Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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6177649 | The effect of protease inhibitors on the polyclonal B cell activator from the serum of pat | 1982 | It has been reported that polyclonal B cell stimulation results in formation of autoantibodies and immune complexes. We have previously reported that a polyclonal B cell activator (PBA) associated with alpha 2-macroglobulin (alpha 2M) is present in the serum of patients with rheumatoid arthritis and related diseases. Here we studied the possibility that patient alpha 2M (Pt-alpha 2M) carries a trypsin-like protease responsible for the PBA activity. This activity was determined by the Ig-turnover assay developed in our laboratories. The small molecular weight protease inhibitors, aprotinin (Trasylol, Bayer) and phenylmethylsulfonylfluoride (PMSF), and the large molecular weight soybean trypsin inhibitor (SBTI) were used. These inhibitors did not affect the PBA activity of dextran sulfate of LPS. However, as expected, trypsin had a PBA-activity which was blocked by all of the above mentioned inhibitors. A trypsin-normal alpha 2M complex (Tr-N alpha 2M) and PBA activity which was inhibited by PMSF or aprotinin but not by SBTI. The PBA associated with Pt-alpha 2M was also inhibited by PMSF or aprotinin but not by SBTI. Moreover, the Tr-N alpha 2M complex and the Pt-alpha 2M, but not that from normal donors, had esterase activity for p-toluenesulfonyl-L-argininemethyl ester. These data suggest a similarity between the Pt-alpha 2M and Tr-N alpha 2M complex. Thus, we concluded that the esterolytic activity is sufficient for PBA activity, that Pt-alpha 2M has esterolytic activity and that this PBA activity can be blocked by small molecular weight protease inhibitors. | |
6968087 | Scanning electron microscopic study of microcrystals implicated in human rheumatic disease | 1980 | Scanning electron microscopy has been used in conjunction with wavelength dispersive X-Ray spectroscopy and in correlation with X-Ray diffraction to define the populations of crystals present in rheumatic diseases. Microcrystals of monosodium urate, triclinic and monoclinic calcium pyrophosphate dihydrate, apatite, calcium hydrogen phosphate dihydrate and corticosteroids, among others, have been found in synovial fluid, in the intraarticular tissues (fibrocartilage, cartilage, and synovial membrane), and in the periarticular tissues (tendons and ectopic calcifications). Scanning electron microscopy in conjunction with wavelength dispersive X-Ray spectroscopy has made it possible to detect microcrystals, even isolated, to describe their morphologies, and to study their relations with the cells of the synovial fluid and with the collagenous and cellular structures of the synovial membrane and of the cartilage. It cannot replace X-Ray diffraction for the conclusive identification of microcrystals, but it can certainly help to improve the analysis of the various populations of crystals present in articular and periarticular rheumatic diseases. | |
6382565 | [IgG-type antihistone antibodies. Diagnostic value in rheumatoid polyarthritis, scleroderm | 1984 Jun | IgG anti-histone antibodies were detected by indirect immunofluorescence in 6 out of 70 sera from rheumatoid arthritis with antinuclear factors, in 1 out of 13 from scleroderma, in 14 out of 25 from spontaneous systemic lupus erythematosus (SLE) and in 11 out of 14 from drug induced lupus. Rheumatoid arthritis patients with IgG anti-histone antibodies were characterized by the severity of joint involvement and by the high frequency of extraarticular features of the disease. SLE patients with anti-histone antibodies only differed from patients without such antibodies by a higher frequency of Raynaud phenomenon (p less than 0.05). Longitudinal studies of spontaneous SLE showed that IgG anti-histone antibodies correlated with disease activity (p less than 0.001). A significant correlation was demonstrated between anti-histone IgGs and anti-ds-DNA antibodies assessed by the Farr binding assay (p less than 0.0001). IgG anti-histone antibodies were rarely found in sera from patients with drug induced antinuclear antibodies without symptoms of SLE (1 out of 6 sera). In drug induced lupus, IgG anti-histone antibodies were found in the absence of high titers of anti-ds-DNA antibodies, and this discrepancy appeared to suggest the diagnosis of drug induced lupus. Finally, anti-histone antibodies were present in 5 out of 7 sera from acebutolol induced lupus. | |
6791172 | Glycoproteins behaviour in ankylopoietic spondylarthritis. | 1981 | Glycoproteins behaviour in ankylopoietic spondylarthritis (SA) is studied by dosing sialic acid in blood and urine on 12 patients in comparison with 10 rheumatoid polyarthritis (RP) and 39 other nonspecific osteo-articular disease cases; the values are referred to those found on normal persons. A significant statistic increase of the sialic acid is found in SA. There are also comparatively studied, on the same lots of patients, the ratio albumin/globulin (A/G), the values of the proteinaemia, of the globulins and the blood sedimentation rate (BSR). | |
