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ID PMID Title PublicationDate abstract
9818058 The frequency of serum amyloid A2 alleles in the Japanese population. 1998 Sep The incidence of serum amyloid A2 alleles (SAA2 alpha and SAA 2 beta) in the Japanese population was analyzed by PCR-RFLP analysis. The SAA2 alpha allele was predominant (approximately 90%) in both healthy controls and adult patients with rheumatoid arthritis. There was no significant association of allele patterns with AA amyloidosis in the patient group. These results are discussed in comparison with those of previous reports from other areas.
11083258 Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients f 2000 Nov OBJECTIVE: To compare the incidence of anti-double-stranded DNA (anti-dsDNA) antibodies in rheumatoid arthritis (RA) patients receiving either single or multiple doses of a chimeric anti-tumor necrosis factor alpha (anti-TNFalpha) antibody or placebo infusions, with or without methotrexate, in open-label, randomized, placebo-controlled trials. METHODS: Multiple sera obtained from 156 patients before and after treatment with infliximab and from 37 patients treated with placebo infusions were tested for anti-dsDNA antibodies by 3 methods: Crithidia luciliae indirect immunofluorescence test (CLIFT), a commercial Farr assay (Ortho Diagnostics radioimmunoassay [RIA]) in which the antigen source is mammalian DNA, and a Farr assay employing 125I-labeled circular plasmid DNA (Central Laboratory of The Netherlands Red Cross Blood Transfusion Service [CLB] RIA). Patients with positive findings on the CLIFT were also tested for antibodies to histones (H1-H5) and chromatin and for IgM rheumatoid factors (IgM-RFs). RESULTS: None of the RA patients had a serum sample that was positive for anti-dsDNA antibodies by the CLIFT prior to infliximab therapy. Of the 22 patients who developed a positive CLIFT result, 11 (7% of 156 exposed to infliximab) also had positive findings on the Ortho RIA at a concentration of >10 units/ml and another 8 (5%) were positive at a concentration of >25 units/ml. In all but 1 patient, the anti-dsDNA antibodies were solely of the IgM isotype. Only 1 patient had detectable anti-dsDNA antibodies by the CLB RIA. All sera containing anti-dsDNA by the CLIFT contained antibodies to chromatin, and sera from 2 patients also contained antibodies to histones. IgM-RF titers showed a significant reduction following infliximab therapy in these 22 patients. One patient developed anti-dsDNA antibodies of IgG, IgA, and IgM isotype and had positive results on both Farr assays (peaking at 22 weeks and resolving by 54 weeks); this was associated with a reversible lupus syndrome. CONCLUSION: Anti-dsDNA antibodies of IgM class are induced by infliximab therapy; the frequency is dependent on the assay method used. Only 1 of the 156 patients who were treated with infliximab developed a self-limiting clinical lupus syndrome; that patient developed high titers of anti-dsDNA antibodies of IgG, IgM, and IgA class, as detected by the CLIFT and by 2 different Farr assays.
10620700 The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF- 2000 Jan 7 We examined the role of p38 mitogen-activated protein (MAP) kinase in the tumor necrosis factor alpha (TNF-alpha)- or interleukin-1beta (IL-1beta)-induced production of interleukin-6 (IL-6) and interleukin-8 (IL-8) in fresh rheumatoid synovial fibroblast (RSF) cultures concomitantly with the induction of p38 MAP kinase activity. Pretreatment of RSF with a specific p38 MAP kinase inhibitor, SB203580, blocked the induction of IL-6 and IL-8 without affecting nuclear translocation of nuclear factor kappaB (NF-kappaB) or IL-6 and IL-8 mRNA levels. These findings suggest that p38 MAP kinase inhibitor may have synergistic, rather than additive, effect for the treatment of rheumatoid arthritis.
