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ID PMID Title PublicationDate abstract
8408648 Infection of human synovial cells by human T cell lymphotropic virus type I. Proliferation 1993 Oct The present study was performed to clarify the relationship between human T cell lymphotropic virus type I (HTLV-I) infection and chronic inflammatory arthropathy. To determine the ability of HTLV-I to infect synovial cells and the effect on synovial cell proliferation, synovial cells were cocultured with the HTLV-I-producing T cell lines (MT-2 or HCT-1). After coculture with HTLV-I-infected T cells, the synovial cells expressed HTLV-I-specific core antigens, and HTLV-I proviral DNA was detected from the synovial cells by polymerase chain reaction. These cocultured synovial cells with HTLV-I-infected T cells proliferated more actively than the synovial cells cocultured with uninfected T cells. This stimulatory effect of HTLV-I-infected T cells on synovial cell proliferation seems necessary to contact each other. After being cocultured with MT-2 cells, synovial cells proliferated more actively than control cells even after several passages. Furthermore, HTLV-I-infected synovial cells produced significant amounts of granulocyte/macrophage colony-stimulating factor. These results suggest that HTLV-I can infect synovial cells, resulting their active proliferation and may be involved in the pathogenesis of proliferative synovitis similar to that found in rheumatoid arthritis.
8612199 VH3-21 B cells escape from a state of tolerance in rheumatoid arthritis and secrete rheuma 1995 Nov BACKGROUND: Rheumatoid factor (RF) is a characteristic but not pathognomic feature in patients with rheumatoid arthritis (RA). It is unknown whether the repertoire of immunoglobulin genes utilized by RF+ B cells of RA patients is unique and whether RF+ B cells in normal individuals are silenced or deleted. MATERIALS AND METHODS: Clonal B cell populations were established from the peripheral blood of normal donors (127 B cell clones), RA patients (113 RF- and 60 RF+ B cell clones) and patients with primary Sjögren's syndrome (82 RF- and 47 RF+ B cell clones) by coculturing with anti-CD3-stimulated T helper cell clones. The cross-reactivity pattern of antibodies secreted by the B cell clones was determined by ELISA on a panel of antigens. The molecular structure of the IgM heavy chains was characterized by VH family-specific RT-PCR and sequencing. VH elements which correlated with RF specificity were identified. The responsiveness of B cells expressing these VH elements to T helper cell signals was compared in normal individuals and RA patients. RESULTS: The majority of RF+ B cells were monospecific when specificity was tested on five antigens. RF+ B cells expressed a significantly different repertoire of VH gene segments than RF- B cells. In particular, the VH3 gene segment V3-21 was not detected in B cell clones from normals but was the most frequent VH element in RF+ B cell clones from RA patients. Most of the V3-21 sequences were in germline configuration. The correlation between RF specificity and V3-21 gene segment usage was maintained in patients with Sjögren's syndrome. V3-21 transcripts were present in peripheral blood B cells from normal individuals. VH3-21+ B cells from RA patients but not from normal donors were responsive to preactivated T helper cells. Stimulation with a bacterial superantigen could overcome the nonresponsiveness of V3-21+ B cells in normal donors and induce the secretion of RF. CONCLUSIONS: RF production is correlated with the usage of the V3-21 gene segment in two distinct RF+ diseases. In patients with these diseases, V3-21+ B cells secrete antibodies with RF activity in response to activated T helper cells. V3-21+ B cells remain in a state of nonresponsiveness in normal individuals that can be broken by superantigen stimulation. The germline configuration of VH3-21+ RF+ immunoglobulins in RA patients suggests that the loss of tolerance is not an antigen-driven process.
1285067 Immunohistochemical determination of complement activation in joint tissues of patients wi 1992 Murine monoclonal antibodies specific for neoepitopes expressed by C9 incorporated into membrane attack complexes and by membrane-bound C3b and iC3b have been prepared and characterised. These reagents were used to determine the extent and locus of complement activation in synovial-tissues obtained from patients with rheumatoid arthritis and osteoarthritis. In the four rheumatoid arthritis patients there was extensive deposition of C3 activation products and C5b-9 complexes onto the synovial membrane and the pattern of deposition of both neoantigens in serial tissue sections was very similar. There was less extensive staining for C3 and, particularly, C9 neoepitopes on the apical surface of vessel endothelia. In two of four osteoarthritic patients a similar pattern of C3 and C9 neoepitope deposition was found; in the remaining patients no C5b-9 could be located. Synovial vessel walls, but not synovial cells, from both groups of patients stained extensively for the complement regulatory protein CD59. In synovial membranes from patients with osteoarthritis, C9 appeared to be present predominantly in SC5b-9 complexes whereas in rheumatoid arthritis patients no evidence of S-protein incorporation into membrane attack complexes could be demonstrated, suggesting that in rheumatoid arthritis there is damage to the synovial membrane as a result of complement activation and C5b-9 deposition.
