripheral blood mononuclear cells (PBMC) obtained from 25 patients with RA and 14 healthy subjects was analysed by flow cytometry. Additionally, PBMC from the two groups of subjects were cultured in RPMI 1640 medium with or without IL2 for 48 hours, and then their CD158a/b expression was analysed. RESULTS: The rate of CD158a expression on the CD8+ cells was lower in patients with RA than in healthy subjects, though there was no significant difference in the CD158a/b expression on the CD16+ cells between the two groups. The upregulation of CD16+CD158a/b+ cells in response to IL2 was significantly reduced in patients with RA compared with healthy subjects. CONCLUSION: The reduced induction of KIR expression in response to IL2 may provide insight into the reason for the high susceptibility of patients with RA to microbial infection.
9431462 Identification and characterization of rat 364-kDa Golgi-associated protein recognized by 1997 Oct Autoantibodies from a patient with rheumatoid arthritis recognized an antigen localized in the Golgi complex of various cells tested. The autoantibodies were used as a probe for screening rat NRK cDNA library, resulting in identification of an 11 kbp cDNA. The cDNA contained an open reading frame which encodes a 3,187-residue protein with a calculated mass of 364 kDa. The predicted protein, GCP364 (for a Golgi complex-associated protein of 364 kDa), was found to have no NH2-terminal signal sequence but a single hydrophobic domain at the COOH terminus and characteristically contain many coiled-coil domains with various sizes throughout the entire sequence. The identity of GCP364 with the autoantigen was confirmed by immunofluorescence and immunoblot analysis with the autoantibodies and anti-recombinant GCP364 produced in rabbits and by transfection/expression experiments. Search for the protein sequence data base revealed that GCP364 has 75% identity in amino acid sequence with human GCP372/giantin, indicating that it is a rat homolog of the latter. Immunogold electron microscopy showed that GCP364 was not detected on coated vesicles derived from the Golgi membrane, suggesting no involvement in the formation of transport vesicles. When cells were perforated and incubated with anti-GCP364 serum, the Golgi complex localized at perinuclear regions was dispersed into fragment-like structures as observed in nocodazole-treated cells. Taken together, these results suggest that GCP364 is anchored to the membrane by the COOH-terminal hydrophobic domain and has an extremely long cytoplasmic domain with coiled-coil structures, which may be involved in the formation and/or maintenance of the characteristic Golgi structure.
10323462 Cross-restriction of a T cell clone to HLA-DR alleles associated with rheumatoid arthritis 1999 May OBJECTIVE: To identify distinctive sequence motifs required for productive peptide presentation by those HLA-DR alleles/DR4 subtypes that predispose to rheumatoid arthritis (RA). METHODS: We tested 10 different HLA-DR4 subtypes for presentation of acetylcholine receptor peptides to 8 different DR4-restricted T cell lines/clones in proliferation assays. RESULTS: Seven of the 8 T cells depended absolutely on either the autologous Lys71 (in Dw4) or Arg71 (e.g., Dw14), despite these alleles' similar charge and RA associations. In contrast, the PM-A T cell was only mildly affected by this interchange. Moreover, after minor modifications, peptides were presented to this unusual T cell preferentially by all the RA-associated subtypes of DR4 as well as by 2 other DR alleles (DR1 and DR1402) that predispose to RA. CONCLUSION: This coincident cross-restriction to all the RA-associated HLA-DR alleles except DR10 shows that there could even be a single arthritogenic peptide; we now suggest a possible consensus motif.
11302782 Monograph. Plant sterols and sterolins. 2001 Apr Sterols and sterolins, also known as phytosterols, are fats present in all plants, including fruits and vegetables. Although they are chemically similar to the animal fat, cholesterol, they have been shown to exert significant unique biochemical effects in both animals and humans. Because they are bound to the fibers of the plant, they are difficult to absorb during the transit of digested food through the gut, particularly in individuals with impaired digestive function. For this reason, and because much of the modern diet is over-processed and low in fresh plant materials, sterols and sterolins appear in the serum and tissue of healthy humans at 800-1000 times lower concentrations than that of cholesterol. Beta-sitosterol (BSS) is the major phytosterol in higher plants along with its glycoside, beta-sitosterolin (BSSG). Animal studies have demonstrated BSS and BSSG possess anti-inflammatory, antipyretic, antineoplastic, and immune-modulating properties. In other in vitro, animal, and human studies, a proprietary BSS:BSSG mixture has shown promise in normalizing T-cell function, dampening overactive antibody responses, and normalizing DHEA:cortisol ratios. Research has shown plant oils contain the highest concentration of phytosterols, nuts and seeds contain moderate amounts, and fruits and vegetables generally contain the lowest phytosterol concentrations. Because only low levels of these substances are found in humans, increased dietary intake of unprocessed fruits and vegetables or supplementation with commercial phytosterols may be of benefit in re-establishing optimal immune parameters. Restoring balance to the immune system may be of therapeutic benefit in disease processes such as chronic viral infections, stress-induced immune suppression, tuberculosis, allergies, cancer, and rheumatoid arthritis and other autoimmune conditions.
