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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
8733439 Plasminogen activators and their inhibitors in synovial fluids from normal, osteoarthritis 1996 Apr OBJECTIVES: To establish baseline concentrations of plasminogen activators and their inhibitors in normal knee synovial fluids, and to compare them with well characterised osteoarthritis (OA) and rheumatoid arthritis (RA) knee fluids. METHODS: A total of 26 normal subjects, 71 patients with OA, and 17 patients with RA underwent knee aspiration. Patients with OA were subclassified according to presence of nodal generalised OA (NGOA) and synovial fluid calcium pyrophosphate crystals. Clinical assessment of inflammation (graded 0-6) was undertaken in OA and RA patients. Plasminogen activator (PA), plasminogen activator inhibitor (PAI), and urokinase-type PA receptor (uPAR) antigen concentrations were determined by enzyme linked immunosorbent assay. The species of PAs present were determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. RESULTS: Concentrations of all antigens (uPA, tissue-type PA (tPA), uPAR, and PAI-1), were significantly greater in RA than OA; those in OA were significantly greater than normal. The concentrations showed no direct association with clinically assessed inflammation of the knee. In normal fluids, no associations with age were observed. Antigen concentrations (uPA, tPA, and uPAR) in NGOA differed from those in other subclasses of OA, but the species of PA present did not appear to vary between disease groups. The predominant PA appeared to have identity with uPA. CONCLUSION: Because of the greater concentrations of these antigens in OA compared with normal fluids, OA cannot be used as a surrogate normal control in studies of the PA/PAI system. Alteration of the PA/PAI system was confirmed in RA and OA knee fluids, with greater changes evident in RA. The finding of different concentrations of PA antigens in NGOA compared with other OA fluids further supports a different pathogenic mechanism in this subset.
8203949 Infection rate and use of antibiotics in patients with rheumatoid arthritis treated with m 1994 Apr OBJECTIVE: To investigate prospectively the frequency and type of infections and the use of antibiotics among patients with rheumatoid arthritis (RA) on methotrexate (MTX) and patients with RA without MTX. METHODS: Every three months for one year 77 patients on MTX and 151 patients without MTX were asked about infections and the use of antibiotics by means of a standardised questionnaire. Medication was checked with the pharmacist. RESULTS: In the MTX group there were significantly more infections and more antibiotic therapy. The relative risks for patients on MTX of infection or antibiotics use were 1.52 (95% Confidence Interval (CI) 1.04-2.22) and 1.49 (95% CI 1.04-2.13), respectively. The relative risk of MTX for respiratory tract infections was 1.43 (95% CI 0.96-2.14) and for skin infections 2.19 (95% CI 1.45-3.31). The increased risks could only partly be explained by differences in disease severity and were not related to either duration of MTX therapy or use of prednisone. Three patients in the MTX group had herpes zoster versus one in the control group. CONCLUSIONS: Treatment with MTX increases the rate of infection and thus the use of antibiotics but does not lead to serious complications necessitating discontinuation of the drug.
8536370 Changes in the phenotype of monocytes/macrophages and expression of cytokine mRNA in perip 1995 Dec Data from a previous study suggested that peripheral blood monocytes in patients with rheumatoid arthritis (RA) may be activated. Therefore, in this study we sought further evidence of 'presynovial' activation of monocytes. Our results show that phenotypic changes are demonstrable in peripheral blood monocytes in patients with RA, including increased expression of CR3 (CD11b/CD18) and FcRI (CD64). However, changes are most extensive in synovial monocytes/macrophages and especially for HLA-DR and intercellular adhesion molecule-1 (ICAM-1) (CD54). We conclude that monocyte/macrophage activation is most evident within the joint, and that 'presynovial' changes occur but are of limited extent.
