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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9122003 [Prolonged gold therapy for nephrotic syndrome in a patient with undiagnosed polyarthritis 1996 Aug A 36-years old female patient with undiagnosed arthritis developed nephrotic syndrome following chronic gold therapy. After prolongated and active treatment with pulses and oral steroids complete recovery was achieved. The likely nephrotoxic mechanism involved and clinical implications are discussed.
8087200 Behavioral interventions for managing chronic pain. 1994 Apr Behavioral interventions result in reliable improvements for patients with chronic LBP, RA, and OA. It should be emphasized, however, that these interventions rarely eliminate pain. Nevertheless, they often help patients reduce their suffering and health care costs. There also is evidence that preventive efforts may be especially beneficial to patients with recent back injuries (17, 18). There are two major differences between the outcomes produced by behavioral interventions for LBP and those produced by interventions for RA and OA. Interventions for LBP reduce pain and improve function, whereas treatments for RA and OA primarily reduce pain and psychological distress. Furthermore, in contrast to the effects of interventions for LBP, the beneficial outcomes achieved by patients with RA and OA tend to diminish after treatment termination. These differences probably are due to the fact that patients who have chronic LBP do not experience progressive changes in joint and bone tissues. Therefore, greater effort should be devoted to helping patients with RA and OA adapt to changes in disease progression following treatment termination. Keefe and Van Horn (36) have provided a model for improving patients' post-treatment adaptation that currently is being evaluated in a controlled study. Although physicians often wish to refer patients to pain treatment centers or behavioralists who treat chronic pain, they tend to have difficulty judging the quality of care offered by these centers and specialists. When you select a pain treatment center, first determine whether it meets the standards of the Commission on Accreditation of Rehabilitation Facilities (CARF, 101 North Wilmot Road, Suite 500, Tucson, AZ 85711).(ABSTRACT TRUNCATED AT 250 WORDS)
8778952 Immunohistochemical analysis of proliferating and antigen-presenting cells in rheumatoid s 1996 We analysed the proliferative activity of synovial lining cells (SLCs), the distribution of proliferating B and T lymphocytes and the relationship of proliferating B and T lymphocytes to the pattern of antigen-presenting cells (APCs) within the rheumatoid synovial tissue (n = 21). The immunohistochemical detection of the proliferation-associated antigen Ki67 revealed low proliferative activity of SCL with and without expression of the Kim 8 (CD68) antigen. Ki67-positive B lymphocytes could be observed within secondary follicles (2/21), in small follicular dendritic reticulum cell (FDC)-containing follicle-like aggregates (7/21) and near the enlarged synovial intima (6/21). Ki67-positive T lymphocytes could be detected in T-lymphocyte aggregates (8/21), in the vicinity of blood vessels (18/21) and within the enlarged synovial intima (15/21). Semiquantitative analysis showed a strong correlation between the numbers of Ki67-positive B lymphocytes and FDCs and between the numbers of Ki67-positive T lymphocytes and interdigitating dendritic reticulum cells (IDC). There were significant differences in the number of Ki 67-positive B and T lymphocytes, IDCs and FDCs between the two groups of rheumatoid arthritis (RA) patients with different local clinical activity. These findings demonstrate a low proliferation of SLCs with and without expression of the monocyte-specific antigen Kim 8 and imply that B and T lymphocyte proliferation occurs in the presence of FDCs and IDCs. These results indicate that the RA synovial tissue is a site for antigen-dependent proliferation and maturation of B and T lymphocytes. The atypical pattern of FDC distribution within the rheumatoid synovial tissue "dysmorphic follicle" may be regarded as morphological substrate for a dysmaturation compartment of B lymphocytes leading to pathogenetic autoimmune phenomena in RA patients.
7611589 Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid art 1995 Aug 15 OBJECTIVE: To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN: 6-month randomized, double-blind, placebo-controlled trial. SETTING: 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada. PATIENTS: 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993. INTERVENTION: Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day. MEASUREMENTS: Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy). RESULTS: Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months. CONCLUSIONS: In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.
