Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6696523 | Mast cells at sites of cartilage erosion in the rheumatoid joint. | 1984 Feb | Cartilage-pannus junctions of the rheumatoid lesion have been examined by histochemical and ultrastructural techniques in an attempt to identify the cells responsible for cartilage degradation. Mast cells have been identified at sites of cartilage erosion in 3 specimens of rheumatoid joint. It is known that mast cells participate in immunological reactions, produce the vasoactive and proteinase-modulating agents histamine and heparin as well as their own degradative proteinases. The close association of mast cells with sites of cartilage erosion suggests they may play an important role in the pathophysiology of joint destruction in rheumatoid arthritis. | |
| 594297 | Progressive airway obliteration in adults and its association with rheumatoid disease. | 1977 Oct | Six patients with rapidly progressive airway obliteration in the absence of chronic bronchitis or emphysema are reported. Because this pattern of lung disease is very uncommon and five of the six patients had classical rheumatoid arthritis an association between the two diseases is suggested. The patients presented with rapidly developing breathlessness, and râles and a high-pitched mid-inspiratory squeak were heard over the lung fields. Chest radiographs showed distended lungs but were otherwise normal. Tests of lung fuction showed airflow obstruction, most marked at low lung volumes, with air trapping. The carbon monoxide gas transfer coefficient, maximum static recoil pressure and static compliance were normal. In spite of treatment with antibiotics, bronchodilators and corticosteroids, five died in respiratory failure five to 18 months after first becoming breathless. Post-mortem examination in four patients showed an obliterative bronchiolitis but no mucous gland hypertrophy or significant emphysema. | |
| 3877808 | Measurement of outcome in rheumatic diseases. | 1985 Dec | In the assessment of outcome in rheumatic diseases a number of factors must be taken into account. It is important to make an accurate diagnosis, so that the response to treatment is not confused by heterogeneity of the population. The meaning of outcome needs to be defined. The quality of life over a prolonged period is just as important as the ultimate outcome. Subjective symptoms are important to the patient. Pain is the most important, followed by disability and then stiffness. Despite attempts to produce numerical values for pain, particularly visual analogue scales, patients' accuracy in recalling pain experienced more than an hour previously is dubious. In an attempt to quantify this aspect we have measured disturbance of sleep by changes in the EEG and in the motility of the patient. Objective clinical measures are desirable for accuracy. Arthrographs of the knees and metacarpophalangeal joints have produced useful data for physical stiffness. It is doubtful, however, whether they truly reflect the subjective stiffness of which the patient complains. That is more likely to be due to limitation of motion. Grip strength is commonly measured by a pneumatic dynomometer, but a pinch/hand grip analyser promises to give more extensive information. Active movement has been measured goniometrically. The value of electrogoniometers should be enhanced by telemeterization of the apparatus. Passive movement has been measured with a hyperextensometer in patients with hypermobility. Ligamentous laxity of the knee can be measured on the Leeds Knee Analyser and differentiates collateral ligament damage and anterior cruciate ligament damage. Laboratory variables are important in a patient model system in which potential antirheumatoid drugs can be screened and their mechanism of action investigated. Correlation matrices separate second-line agents from NSAIDs. Although mini-matrices have been produced, it would not appear that any single biochemical test will suffice to differentiate these two classes of drugs. A therapeutic index, in which the efficacy is expressed as a ratio of the toxicity of the drug, is important in determining its value. The nearest we can get to serial assessment of the pathological changes in the joint is by X-ray assessment. Changes radiologically correlate to some extent with the height of the ESR, and their progress with changes in the ESR. Functional impairment is important to the patient in the long term, and the Disability Index devised by the Stanford group commends itself for extensive long-term studies. | |
| 6233326 | Optic neuropathy associated with penicillamine therapy in a patient with rheumatoid arthri | 1984 Jun | Optic neuropathy developed in a patient with rheumatoid arthritis who had been receiving D-penicillamine for about 1 year. An associated finding included a 2+ positive antinuclear antibody test with a titer of 1:320. Optic disc swelling was resolved on high doses of intravenous steroids. The case resembles two previously reported cases of optic neuropathy which occurred in patients with Wilson's disease who were receiving penicillamine. | |
| 7178862 | Defective responsiveness to natural and pharmacological molecules of neutrophil locomotion | 1982 | Neutrophils derived from peripheral blood of patients with rheumatoid arthritis (RA) exhibited a defective responsiveness to natural mediators of inflammation, namely histamine and serotonin, and to the anti-inflammatory drugs ibuprofen and naproxen, in spite of the fact that the basic status of motility was normal. Not even pretreatment of granulocytes with substances restored the capacity to modulate the random and directional locomotion. This neutrophil functional defect was correlated with an anomalous response to rifamycin SV, previously observed in rheumatic states. | |