8089775 Incidence patterns of immunogenetic diseases in the North American Indians. 1994 Jul Epidemiologic studies have defined a number of disease susceptibility patterns based on host-environment interaction. The antithetical approach of studying disease resistance patterns has been utilized less frequently. This preliminary data report describes the incidence of certain immunogenetic diseases in North American Indians for "internal comparison" of tribal population groups residing in disparate geographic areas and for "external comparison" with incidence patterns of Caucasian populations residing in the same geographic areas. The preliminary nature of the data precludes any conclusionary statements.
8055210 Non-steroidal anti-inflammatory induced diaphragm disease of the small intestine: complexi 1994 Aug A 52-yr-old lady with RA on long term NSAIDs developed an iron-deficiency anaemia and subsequently presented with subacute intestinal obstruction. After intensive investigation, a diagnosis of diaphragm disease of the small intestine was made at laparotomy. The features of diaphragm disease and the difficulties with diagnosis and management of the condition are discussed.
8484669 Identification of tissue inhibitor of metalloproteinase-2 (TIMP-2)-progelatinase complex a 1993 Mar The metalloproteinases are a family of enzymes that can degrade all the components of the extracellular matrix. These potent enzymes are often found in proenzyme forms and require activation before the substrate can be digested. To prevent unlimited connective tissue destruction a number of inhibitors exist to limit their activity. In a previous study it was found that metalloproteinases in proenzyme form and metalloproteinase inhibitors were often present in rheumatoid synovial fluids. Two of these inhibitors were identified in rheumatoid synovial fluid as alpha 2 macroglobulin and tissue inhibitor of metalloproteinase (TIMP), the specific metalloproteinase inhibitor. A third inhibitory peak was unidentified. In the study reported here it was shown that this third inhibitor can be purified using gelatin-Sepharose chromatography and consists of TIMP-2 bound to progelatinase (relative molecular weight 72,000) in a similar way to that found in concentrated connective tissue culture medium. The importance of these proteinase inhibitors in synovial fluid is discussed.
1380240 The forces driving autoimmune disease. 1992 Apr There are two classes of autoimmune disease, organ-specific and non-organ specific or systemic. That cells producing autoantibodies are selected by antigen is strongly suggested by the presence of mutations and high affinity antibody. T-cells are pivotal in all forms of autoimmunity as evidenced by the therapeutic benefit of anti-T-cell monoclonals such as anti-CD4, and the frequent development of high affinity IgG autoantibodies. The production of anergic T-cells by the use of non-depleting anti-CD4 in the presence of antigen is discussed with particular reference to its potential for immunological intervention in autoimmune disease. It is possible to identify T-cell epitopes in organ-specific autoimmunity using pathogenic T-cell clones or hybridomas to identify the peptide sequences which are reactive. Antigen-specific therapy may ultimately be based on such peptide epitopes. The specificity of the T-cells in systemic autoimmunity is still obscure, but there is some evidence that reactivity with certain germ-line idiotypes can lead to the development of systemic autoimmunity. The possibility of stimulating B-cells specific for auto-antigens such as DNA becomes feasible if a complex of antibody and DNA is taken up by these specific B-cells and processed idiotype is presented to T-helpers specific for those idiotype epitopes. Evidence is presented that there may be pre-existing defects in the target organ in certain organ-specific disorders, and the evidence for a glycosylation defect in the IgG in patients with rheumatoid arthritis is explored. It is noted that the spouses of probands with rheumatoid arthritis is explored. It is noted that the spouses of probands with rheumatoid arthritis also tend to have this glycosylation defect and this raises the possibility of an effect due to an environmental factor, such as a microbial infection. Molecular mimicry of autoantigens by microbes can stimulate autoreactive cells by their cross-reactivity. It is emphasized that cross-reaction which gives rise to the priming of autoreactive T-cells could give rise to the establishment of a chronic autoimmune state. In animals with normal regulatory immune systems, such induced autoimmunity is ultimately corrected and it is only in animals where there are defects in regulation, that autoimmunity persists. Thus, there are many factors giving rise to autoimmunity, and the diseases are rightly regarded as multifactorial in origin.