6398502 | [The evaluation of anti-native dna antibodies. Comparison of two methods of dosage, study | 1984 Nov | The duplicatibility of dosing anti-native (double-stranded) DNA antibodies using Farr's radioimmunological method (RIE) and indirect immunofluorescence on Crithidia luciliae (IF-CL) has been demonstrated in the literature and from a multicenter study undertaken in 10 immunological laboratories. The duplicatibility of tests run at the same time and also between tests done at different intervals by RIE in our laboratory was better than that by IF-CL. The coefficients of maximum change were respectively 3% (variation in results during one run of the test), and 6% (variation in results between different runs of the test) for the RIE method and 34% (variation during one run) and 38% (variation between different runs) using the IF-CL method. This multicenter study showed that the duplicatibility of Farr's radioimmunological test was good among the different laboratories, only antibody levels near the upper limit of normal giving some discordant results were found in 91%, the discordant results being due to falsely-positive or falsely-negative tests, and sometimes also to the differing affinity of the anti-native DNA antibodies in the two methods. The sensitivity of both methods in making a diagnosis of systemic lupus erythematosus from the literature varies from 60 to 98% for the RIE method and from 44 to 98% for the IF-CL method. The predictive value of a positive test between these two methods varies from 65 to 100% depending on the series, which means that there are other conditions than systemic lupus erythematosus (SLE) (rheumatoid arthritis, Sjögren's syndrome, hepatitis...) where anti-native DNA antibodies can be found. | |
7152379 | The Niebauer-Cutter prosthesis in excision arthroplasty of the trapezium. | 1982 Oct | Sixteen patients had excision arthroplasty of the trapezium, using the Niebauer-Cutter prosthesis. The average period of postoperative follow-up was thirteen months. All patients had severe preoperative disabilities and the majority were relieved from resting pain and pain during active use of their hands. The postoperative range of motion with regard to the palmar and radial abduction was found to be satisfactory, while varying degrees of limitation of circumduction was the rule. There was no correlation between the patients' own judgment of the postoperative benefits and the objectively measured range of motion. One patient had a luxation of the prosthesis, while another had a subluxation when opposing the thumb. This frequency of luxation/subluxation seems to be less than that experienced with the other common type of prosthesis, the Swanson prosthesis. Although it is obvious that the ideal prosthesis for treatment of disabilities in the carpometacarpal joint of the thumb is still not available, it was concluded that the Niebauer-Cutter prosthesis is the best choice at the present. | |
3970040 | Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive tr | 1985 Jan 21 | A prospective study in the United Kingdom of 1,634 patients without transplants treated with immunosuppressive drugs (68 percent with azathioprine, 28 percent with cyclophosphamide) found an excess of non-Hodgkin's lymphoma and squamous cell skin cancer, suggesting that the excesses (although larger) of the same malignancies found among transplant recipients are not due solely to the foreign antigens of the graft. A separate analysis of the 643 patients with rheumatoid arthritis found a 13-fold increase of non-Hodgkin's lymphoma (whether treated with azathioprine or cyclophosphamide). This increase is not significantly different from the excess in similarly treated patients with other disorders in the study. In patients with rheumatoid arthritis not receiving immunosuppressive drugs, this excess is greater than that in a Finnish population and lower than that in another United Kingdom population. The findings are consistent with other evidence that immunosuppression favors the development of non-Hodgkin's lymphoma, which includes the excess of malignancies found among transplant recipients, long-term renal dialysis patients, and patients with certain primary immunodeficiency disorders. The higher risk among transplant recipients may reflect the effects of the foreign antigens, the more intensive immunosuppressive therapy, or both of these factors. In addition, the predilection for the brain, which is a well-known feature of the lymphomas after transplantation, may also apply (to a lesser extent) to other patients after immunosuppressive treatment, judging from the increasing numbers of case reports in such patients of this exceedingly rare type of malignancy. In view of the evidence of an increase of non-Hodgkin's lymphoma in rheumatoid arthritis in the absence of immunosuppressive treatment, any additional increase is likely to be small in absolute terms. Nevertheless, it needs to be weighed against the clinical benefits. | |