9382210 [Interscalene brachial plexus catheter for anesthesia and postoperative pain therapy. Expe 1997 Aug OBJECTIVES: This study was conducted to evaluate a modified technique of interskalene brachial plexus anaesthesia (ISB) and postoperative catheter analgesia for shoulder surgery. The original method described by Winnie bears some rare but life-threatening complications (inadvertent subarachnoid or intra-arterial injection, pneumothorax). MATERIALS AND METHODS: Ninety-one patients with chronic rheumatoid arthritis who were scheduled for open or closed shoulder surgery received a modified ISB with catheter insertion. The injection site was more cephalad than that described by Winnie and the cannula was directed towards the junction between the medial and lateral third of the clavicle. Intra- and postoperative management, complications, and patients' satisfaction were recorded and evaluated. RESULTS: Implementation of ISB was possible in all cases, however, 3% of these presented technical problems. Anaesthesia with 300 mg mepivacaine 1% was successful in 94% of patients without and in 96% with augmentation after an average of 32 min; 10% of the patients suffered a drop in blood pressure after being placed in the beach-chair position for surgery. Postoperatively, all patients received 20 ml bupivacaine 0.25% for pain management via the catheter; 11% needed an additional analgesic drug. The catheter was removed after an average of 5 days. Signs of superficial local infection were noticed in 8 cases. Side effects occurred in 13% as Horner's syndrome, in 6.5% as recurrent laryngeal nerve block, and in 3.3% as phrenic nerve block. The acceptance of this anaesthetic technique among the patients was very high (96.7%). CONCLUSION: We consider the modified ISB with catheter a safe and effective procedure for anaesthesia and postoperative pain management of open and closed shoulder surgery.
11035130 Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg dail 2000 Oct BACKGROUND: It is postulated that some aspects of methotrexate toxicity may be related to its action as an anti-folate. Folic acid (FA) is often given as an adjunct to methotrexate therapy, but there is no conclusive proof that it decreases the toxicity of methotrexate and there is a theoretical risk that it may decrease the efficacy of methotrexate. OBJECTIVES: To look at the effect of stopping FA supplementation in UK rheumatoid arthritis (RA) patients established on methotrexate <20 mg weekly and FA 5 mg daily, to report all toxicity (including absolute changes in haematological and liver enzyme indices) and to report changes in the efficacy of methotrexate. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 75 patients who were established on methotrexate <20 mg weekly and FA 5 mg daily were asked to stop their FA and were randomized to one of two groups: placebo or FA 5 mg daily. Patients were evaluated for treatment toxicity and efficacy before entry and then at intervals of 3 months for 1 yr. RESULTS: Overall, 25 (33%) patients concluded the study early, eight (21%) in the group remaining on FA and 17 (46%) in the placebo group (P = 0.02). Two patients in the placebo group discontinued because of neutropenia. At 9 months there was an increased incidence of nausea in the placebo group (45 vs. 7%, P = 0.001). The placebo group had significantly lower disease activity on a few of the variables measured, but these were probably not of clinical significance. CONCLUSIONS: It is important to continue FA supplementation over the long term in patients on methotrexate and FA in order to prevent them discontinuing treatment because of mouth ulcers or nausea and vomiting. Our data suggest that FA supplementation is also helpful in preventing neutropenia, with very little loss of efficacy of methotrexate.
10390127 Cyclooxygenase-2 specificity and its clinical implications. 1999 May 31 Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation by inhibiting the synthesis of prostanoids. However, these drugs inhibit both cyclooxygenase-1 (COX-1), which is essential for the regulation of homeostasis in many tissues, as well as COX-2, which is an important mediator of pain and inflammation. Disruption of COX-1 enzymatic activity by NSAIDs leads to such side effects as interference with platelet functions and gastric ulcers. The recent development of COX-2-specific inhibitors, such as celecoxib, raises the possibility of relieving pain and inflammation with reduced risk of gastrointestinal complications. In Phase II and III studies, celecoxib has demonstrated efficacy in alleviating dental pain and the signs and symptoms of osteoarthritis and rheumatoid arthritis. This COX-2-specific inhibitor was also associated with a markedly lower rate of gastroduodenal injury than is seen typically with NSAIDs. Incidence of most adverse events (including gastrointestinal) and withdrawal rates resulting from adverse events with celecoxib were similar to placebo. Celecoxib appears to be both safe and effective in the treatment of osteoarthritis and rheumatoid arthritis. Its COX-2-specific inhibitory properties thus introduce the possibility of effective relief of arthritic and other types of pain and inflammation with less risk of the mechanism-based toxicities observed with conventional NSAIDs.