8582358 Immunoprinting reveals different genetic bases for (auto)immuno diseases. 1995 Sep The genetic basis of complex (auto)immune diseases has been studied for an ovine nematode infection, human rheumatoid arthritis (RA), early onset pauciarticular arthritis (EOPA) and multiple sclerosis (MS). Immunoprinting combines the powerful simplicity of polymerase chain reaction (PCR)-based amplification of discrete, highly informative microsatellite loci with the principle of genetic associations. This approach has allowed us to define novel genetic risk factors in adult RA patient categories whereas EOPA forms in juveniles display other prominent genetic contributions. Differentially regulated tumor necrosis factor (TNF) expression may lead to a better understanding of the causal pathogenesis of EOPA while T cell receptor (TCR) gene polymorphisms appear crucial for RA manifestations in certain patient groups. Statistically significant marker associations have still to be defined for MS in larger panels of patient and control cohorts. The clinical course of the disease will probably have to be taken into account when associations with lymphokine levels are evaluated. In essence a convoluted myriad of negative and a few positive disease association data have been generated efficiently by immunoprinting. As expected, the interrelationships are truly complicated between the polymorphic genetic instances predisposing to autoimmune disease. Nevertheless, risk factors may be defined on an individualized basis by indirect gene diagnosis revealing predispositions and providing a more solid basis for differential diagnosis and treatment.
8674237 CD26 surface molecule involvement in T cell activation and lymphokine synthesis in rheumat 1996 Jul T cell surface expression and the functional role of CD26 antigen (Ag), a surface ectoenzyme involved in T cell activation and migration across the extracellular matrix, were analyzed in the peripheral blood (PB) and synovial fluid (SF) from patients with inflammatory arthritides. CD26 membrane expression on T cells was detected by cytofluorometry using two different monoclonal antibodies, anti-Ta1 and anti-1F7, while cell proliferation and both IL-2 and IFN-gamma production were evaluated in anti-CD3- or anti-CD2-stimulated cell cultures after Ag surface modulation with anti-1F7. The results showed that Ta1 and 1F7 Ag expression were increased on T cells from PB of patients with active, but not inactive, rheumatoid arthritis (RA). Most SF T cells from RA or other inflammatory arthritides displayed the memory marker CD45R0 and the Ta1 Ag, but lacked the 1F7 molecule. In addition, in vitro 1F7 modulation, which enhanced RA PB T cell proliferation and both IL-2 and IFN-gamma synthesis, did not synergize with anti-CD3 or anti-CD2 in inducing IL-2-dependent activation of SF T cells, but reduced IFN-gamma production. A spontaneous reappearance of 1F7 Ag on the SF T cell surface was seen after 2-5 days in culture. Phorbol myristate acetate, able to accelerate its reexpression, also restored a normal response of SF T cells to anti-1F7 comitogenic effects. These data confirm a role of the CD26 surface molecule in regulating T cell activation and lymphokine synthesis. This observation may have important implications in the regulation of T cell activity at the joint level during chronic inflammatory processes.
9157088 The role of HLA-DR-DR and HLA-DR-DP interactions in genetic susceptibility to rheumatoid a 1996 Mar In order to analyze the relationships between the DR and DP loci in the genetic susceptibility to RA, HLA-DRB1 and -DPB1 polymorphism was studied in 155 RA patients compared to 150 controls, using a reverse dot-blot analysis. Our data were consistent with the involvement of the amino acid in position 71 of the third hypervariable region of the DR beta 1 chain in susceptibility to the disease. The higher risk for RA was observed in patients who carried the association of a lysine (K), characterizing the DRB1* 0401 susceptibility allele, with an arginine (R), observed in all the other DRB1* susceptibility alleles (21.9% vs 0.6%, p(c) < 10(-6), OR = 42) In the absence of arginine, the presence of lysine was still associated with the disease (33% vs 19%, p(c) < 0.03, OR = 2). In contrast, in the absence of lysine, the frequency of arginine in position 71 was similar in patients and controls (30% vs 26%, p = NS). On another hand, the analysis of the HLA-DPB1 locus showed that the DPB1 *0401 allele frequency was significantly increased in the RA patient group (n = 47) who expressed only arginine at the position 71 of the beta 1 chain (82% vs 56% in controls, p < 0.008), with role of HLA-DR--DR and -DR-DP interactions in the genetic susceptibility to RA.