6290528 | T cell subset abnormalities in tissue lesions developing during autoimmune disorders, vira | 1982 Jul | The authors review a large body of contemporary immunohistologic findings on the tissue distribution of T lymphocytes in normal and pathological conditions. The suggestions for technological advances in this field are: signal amplification using mixtures of monoclonal antibodies directed against different epitopes on the same antigen (e.g. OKT4A+B+D), triple layer amplification systems using hapten-labelled antibodies, and informative double staining methods with combinations of antibodies labelled with different fluorochromes or enzymes. Review of histological observations in a series of human diseases suggests that imbalances of OKT4+ and OKT8+ subsets of T lymphocytes may represent different types of immunoregulatory disorders. Rheumatoid arthritis and sarcoidosis appear to involve a high level of OKT4+ subpopulation response coupled with an associated appearance of a special type of HLA-DR+ macrophages. It remains to be seen whether normal or self-limited immunological responses (early stages of bacterial infection or delayed-type hypersensitivity reactions) produce OKT4+ and macrophage responses that are characteristically different. Meanwhile, excessive levels of OKT8+ cells have been found in a wide range of recognized or presumed immunoregulatory disorders including: graft-vs.-host reaction and viral infections. These disorders, as well as primary biliary cirrhosis and lichen planus, appear to possess both overlapping and disparate clinical characteristics, and the immunohistological observations may reflect the functional heterogeneity of OKT8+ populations in these diseases. These studies show that histologically meaningful heterogeneity can already be demonstrated for the OKT8+ lymphocyte group. | |
6697073 | Haematuria occurring during antirheumatoid therapy. | 1984 Feb | One hundred and ninety-one patients treated with gold and penicillamine over a seven-year period were reviewed retrospectively for the occurrence of haematuria. Over this period 10% had shown haematuria, and in over half of these an identifiable cause was found. In the remaining patients, a clear relationship with their treatment seemed likely in only two. Penicillamine therapy was discontinued in all patients with unexplained haematuria, but two patients have continued to show haematuria. Gold therapy has been continued in the presence of haematuria without ill effect. There has been no deterioration in renal function in those patients who have continued to show unexplained haematuria and at no time was proteinuria an accompanying feature. | |
535211 | Patellaplasty or patellectomy? | 1979 Oct | A series of patients whose patella has been resurfaced by a prosthesis has been compared with a similar group whose patella has been resected. Patellectomy has been an acceptable procedure in the treatment of severe injuries and degenerative changes of the patella, but the indications for this operation are not well defined in all fields. Satisfactory results following Vitallium patellaplasty have been better than those following patellectomy in osteoarthrosis. Extension is more complete; flexion has been satisfactory; cosmetic appearance is more desirable. Prosthetic resurfacing with a Vitallium prosthesis has been a satisfactory procedure in individuals who develop symptoms from a painful patellofemoral joint when the remainder of the joint has not deteriorated sufficiently to indicate need for total knee replacement. Patellaplasty has provided years of pain-free patellofemoral function and prevented the alteration of normal joint mechanics that occurs with patellectomy. | |
796948 | Ketoprofen suppositories in rheumatological practice. | 1976 | Preliminary results are reported on 30 patients treated with suppositories of ketoprofen at a dosage of two daily (200 mg). Local side-effects, rectal burning and difficulty in retaining the suppository, were recorded in seven patients and caused treatment to be stopped from the first day, and in five others local (burning) or systemic (gastric pain) side-effects caused treatment to be abandoned at a later period. Interest in the suppository presentation may lie in its more prolonged action and this presentation, when given at night, may improve the over-all results obtained with ketoprofen capsules in inflammatory rheumatism. | |