| 7083658 | Management of the deformed rheumatoid forefoot. A comparison of conservative and surgical | 1982 Jun | In a retrospective survey of 65 patients who had rheumatoid arthritis, the late results of excision arthroplasty of the forefoot were investigated and compared with nonoperative management. Subjective assessment of foot shape and severity of pain as well as objective changes in gait and deformity were considered. Surgery relieved pain initially, but the recurrence rate of metatarsalgia was high. In those who wore surgical shoes, lack of cosmesis was the most important factor in determining poor compliance. The operation was recommended at random, and there was little difference in the outcomes of nonoperative and surgical treatments. A long-term randomized prospective trial is required to establish the criteria for selection of a management regime. | |
| 6743361 | Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthri | 1984 Jul | Oxygen free radicals are probably involved in the pathogenesis of rheumatoid arthritis (RA). The enzymes involved in protection against oxygen free radicals and H2O2 (superoxide dismutase, catalase, and glutathione peroxidase) were measured. Superoxide dismutase was not increased, glutathione peroxidase was slightly and catalase was strongly elevated in RA synovial fluid (SF) compared with control SF. Although these enzymes are present in SF, the activities are insufficient to protect against oxygen free radicals and H2O2. In contrast to transferrin, ferritin was increased in RA synovial fluid. Ceruloplasmin was also elevated. When rat liver microsomes were used as a target for oxygen free radicals, serum and SF were both protective. Gel filtration experiments showed that the fraction pattern in which there was maximal protective potential against lipid peroxidation corresponded closely to the level of ceruloplasmin. After removal of ceruloplasmin from serum or SF, about 70% of the protective capacity disappeared. It is concluded that ceruloplasmin is an important protector against oxygen free radicals. | |
| 6220847 | The involvement of interdigitating (antigen-presenting) cells in the pathogenesis of rheum | 1983 Feb | Macrophage like cells expressing high concentrations of HLA-DR antigen have been identified in situ within the synovium of patients with rheumatoid arthritis. The characteristics of these cells have been determined using immunohistological analysis and combined cytochemical techniques. It was found that the majority (greater than 80%) of these cells were interspersed within the perivascular lymphocytic infiltrates occurring in the synovium. These cells did not stain with antisera against surface immunoglobulin or any Mc Abs to T lymphocyte markers. Further combined staining demonstrated that the HLA-DR + ve cells did stain with an anti-monocyte monoclonal (FMC-17), but could not be stained with a Mc Ab against C3b receptors. The interfacing of cytochemical reactions for acid phosphatase (ACP) and adenosine triphosphatase (ATPase) with immunofluorescence staining for HLA-DR demonstrated that these cells were ACP - ve ATPase + ve. This analysis led to the conclusion that the HLA-DR + ve cells found in abundance in the rheumatoid synovium expressed identical characteristics to the interdigitating cells of the normal lymph node paracortex. The possible significance of the presence of large numbers of such antigen presenting cells in the rheumatoid synovium is discussed. | |
| 356761 | Continuous and intermittent levamisole. A controlled trial. | 1978 Jun | A double-blind comparative trial showed that intermittent levamisole therapy (150 mg daily for 3 days of each week) was as effective as continuous therapy (150 mg daily) in rheumatoid arthritis and with slightly fewer side effects. | |
| 7046758 | Tiopronin (N-[2-mercaptopropionyl] glycin) in rheumatoid arthritis. | 1982 Jun | Two controlled trials have demonstrated that tiopronin, a new sulfhydryl compound, is active as a slow-acting antirheumatic drug in rheumatoid arthritis. One trial compared 10 patients receiving placebos and 20 receiving tiopronin, 1 gm/day; the second compared two groups of 16 patients who received either placebos or tiopronin, 1.5 gm/day. In addition, 80 patients (56 from the 2 trials plus 24 other patients) were followed up for a long period. Dropout rate for intolerance or inefficacy was comparable to that fund with D-penicillamine. Secondary toxic reactions resembled those of other sulfhydryl compounds. | |
| 1267586 | Clinical applications of a standardized mobility test. | 1976 Mar | Four patients with mobility problems were evaluated in relation to their performances on a standardized mobility test throughout the course of their rehabilitation programs. While each of the four cases demonstrates the value of an objective measurement of independent function, each also reflects individual points of merit. Clinical application demonstrated the test's ability to separate out areas of mobility deficit, evaluate forms of treatment, and indicate need for follow-up. Further, the sensitivity of the test in long-term follow-up of mobility problems was illustrated. | |