11809123 [Comparison of the efficacy and safety of nabumetone and diclofenac sodium in the treatmen 2001 May 10 OBJECTIVE: To compare the efficacy and safety of nabumetone and diclofenac sodium in the treatment of patients with rheumatoid arthritis (RA). METHODS: A hundred and twenty-five patients with active RA were enrolled in a randomized, open-label, controlled, multicenter, 12-week study treating with nabumetone (1 000 mg/day) or diclofenac sodium (75 mg/day). Clinical assessments were performed before beginning therapy, and after 4, 8, and 12 weeks of treatment. Endoscopy was performed respectively before and 12 weeks after the medication in all patients. RESULTS: The total efficacy rate of nabumetone was as high as that of diclofenac sodium (92.31% vs 88.52%, chi(2) = 1.114, P = 0.573). nabumetone treated patients showed significant improvement both in erythrocyte sedimentation rate (38.74 mm/1 h vs 25.56 mm/1 h, F = 14.005, P < 0.01 in nabumetone group, and 42.74 mm/1 h vs 34.36 mm/1 h, F = 3.811, P > 0.05, in diclofenac sodium group respectively) and C-reactive protein (2.08 mg/dl vs 1.21 mg/dl, F = 6.495, P < 0.05 in nabumetone group; and 3.29 mg/dl vs 2.31 mg/dl, F = 2.968, P > 0.05 in diclofenac sodium group respectively). The variety and incidence of gastrointestinal (GI) symptoms attributed to nabumetone was comparable to that of diclofenac sodium. The mean score of endoscopic lesions in the nabumetone group was significantly lower in the end of the treatment than those of their base line scoring (P < 0.01), and there was no significant change with regard to the diclofenac sodium group. The incidence of ulcer disease associated with nabumetone was 0% and 2.70% with diclofenac sodium. CONCLUSION: nabumetone is as effective as diclofenac sodium in controlling the signs and symptoms of RA. However, GI lesions under the endoscope in the nabumetone group seemed to be less severe than that of the diclofenac sodium group.
10694479 Regulation of rheumatoid synovial cell growth by ceramide. 2000 Mar 5 Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between cell proliferation and cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid synovial cells. Human synovial cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated synovial cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced cell cycle progression of rheumatoid synovial cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid synovial cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated synovial cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid synovial cells.
10685793 Rheumatoid synovial fluid contains bioactive leukemia inhibitory factor with cartilage deg 2000 Feb OBJECTIVE: To determine if the procatabolic activity of inflammatory synovial fluids (SF) from patients with rheumatoid arthritis (RA) could be attenuated by the cytokine antagonists murine leukemia inhibitory factor (LIF) binding protein (mLBP) and interleukin 1 receptor antagonist (IL-1ra). METHODS: Pig articular cartilage explants were cultured in the presence of either 20% v/v rheumatoid (RA) or osteoarthritic (OA) SF and varying concentrations of either mLBP and/or IL-1ra. The catabolic activity of the SF and the relative effects of mLBP and/or IL-1ra were assessed by determining the percentage release of sulfated glycosaminoglycans from cartilage explants. LIF concentrations were measured by ELISA. RESULTS: RA SF but not OA SF stimulated release of proteoglycans from pig cartilage explants in vitro (47.3 +/- 2.2% vs 24.6 +/- 2.0%; p < 0.0001). Murine LBP at 100 ng/ml and recombinant human (rh) IL-1ra at 5000 ng/ml produced a dose dependent inhibition of this proteoglycan release (p < 0.0067 and p < 0.0111, respectively). The RA SF stimulated proteoglycan release was attenuated by mLBP and rhIL-1ra independently. No additive effect of this attenuation was observed when maximal inhibitory doses were used in combination. The decrease in proteoglycan release produced by mLBP correlated significantly with LIF concentrations in RA SF. CONCLUSION: These findings are consistent with the concept that IL-1 stimulates cartilage proteoglycan resorption in RA. They also support the hypothesis that LIF, too, contributes to cartilage proteoglycan resorption in RA. The residual stimulation not accounted for by IL-1 or LIF suggests other cytokines may contribute. The role of LIF and related or unrelated cytokines may need to be taken into account to optimize chondroprotection in RA and other rheumatic diseases.
