Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 952090 | [Immunopathology and pathogenesis of chronic erysipelas polyarthritis of swine]. | 1976 May | Several immuno-pathological aspects of polyarthritis following experimental infection with erysipelas in pigs were studied for two years. Aseptic and specifically pathogenfree animals were infected subcutaneously and intravenously-intraarticularly with living erysipeals bacteria (erysipelothrix rhusiopathiae) of serotype B. After an initial febrile phase a progressive polyarthritis and disco-spondylitis developed. Some animals also developed thrombo-endocarditis. Hypergammaglobulinemia and high titers of specific antibodies were observed during the whole experimental period. Antiglobulin factors, however, were not detected in the serum or the synovium. In some animals collagen antibodies were demonstrated in synovial tissue. Bacterial examination of the synovium showed that erysipelas bacteria were present in arthritic joints for months. Living erysipelas bacteria were isolated 24 months after the experimental infection from synovial tissue of two pigs. The polyarthritis was characterised by exudates rich in fibrin, villous proliferation, pannus formation, cartilage erosions, and peri-articular fibrosis. IgG and specific erysipelas antibodies were demonstrated in plasma cells from synovial tissue by immuno-histological methods. The findings emphasize the morphological resemblance of the erysipelas induced chronic polyarthritis in pigs to human rheumatoid arthritis. | |
| 781232 | Some problems in the interpretation of clinical trials: longterm parallel study of fenopro | 1976 | Fenoprofen calcium was compared with acetylsalicylic acid in the treatment of 27 patients with definite or classic rheumatoid arthritis, over a period of one year. Both drugs appeared efficacious, with a slight edge to fenoprofen in the doses employed. Fewer side effects were noted with fenoprofen. Effectiveness continued undiminished throughout the year, and mean values of most parameters continued to improve in both groups over the entire period. Three problems which influence extrapolation of results from this and similar studies to the general setting are discussed. (1) Individual patients show great variation from the mean and from one observation point to another. Thus, expectations developed from mean values will seldom be accurate in a particular patient. (2) The relative doses chosen for two drugs in the clinical trial can profoundly influence both efficacy and toxicity. The qualification "at the doses employed" is seldom emphasized in clinical reports. (3) Patient compliance in the general clinical setting is importantly different from that in a clinical trial, and this potential problem must be assessed by the physician choosing an appropriate medication for a particular patient. | |
| 749701 | The effect of zinc on alkaline phosphatase activity in rheumatoid synovial tissue. | 1978 Dec | To examine the reported beneficial effect of zinc in rheumatoid arthritis, rheumatoid synovial tissue has been maintained in vitro in non-proliferative culture with or without zinc sulphate in the culture medium. Alkaline phosphatase activity was measured by microdensitometry of the cytochemical reaction in cryostat sections; the activity in blood vessels was measured separately from that in the supporting tissue below the synovial surface. Zinc enhanced this activity optimally at concentrations of between 10(-5) and 10(-4) mol/l. | |
| 1016531 | [Australia antigen in rheumatoid arthritis]. | 1976 Nov | Australian antigen (Au Ag) was first described by Blumberg in the serum of an Australian aborigen. Its main clinical significance is based on the fact of its association with the presence of hepatitis B (Okochi, Nurakami, 1968; Prince, 1968) (9). Almeida (1969) outlines the intervention of immune complexes on the production of the referred illness. Later works show the importance of the type of immunologic response created by Au Ag (2). Alpert et al. (1) (1970) state the possibility that immune complexes developed by Au Ag and anti Au Ag antibodies may produce in patients with hepatitis B other allied manifestations including arthritis. On the basis of similar immunopathological findings (illnesses including immunocomplexes on their production), Au Ag investigation in rheumatoid arthritis (RA) has been the object of several works, whose results reveal certain discrepancies. We have investigated the presence of Au Ag on 70 patients whose diagnostic was RA "classical (according to the