10506917 Sodium transport systems in human chondrocytes. I. Morphological and functional expression 1999 Oct The chondrocyte is the cell responsible for the maintenance of the articular cartilage matrix. The negative charges of proteoglycans of the matrix draw cations, principally Na+, into the matrix to balance the negative charge distribution. The Na+,K(+)-ATPase is the plasma membrane enzyme that maintains the intracellular Na+ and K+ concentrations. The enzyme is composed of an alpha and a beta subunit, so far, 4 alpha and 3 beta isoforms have been identified in mammals. Chondrocytes are sensitive to their ionic and osmotic environment and are capable of adaptive responses to ionic environmental perturbations particularly changes to extracellular [Na+]. In this article we show that human fetal and adult chondrocytes express three alpha (alpha 1, alpha 2 and the neural form of alpha 3) and the three beta isoforms (beta 1, beta 2 and beta 3) of the Na+,K(+)-ATPase. The presence of multiple Na+,K(+)-ATPase isoforms in the plasma membrane of chondrocytes suggests a variety of kinetic properties that reflects a cartilage specific and very fine specialization in order to maintain the Na+/K+ gradients. Changes in the ionic and osmotic environment of chondrocytes occur in osteoarthritis and rheumatoid arthritis as result of tissue hydration and proteoglycan loss leading to a fall in tissue Na+ and K+ content. Although the expression levels and cellular distribution of the proteins tested do not vary, we detect changes in p-nitrophenylphosphatase activity "in situ" between control and pathological samples. This change in the sodium pump enzymatic activity suggests that the chondrocyte responds to these cationic environmental changes with a variation of the active isozyme types present in the plasma membrane.
9714346 Analysis of cartilage oligomeric matrix protein (COMP) in synovial fibroblasts and synovia 1998 Jul We investigated the expression of cartilage oligomeric matrix protein (COMP) in normal and rheumatoid arthritis (RA) synovial fibroblasts. In situ hybridization (ISH) was conducted on synovial specimens from five RA patients applying specific probes for COMP or fibroblast collagen type I. ISH was combined with immunohistochemistry, applying antibodies to the macrophage marker CD68. Ribonuclease protection assay (RPA) and rapid amplification of 3'-cDNA ends (3'-RACE) were performed on total RNA from normal and RA synovial fibroblast cultures. Protein extracts from fibroblasts and culture supernatants were compared with synovial fluids and protein extracts from isolated chondrocytes by Western blot utilizing polyclonal and monoclonal antibodies (18-G3 mAb) to COMP. COMP mRNA was detected in fibroblasts of RA synovium by ISH, and in normal and RA synovial fibroblast cultures by RPA. 3'-RACE demonstrated sequence homology of chondrocyte and synovial fibroblast COMP along the coding sequence. COMP protein was detected in synovial fibroblasts and culture supernatants by immunoblot. Using polyclonal antibodies, the major portion of COMP from fibroblasts and culture supernatants was present as low-molecular-weight (LMW) bands, corresponding to those found in synovial fluids. These LMW COMP bands, however, were not detected in any of the cells or tissues tested using 18-G3 mAb. In protein extracts from chondrocytes and in COMP purified from cartilage, these LMW bands could not be detected. In conclusion, the data suggest that certain forms of COMP detected in synovial fluid are secreted from synovial fibroblasts and could be distinguished by specific mAbs from COMP secreted by chondrocytes.
9776117 Results of the Kudo elbow prosthesis in patients with rheumatoid arthritis: a preliminary 1998 Sixteen elbows in 15 rheumatoid arthritis patients had a total elbow replacement with insertion of a non-constrained surface-replacement prosthesis. One patient died of an unrelated cause, but all the others were available for follow-up (mean follow-up period: 35.4 months). The results were graded according to a modified version of the Morrey elbow score. A good result was seen in 13 elbows and a fair result in two. One infection occurred, which was cured with intravenous antibiotics and maintenance of the prosthesis in place; however, recurrent dislocation persisted. Another patient had postoperative instability with recurrent subluxations. Eleven patients were very satisfied and one was satisfied. The total active range of motion increased significantly from 70.3 degrees (SD 29.6) to 97.0 degrees (SD 15.4), mainly by increased flexion. The modified Morrey score increased significantly from 32.7 (SD 13.1) to 89.3 (SD 10.3). Pain decreased from severe (n = 12) and moderate (n = 3) preoperatively to mild (n = 5) and absent (n = 10) postoperatively.