9754727 Nonsteroidal anti-inflammatory drug-associated upper gastrointestinal lesions in rheumatoi 1998 Aug BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are risk factors for peptic ulcer in rheumatoid arthritis (RA) patients, but the contribution of reactive gastritis, concomitant Helicobacter pylori infection, or RA activity to NSAID ulcer pathogenesis is unknown. METHODS: Ninety-six RA patients taking NSAIDs and dyspeptic sex- and age-matched control patients without NSAID use or an RA diagnosis were enrolled in the study. RESULTS: Gastric ulcer (GU) was detected in 29 (30%) RA patients and 3 control patients (P < 0.001). Sixteen RA patients and no control patient had an H. pylori-negative GU. The GUs of the RA patients were mainly located in the prepyloric region (28%) and antrum (62%). Nine of the 29 RA patients (31%) with GU had more than 1 ulcer. Erosive gastropathy was detected in 34 (71% H. pylori-negative) RA patients and in 13 (62% H. pylori-negative) control subjects (P < 0.001). Chronic gastritis was observed in 65 RA patients (48% H. pylori-negative) and in 58 control subjects (43% H. pylori-negative) (NS). whereas reactive gastritis was found in only 2 RA patients and in none of the controls. Corticosteroid use was the only independent risk factor for GU: odds ratio was 6.8 (95% confidence interval, 1.3-36.0). The prevalences of duodenal ulcer or esophagitis were not increased in RA patients. CONCLUSIONS: RA patients using NSAIDs continuously are at a greatly increased risk of developing both H. pylori-negative and -positive GUs, and corticosteroid use is an independent risk factor for ulcer development. Most RA patients have chronic gastritis, whereas reactive gastritis is rarely associated with continuous NSAID use in RA patients.
11469451 Influence of HLA-DR alleles on rheumatoid arthritis: susceptibility and severity in Argent 2001 Jul OBJECTIVE: To determine the frequency of shared epitopes in our population of patients with rheumatoid arthritis (RA) and to investigate whether the presence of these alleles is associated with a more aggressive form of disease. METHODS: Demographic and clinical data were obtained from 140 patients with RA, 123 female, mean age 49.9+/-11.7 years and mean disease duration 9.4+/-6.3 years. Radiographs of both hands were taken and scored by Larsen's method. HLA-DR alleles were determined by PCR-SSP. The control group comprised 202 healthy ethnic-matched subjects. RESULTS: DR4 was significantly more frequent in patients with RA than controls, and was observed in 70/140 patients (50%) versus 47/202 controls (23.27%) (odds ratio 3.25, CI 1.99-5.35, Pcorr 5 x 10(-5)). Within DR4 subtypes *0404 and *0401 were the most commonly found (37.7 and 29%, respectively). DR3 and DR11 exerted a protective effect with significantly higher frequency in controls than in patients with RA. When patients were divided into 2 groups according to disease severity (radiographic score) the frequency of alleles with QKRAA and QRRAA sequences was similar in both groups. Although with lower frequency, subtype *1001 alone was significantly more frequent in the severe-condition group [7 (13.5%) vs 3 (3.4%), p = 0.03]. CONCLUSION: These results are in accordance with findings observed in Caucasians and differ from other Latin American populations. However shared epitope alleles failed to correlate with more severe disease with the exception of subtype *1001 which, although infrequent, was significantly more frequent in patients with relevant radiological damage.
10399797 Analysis of functional elements in the human Egr-1 gene promoter. 1999 The early growth response (Egr)-1 gene encoding a zinc-finger transcription factor is transiently induced in many different cell types upon various differentiation signals. However, in synovial fibroblasts of rheumatoid arthritis patients, Egr-1 is constitutively expressed at high levels, and several genes with Egr-1 binding sites in their promoter regions have been associated with disease progression of RA. We analyzed the control of Egr-1 transcription by characterizing those regulatory elements in the Egr-1 promoter that induce Egr-1 expression in fibroblasts. Using reporter gene assays and deletion mutants of the Egr-1 promoter we could demonstrate that Egr-1 transcription is mainly activated by a single serum response element, whereas other transcription factor binding sites, including binding sites for AP-1 or Egr-1, were found to play a minor role. Furthermore, we identified a novel regulatory element in the human Egr-1 promoter similar to a NF kappa-B binding site. Deletion of this element enhanced Egr-1 promoter activity in 3T3 but not in L929 fibroblasts. Stimulation by phorbolester induced only transient Egr-1 expression in 3T3 fibroblasts but a extended expression of Egr-1 in L929 cells. These data suggest that in fibroblasts the most proximal serum response element in the Egr-1 promoter represents the major activation site, whereas binding of the NFkB-like factor may serve as negative regulatory signal for Egr-1 transcription in fibroblasts.