judgement of the American Rheumatism Association). We used immunoelectrophoresis (counter immunoelectrophoresis-CIEP-) and radioimmunoassay (RIA) techniques. We prepared individual records including clinical, epidemic, biochemical and personal data. Au Ag investigation both through different techniques gave negative results in 70 cases, of which only four referred a possible previous hepatitis B clinic history, not showing during the investigation suggestive clinical data of hepatitis or biochemical alterations. Panus et al. (1970) (5), Desche-Labarte et al. (1972), Trempo (1972), Burrel (1973) (6), Serré et al. (1973) (8), obtained negative results in the matter, with similar or lower casuistics than ours. Notwithstanding Roqués et al. (1975) (7), in 300 cases of RA showed the presence of Au Ag in a significant number of cases (5%) as compared to Au Ag incidence in the French population (estimated in about 0.22%) (6). However, Roqués did not find in their Au Ag positive cases any evidence which enables to think that this antigen has played an important role on the origin and development of the rheumatic illness. These important discrepancies may be due to different reasons: a) Use of different techniques for Au Ag detection. b) The transitory character of the presence of Au Ag in the serum. c) Important differences in the antigen geographic distribution. d) Previous hepatitis B. There are som other factors which have attained importance recently, as a consequence of the broad epidemiological studies carried out. So, Au Ag increased incidence has been found--statistically significant--on groups of persons who have been submitted to several surgical interventions and/or have needed repeated hospitalizations or reiterated blood transfusions (6). These three conditions--especially the first two--are accomplished in an illness with chronic and invalidating characteristics as RA... | |
| 6167213 | Prevalence of anti-beta-2 microglobulin autoantibodies in sera of rheumatoid arthritis pat | 1981 Aug | The frequency and concentration of specific factors binding beta 2 microglobulin were investigated in sera and synovial fluids of patients and in sera of normal controls. High anti-beta 2 m activity was detected in the sera of adult RA patients, particularly in those of with extra-articular disease. Similarly, anti-beta 2 m was present in the synovial fluids of RA but not of osteoarthrosis patients. Both the binding of anti-beta 2 m activity to the Sepharose staphylococcal protein A and its elution position in the second 'IgG' peak after Sephadex G-200 gel filtration suggest the antibody nature of the activity. The possibility of differences not only in titre but also in the specificity of heterologous and homologous anti-beta 2 m antibodies are discussed. | |
| 6199906 | [Use of the proteinase inhibitor alpha 2-macroglobulin in synovial fluids of arthritis of | 1983 Dec 23 | Collagen and proteoglycan are major constituents of the articular cartilage. In rheumatic disorders joint damage is attributed to the excessive action of proteoglycan degrading proteinases (P) and specific collagenases, which are released by connective tissue- and inflammatory cells in the synovial compartment. Collagenase is secreted in a latent form, which requires activation by a variety of serine-proteinases. Thus, several different proteinases are involved in pathogenesis of joint disease. alpha 2-macroglobulin was shown to be the major inhibitor of proteinases in complex biological fluids. To assess the utilization of alpha 2M by proteinases in synovial fluids (SF) from different arthritides we have employed a newly introduced solid phase immuno-sorbent assay, which allows concentration of alpha 2M and its proteinase-complexes from biological fluids. Most pronounced utilization of alpha 2M (up to 50% of total SF alpha 2M) was found in marked joint inflammation as judged from RF, immunocomplexes, C3 complement activation and acute phase reactants. Supported by animal experiments, which revealed that alpha 2M.P complexes but not native alpha 2M induce synovitis in rabbits after repeated intra-articular administration, it is suggested that pathophysiological rise of alpha 2M.P may impair cellular functions in inflammatory connective tissue, e.g. synovial tissue. | |
| 6316858 | Leukotriene B4, a mediator of inflammation present in synovial fluid in rheumatoid arthrit | 1983 Dec | Leukotriene B4 (LTB4), generated from arachidonic acid following lipoxygenase activity by a variety of inflammatory leucocytes, has been shown to be present in synovial fluid from patients with active rheumatoid arthritis. It does not persist as such, being converted to less active metabolites. The role of LTB4 as one of the natural mediators of inflammation is discussed. | |