9566800 Suppression of IL-6 biological activities by activin A and implications for inflammatory a 1998 Apr Activin A is a cytokine whose multiple functions have yet to be fully determined. In this study, the role of proinflammatory cytokines in regulatory control of activin A production was shown in synoviocytes and chondrocytes. Additional facets of functional inflammation-related activities of activin A were also determined. Results showed that activin A concentrations in the synovial fluid of patients with rheumatoid arthritis and gout were elevated relative to those in patients with osteoarthritis. Further studies showed that production of activin A by synoviocytes and chondrocytes in culture was stimulated by cytokines such as IL-1, transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma), and IL-8, consistent with previous studies in regard to the control of activin A production in marrow stromal cells and monocytes by cytokines, glucocorticoids and retinoic acid. In addition, the relationship of activin A to IL-6-induced biological activities was investigated. Three major IL-6 activities involved in inflammatory responses were found to be suppressed by activin A. In a dose-dependent manner, activin A efficiently suppressed IL-6-induced proliferation of 7TD1 B lymphoid cells, phagocytic activity of monocytic M1 cells, and fibrinogen production in HepG2. Therefore, it is likely that activin A serves as a suppressor for IL-6, dampening inflammatory responses, and has the potential to perform some previously unrecognized roles in inflammation.
14635289 Symptoms of depression and psychological distress among Hispanics with rheumatoid arthriti 2000 Jun OBJECTIVE: To explore the roles played by Hispanic ethnic background and acculturation to the mainstream English language culture of the United States in the depressive symptoms and mental health of rheumatoid arthritis (RA) patients. METHODS: Members of a consecutive cohort of patients with RA were studied cross-sectionally. All underwent a comprehensive clinical and psychosocial evaluation. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D), and psychological distress was measured with the Medical Outcomes Study Short Form 36 (SF-36) mental health scale. RESULTS: Two hundred thirty-six patients were studied. Women had significantly higher median CES-D scores than men (19 versus 14, P = 0.0004), Hispanics scored higher than non-Hispanics (14 versus 8, P = 0.0002), and foreign-born scored higher than US-born patients (14 versus 10, P = 0.009). Compared with those who were fully acculturated, patients who were partially acculturated were more likely to have a score > or = 16 on the RA-adjusted CES-D (odds ratio [OR] = 1.79, 95% confidence interval [95% CI] 1.37 to 2.35, P < or = 0.001). Among unacculturated patients, the likelihood of a score > or = 16 increased 6-fold (OR = 6.68; 95% CI 3.50 to 12.72; P < or = 0.001). A similar, inverse pattern was observed for the SF-36 mental health scale. In multivariate models accounting for age, sex, education, income, articular pain, deformity, and the level of disability, low acculturation was independently associated with high depressive symptoms, and a Hispanic background was independently associated with lower SF-36 mental health. CONCLUSIONS: In this consecutive series of RA patients, Hispanics, particularly those who are not fully acculturated to the mainstream Anglo society, had more depressive symptoms and psychological distress than did non-Hispanics.
11155811 Effects of long-term glucocorticoid therapy in rheumatoid arthritis. 2000 Radiographic erosions develop in about two thirds of patients with rheumatoid arthritis (RA). Glucocorticoids offer rapid and substantial control of the symptoms of inflammation in the short and medium term. Data are reviewed which suggest that this benefit may not last into the longer term (more than 1 year). However, recent studies provide unequivocal evidence that joint destruction can be halted in this disease. Also, by separating the short-term anti-inflammatory effect from a more prolonged suppression of joint destruction, these studies have shed light on the underlying pathological processes. The evidence from these therapeutic clinical trials strengthens the view that inflammation and joint destruction are parallel processes, loosely linked by the underlying cause of RA, but progressing to some extent independently. It is intriguing to speculate that different effects of glucocorticoids might relate to their different modes of action outlined elsewhere in this symposium.