1136598 | [Peroxidase activity in the paw of animals in adjuvant arthritis and its changes by antiph | 1975 Mar | The peroxidase activity is increased in the inflamed paw of rats with adjuvant arthritis. The increase is biphasic like for other enzymes. The higher peak occurs during primary inflammation in the injected paw according to the behaviour of polymorphonuclear leucocytes. Of 32 substances tested in vitro, among them 19 antiphlogistics and derivatives, especially the antiphlogistics inhibited the peroxidase reaction. Therfore it seems not unlikely that inhibition of the peroxidase reaction is involved in the mechanism of activity of anti-inflammatory agents. | |
3978895 | Inhibition of in vivo leucocyte migration by NSAIDs. | 1985 Jan | Leucocyte migration was studied in vivo using a skin window technique, and in vitro by migration under agarose. No difference was found between 28 patients with rheumatoid arthritis (RA), 10 patients with psoriatic arthritis (PA) and 30 healthy controls. Most patients were under treatment with anti-rheumatic drugs. Patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) had significantly lower values (p less than 0.01) than untreated patients. In vivo but not in vitro migration decreased during short-term treatment with diclofenac and naproxen, an effect observed both in patients and in healthy individuals. After pre-incubation of normal polymorphonuclear leucocytes with diclofenac, in vitro migration was diminished only at concentrations of 50 micrograms/ml and above, which are at least 10 times higher than those attained clinically. The in vivo effect of NSAIDs on leucocyte migration may imply a long-term disease modifying influence in chronic arthritides. | |
59600 | Inhibition of denaturation of human gamma globulin by a mixture of L-histidine, L-cystine, | 1976 May | A mixture of histidine, cystine, and copper mimicked gold thiomalate, N-ethylmaleimide, and p-chloro-mercuribenzoic acid in inhibiting sulfhydryl-disulfide interchange-mediated denaturation of human gamma globulin, bovine serum albumin, and diluted human serum. Measurable inhibitory effects were obtained with a mixture of physiologic concentrations of L-histidine, L-cystine, and copper. This work suggests a mechanism by which the hypohistidinemia of rheumatoid arthritis could contribute to the pathogenesis of the disease. | |
6322810 | Metalloproteinases and collagenase inhibitors in rheumatoid synovial fluid. | 1984 Mar | The levels of metalloproteinases and metalloproteinase inhibitors were measured in rheumatoid synovial fluid. Reliable estimates of total enzyme and inhibitor levels in the synovial fluids were obtained only after hyaluronidase treatment and gel filtration. Three latent metalloproteinases were found which, after activation, degraded collagen, proteoglycan, and gelatin. These enzymes closely resembled the metalloproteinases secreted into connective tissue culture medium. In addition to alpha 2 macroglobulin, an Mr 30,000 collagenase inhibitor was detected which closely resembled the tissue inhibitor of metalloproteinase found in tissue culture medium. | |
6998692 | [Antibodies against native deoxyribonucleic acid (anti-nDNA) without antinuclear antibodie | 1980 Sep 12 | Antinuclear antibodies (ANA) by indirect immunofluorescence and antibodies against native deoxyribonucleic acid (anti-nDNA) by radiommunoassay were measured simultaneously in 6,000 sera from about 5,000 patients. Usual findings about 5,000 patients. Usual findings were: (a) both tests negative (75%), (b) only ANA positive (20%), and (c) both tests positive (3%). The unusual combination of ANA-negative/anti-nDNA positive was found in 117 sera from 24 patients. These patients were examined more closely clinically and the mentioned tests repeated. In five with systemic lupus erythematosus, in two with chronic rheumatoid arthritis and one with chronic urticaria this finding occurred repeatedly over some time. In five additional patients (two with chronic hepatitis, one each with drug-induced systemic lupus erythematosus, chronic rheumatoid arthritis, and drug related haemolytic anaemia) this unusual finding occurred only once but with high levels of anti-nDNA. In 11 patients with various diseases the combination of ANA-negative/anti-nDNA positive occurred only once, with the anti-nDNA value being low. In a control group of patients with mononucleosis, cytomegalic disease, acute or chronic hepatitis or hepatoma, anti-nDNA results were never positive. | |
7044796 | Benoxaprofen and its effect on serum alkaline phosphatase: a review. | 1982 | Benoxaprofen is a nonsteroidal anti-inflammatory agent with a novel spectrum of pharmacological activity including regulatory effects on monocytes. It significantly reduces the serum alkaline phosphatase in patients with osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The reduction usually has been within the normal range, but sometimes there has been a change from an abnormal to a normal value. The possible significance of this observation and ways of examining it further are discussed in this review. The reduction may be an effect on osteoblasts secondary to an effect on osteoclasts, cells known to be derived from monocyte precursors. If so, benoxaprofen should be effective in Paget's disease of the bone and preliminary data suggest this may be so. | |