8814070 Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthriti 1996 Sep OBJECTIVE: To determine the expression of matrix metalloproteinase 9/gelatinase B (MMP-9) in synovial fluid (SF), plasma, and synovial tissue from individuals with rheumatoid arthritis (RA), inflammatory arthritis (IA), and osteoarthritis (OA), using specific monoclonal antibody reagents. METHODS: Gelatinolytic activity in the SF and plasma of patients with RA, IA, and OA was assessed by gelatin zymography. A mouse monoclonal antiserum, 277.13, which selectively recognizes soluble latent forms of human MMP-9, was used to quantitate MMP-9 levels in patient synovial effusions, plasma, and synovial tissue with a capture sandwich enzyme-linked immunosorbent assay (ELISA). Fifty-one SF samples (31 RA, 9 OA, 11 IA) were analyzed. Immunolocalization of MMP-9 in RA, OA, and normal synovium was investigated using MMP-9-specific antisera. RESULTS: MMP-9 antigen levels in synovial effusions were elevated 67-fold in RA samples compared with OA samples. In addition, although MMP-9 antigen levels in IA synovial effusions were 2.7-fold less than the values in RA samples, they were elevated 34-fold over the values in OA samples. These data indicate an association between increased MMP-9 levels and inflammatory arthritis. A predominant 92-kd gelatinolytic activity (specifically inhibited by EDTA) was evident in RA and IA samples, but no activity was observed in OA samples. Among 86 plasma samples (17 RA, 9 IA, 60 normal controls) analyzed for MMP-9 antigen levels by immunocapture ELISA, MMP-9 antigen levels were elevated 7-fold in RA plasma compared with normal plasma. RA synovial tissue extracts demonstrated elevated levels of MMP-9 antigen compared with OA synovial tissue. MMP-9 immunolocalization studies demonstrated expression in infiltrating leukocytes (neutrophils and macrophages), endothelial cells, and synovial fibroblasts in RA synovium. CONCLUSION: Latent MMP-9 and/or MMP-9-tissue inhibitor of metalloproteinases 1 (TIMP-1) complexes are elevated in RA and IA SF compared with OA SF. In addition, MMP-9 is increased in RA plasma versus normal control plasma. Synovial tissue levels of MMP-9 antigen are also elevated in RA versus OA. The tissue distribution of MMP-9 within RA synovium is localized to sites of inflammation comprising surface synovial lining cells, endothelium, and leukocytes. Taken together, these observations suggest that connective tissue turnover occurs as a result of excessive MMP activity over TIMP action in the invading pannus, periarticular tissue, or SF. Further studies such as those used in the present investigation will help elucidate the role of a number of different enzymes and inhibitors in the destructive arthropathies.
8508280 Susceptibility to rheumatoid arthritis is not associated with a single common allele of th 1993 Jun Type 2 collagen is quantitatively the most important constituent of articular cartilage which is the target of progressive destruction in RA. Polymorphism of type 2 collagen could theoretically influence the development of RA either by rendering the cartilage matrix particularly susceptible to autoimmune attack or subsequent degradation. We have investigated the possibility that there is a common allele of type 2 collagen associated with RA by analysing a dimorphism of the corresponding structural gene (COL2A1) in healthy and diseased individuals. We compared haplotype frequencies, defined by the presence or absence of a Hind III restriction site at the COL2A1 locus (encoding type 2 collagen), in 98 patients with classical/definite RA and 158 controls. No differences were seen between the frequencies of individual genotypes in the two groups (maximum chi 2 = 0.7), indicating that susceptibility to this disease does not appear to be determined by the presence of a single common allelic variant at this locus.
