Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6362406 | Antimalarial drugs for rheumatoid arthritis. | 1983 Dec 30 | Chloroquine and hydroxychloroquine effectively suppress rheumatoid arthritis with a superior benefit to risk ratio. Controlled studies demonstrate moderate efficacy in about 70 percent of patients. High-grade suppression is seen in 15 percent and partial suppression in 55 percent. The dropout rate for poor efficacy is 30 percent and for side effects 3 to 7 percent. Most studies show antimalarials to be almost equivalent to chrysotherapy in potency. Antimalarials are indicated for active rheumatoid arthritis not optimally controlled with nonsteroidal anti-inflammatory drugs and for all cases of progressive disease. Therapy is continued indefinitely. Safe use of these drugs depends on daily dosage. With the single exception of late stage retinopathy, other adverse effects are fully reversible. Strict adherence to three tested safety rules virtually eliminates retinopathy and prevents loss of vision: (1) limit the daily dosage: chloroquine 3.5 to 4.0 mg/kg per day or hydroxychloroquine 6.0 to 6.5 mg/kg per day based on lean body weight; (2) subject the patient to an annual ocular examination to age 65, twice annually thereafter; (3) adjust treatment for pharmacokinetic variables. The lower risk and nearly comparable efficacy make antimalarials first choice among remittive drugs. | |
| 6609427 | T lymphocyte subclasses in rheumatoid synovia as analysed with monoclonal antibodies and f | 1984 | Inflammatory synovial T lymphocytes were released by mincing rheumatoid arthritis (RA) affected synovium, by digesting the material with collagenase plus DNAse, and isolating by sheep red cell rosetting and density centrifugation. There was a wide variation in the T-helper (Tm, OKT4) and T suppressor (Tg, OKT8) lymphocyte ratio in the individual synovia, ranging from 0.55 to 1.57. The mean ratio of Tm/Tg lymphocytes as well as OKT4/OKT8 lymphocytes was somewhat lower in the synovium (and in the blood) of RA patients than in the blood of healthy persons, but the differences were not significant (p = 0.56 and 0.09, respectively). The helper and suppressive capacity of synovial T lymphocytes on T-dependent B-cell maturation to immunoglobulin synthesis was analysed by co-culturing them with normal B or (unseparated) T+B cells in the presence of pokeweek mitogen. Eluates where the helper/suppressor ratio was above 1.2 produced at least some T cell help and lacked suppressor capacity, whereas eluates with a T helper/suppressor ratio below 1.20 provided a strong suppression and lacked the capacity of T-cell help. On the whole, we were unable to demonstrate any uniform pattern of inflammation with regard to T-cell subsets in the rheumatoid synovium. However, it seems that monoclonal antibodies provide good markers with which to analyse the inflammatory T cells in situ, and that these markers correlate well to the functional capacity of these cells in vitro. | |
| 4133792 | The roles of IgG, IgM rheumatoid factor, and their complexes in the induction of polymorph | 1974 Jun | The induction of chemotactic factor by rheumatoid factor (RF) and by rheumatoid complexes and their constituents was investigated. The presence of chemotactic factor was measured by the number of polymorphonuclear leukocytes (obtained from normal individuals) attracted through a 3 mum Millipore filter and is expressed as a "chemotactic index." The chemotactic index was used to measure the effect of immunoglobulins and their complexes in stimulating production of complement-derived chemotactic factors from the sera of normal individuals. Two sources of IgG (F-II and DEAE-purified IgG) were used. These were prepared for use in the native and heat-aggregated states. The same chemotactic index was obtained with both these preparations of IgG. The chemotactic index increases when (a) increasing concentrations of gamma globulin were added to a constant concentration of complement and (b) when the amount of complement alone was increased. The addition of a purified IgM RF to the mixture of IgG and complement caused a decrease in the chemotactic index. Incubation of IgG and complement before addition of IgM RF produced no change in the chemotactic index. The addition of a nonrheumatoid factor IgM to IgM and complement had no effect on the chemotactic index. IgM RF and IgG alone were not chemotactic. These studies confirm the concept of "complement deviation" by IgM RF which occurs with, and as a result of, the immune complex formation between IgG and IgM RF. The successful activation of complement chemotactic factors by IgG may explain the synovitis with high polymorphonuclear leukocyte counts found in RF-negative arthritis. | |