11385610 Cartilage-specific autoimmunity in rheumatoid arthritis: characterization of a triple heli 2001 Jun Cartilage-specific proteins are considered potential autoantigens that could continuously fuel autoimmune responses directed to the joints in rheumatoid arthritis (RA). Using recombinant chimeric collagen type II we have identified one major type II collagen (CII) epitope (denoted U1) recognized by RA sera. The U1 epitope is a triple helical structure formed by 11 amino acids (triple helical position 494-504) and colocalizes with the recently described alpha1beta1/alpha2beta1 integrin binding site. It is a major epitope, found in 14/22 RA sera positive for antibodies to CII. One individual could be followed for a long time and the results showed that IgG antibodies specific for the U1 epitope were maintained along the chronic disease course but suppressed during periods of cyclosporin A and anti-CD4 treatment. We also found that the U1 epitope was recognized in rats susceptible to collagen-induced arthritis. A monoclonal autoantibody (mAb 126.30) was raised from DA rats, which bound the same epitope. The antibodies bound the cartilage in vivo showing that the epitope is exposed to the immune system for immune complex formation in the intact joint.
11429432 Lymphadenopathy and lymph node infarction as a result of gold injections. 2001 Jul This report describes a case of lymphadenopathy and lymph node infarction as a consequence of intramuscular gold administered to a patient suffering from rheumatoid arthritis, to highlight this rare association. A 34 year old woman with a four year history of rheumatoid arthritis affecting multiple joints was started on intramuscular gold injections after little response to anti-inflammatory medication. After her sixth injection the patient developed enlarged neck and axillary lymph nodes. Biopsy showed subtotal infarction of a reactive node, confirmed by histochemical, immunohistochemical, and molecular techniques. The patient continued to suffer from rheumatoid arthritis with no evidence of malignant lymphoma after three years. This case provides strong evidence that lymphadenopathy with infarction is a rare complication of gold injections. In such a situation, it is particularly important to exclude a diagnosis of lymphoma, because this is the most common cause of spontaneous lymph node infarction. This can be achieved through awareness of the association, and by the use of ancillary histochemical, immunohistochemical, and molecular techniques on the biopsy material.
10088772 Gene transfer of cytokine inhibitors into human synovial fibroblasts in the SCID mouse mod 1999 Mar OBJECTIVE: To investigate the effects of retrovirus-based gene delivery of inhibitory cytokines and cytokine inhibitors into human synovial fibroblasts in the SCID mouse model of rheumatoid arthritis (RA). METHODS: The MFG vector was used for gene delivery of tumor necrosis factor alpha receptor (TNFalphaR) p55, viral interleukin-10 (IL-10), and murine IL-10 into RA synovial fibroblasts. The effect on invasion of these cells into human articular cartilage and on perichondrocytic cartilage degradation was examined after 60 days of coimplantation into the SCID mouse. RESULTS: TNFalphaR p55 gene transfer showed only a limited effect on inhibition of RA synovial fibroblast invasiveness and cartilage degradation. In contrast, invasion of the RA synovial fibroblasts into the coimplanted cartilage was strongly inhibited by both viral and murine IL-10. Perichondrocytic cartilage degradation was not affected by either form of IL-10. CONCLUSION: The data show that cytokines can be successfully inserted into the genome of human RA synovial fibroblasts using a retroviral vector delivery system, and that the SCID mouse model of human RA is a valuable tool for examining the effects of gene transfer. In addition, inhibition of more than one cytokine pathway may be required to inhibit both synovial- and chondrocyte-mediated cartilage destruction in RA.