8871837 The releasability of lysosomal enzymes from neutrophil leukocytes in patients with rheumat 1996 Jul OBJECTIVE: To study the enzyme content and the "releasability" of lysosomal enzymes (lysozyme and beta-glucuronidase) in neutrophils purified from peripheral blood of patients with rheumatoid arthritis (RA) or normal subjects. METHODS: Neutrophils were obtained from 13 patients (10 women and 3 men) with rheumatoid arthritis and from 11 healthy subjects (8 women and 3 men). We measured: (1) lysosomal enzyme (lysozyme and beta-glucuronidase) content; (2) spontaneous enzyme release; (3) lysosomal enzyme release after cell challenge with different segretagogues (FMLP, C5a, aggregated IgG, zymosan and Ca2+ ionophore A23187). RESULTS: The lysosomal enzyme content was not statistically different in control subjects and in patients with RA (7.4 +/- 1.9 vs 6.3 +/- 0.8 micrograms/10(6) neutrophils for lysozyme; 102.9 +/- 16.4 vs 78.9 +/- 11.2 micrograms/10(6) neutrophils for beta-glucuronidase in control and RA subjects, respectively, p = NS). Unstimulated release of lysozyme was significantly lower in RA patients (3.8 +/- 1.1%) when compared to control subjects (9.5 +/- 2.1%) (p < 0.05). In contrast, spontaneous release of beta-glucuronidase did not differ in the two groups (5.5 +/- 0.9% and 3.8 +/- 1.1% in control and RA subjects, respectively). Enzyme release induced by FMLP (3 x 10(-9)-3 x 10(-7) M), C5a (10(-8)-10(-7) M), aggregated IgG (0.1-0.6 mg/ml), or Ca2+ ionophore A23187 (0.1-1 microgram/ml) did not differ statistically in the two groups of subjects. Neutrophil stimulation by serum-treated zymosan, at the concentration of 0.3 mg/ml, induced a release of lysozyme that was significantly higher in patients with RA when compared to control subjects (p < 0.05), whereas zymosan-activated beta-glucuronidase secretion was similar in the two donor populations. CONCLUSIONS: This study suggests that the contribution of leukocytes to the inflammatory processes typical of RA does not depend on an altered "releasability" of preformed mediators from peripheral blood neutrophils.
7683881 Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Res 1993 May OBJECTIVE: To evaluate the safety and activity of an immunoconjugate of ricin A chain and anti-CD5 monoclonal antibody (anti-CD5 IC), with and without concomitant methotrexate and/or azathioprine, in the treatment of rheumatoid arthritis (RA). METHODS: Seventy-nine patients with active RA were enrolled in 2 prospective open-label protocols. RESULTS: Using composite criteria, response rates were 50-68% at 1 month and 22-25% at 6 months. Transient depletion of CD3/CD5 T cells was observed on days 2 and 5 of treatment, with reconstitution on day 15 or day 29. Treatment-associated adverse effects were common but resolved rapidly without sequelae. CONCLUSION: These findings suggest activity of anti-CD5 IC in active RA and warrant confirmation in a multicenter randomized study (currently underway).
8257957 A prospective analysis of risk factors for the discontinuation of second-line antirheumati 1993 Oct 15 Clinical and laboratory factors influencing the discontinuation of second-line antirheumatic drugs were prospectively studied using survival analysis in a consecutive series of 245 patients with recently diagnosed rheumatoid arthritis. A statistically significant influence of age, sex, serum IgA and HLA-DR3 on the discontinuation rate of chrysotherapy because of toxicity was observed. The discontinuation of sulfasalazine was increased by advanced age and high rank order of prescription. With respect to efficacy, high initial disease activity appeared to predispose to treatment termination of hydroxychloroquine, sulfasalazine and penicillamine. Furthermore, an influence of the rank order of prescription on discontinuation of sulfasalazine therapy because of lack of efficacy was found. Of interest is that discontinuation of hydroxychloroquine therapy because of lack of efficacy occurred less frequently in HLA-DR3-positive than in HLA-DR3-negative patients. Although these prognostic factors are of secondary importance in clinical practice, they may be of significance in the interpretation and comparison of clinical trials.
8948294 Assessment of urinary hydroxypyridinium cross-links measurement in osteoarthritis. 1996 Nov The aim of this study is to re-evaluate urinary collagen cross-links, previously proposed as markers of osteoarthritis (OA). The urinary excretion of collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), was measured using high-performance liquid chromatography (HPLC) in 114 patients with OA, 19 patients with rheumatoid arthritis (RA) and 40 healthy subjects. An increase in PYD and DPD, expressed per millimole of creatinine, was confirmed in RA. However, PYD and DPD in patients with hip OA, knee OA and polyOA were similar, and did not differ from controls. In patients with radiographic end-stage OA, PYD and DPD were significantly higher than in patients with an early OA, but not significantly higher than in controls. The PYD/DPD ratio did not vary with the OA stage. Thus, urinary collagen cross-links are not elevated in OA, but could reflect bone sclerosis and/or erosion in late OA.