| 516279 | [Results of helium-neon laser radiation action on the hematopoietic system experimentally | 1979 Aug | The investigation of effects of the red light of the helium-neon laser on hemopoiesis of experimental animals has provided data on the activation of erythropoiesis and the presence of the leucocyte redistribution reaction in the peripheral blood. No pathological changes in the morphological composition of the peripheral blood were detected in patients with a deforming arthrosis and patients with gastric ulcer in the process of laser therapy. Favourable changes were noted. | |
| 6403624 | Detection of immune complexes by their complement-dependent binding to bovine conglutinin: | 1983 Mar 11 | A micromethod for the solid-phase conglutinin binding assay (Con BA) for the detection of circulating immune complexes (CIC) is described, in which the use of microplates, glucose oxidase-coupled anti-human immunoglobulins and automatic OD recorder contributed to the speed and low cost of this reproducible and sensitive test. The Con BA values of a large population of healthy blood donors had a wide distribution which in our series of 189 appeared to be trimodal. The Con BA values clearly reflected the levels of the main Ig classes (M, G, and A). This was confirmed by follow up of 6 individuals with high initial Con BA values. For 4 of them, a parallel decrease in Con BA value and IgG concentration was observed. In the 2 others, the sustained high level of Con BA remained unexplained. Complement components and activity of these sera were within normal limits. Because of fluctuation in the aggregated human gamma-globulins (AHG) reference curve, expression of results was based upon the standard deviation of 6 normal sera. In view of the above results, these sera were selected from those with the lowest Con BA values. On the basis that Con BA and C1q BA may detect CIC differing in their ag/ab ratio, sera from rheumatoid arthritis and chronic active B hepatitis patients with or without conventional rheumatoid factors (RF) were analyzed by both Con BA and C1q BA. RF-containing sera, likely to contain CIC in antigen excess, contributed exclusively to the highest C1q BA and lowest Con BA values. In contrast C1q BA-Con BA+ sera were preferentially RF negative. It is proposed that the complexes thus detected may be of idiotype-anti-idiotype nature. | |
| 6713771 | Disposition of and clinical response to salicylates in patients with rheumatoid disease. | 1984 May | The disposition of salicylic acid (SA) and its metabolites and the clinical response to long-term aspirin treatment at varying doses were assessed in patients with rheumatoid disease. Steady-state kinetics of SA (total and unbound), salicyluric acid (SUA), gentisic acid (GA), and clinical status were estimated weekly in 10 patients with rheumatoid arthritis. Eight received a soluble aspirin form and two received an enteric-coated form. The starting dose of aspirin in each patient was 1.8 gm (soluble) or 1.95 gm (enteric-coated) daily. Weekly increments in dose were made until a satisfactory clinical outcome was achieved. The final aspirin dose range was 3.6 to 8.1 gm daily, which resulted in mean steady-state plasma SA concentrations (CpSA) from 56 to 375 mg/l. Since the mean total CpSA increased approximately proportionately over the dose range, there was little change in total SA clearance. By contrast, increasing aspirin dosage resulted in decreased clearance and disproportionate increases in unbound SA (CpuSA). The maximum velocity of conversion of SA to SUA (Vm) increased significantly, from 57.3 +/- 11.7 mg/hr at an aspirin dose of 1.8 gm/day to 71.4 +/- 19.4 mg/hr at the next highest dose (2.7 to 3.6 gm/day), with no further change with increasing dosage. Km ranged from 0.4 to 1.2 mg/l for CpuSA and from 5.5 to 17.2 for total CpSA. Renal clearance of SUA (ClSUA) ranged from 124 to 893 ml/min and correlated with creatinine clearance. ClGA ranged from 23 to 164 ml/min, and ClSA ranged from 0.1 to 17.1 ml/min; neither correlated with creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 7015496 | [Which anti-inflammatory agents should be used in rheumatology?]. | 1981 Feb 21 | The principles governing the use of anti-inflammatory drugs in rheumatology are reviewed. Non-steroidal anti-inflammatory drugs and corticosteroids, either systemic or local, have a transient effect. On the other hand, treatments with basic medications such as gold salts of D-penicillamine induce prolonged beneficial action. They are, however, useful chiefly in rheumatoid arthritis but not in ankylosing spondylitis or variants, nor in gout or osteoarthrosis. The side effects and contraindications are described and discussed. | |