7793161 [Use of cyclosporin A in chronic polyarthritis and other rheumatic diseases]. 1995 Mar Cyclosporin A (CyA), a well-established drug in human transplantation for more than 10 years, has been used as an experimental treatment in autoimmune diseases increasingly since 1985. Its efficacy in rheumatoid arthritis (RA) and psoriasis/psoriatic arthritis has been demonstrated in numerous placebo-controlled studies. In RA is seems to be equal to azathioprine and D-penicillamine. CyA may also be of considerable benefit in other systemic diseases like polymyositis and primary biliary cirrhosis. The risk of side-effects, mainly nephrotoxicity has led to dosage guidelines, including a starting dose between 2.5 and 3.5 mg/kg/day and an upper dose limit of 5 mg/kg as well as dose reduction if serum creatinine is persistently raised by more than 30% of pre-treatment values. In the future, CyA may be an ideal partner for drug combinations because of its well-defined mechanism of action (inhibition of lymphokine-, especially interleukin-2-production) and possibly the low-dose sufficient for efficacy in combination. Studies relating to this are on-going.
7719685 Technical note: an X-ray fluorescence system for the determination of gold in vivo followi 1993 Aug This paper describes a low cost mobile measurement system for the determination of gold in vivo base around a 153Gd radiation source and a hyper pure germanium detector. Early clinical results are also presented to demonstrate the efficacy of the system.
1622706 A surgical approach in total shoulder arthroplasty. 1992 The long deltopectoral approach promoted by Neer is the standard for performing a total shoulder arthroplasty. However, this exposure is inadequate for preparation and bone grafting of the glenoid cavity or repairing an associated large rotator cuff tear. In the anatomy laboratory we looked for an alternative approach to the glenohumeral joint which would accommodate these difficulties. Afterwards we used this approach in 7 of 13 patients in whom a Biomet Bio-modular shoulder arthroplasty was planned. The study is prospective with a 1-year follow-up of 12 cases.
8727338 Long-term results of forefoot arthroplasty in patients with rheumatoid arthritis. 1996 May Disabling forefoot deformity of rheumatoid origin frequently requires surgical intervention. Twenty-three patients (36 feet) who underwent excision of the metatarsal heads in our unit between 1980 and 1987 were assessed clinically and radiologically (n = 12) and by questionnaire (n = 11) at an average 10.5 years (range: 4 to 15) following surgery. Although the procedure was initially successful at the time of review, the result was classified as unsatisfactory because of restriction of walking ability due to pain in the forefoot area in 56% of patients. Recurrence of the deformity--more frequently involving the great toe--had occurred in 72% of patients, and painful callosities were present in 61%. In the patients examined clinically and radiologically, unsatisfactory results were due mainly to mal-alignment of the great toe and extensor tendon tightness. Hindfoot deformity also significantly contributed to pain in the forefoot area. Diminished arthroplasty space, irregular resection cascade, and development of bony spikes were frequently associated with recurrence and callosities. The result of forefoot arthroplasty deteriorates with time. Failure to maintain a plantigrade great toe, intrinsic weakness, and hindfoot deformity were the main factors contributing to an unsatisfactory result.
9008306 Significance of antibodies to streptococcal M protein in psoriatic arthritis and their ass 1996 Dec Psoriatic arthritis (PA) is an immune disease associated with HLA-A2 in the Japanese population. To investigate mechanisms the association between HLA-A2 and PA, we examined in vivo immune responsiveness to Streptococcus pyogenes. Recombinant M proteins for the subtype specific N-terminal half (AB region) and conserved C-terminal half (C region) were produced separately. IgG antibody level against each region was measured by ELISA in 31 PA patients, 88 patients with psoriasis vulgaris, 6 patients with rheumatoid arthritis and 77 healthy controls. We found that IgG antibody levels against the C region were markedly higher in the PA patient group than in the other disease groups or controls. Further, IgG antibody levels were higher in PA patients with spondylitis and polyarticular arthritis than in PA patients with rheumatoid-like arthritis and arthritis mutilans. In contrast, no significant difference in the IgG antibody levels against the AB region was observed among the tested groups. HLA-A2 DNA typing showed that HLA-A*0207 was associated with PA (RR = 17.6; pcorr < 0.01) and the IgG antibody responses to the C region correlated well with the presence of HLA-A*0207. These results suggest that streptococcal infection may be involved in the pathogenesis of PA by participating in the HLA-linked immune responsiveness.