| 6605118 | Penicillamine-induced myasthenia in rheumatoid arthritis: its clinical and genetic feature | 1983 Oct | The clinical features and genetic background of 18 patients with rheumatoid arthritis were investigated following the development of penicillamine-induced myasthenia (PIM). The initial myasthenia symptoms in all patients consisted of variable diplopia and/or ptosis with progression to a more generalized involvement in 7 of them. No clinical, humoral, or genetic factor was determined which would allow identification of individuals developing generalized as opposed to ocular myasthenia. Withdrawal of penicillamine was associated over 4-60 weeks with a slow resolution of symptoms, facilitated in 12 patients by the use of anticholinesterase agents. In 2 patients a persistent partial unilateral ptosis remains after 15 and 25 months, while in a further patient diplopia is present 42 months after resolution of the other myasthenic symptoms. The patients with PIM when compared with a healthy 'control' population had a significant increase in HLA Dr1 (p corr less than 0.005) and an absence of HLA Dr 3. A genetic susceptibility to the development of PIM, distinct from that observed in myasthenia gravis of spontaneous onset, is suggested by this abnormal distribution of HLA Dr antigens. | |
| 6334691 | High-performance liquid chromatographic analysis of tiaprofenic acid and its metabolites i | 1984 Oct 12 | A rapid, convenient, sensitive and selective reversed-phase high-performance liquid chromatographic method was developed to measure tiaprofenic acid, its reduced and oxidized metabolites and their conjugates in biological fluids. The method involved direct injections of plasma and urine samples into the chromatograph before and after alkaline hydrolysis of the conjugates. Concentrations as low as 0.5 micrograms/ml of the drug in plasma and urine were quantifiable. The method was suitable for analysis of tiaprofenic acid and its metabolites in biological fluids after administration of therapeutic doses. Several other non-steroidal anti-inflammatory drugs which were applied to the system did not interfere with the assay. | |
| 6112411 | Intrasynovial orgotein therapy in rheumatoid arthritis. | 1981 May 9 | 30 patients with active classical rheumatoid arthritis affecting the knee took part in a 12-week double-blind trial in which intra-articular injections of orgotein (4 mg/week for 6 weeks) were compared with intra-articular aspirin 4 mg/week for 6 weeks. After 12 weeks clinical and biochemical assessments showed that orgotein was superior to aspirin. Clinical response was measured in terms of the cumulative rheumatoid activity index (RAI) which was based on scores for morning stiffness, range of flexion, pain and 25-foot (7.5 m) walking time. Treatment with orgotein resulted in significant improvement of the RAI; the improvement correlated with findings on knee-joint scanning which showed reduced mean uptake of 99mTc-pyrophosphate. After intra-articular orgotein injections, synovial fluid IgM and IgG rheumatoid factor levels fell significantly; so did prostaglandin E2 formation and lactate dehydrogenase activity. The changes in the synovial fluid suggest that the anti-inflammatory properties of orgotein may lie in its effect on proliferating synovia. | |
| 6380504 | Quantitation of human synovial mast cells in rheumatoid arthritis and other rheumatic dise | 1984 Aug | We examined sections of synovial membranes from 14 patients with rheumatoid arthritis (RA), 7 with other rheumatic diseases, and 10 with no apparent joint disease. Patients with RA and other rheumatic diseases had significantly more synovial mast cells/vessel than patients with no joint disease (0.49 and 0.20, respectively, versus 0.03). They also had significantly more total mast cells/10 fields than patients with no joint disease (9.9 and 5.0, respectively, versus 0.4). Within the rheumatoid group, patients with active disease had more total mast cells/10 fields than patients clinically considered to have end-stage disease (P less than 0.05). Synovial basophils were not identified in any patient. Synovial vascularity was similar for all groups (2.3 vessels/field). The role of the synovial mast cell in RA and other rheumatic diseases remains to be determined. | |