6797049 | Quantitative precipitin analysis of free and hidden RF IgM. | 1981 Jul | Quantitative precipitin analysis using rabbit IgG anti-human Fc mu was performed with 16 RF IgM, six macroglobulinaemic IgM and four normal IgM. Abnormal precipitin curves were obtained for all RF IgM, even when the latter were not readily demonstrated with conventional serological tests for RF, and for macroglobulinaemic IgM with sedimentation rates greater than 19S. These IgM formed significantly more precipitates with IgG anti-Fcmu in the antigen excess zone than did normal IgM, but the precipitin curves for the other zones were similar for all IgM. The underlying mechanisms of some of the reactions were studied and discussed. Because the divergence in the precipitin reaction for normal IgM and RF IgM was so pronounced, a model precipitin curve was constructed. This could be used to detect RF IgM, even when not readily demonstrable with conventional serological tests for RF, by direct analysis of serum. The results obtained for RF IgM suggested that the method might be applied to RF IgG and intermediate complexes comprised of IgG. The mechanisms demonstrated here might be used to develop immunological methods for routine use. | |
717203 | [Inhibition of expontaneous cytotoxicity and antibody dependency by rheumatoid synovial fl | 1978 May | A number of authors have pointed out a diminution of ADCC (Antibody dependent cellular cytotoxicity) in lymphocytes from peripheral blood of patients with rheumatoid arthritis (RA). It has also been found that the addition of rheumatoid serum inhibits ADCC and also spontaneous cellular cytotoxicity (SCC). This effect could be the result of blocking of effector cell receptors for the Fc fragment of IgG by anti-immunoglobulins and/or immune complexes, present in great quantities in rheumatoid serum. We investigated the effect of synovial fluid on the ADCC and SCC shown by purified suspensions of lymphocytes from healthy donors and RA patients towards chicken erythrocytes tagged with 51 Cr. The samples of synovial fluid from patients with RA or arthrosis did not influence per se the spontaneous release of 51 Cr, once their complement had been removed. Seven-eight of the rheumatoid synovial fluid (RSF) produced a significant decline (p less than 0.01) of SCC. Lymphocytes from the peripheral blood of RA patients showed a greater decline in SCC after the addition of RSF than those from healthy subjects (p less than 0.02). In 14/16 RSF and 5/7 samples of arthrosis synovial fluid (ASF) the ability to diminish ADCC significantly (P less than 0.01) was shown. RSF maintained this inhibitory effect in 1:40 and 1:80 dilutions, whereas in these conditions ASF had no effect on ADCC. RSF and ASF, before their complement was removed, showed an opposite effect, provoking an increase in cytotoxic activity, both SCC and ADCC, though in different proportions. These experiments show that RSF, like rheumatoid serum, inhibits ADCC and SCC, possibly by the same mechanism which blocks the Fc receptors by means of immune complexes, and coincides in its general lines with the recent findings of DÃaz Jouanen et al. The pathogenetic implications of this phenomenon are difficult to clarify at present. Its occurrence in vivo would represent the establishment of a local block of cytotoxic effector cells (protector effect), which, on the other hand, would no longer be able to exercise their destructive action against cells responsible for the initiation and/or maintenance of articular damage (pathogenic effect). The non-participation of T cells, in these types of cytotoxicity, previously shown by other authors, accentuates the importance of thymus-independent regulatory systems in the mechanisms which maintain articular damage in RA. | |
1229738 | [Joint scintigraphy using 99mTc pyrophosphate]. | 1975 May | Joint scintigraphy was performed in 85 patients suffering from a variety of rheumatic diseases, using a gamma camera and line scanner. Tc-pyrophosphate was the radio nuclide employed; it accumulates selectively in the juxta-articular parts of the bone. The method provides an objective demonstration of inflammatory and degenerative rheumatic joint changes. More over scintigraphic changes can be demonstrated in joint disease which is too early to be clinically apparant or before there are any corresponding changes in serological parameters. The method is useful both in the localisation and staging of disease, in the evaluation of treatment and as an objective control of clinical skills. |