| 552296 | Plasma propranolol concentrations and the erythrocyte sedimentation rate. | 1979 Jul | 1. The plasma propranolol concentrations after a single oral dose of 40 mg were measured in 25 patients with rheumatoid arthritis and compared with those of 16 patients with Crohn's disease from a previous study. Thirteen healthy volunteers were used as controls. 2. In both diseases some high and some low values occurred. This scatter did not correlate with any symptoms or biochemical or haematological data other than with the erythrocyte sedimentation rate (ESR). 3. Both sets of patients were therefore separated into two groups depending on whether or not their ESRs were above or below 20 mm/l h. In both diseases the plasma propranolol concentrations of the patients with a raised ESR were significantly higher than the controls as well as those of the low ESR group. 4. In rheumatoid arthritis the plasma propranolol concentrations of the patients with a low ESR did not differ from those of the controls, but in Crohn's disease they remained significantly higher. 5. In one patient with Crohn's disease there was a dramatic rise in propranolol concentrations during an exacerbation (ESR 91 mm/l h) compared with those during a remission (ESR 20 mm/l h). 6. A difference in smoking habits did not seem to have been responsible for the difference in plasma propranolol concentrations. | |
| 385876 | Gold and modulation of the immune response. | 1979 | The effects of gold on immune responses are reviewed. Gold salts used therapeutically can be followed by a decline in serum immunoglobulin levels, and rheumatoid factor titers in rheumatoid arthritis; in pemphigus there is similarly a drop in anti-epithelial antibody titers. Gold inhibits stimulation of immunoglobulin-secreting cells. Gold inhibits the activation of the classical and alternate complement pathways. Gold compounds inhibit numerous cell-mediated immune responses to various mitogens and antigens. Inhibition may be due to the effect of gold on macrophages acting as helper cell in these reactions. Auranofin is a new oral compound which seems to be particularly potent in its immuno-regulatory actions; it differs from other gold compounds in its pharmacokinetics, and in the nature of its ligand. Gold has also been reported to enhance certain immune reactions. The extent of the immuno-regulatory effects of gold in vivo is unknown, and the relation of these effects to its therapeutic actions remains to be clarified. | |
| 6305039 | [A chemically induced polyneuropathy in chronic polyarthritis treated with D-penicillamine | 1983 Feb 4 | Polyneuropathy occurring during therapy with D-penicillamine is reported in a 63 year-old women with chronic rheumatoid arthritis. 6 weeks after recommending therapy with 500 mg D-penicillamine/day the patient developed bilateral oculomotor palsy and axonal peripheral neuropathy. The development of clinical symptoms was accompanied by the observation of high levels of antinuclear antibodies and antibodies against native DNA. The appearance of polyneuropathy after repeated administration of penicillamine, the regression of symptoms and the rapid decrease in antinuclear antibodies after discontinuation of the drug plus the absence of signs of a malignant form of rheumatoid arthritis show a remarkable correlation. | |
| 2409740 | Baseline and interferon-enhanced natural killer cell activity in rheumatoid arthritis. | 1985 Apr | Natural killer (NK) cell activity against the leukemia cell line K-562 was tested in 45 patients with rheumatoid arthritis (RA) who either had not received any remission-inducing drugs for more than 6 months or had received penicillamine for at least 6 months. Baseline NK cell activity and interferon (IF)-enhanced NK cell activity did not differ from that observed in 45 controls matched for age and sex, and neither NSAID (non steroidal anti-inflammatory drugs) nor penicillamine influenced NK cell activity. There was no correlation between NK cell activity and acute-phase reactants. | |