| 7415587 | Protein-corticosteroid interactions in peripheral plasma and synovial fluid of patients wi | 1980 May | The individual protein fractions, together with the unbound (biologically active) and specifically globulin-bound 11-hydroxysteroids, were determined in the plasma and synovial fluid of patients with rheumatoid arthritis (RA). The values were compared with those measured in control subjects and in patients with severe osteoarthrosis (OA). Hypoalabuminaemia and hyperglobulinaemia, as well as an increase in the unbound and a decrease in the specifically bound corticosteroids were found in the plasma of the RA patients. The protein and corticosteroid levels were lower, and the level of the protein-bound corticosteroid fraction higher, in the synovial fluid than in the plasma. Significant differences between the RA and OA patients in respect of these parameters were also observed. The findings indicate that the altered hormone pattern is not a nonspecific result of the permanent stress situation to which RA patients are subjected. They point out the existence of a fairly specific but still unknown mechanism that compensates the high level of unbound corticosteroids, thus accounting for the absence of any clinical signs of hypercortisonism. | |
| 1018652 | A functional assessment of total knee replacement in the arthritic patient. | 1976 Dec 4 | The aims of knee replacement are to provide freedom from pain and a return to a resonable level of function. A survey was undertaken to determine the functional advantages of knee replacement and problems that may still be encountered by the patient. The results of the survey highlighted certain advantages and problem areas. It also pointed out the seemingly greater functional value of the knee replacement in those patients who had no problems in other joints. | |
| 4068773 | The effect of human bone matrix extracts on the biosynthesis of macromolecules by human mo | 1985 | In chronic rheumatoid arthritis, mononuclear cells (MC) accumulate in the subchondral bone and form a prominent part of both destructive lesions and repair reactions. A fraction from human bone matrix extracts (BME) stimulated glycosaminoglycan (gag) and glycoprotein synthesis by fibroblastic cells but its effects on MC metabolism had not been studied. A method was established for the study of incorporation of radioactive precursors into total protein, IgG and gag synthesized and secreted by peripheral blood MC cultured in microwells in the presence or absence of Concanavalin A (ConA). Relatively low concentrations of BME suppressed spontaneous synthesis of radioactive IgG (protein A bound) and TCA precipitable protein but had little effect on gag synthesis. In general, stimulation of the cultures with ConA overcame the inhibitory effects on protein synthesis by the BME. A large stimulation of gag synthesis induced by ConA was not affected by BME. The interactions between the BME and the stimulatory effect of ConA on DNA synthesis were studied in detail and were found to be complex, not immunologically specific and appeared to be due to binding of lectin by the carbohydrate moieties of the glycoproteins in the BME. On the basis of a model of the lectin-BME interaction, the hypothesis is postulated that the carbohydrate moieties of subchondral bone glycoproteins may have the capacity to act as a solid state "trap" for certain circulating antigens which may then also interact with surface glycoproteins of the MC accumulating in the subchondral bone. The physiological role of gag synthesis by MC is not known. | |
| 6725355 | Cervical cord compression due to extradural granulation tissue in rheumatoid arthritis. A | 1984 May | Five patients with long-standing, severe rheumatoid arthritis who developed cervical myelopathy at the subaxial levels are presented. In each patient the myelopathy occurred in the absence of major subluxation. At laminectomy the cause of the cord compression was found to be a band-like mass of ligamentous and granulation tissue in the posterior half of the extradural space, extending to the underlying portion of the dura and forming a constricting ring. In three patients this constricting ring was released by longitudinal division of the dura followed by application of a fascial patch graft. This release seems to be essential for effective decompression of the cord and good neurological recovery was achieved in these three patients. Of the other two patients, the result was fair in one and poor in the other, this latter result being due to severe intra-operative bleeding with a massive wound haematoma. | |