10360187 [Polymyositis induced by tiopronine]. 1999 May 1 BACKGROUND: D-penicillamine-induced muscle disorders are well-known, tiopronine-induced disorders are less often reported. CASE REPORT: A 62-year-old patient, given tiopronine for rheumatoid arthritis, developed severe polymyositis with characteristic clinical and pathology features. The course was favorable after tiopronine withdrawal and substitution with methotrexate. DISCUSSION: Clinicians should be aware of the side-effects of tiopronine, particularly muscle disorders, and implement careful surveillance to achieve early diagnosis and appropriate therapy.
9830779 [The role of superantigens in infectious diseases]. 1998 Jul Exogenous antigens are presented to T lymphocytes through mechanisms that ensure high recognition specificity. Recently described superantigens in contrast to conventional antigens are particles that follow a different processing and presentation route not binding to a specific region of T lymphocyte receptors. These particles bind to a large number of T lymphocytes, generating a disproportionate and non-specific immune response. Two types of superantigens have been described. Endogenous superantigens, transported in the host genoma, have been involved in clonal depletion and immunological tolerance phenomena. Exogenous superantigens, mainly bacterial toxins, have been involved in several diseases. There is evidence that these antigens participate in diseases such as Kawasaki disease, toxic shock caused by Staphylococcus aureus, rheumatoid arthritis, HIV infection and Streptococcus pyogenes infections.
10614157 [Sensory ataxic neuropathy presenting anti-a-fodrin antibody associated with rheumatoid ar 1999 Sep We reported a 41-year-old woman with severe rheumatoid arthritis who developed chronic sensory ataxic neuropathy and anti-a-fodrin antibody. Neurological examinations, electrophysiological studies and sural nerve biopsy findings suggested dorsal root ganglioneuronopathy. T2*-weighted MRIs showed high signal intensities in the posterior column of the cervical and thoracic spinal cord, suggesting the degeneration of the posterior column of the spinal cord caused by ganglioneuronopathy. She showed xerophthalmia but no other manifestations indicating Sjögren's syndrome including sialography and salivary gland biopsy findings. In serological studies, although anti-SS-A/SS-B antibodies and anti-ganglioside antibodies were negative, her serum reacted to a-fodrin, a 120kD protein degraded from a chain of fodrin. As a-fodrin has been recently regarded as an autoantigen highly specific to Sjögren's syndrome and its antibody is likely to appear preclinically, she may develop Sjögren's syndrome in the future. It is essential to accumulate clinical and pathological findings of cases like ours in order to elucidate an etiological relationship between anti-a-fodrin antibody and dorsal root ganglioneuronopathy.
11752506 Soluble HLA class I antigens in serum and synovial fluid from patients with rheumatoid art 2001 Dec OBJECTIVES: To investigate the presence of soluble HLA class I (s-HLA) antigens in serum and synovial fluid (SF) from a large cohort of rheumatic patients. METHODS: We studied clinical and analytical data and serum samples from 300 patients [122 patients with rheumatoid arthritis (RA), 38 with osteoarthritis or osteoporosis, 29 with seronegative spondyloarthropathies, 45 patients with other rheumatic diseases] and 66 healthy controls. In addition, we studied 25 paired samples of serum and SF from these groups of subjects. In RA patients, we examined whether the levels of s-HLA in serum and SF were related to the activity of the disease. RESULTS: The mean concentrations of s-HLA molecules in serum were slightly higher in RA patients (1.2 microg/ml) than in the other four groups (1.08, 1.01, 1.09 and 0.94 microg/ml respectively). We found no correlation between serum s-HLA levels and any variable of inflammatory disease activity in RA patients. s-HLA molecules were found in SF and at levels that correlated with those found in serum (P=0.04; r=0.4). Furthermore, s-HLA levels were higher in SF from patients with RA (1.3 microg/ml) or crystal-induced arthritis (0.98 microg/ml) than in SF from those with osteoarthritis (0.38 microg/ml) (P<0.05 and P<0.005 respectively), and these levels were correlated inversely and significantly with the score on the visual analogue scale of pain (P=0.02), the number of painful joints (P=0.05) and the level of C-reactive protein (P=0.03) in RA patients. CONCLUSIONS: This is the first report to demonstrate the presence of s-HLA molecules in SF at levels that correlate with serum levels. The mean levels of s-HLA molecules were significantly higher in SF from patients with RA and crystal-induced arthritis than in SF from cases of osteoarthritis, and correlated inversely with certain variables of disease activity in RA patients.