| 6877115 | Altered oligosaccharides as the initiating autoantigen in rheumatoid arthritis. | 1983 Apr | The linkage of rheumatoid arthritis (RA) to infection though vague has remained a persistent notion for the past fifty years. The hypotheses that streptococcus was responsible; then M. Pneumoniae; the implication of a viral pathogenesis and, more especially, the Epstein-Barr virus, have all not withstood the test of Koch's postulates. Today, autoimmunity holds the field in the pathogenesis of RA. We know in fair detail what happens after failure of self-recognition develops. Why does synovial tissue become antigenic? Altered receptors of cell surface may be the loci of change, namely, glycoproteins and glycolipids. A hypothesis is constructed based on alteration by viral DNA of these cell surface markers that are then recognized as alien. Evidence is drawn from insulin dependent juvenile diabetes, glomerulonephritis, and Landsteiner blood groups. The initial lesion may be initiated by an infectious agent leading to a chain of events, the first link constituting change of the specific glycoprotein or glycolipid of a cell to one of antigenic challenge, thus stimulating an autoimmune reaction. The ultimate destructive-proliferative sequences of RA are then set in motion. | |
| 7410829 | Inhibitory factor(s) of lymphoproliferation produced by synovial fluid mononuclear cells f | 1980 Sep | Synovial fluid (SF) and synovial fluid mononuclear cells (SFM) were obtained from patients with rheumatoid arthritis (R.A.). The SF stimulated normal blood monocytes for nitroblue tetrazolium (NBT) reduction and inhibited normal lymphocyte response to PHA. Similar activities were found in supernatants from the cultures of SFM cells. Molecular weight of the lymphocytes inhibitory factor(s) produced by SFM was in range 50,000 to 100,000. The factor exerted its inhibitory activity via monocytes and had no direct toxic or blocking effect on lymphocytes. Monocytes played an active role in suppression presumably via production of a second-step inhibitory signal(s). It is suggested that the monocytes activated by the SFM-produced factor(s) are in turn triggered on for suppression of lymphoproliferation. These studies implicate that the state of monocyte activation is important in the regulation of lymphocyte responsiveness. This model of suppression may provide some explanation for SF lymphocyte hyporeactivity to mitogens in R.A. | |
| 3892637 | Evaluation of plasma C3d and immune complex determinations in the assessment of disease ac | 1985 | Patients with rheumatoid arthritis, systemic lupus erythematosus, and spondylitis ancylopoetica were examined, along with healthy controls, for C3d plasma levels, circulating immune complexes, C3 serum levels, and CRP. Immune complexes were determined using a Clq binding assay, a 2.75% PEG precipitation technique, including the analysis of IgG and C3, and a new laser nephelometric latex test. C3d plasma levels were significantly (P less than 1%) elevated in all groups of patients as compared to controls. With regard to the demonstration of circulating immune complexes, the PEG precipitation method discriminated best between patients and the control population. It was not possible to differentiate between the different disease entities with neither C3d serum levels or immune complexes. Concerning the assessment of disease activity, none of the evaluated parameters alone appears to be of clinical relevance. The individual application of more than one immune complex assay in combination with the measurement of C3d serum levels must be recommended if disease activity is to be assessed. | |
| 682687 | Effect of aspirin on prevention of coronary and cerebrovascular disease in patients with r | 1978 Sep | Between 1950 and 1975, 473 Rochester patients had the diagnosis of rheumatoid arthritis and received aspirin treatment. These patients were followed for an average of 10 years to determine whether they experienced myocardial infarction, classic angina pectoris, sudden unexpected death, or cerebral infarction less often than expected on the basis of age- and sex-specific incidence rates of each event known for the Rochester population. In none of these disease entities, separately, or combined, was the expected number significantly different from the observed. However, when we examined these events separately by sex, observed numbers in males were 30 to 50% less than expected in all four studied end-events. Because the male population was small, none of these differences reached statistical significance. The possible effect of aspirin in the primary prevention of vascular disease in males is discussed in light of the recent similar reported results in secondary prevention. | |