8218829 Antibodies to human cytomegalovirus 65-kilodalton Fc binding protein in rheumatoid arthrit 1993 We previously reported that rheumatoid factors (RFs) might bear the internal image of Fc gamma-binding proteins (FcBPs) of herpes family viruses, suggesting the possibility that some RFs may be produced as antiidiotypic antibodies to anti-viral FcBP antibodies. Since human cytomegalovirus (HCMV) has been implicated in the pathogenesis of RA, we made an attempt to detect antibodies to 65 KD major HCMV FcBP in sera and synovial fluid from patients with RA. Western blotting was performed using HCMV-infected MRC-5 cell lysate as the antigen. Eleven of 23 patients with RA possessed strong serum antibodies to HCMV-65 KD protein, whereas such antibodies were found in only 2 of 23 normal controls. In the synovial fluid, 10 of 19 RA patients showed anti-HCMV 65 KD reactivity. Pepsin-digested IgG retained anti-65 KD reactivity, indicating that false-positive reaction due to the presence of IgG Fc portion and/or RF was unlikely. 65 KD protein was shown to be different from human heat shock proteins (hsps) using monoclonal antibodies against human hsps. Patients' IgG F(ab')2 also reacted with the 65 KD protein of purified HCMV virion itself. These results support the possibility that some RFs could be produced as antiidiotypic antibodies to anti-viral FcBP antibodies.
8730111 Intact adrenocorticotropic hormone secretion but impaired cortisol response in patients wi 1996 Apr OBJECTIVE: To study the hypothalamic-pituitary-adrenal axis in rheumatoid arthritis (RA) and the influence of glucocorticoid treatment. METHODS: Consecutive untreated patients with RA with moderately high inflammatory activity were studied and compared with healthy subjects of similar age. Subjects were studied both at baseline and after multiple releasing hormone (MRH) stimulations. Patients were reexamined one week after starting prednisolone. RESULTS: The baseline cortisol/adrenocorticotropic hormone (ACTH) ratio was significantly lower in patients with RA. After corticotropin releasing hormone (CRH) stimulation, their serum cortisol response was reduced during the later test phases in spite of intact ACTH response. The baseline and stimulated levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) were normal. An impaired prolactin response was seen after MRH stimulation. After one week of prednisolone therapy the absolute response of serum cortisol to CRH was decreased and the stimulated prolactin response was normalized. CONCLUSION: Impaired cortisol secretion in patients with RA in the presence of intact ACTH secretion is consistent with relative adrenal glucocorticoid insufficiency. Adrenal impairment may be secondary to the inflammatory disease process.
1411581 Collagenase in synovitis of rheumatoid arthritis. 1992 Aug There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.
1574935 [Does silicone induce autoimmune diseases? Review of the literature and case reports]. 1992 Jan Silicone is able to induce different immunological reactions: Local foreign body reactions with activation of fibroblasts, granuloma formation and clinical manifestation of autoimmune diseases may occur. We report 4 cases with possible autoimmune disease in connection with breast augmentation. In one case explantation lead to both clinical and serological improvement with a decrease of antinuclear antibodies from 1:1280 to 1:160. In addition we report the spectrum of silicone induced systemic side effects and discuss the possible cellular reactions as well as the immunological changes.
7482340 [The combined intensive therapy of rheumatoid arthritis with systemic manifestations]. 1995 The efficacy of pulse therapy in combination with hemosorption or plasmapheresis, pulse therapy without extracorporeal treatment and methotrexate has been compared for 40 patients with rheumatoid arthritis (RA) with extra-articular manifestations. All kinds of intensive treatment were effective. Extracorporeal methods and pulse therapy relieved extra-articular symptoms. Isolated pulse therapy alleviated articular syndrome. The best results were obtained in double filtration of plasma in combination with pulse therapy. Such approach ensured improvement both articular and extra-articular inflammation. Combined intensive therapy proved an effective modality in RA able to produce responses in severe disease.