| 788118 | Dapsone in rheumatoid arthritis. | 1976 Aug | After a preliminary period of observation, 71 patients with consistently active rheumatoid arthritis (RA) were given dapsone 50 mg daily for one week, then 100 mg daily. There was a significant improvement in subjective clinical state and there were significant falls in serum C-reactive protein (CRP) and the ESR; the Rose-Waaler titre (RW) did not fall. The results were compared with those in 78 patients who had gold. Subjective clinical improvement was slower with gold, but from six weeks the pattern of changes in clinical score, CRP and ESR was similar for both drugs. The RW fell during gold treatment. The results suggest dapsone is effective in RA; over-all it appears to be slightly less effective than gold but much less toxic. | |
| 1257709 | Retention and extra-articular spread of intra-articularly injected 90Y silicate. | 1976 | A study was performed on the retention and distribution of intra-articularly injected colloidal 90Y silicate in 7 patients with rheumatoid arthritis (8 knees). In 5 knees retention was complete within the limits of measuring accuracy, and in the remaining 3, 82-84% was retained. No radioactivity was detected in the liver and heart areas or in the blood samples. The cumulative urine activity was less than 1.8%. In the inguinal lymph nodes, activity was detectable %0.5-2%) in only 3 cases. We conclude that 90Y silicate is a safe radioactive agent for the treatment of knee effusions, provided the limb is strictly immobilized after the injection. | |
| 6836238 | Prognosis of inflammatory joint diseases. A three-year follow-up study. | 1983 | The prognosis 3 years after the onset of the disease was studied in 107 patients with definite rheumatoid arthritis, 161 with probable RA or non-specific arthritis, 84 with either ankylosing spondylitis, Reiter's disease or reactive arthritis, 14 with psoriatic arthritis and 10 with a systemic connective tissue disease. Prognosis was measured by clinical involvement of joints, radiological erosions in joints, deterioration in joint function, ESR, and working ability. A total of 44% of all patients were symptomless after 3 years. The prognosis was best in patients with an "HLA B 27-associated" disease and non-specific arthritis, and worst in RA. Two patients died during the follow-up of systemic connective tissue disease and one committed suicide with an overdose of hydroxychloroquine. Two HLA B27-positive patients developed systemic amyloidosis. | |
| 314202 | [Synovial membrane permeability for plasma proteins and protein syntheses in rheumatic dis | 1979 Apr 15 | 1. The permeability of the synovial membrane for proteins is larger in rheumatoid arthritis than in osteoarthrosis, in rheumatoid arthritis with high CRP activity larger than in rheumatoid arthritis with low CRP activity. 2. The diffusion by the synovial membrane in most plasma proteins takes place depending on their molecular weight. Of the 14 proteins tested only haptoglobin and fibrinogen did not follow this regularity. 3. While the non-immune proteins proved in the synovial fluid only come from the blood plasma, the immune globulins IgG, IgA, and IgM as well as lysozyme are partly also locally synthetized and enriched in rheumatoid arthritis. In rheumatoid arthritis lysozyme is present in the synovia not only in free, but in most cases also in cell-bound form. | |
| 6238529 | Nonsteroidal anti-inflammatory drugs and immunologic function. Overview of the European ex | 1984 Oct 15 | A large number of nonsteroidal anti-inflammatory drugs are available in Europe. There appears to be little difference in overall clinical effectiveness of these drugs, despite individual patient variation, suggesting a common mode of action. Occasionally, a nonsteroidal anti-inflammatory drug will show some evidence of a more impressive anti-rheumatic effect, perhaps related to a more prolonged or different mode of action. The evidence for an immunologic effect of nonsteroidal anti-inflammatory drugs is largely derived from in vitro studies. In patients with rheumatoid arthritis treated with piroxicam, there are no overall changes in lymphocyte numbers or T4/T8 ratios, but numbers of activated cells expressing la decrease and rheumatoid factor titers may also fall. It is suggested that this is not a direct immunosuppressive effect, but one that is related to local inhibition of polymorphonuclear leukocyte-derived free radical production within the joint, which may lower the antigenic load of IgG altered by free radicals, with subsequent diminished immune stimulation. |