10320838 Autoimmune rheumatic diseases and the heart. 1999 Feb Involvement of the heart is a common finding in autoimmune rheumatic diseases. Although clinically silent changes are common, potentially life-threatening manifestations are well known but early recognition is important if appropriate therapy is to be instituted.
9733787 Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast- 1998 Sep 18 Involvement of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-6 gene expression of human fibroblast-like synoviocytes (FLSs) was assessed. p38 MAP kinase was constitutively expressed in human FLSs and activated in response to IL-1beta. A pyridinylimidazole compound, SB203580, inhibited p38 MAP kinase activity in vivo, since the activity of MAPKAP kinase-2 (a substrate of p38 MAP kinase) in IL-1beta-stimulated FLSs was totally suppressed by it. SB203580 concentration-dependently inhibited protein production and gene expression of IL-6 by human FLSs. The effect of SB203580 was dependent on de novo protein synthesis. SB203580 significantly reduced the stability of IL-6 mRNA without affecting the rate of IL-6 gene transcription. Here, we provide evidence that p38 MAP kinase is activated in response to IL-1beta in human FLSs and is involved in IL-6 synthesis by stabilizing IL-6 mRNA.
11253903 Measuring disability: application of the Rasch model to activities of daily living (ADL/IA 2000 This paper describes a comparative analysis of (ADL) and (IADL) items administered to two samples, 4,430 persons representative of older Americans, and 605 persons representative of patients with rheumatoid arthrisit (RA). Responses are scored separately using both Likert and Rasch measurement models. While Likert scoring seems to provide information similar to Rasch, the descriptive statistics are often contrary if not contradictory, and estimates of reliability from Likert are inflated. The test characteristic curves derived from Rasch are similar despite differences between the levels of disability with the two samples. Correlations of Rasch item calibrations across three samples were .71, .76, and .80. The fit between the items and the samples, indicating the compatibility between the test and subjects, is seen much more clearly with Rasch with more than half of the general population measuring the extremes. Since research on disability depends on measures with known properties, the superiority of Rasch over Likert is evident.
10699018 Plasmodium falciparum histidine-rich protein 2-based immunocapture diagnostic assay for ma 2000 Mar Recently introduced rapid nonmicroscopic immunocapture assays for the diagnosis of malaria infection are being evaluated for their sensitivity and specificity in various epidemiological settings. A Plasmodium falciparum histidine-rich protein 2 (PfHRP-2)-based assay (ICT) and a Plasmodium-specific lactate dehydrogenase test (OptiMAL) were evaluated for their specificities in different groups of patients who tested negative for malaria infection by microscopy. The patients were selected from different disease groups: rheumatoid arthritis, hepatitis C, toxoplasmosis, schistosomiasis, and hydatid disease. One hundred thirty-three of the 225 patients were positive for rheumatoid factor. Thirty-five of the 133 (26%) rheumatoid factor-positive patients gave a false-positive reaction with the ICT assay, but only 4 of these gave false-positive reactions with the OptiMAL test. Thirty-three of the 35 false-positive specimens became negative when repeat tested with the ICT assay after absorbing out the rheumatoid factor activity. Our study shows that the PfHRP-2-based ICT assay gave a false-positive reaction in 26% of the patients who had rheumatoid factors, but were negative for malaria by microscopy.