| 6611230 | Interleukin-2 reverses deficient cell-mediated immune responses in rheumatoid arthritis. | 1984 Jul | The depressed cell-mediated immunity in rheumatoid arthritis was investigated in vivo by cutaneous hypersensitivity responses to seven antigens including tuberculin PPD, and in vitro by lymphocyte transformation to the latter antigen. In vivo 40% of rheumatoid patients were anergic compared to 2% of controls (P less than 0.001) with an associated reduction in sum score (5.9 +/- 6.5 vs 15.3 +/- 8.7, P less than 0.001). In vitro lymphocyte proliferation to PPD was also significantly depressed (P less than 0.001) and could not be reversed by indomethacin. A significant correlation between the in vivo sum scored (induration in mm) and in vitro thymidine incorporation (d/min) (r = 0.59, P less than 0.001) was found. In an attempt to overcome the depressed in vitro response the addition of a crude supernatant from a mixed lymphocyte reaction was found to return the PPD stimulated lymphocyte proliferation to the normal range. This effect was mimicked by purified IL-2 but not purified IL-1. The implications of this finding are are discussed. | |
| 1129092 | [Quantitative functional exploration of the salivary glands. Measurement of salivary elimi | 1975 Feb 8 | The authors propose a method for the quantitative functional exploration of the salivary glands using two objective criteria, on the one hand the level of fixation in the parotid of technetium 99m injected in the form of its pertechnate and on the other hand by the fraction of radioactivity found in different specimens of saliva collected in the course of a test carried out using a pharmacological agent free of toxic effects--lemon juice. The quantitative results obtained and its simplicity render the method particularly useful in evaluating the course of salivary function in all forms of disorder, pathological or iatrogenic. | |
| 7017914 | Proteolytic enzymes in joint destruction. | 1981 | An increase in both neutral and acid proteolytic activity and proteinase inhibitors is reported in synovial fluid of osteoarthrotic and rheumatoid joints, compared with controls, but in subchondral bone and articular cartilage only Cathepsin D and in synovial tissue only neutral caseinolysis were elevated. Especially high proteolytic activities were found in joint compartments of seronegative rheumatoid and in sera of osteoarthrotic patients. The source of the main part of neutral caseinolytic activity in joint fluid is inflammatory cells, in the case of Cathepsin D the tissues of origin seem to be bone and cartilage. | |
| 1080403 | Proteinase inhibitors in rheumatoid arthritis. | 1975 Jun | The concentrations of five normally occurring protease inhibitors in serum and synovial fluid were compared in patients with rheumatoid arthritis, osteoarthrosis, and normal controls. The patients with rheumatoid arthritis showed a significant rise in alpha1-antitrypsin, alpha1-antichymotrypsin, and inter-alpha-trypsin inhibitor (in decreasing order) in serum as well as in synovial fluid. In synovial fluid the inhibitors were present in their native form and bound to hyaluronate. A large molecular protein with immunological specificity of alpha1-antitrypsin, presumably a complex of alpha1-antitrypsin and a protease, could be shown in synovial fluid of all patients with classical and probable rheumatoid arthritis and not in that of the other subjects studied.23Author | |
| 61660 | [Differential-diagnostic and prognostic significance of antinuclear factors]. | 1976 Jan 1 | On the patients of the consulting point for rheumatic diseases of the policlinical institute of the Karl-Marx-University Leipzig analytic examinations of the course for the existence of the LE-cell factor were carried out. We used the loose-body-test after van Soeren as screening test, controlled positive test results for several times under the same experimental conditions and supplemented it by the LE-cell test after Zinkham and Conley or later on by the immune fluorescence test. All patients with positive proof of LE-cells were examined for reference signs concerning a visceral lupus erythematodes, in which cases at the beginning of the examination nobody fulfilled the criteria of the diagnosis of a visceral lupus erythematodes. We tested the constancy of the proof of the LE-cells as well as the diagnosis in the course of longer periods. Typical changes of a visceral lupus erythematodes were seen only rarely. In 2 patients the joint processes were concomitant symptoms of a chronic aggressive hepatitis. In the p.c.p. at stage II to IV with positive LE-cell factors in the first place must be thought of a proof of LE-cell factors induced by drugs. In these cases gold is of practical importance. We could confirm that in contrast to the typical active visceral lupus erythematodes in p.c.p. the antinuclear factors have only a weakly positive result and are above all inconstant. |