| 6420100 | Pathogenesis of rheumatoid arthritis. | 1984 Jan | Rheumatoid arthritis (RA) is initiated by an unknown antigen(s) in the genetically programmed host. HLA-DR4 is associated with RA. The antigen could be exogenous (e.g., Epstein-Barr virus, bacterial cell wall products) or endogenous (e.g., collagen or immunoglobulin). Within the synovium, where the immune response begins, monocytes and lymphocytes are activated. Polyclonal B-cell proliferation results, as well as production of monokines and lymphokines. The antibodies form immune complexes with other antibody molecules or antigens. Phagocytosis of immune complexes results in production of many autacoids and activation of other soluble mediator systems, e.g., the coagulation, kinin, complement, and fibrinolytic systems in synovial fluid. Chemotactic factors draw polymorphonuclear leukocytes into the joint space. Monokines stimulate synovial cell proliferation; these cells, in turn, synthesize proteinases and products of arachidonate metabolism capable of destroying normal articular structures. | |
| 629599 | Altered phospholipids in human rheumatoid synoviocytes. | 1978 Feb | A specific cytochemical reaction for freely available phospholipids has shown a raised concentration of such phospholipids in the lining cells of human synovial membranes removed from rheumatoid joints. Quantitative measurement, by microdensitometry, of the amount of reaction-product per cell showed that the rheumatoid synoviocytes contained almost three times the amount of free phospholipids present in the equivalent nonrheumatoid cells; statistically the difference was highly significant. Evidence from studies in which the bound phospholipids were 'unmasked' by methanol-chloroform confirmed the view that the increased content of freely available phospholipids was related to altered lipid-protein binding rather than to an increase in total phospholipids. | |
| 396108 | Kinin system in clinical and experimental rheumatoid inflammation: a short review. | 1979 | The kallikrein, kininogen, kinin and kininase system along with other inflammatory chemical mediators are important components for the initiation and maintenance of clinical and experimental rheumatoid-like inflammatory conditions. Numerous studies carried out in the last few years, however, strongly suggest that the kinin-forming system intervenes in a far wider range of physio-pathological processes than has been considered previously. The authors summarize present knowledge concerning the system and review some of the latest experimental findings and opinions. | |
| 330914 | Felty's syndrome: an analytical review. | 1977 Sep | The clinical and laboratory features of 72 patients with Felty's syndrome described within the last ten years have been compared with Felty's five original patients. Felty's syndrome appears to be a variant of rheumatoid arthritis with extra-articular manifestations in which leukopenia (usually due to neutropenia) and splenomegaly occur, although not always at the same time. Both are manifestations of the underlying disease process and are not necessarily otherwise related. The mechanism of the leukopenia is complex and abnormalities in leukocyte function appear to be as important as the leukopenia in predisposing patients with Felty's syndrome to infection. Functional abnormalities of the leukocytes in this syndrome are due in part to immune complex formation. Hypocomplementemia associated with this process may be another cause for the increased susceptibility to infection. It is proposed, therefore, that therapy in Felty's syndrome be directed at the underlying disease process, and gold salts and penicillamine should be considered for this purpose. Splenectomy should be reserved for specific situations, such as hemolytic anemia, severe thrombocytopenia, leg ulcers, and infections associated with profound leukopenia that are not responsive to medical therapy. | |
| 1121633 | Blood and urine gold levels during chrysotherapy for rheumatoid arthritis. | 1975 Feb | In this study the value of undertaking routine blood and urine estimations was assessed in relation to achieving maximum efficacy and safety in chrysotherapy. It was found that a favourable response to gold was forthcoming in approximately two-thirds of patients and occurred irrespective of the patients' disease duration or severity, or the mean serum gold level or the mean urinary gold excretion, estimated immediately before the next gold injection was due. The presence of rheumatoid nodules and the patients' advancing age were associated with a less favourable clinical response to gold. Those patients who derived a marked benefit from chrysotherapy did so significantly earlier in their course than those who derived only moderate benefit. A frequent correlation was seen in individual patients between serum gold levels and urinary gold excretion. This was most marked in those patients showing a favourable response to gold. | |