8077976 Results of the Souter-Strathclyde total elbow arthroplasty in patients with rheumatoid art 1994 Jun The results of 19 consecutive Souter-Strathclyde total elbow arthroplasties (Zimmer, London) in 17 patients with a mean follow-up time of 41 months are reported. Pain relief was achieved in all cases, with 13 elbows becoming entirely pain-free. The mean range of flexion increased 24 degrees and extension improved 8 degrees, with upper limb function greatly improved. The complication rate was 32%, including three nerve palsies, of which two resolved completely, and three early postoperative dislocations. There were two cases of prosthetic loosening, one following revision surgery for a traumatic humeral fracture in the early postoperative period. The authors consider the overall functional results with the Souter-Strathclyde prosthesis to be satisfactory in this group of patients.
7912229 Applications of extracorporeal photochemotherapy in "non-oncological" diseases. 1993 Dec Photopheresis (ECP) is a new therapy for oncological and autoimmune diseases consisting in the reinfusion of 3-9 x 10(9) leukocytes, taken from the patient by leukapheresis, and treated in an extracorporeal system with 8-methoxypsoralen and ultraviolet light A. Nine patients affected by T cell immunomediated diseases (2 scleroderma, 1 chronic GVHD, 1 polyarteritis, 1 rheumatoid arthritis and 4 heart transplant patients with numerous episodes of acute rejection) were treated with ECP. Photopheresis was performed on 2 consecutive days every 3-4 weeks. All patients affected by autoimmune diseases experienced an improvement during treatment with ECP. In 2 of the 4 patients with heart transplant, rejection was reversed by photopheresis. No major side effects were observed during the treatment. In conclusion ECP is a safe and well tolerated therapy. Although the number of patients is small, ECP seems to be an effective modality in many diseases.
1628425 Expression of antigen reactive with a monoclonal antibody to HTLV-1 P19 in salivary glands 1992 Jul To examine the possible involvement of retroviruses in Sjögren's syndrome (SS), labial salivary gland sections from 99 individuals were probed with three MoAbs to core (gag) proteins of human T cell leukaemia virus-1 (HTLV-1) and two MoAbs to HIV-1. Sections from 31% of 39 patients with primary SS (pSS) contained an epithelial cytoplasmic protein reactive with a MoAb (197) to the p19 group specific antigen (gag) of HTLV-1. The antigen was also detected in samples from 24% of 17 patients with rheumatoid arthritis (RA) and SS, 21% of 14 patients with sicca symptoms and 12.5% of 16 patients with other connective tissue diseases. It was not found in the salivary glands of 13 normal controls. A second MoAb to p19 gag, a MoAb to the p24 gag of HTLV-1 and MoAbs to HIV-1 p17 and p24 gags gave negative reactions. Serum antibodies to HTLV-1 were negative, confirming that the antigen was not part of HTLV-1. The antigen showed properties consistent with an endogenous retrovirus in that it was absent in healthy tissues or resting cells but inducible by stimulation with phytohaemagglutinin (PHA) or interferon-gamma (IFN-gamma). It appeared to be distinct from the endogenous retroviral sequence HRES-1. These data suggest the presence of an endogenous retrovirus in salivary gland epithelium which could contribute to the chronic inflammation of SS.
8324360 Effect of psychological processes on chronic pain. 1993 May 13 The influence of psychological factors on the evolution of acute to chronic pain is reviewed with respect to attributional style. Training patients in coping strategies can help them to alter their beliefs and develop greater confidence in their own ability to manage their pain.
8484320 The Geomedic knee prosthesis. A long-term follow-up study. 1993 A retrospective long-term follow-up study of 189 Geomedic total knee arthroplasties in 143 patients was performed. One hundred and eighteen knees were replaced in patients with rheumatoid arthritis and seventy-one knees were replaced in patients with osteoarthritis. Fifty-seven knees were examined clinically with an average follow-up of 11 years. Seventy percent of these knees were painless. Lucent lines at the tibial bone-cement interface were observed in 62% of the follow-up radiographs (81 knees, mean follow-up: 10.5 years). Thirty-four prostheses (18%) were removed, with loosening of the tibial component as the main cause. Retropatellar pain was not a significant problem. The 13-year survival rate was 78%, with implant removal as an endpoint. Radiographically loosened components included, the 13-year survival rate was 58%.
8359082 Helicobacter pylori infection, ABO blood group, and effect of misoprostol on gastroduodena 1993 Sep Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty-one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers.