8037496 The gut as an inductive site for synovial and extra-articular immune responses in rheumato 1994 Jun OBJECTIVES: To analyse the immunological interactions between the gut lymphoid tissue, synovium, and peripheral blood compartments in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Patients with RA and AS and healthy controls were orally or parenterally immunised with an influenza virus vaccine. Antigen-specific antibody responses were measured at the single cell level by ELISPOT assay using lymphocytes isolated from peripheral blood and from enzymatically dispersed synovial tissues. RESULTS: Both oral and parenteral immunisations induced antigen-specific antibody-secreting cells in the synovial tissue of patients with RA. Parenterally immunised patients with RA showed significantly decreased antigen-specific antibody responses in peripheral blood compared with patients with AS and with healthy controls. In contrast, oral vaccination evoked comparable peripheral blood antibody responses in all three study groups. CONCLUSIONS: Despite a decreased immune responsiveness in the systemic compartment, the functional status of the gut-associated lymphoid tissue in patients with RA is intact. In addition, there is evidence that the lymphocytes in the inflamed joints are accessible for signals both from the systemic and mucosal compartments. The findings of immunological 'cross-talk' are relevant to future vaccination and tolerization procedures in patients with RA.
7848315 Renal biopsy findings and clinicopathologic correlations in rheumatoid arthritis. 1995 Feb OBJECTIVE: To evaluate renal biopsy findings and clinicopathologic correlations in patients with rheumatoid arthritis (RA). METHODS: Retrospective study of renal biopsy specimens from 110 RA patients in whom the clinical renal disease was probably due to RA itself and/or to antirheumatic therapy. RESULTS: The most common histopathologic finding was mesangial glomerulonephritis (GN) (n = 40), followed by amyloidosis (n = 33), membranous GN (n = 19), focal proliferative GN (n = 4), minimal-change nephropathy (n = 3), and acute interstitial nephritis (n = 1). Amyloidosis was the most common finding in patients with the nephrotic syndrome. In patients with isolated proteinuria, amyloidosis, membranous GN, and mesangial GN were almost equally common. Although mesangial GN was found in almost two-thirds of the RA patients with hematuria (with or without proteinuria), there still remained a 1 in 5 chance that the biopsy would reveal membranous GN or amyloidosis. Membranous GN was closely related to gold or D-penicillamine therapies, whereas mesangial GN probably related to RA itself. CONCLUSION: The renal morphologic lesion in RA patients with isolated proteinuria and those with hematuria cannot be accurately predicted on the basis of clinical symptoms and signs. Biopsy is thus useful in differential diagnosis, assessment of prognosis, and decision-making with regard to treatment.
8311556 Serum antioxidants and risk of rheumatoid arthritis. 1994 Jan OBJECTIVES: Oxygen free radicals have been implicated as mediators of tissue damage in patients with rheumatoid arthritis (RA). Thus it is possible that several micronutrients acting as antioxidants and free radical scavengers provide protection against RA. Serum alpha-tocopherol, beta-carotene, and selenium were studied for their associations with the risk of RA. METHODS: A case control study was nested within a Finnish cohort of 1419 adult men and women. During a median follow up of 20 years, 14 individuals initially free of arthritis developed RA. Two controls per each incident case were individually matched for sex, age, and municipality. Serum alpha-tocopherol, beta-carotene and selenium concentrations were measured from stored serum samples. An antioxidant index was calculated as the product of the molar concentrations of these three micronutrients. RESULTS: Elevated risks of RA were observed at low levels of alpha-tocopherol, beta-carotene and selenium, but none of the associations were statistically significant. A significant association, however, was observed with a low antioxidant index (p for trend = 0.03), the relative risk of RA between the lowest tertile and the higher tertiles of its distribution being 8.3 (95% confidence interval 1.0-71.0). CONCLUSIONS: The results of the present study are in line with the hypothesis that a low antioxidant level is a risk factor for RA.