| 169722 | Prostaglandins in the rheumatic diseases. | 1975 Jun 13 | The prostaglandins may participate in the pathogenesis of the inflammatory rheumatic diseases by acting as mediators of inflammation and in promoting bone resorption. Levels of PGB (presumed to arise from PGE) in synovial fluids are elevated in the majority of a group of patients with inflammatory rheumatic diseases, as compared to similar patients treated with aspirin and indomethacin and patients with osteoarthritis. Rheumatoid synovium produces large amounts of PGE2 in organ culture. In addition, fibroblast cell lines derived from rheumatoid synovia synthesize more PGE and more cAMP than do cells from normal synovia or skin. The media from rheumatoid synovial organ cultures contain large quantities of bone-resorbing activity toward mouse calvaria in vitro. The bone resorption can be accounted for by PGE2 produced by the synovia, because the activity and PG synthesis are inhibited by more than 90% by incubation of the tissue with indomethacin, because it is quantitatively extractable into ether, and because it bears a relationship to the concentrations of PGE2 present, as measured by radioimmunoassay. | |
| 4578156 | Phagocytic function of polymorphonuclear leukocytes in rheumatic diseases. | 1973 Jul | Phagocytosis of yeast particles by peripheral blood and synovial fluid neutrophils was compared in the sera and synovial fluids from 16 osteoarthritis, 23 rheumatoid arthritis, and 12 miscellaneous arthritis patients. Phagocytosis by normal peripheral blood neutrophils was decreased equally and significantly in all synovial fluids. All synovial fluid neutrophils demonstrated decreased phagocytic capacity in all media. Rheumatoid arthritis synovial fluid neutrophils showed significantly less phagocytosis than miscellaneous arthritis synovial fluid neutrophils. Normal peripheral blood neutrophils which in vitro had previously ingested monosodium urate crystals or oil red O, subsequently exhibited a normal yeast phagocytic capacity. Normal peripheral blood neutrophils, which had ingested preformed immunoglobulin G-rheumatoid factor complexes exhibited significantly less yeast phagocytic capacity than control cells or cells preincubated with the individual complex components. There was a significant correlation between the log of the reciprocal of the rheumatoid factor titer in sera used to produce complexes and the phagocytic capacity exhibited by test neutrophils. Ingestion of immunoglobulin G-rheumatoid factor complexes may be important in the production of the cellular phagocytic defect which this study has demonstrated in rheumatoid arthritis synovial fluid neutrophils. | |
| 6838906 | Breakdown of cartilage proteoglycan in a tissue culture model of rheumatoid arthritis. | 1983 May 4 | Proteoglycan breakdown was studied in a coculture model which mimics the confrontation between synovium and cartilage that occurs in rheumatoid arthritis. Bovine nasal-septum cartilage discs radioactively labeled (35SO2-4 with or without [3H]glucosamine) and 'chased' in non-radioactive medium were cultured in contact with minced rheumatoid synovial membranes for intervals up to 8 days. Synovium-stimulated (2-3-fold) cartilage breakdown was unaffected by ascorbate supplementation. Labeled products (small molecules plus proteoglycan complexes) in culture media were characterized by chromatographic, sedimentation and enzymic digestion methods. Breakdown was dominated by the release of a range of proteoglycan products, fully disaggregated and incapable of reaggregation with added hyaluronate. Because constituent glycosaminoglycans were of uniform size, proteoglycan polydispersity was attributed to differences in core protein length. Hydrocortisone inhibited degradation and partially prevented the shift of proteoglycans to lower average molecular weight. An additional breakdown pattern occasionally noted during the initial 48 h of coculture was characterized by release of a subpopulation of low charge-density proteoglycan bearing shortened glycosaminoglycan chains, consistent with glycosidase action. We conclude that rheumatoid synovia exhibit two distinct cartilage degradative potencies in vitro that may be important in vivo: (a) A variable hyaluronidase-like activity at early culture times, and (b) a dominant proteolytic activity generating an array of disaggregated proteoglycan products that differ largely on the basis of their core lengths. The response to hydrocortisone is consistent with inhibition of proteolysis through the stabilization of cellular membranes. | |
| 6968220 | [The influence of acemetacin and indometacin on gastrointestinal blood loss in normal volu | 1980 | In a clinical trial on 12 healthy volunteers total gastrointestinal blood loss was measured with 51Cr-labelled erythrocytes. This double-blind cross-over study showed a highly significant difference (p < 0.001) between indometacin and [1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-acetoxy[acetic acid (acemetacin, TV 1322, Rantudil¿) after oral application of 200 mg acemetacin, 200 mg indometacin per day and placebo for a week. Average total blood loss within seven days was 12.4 ml after indometacin, 4.5 ml after acemetacin and 5.0 ml after placebo. In a clinical trial on 16 rheumatic patients taking commercial non-steroidal antiinflammatory drugs over a long time total gastrointestinal blood loss was determined likewise. After a preceding wash-out period the blood loss due to acemetacin (240 mg daily) and indometacin (200 mg daily) for seven days was compared. There was a highly significant difference (p < 0.001) between both drugs. Total weekly blood loss was measured as 13.8 ml due to the treatment with indometacin and 6.5 ml due to acemetacin. During the wash-out period blood loss was detected as 6.0 ml weekly. There was no difference between the results of both trials. These clinical trials on 35 patients and volunteers do not give any indication that the new antiinflammatory drug acemetacin may cause mucosal lesions in the gastrointestinal tract evedenced by blood loss. |