1417134 Glutathione redox cycle enzymes and selenium in severe rheumatoid arthritis: lack of antio 1992 Sep The antioxidant capacity of the glutathione redox cycle and the concentrations of selenium in serum, red blood cells or whole blood, and polymorphonuclear leucocytes was evaluated in nine patients with severe rheumatoid arthritis (RA) and eight healthy controls receiving daily supplementation with 250 micrograms selenomethionine for six months. Serum and whole blood concentrations of selenium and the activity of the selenium dependent enzyme glutathione peroxidase (GSH-Px) were low in the serum, red blood cells, and polymorphonuclear leucocytes of patients with RA before selenium supplementation. During supplementation serum and whole blood concentrations of selenium and the activity of GSH-Px in serum and red blood cells of patients with RA and serum GSH-Px in controls increased. Selenium and GSH-Px in polymorphonuclear leucocytes were unaffected in patients with RA in contrast with the controls where both were augmented. Glutathione reductase activity in the red blood cells and polymorphonuclear leucocytes of patients with RA was low but increased during selenium supplementation. Whole blood concentrations of glutathione were slightly lower in patients with RA than controls and no difference in the content in polymorphonuclear leucocytes was found between the groups. The activity in red blood cells of glucose-6-phosphate dehydrogenase was high in patients with RA, indicating sufficient function of the hexose monophosphate pathway. The reduced antioxidant activity of the glutathione redox cycle in patients with severe RA was mainly due to the low availability of selenium. This was further supported by the response to selenium supplementation in serum and red blood cells. In the polymorphonuclear leucocytes, however, no biochemical effects of selenium supplementation were seen. This lack of antioxidative response could play a pathogenetic part in inflammation in patients with RA.
9384730 Application of micropreparative capillary electrophoresis and polymer gel desalting techni 1996 Sep A component of human synovial fluid (SF) has been separated by micropreparative capillary electrophoresis. The problems associated with application of this technique to a raw body fluid are discussed. Desalting of SF by passage through a capillary formed from polyacrylamide gel is examined and shown to cause loss of hyaluronan polymer as well as low-molecular-mass components of the fluid.
1734905 The rapid assessment of disease activity in rheumatology (radar) questionnaire. Validity a 1992 Feb OBJECTIVE: This study documents the measurement properties of a brief, self-administered questionnaire of disease signs and symptoms in patients with rheumatoid arthritis. METHODS: The Rapid Assessment of Disease Activity in Rheumatology (RADAR) questionnaire assesses joint pain/tenderness and clinical status. One hundred ninety-three pairs of RADAR forms were completed by 45 subjects and their assigned clinician evaluators. RESULTS: Subject-clinician agreement (intraclass correlation coefficients [ICC]) for joint pain/tenderness and clinical status ranged from 0.52 to 0.87 (P = 0.0001), with 83% greater than or equal to 0.65. The ICC for change in joint scores over 6 months was 0.83 (P = 0.0001). CONCLUSION: The 2-page RADAR questionnaire produces valid estimates of joint count and clinical status that are sensitive to change.
8969556 [Rapidly progressive glomerulonephritis associated with myeloperoxidase specific-antineutr 1996 Oct The reports on the patients with rheumatoid arthritis (RA) complicated with the myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO-ANCA) associated glomerulonephritis, whose clinical feature is rapidly progressive glomerulonephritis (RPGN), have been rare. We here report three cases of RPGN with MPO-ANCA in RA patients. Case 1. A 44-year-old woman with RA for 25 years was admitted because of RPGN. The level of MPO-ANCA was markedly high (293 EU) and the histological examination of the kidney showed diffuse crescentic glomerulonephritis. In spite of the intensive immunosuppressive therapy, her renal function did not recover and she underwent hemodialysis (HD). Case 2. A 58-year-old man with RA for 5 years was admitted due to RPGN (MPO-ANCA ; 147 EU, Ccr ; 16 ml/min) with the nephrotic syndrome and fever. The treatment with the immunosuppressive agents and the plasma exchange was partially effective to stop the rapid progression of the disease, but a few months later, his renal function worsened (Ccr 7 ml/min). A recent histological examination of the kidney failed to establish the CrGN because of endstage kidney. Case 3. A 56-year-old woman with RA for the past 10 years was admitted because of RPGN (MPO-ANCA ; 652EU). Intensive therapy could not be performed because of an active duodenal ulcer and markedly impaired renal function (Ccr ; 6 ml/min), and soon she underwent HD. Renal biopsy was not done. These three cases suggest that RPGN can occur in part of RA patients with MPO-ANCA.
7552065 Leukocyte adhesion molecules. 1995 Apr The last few years have seen an enormous expansion of knowledge regarding the role of cell surface adhesion molecules in biological processes. This article discusses the contribution that adhesion molecules make to the traffic of leukocytes into and within synovium and to the capacity of leukocytes to perform their specialised functions. Because of their importance in cellular interactions, adhesion molecules represent a major potential target for antiinflammatory therapy in rheumatoid and other inflammatory arthritides.