8153072 [Differential diagnosis of synovitis. Correlation of arthroscopic-biopsy to clinical findi 1994 Feb Histological examination of 1660 biopsies (2-5 mm) of the synovial membrane of 317 patients were obtained by arthroscopic dissection; in 70% of all cases non-specific changes were revealed and in 30% specific changes. The findings included different stages of proliferation of the superficial layer, uncharacteristic inflammatory reactions of the stratum synoviale and fibrosis of the stroma, vascular proliferation and pseudopolypoid thickening of the synovial membrane. The histomorphological findings can only be interpreted reliably and a pathogenetic classification obtained, e.g., detritus synovialitis, rheumatoid arthritis or post-traumatic changes, if the arthroscopic findings conclude an exact documentation of the biopsy site and the clinical findings.
1526000 Measurement of elastase and cysteine proteinases in synovial fluid of patients with rheuma 1992 Sep Synovial fluid samples were collected from 45 patients with rheumatoid arthritis, spondylarthropathy, or osteoarthritis, to study their content of elastase (EC 3.4.21.37) and of cysteine proteinases (EC 3.4.22.1, 3.4.22.15). We measured both elastase complexed with alpha 1-proteinase inhibitor and elastase activity toward the substrate L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide. Cysteine proteinase activities were measured with the substrates N-benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methylcoumarin (Z-Phe-Arg-AMC) and Z-Arg-Arg-AMC and the inhibitor E-64 [L-trans-epoxysuccinyl-leucyl-amido-(4-guanidino)-butane]. In all these enzyme assays, higher median values were obtained in inflammatory arthropathies than in osteoarthritis. The concentration of the elastase-alpha 1-proteinase inhibitor complex and of elastase and cysteine proteinase activities were statistically higher in patients with rheumatoid arthritis than in patients with osteoarthritis. The difference in results between patients with spondylarthropathy and patients with osteoarthritis was statistically significant only for the elastase-alpha 1-proteinase inhibitor complex. The median values of the complex and of both enzyme activities were higher in patients with rheumatoid arthritis than in patients with spondylarthropathy; however, the difference was statistically significant only for the cysteine proteinase activity measured with Z-Arg-Arg-AMC substrate. These results suggest that both elastase and cysteine proteinases, which are increased in patients with inflammatory arthritis, are involved in cartilage degradation in these arthropathies.
7986219 Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial 1994 Dec OBJECTIVE: To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity. METHODS: Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double-labeling techniques. RESULTS: Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute-phase reactants, but not with histologic scores for inflammation. CONCLUSION: Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.
8098643 Porphyria cutanea tarda associated with methotrexate therapy. 1993 May A 69-year-old lady with RA developed porphyria cutanea tarda 2 weeks following initiation of methotrexate therapy. The clinical and laboratory features are described.
8517067 [Increased level of nitrogen radicals in serum of patients with rheumatic diseases and AID 1993 May 354 sera from venous blood of patients with various rheumatic diseases and AIDS were assayed for the presence of reactive nitrogen intermediates. Compared to healthy individuals, the serum levels of nitric oxides from patients with connective tissue diseases and inflammatory rheumatic diseases were elevated (P < 0.01) by 170-600% and those from HIV-infected patients by 220%.
8792253 The Rotaglide total knee arthroplasty. Prosthesis design and early results. 1996 Jun The Rotaglide knee (Cozim Medical, UK) is a three-part knee containing a mobile polyethylene meniscal platform, imparting reduced loosening forces to the tibia. The femoral component design provides a high degree of congruency throughout the range of motion from 0 degree to 110 degrees, and both femoral and tibial components ensure minimal bone removal. The system is versatile, including a large number of component options, and it may be used in both primary and revision arthroplasties. The first results in 170 cemented knees (161 patients) with 2- to 5-year follow-up periods (average, 3.1 years) were very encouraging (excellent or good in 95% of knees, based on the British Orthopaedic Association knee assessment system). Poor results were seen only in revision cases. There have been no mechanical implant failures and no platform bearing dislocations, and the platforms continue to move as documented by postoperative roentgenograms, which show the metal markers of the platforms moving anteriorly in flexion and posteriorly in extension.