8835253 Lymphocyte adhesion molecules in autoimmune rheumatic diseases: basic issues and clinical 1995 Nov Lymphocyte adhesion molecules are of crucial importance in (auto)immune and inflammatory responses in two ways: on the one hand they mediate the interactions between lymphocytes and vascular endothelial cells during extravasation and homing, and allow local retention by aiding adhesion to extracellular matrix components, and on the other they increase T cell-antigen presenting cell contact and deliver the necessary signals for effective T-helper and T-cytotoxic cell function. Aberrations in adhesive interaction between members of the three major families of adhesion molecules, namely between selectins and their carbohydrate ligands, integrins and their ligands, and between members of the immunoglobulin superfamily, may participate in a vicious circle ending in organ damage. Findings regarding the overexpression of a number of adhesion molecules in patients with autoimmune rheumatic diseases, which is induced at the sites of inflammation and autoimmune injury, probably as a result of cell activation, exposure to cytokines or other soluble mediators, are summarized in the present review. Specific aberrations in adhesion molecule expression confined to one particular disease have not yet been described. Increased levels of soluble forms of various adhesion molecules that have been found in the serum of these patients reflect cell activation and may have physiological in vivo effects by interfering with cell-cell interactions. Although circulating adhesion molecule measurements lack specificity, longitudinal studies may establish their clinical value in the monitoring or the prognosis of patients. Modulation of adhesion mechanisms is likely to play an important role in the treatment of autoimmune rheumatic diseases in the near future. Indeed, preliminary results in patients with long-standing, refractory RA treated with a monoclonal antibody to intercellular adhesion molecule-1 are promising. However, much more has to be learned regarding the function and significance of adhesion molecules in order to successfully apply research findings to the clinical setting.
8129778 Cytokine combinations increase p75 tumor necrosis factor receptor binding and stimulate re 1994 Feb OBJECTIVE: To identify cytokines responsible for the increased levels of tumor necrosis factor receptor (TNFR) in the joints of patients with rheumatoid arthritis. METHODS: Antibodies to TNFR types were used both to inhibit ligand cell binding and to quantify released receptors in rheumatoid synovial fibroblasts. RESULTS: Binding by and shedding of the p75 TNFR was affected by interleukin-1 (IL-1), IL-4, and interferon-gamma. CONCLUSION: IL-1 could cause increased TNF alpha binding and TNFR shedding in inflamed joints.
8670315 Deactivation of vascular endothelium by monoclonal anti-tumor necrosis factor alpha antibo 1996 Jul OBJECTIVE: To assess whether monoclonal antibody to tumor necrosis factor alpha (TNF alpha) reduces endothelial activation in rheumatoid arthritis (RA). METHODS: Levels of serum E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), and circulating leukocytes (differential counts) were measured in RA patients before and up to 4 weeks after infusion of either placebo or chimeric anti-TNF alpha antibody cA2 (1 or 10 mg/kg). RESULTS: Treatment with anti-TNF alpha decreased serum E-selectin and ICAM-1 levels, with the earliest detectable changes observed on days 1-3 after anti-TNF alpha infusion. No effect on VCAM-1 levels was detected. In parallel, there was a rapid and sustained increase in circulating lymphocytes. The extent of the decrease in serum E-selectin and ICAM-1 levels and the increase in lymphocyte counts was significantly higher (P < or = 0.05) in patients in whom a clinical benefit of anti-TNF alpha was observed ( > or = 20% response, by Paulus criteria, at week 4) compared with that in patients who failed to respond to anti-TNF alpha at this time point. CONCLUSION: We propose that decreased serum levels of adhesion molecules may reflect diminished activation of endothelial cells in the synovial microvasculature, leading to reduced migration of leukocytes into synovial joints, and thus prolonging the therapeutic effect of anti-TNF alpha in RA.