7806793 Wrist arthrodesis: a combined intramedullary pin and autogenous iliac crest bone graft tec 1994 Sep Forty-six wrist arthrodeses in 36 patients were reviewed. The technique used provided a reliable fusion method for a variety of wrist disorders. The arthrodeses were performed using an autogenous iliac crest bone graft, with an intramedullary Steinman pin placed within the distal radial and third metacarpal shafts, and an obliquely-placed Kirschner wire across the second metacarpal base into the radius. The distal ulna, instead of the radius, was used in patients with radial agenesis. Three patient populations were identified: group 1, connective tissue wrist disorders; group 2, congenital wrist disorders; and group 3, acquired wrist disorders. A residual flexion, radial deviation deformity was noted with the congenital disorders. All patients had low demand requirements for this fused wrists. The average time of fusion for each group as 14, 15, and 12 weeks, respectively.
8846421 Alterations in neurokinin 1 receptor gene expression in models of pain and inflammation. 1995 Jul Substance P and the related tachykinin peptides are involved in inflammatory processes and in the transmission of sensory nociceptive information. In this article we review the evidence implicating substance P and the neurokinin 1 (NK1) receptor in arthritic disease. We also provide preliminary evidence demonstrating that cultured synoviocytes from a patient with rheumatoid arthritis express NK1 receptor mRNA that can be downregulated by tumor necrosis factor alpha, whereas synoviocytes from a normal patient do not express detectable NK1 receptor mRNA or protein. Data are also presented summarizing recent studies on nociception-induced increases in sensory ganglia of levels of mRNA encoding substance P and increases in dorsal horn NK1 receptor mRNA levels. Morphine pretreatment blocked the increases in dorsal horn NK1 receptor mRNA levels but did not block the nociception-induced substance P encoding mRNA levels in sensory ganglia. These results are discussed with reference to mechanisms that may regulate P turnover and NK1 receptor sensitivity in models of pain and inflammation.
1499418 [Interposition arthroplasty with pedicled island fascia flap. Experimental study and clini 1992 Jan Interposition arthroplasty of knee joint, using island fascia flap, was performed on 90 rabbits. The fascia flap was vessel pedicled in 54 rabbits and not vessel pedicled in 36 for control. Results of the vessel pedicled island fascia flaps showed that clinically, the range of joint motion was 142.5 degrees on the average. Histologically, the transplanted fascia showed good vascularity and elasticity. There were no signs of adhesion or degeneration. Analogous cartilage appeared in 12 to 15 months. In the control group, the average joint motion was 83.61 degrees and the transplanted fascia showed degeneration of varying degree in each cases. On the basis of these experimental findings, we performed interposition arthroplasty with vessel-pedicled island fascia flap on 20 patients suffering from different joint diseases. The joints were 14 hips, 3 knees, and 3 elbows. Follow-up for 9 to 48 months after arthroplasty revealed clear-up of previous troubles with satisfactory function.
9129271 Results of the cementless Mallory-Head primary total hip arthroplasty: a 5 to 7 year revie 1996 We reviewed the results of 172 plasma-sprayed, titanium primary total hip arthroplasties inserted without cement and followed 5 to 7 years. Hips were replaced for a wide range of diagnoses and patient ages. No femoral components had been revised nor were any considered unstable. Clinical results have been excellent; 88% of hips had either no or slight amount of pain and only 5% of patients had thigh pain when specifically asked. Radiographically, this femoral component achieved stability after an initial subsidence in 9% of cases. Extensive femoral bone resorption was rare, and distal cortical hypertrophy was commonly seen. Pelvic osteolysis occurred in 16 (9%) cases and was considered major in 10 of these. It was the cause of failure of 3 acetabular components. Femoral endosteal lysis was not observed. We concluded that mechanical stability of the Mallory-Head titanium total hip prostheses is excellent. However, significant pelvic osteolysis had occurred commonly with this implant design, and will continue to pose major reconstructive problems in the future.