Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
2530015 Differences in the metabolism of C4 isotypes in patients with complement activation. 1989 Oct The metabolism of the C4 allotypes C4A3,B1 and C4A3,BO was studied in five healthy control subjects and six patients with active immunological disease (five with systemic lupus erythematosus and one with rheumatoid arthritis). The specific aim was to identify any differences in the metabolism of C4A and C4B gene products that may be linked to their documented functional differences in vitro. The fractional catabolic rate of C4A3,B1 in patients was significantly greater than that of C4A3,BO (3.98 +/- 1.37 versus 3.31 +/- 0.85%/h; mean +/- s.d.; P less than 0.05) but there was no difference in control subjects (1.95 versus 1.99%/h). The extravascular:intravascular (EV:IV) distribution ratio of C4A3,B1 was also greater in both patients (1.19 +/- 0.36 versus 0.97 +/- 0.35; P less than 0.01) and controls (0.43 +/- 0.11 versus 0.31 +/- 0.13; P = 0.01). We conclude that C4B1 was catabolized more rapidly than C4A3 in patients with pathological complement activation but not in control subjects. This difference could reflect the relatively greater extravascular distribution (i.e. EV:IV ratio) of C4B at sites of immune complex deposition or, alternatively, different rates of catabolism of inactive C4 isotypes (iC4b).
3476966 D-penicillamine effects on prostanoid production in adherent rheumatic synovial cells in p 1987 Jul The effect of D-penicillamine (DPA) on immunoreactive prostanoid concentrations was studied in a primary culture of adherent synovial cells from patients suffering from rheumatoid arthritis (RA). DPA in clinically achievable concentrations increased the levels of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) and reduced those of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthetized from endogenous substrate. The capacity for PGE2 and 6-keto-PGF1 alpha production in the presence of exogenous arachidonic acid was decreased by DPA. These effects may be connected with the antirheumatic and immunosuppressive action of DPA.
3522746 Development of an enzyme immunoassay for the quantitation of cellular antigen expression. 1986 Jul 11 An enzyme immunoassay is described which can be used to quantitate the cellular expression of antigens recognised by mouse monoclonal antibodies (mAb). To provide the sensitivity required, complexes of alkaline phosphatase and mouse monoclonal anti-alkaline phosphatase (APAAP) have been used. The speed and reproducibility of the assay was improved with the aid of immunofiltration methodology. Quantitative measurement of HLA-DR antigen expression by ELISA did not correlate directly with the number of mononuclear cells scored positive following immunohistochemical staining of cytocentrifuged preparations. In patients with rheumatoid arthritis, more HLA-DR was expressed on synovial fluid mononuclear cells than on the corresponding cells obtained from peripheral blood.
2110877 Parenteral methotrexate or gold for rheumatoid arthritis: a follow up. 1990 Mar The forty participants in a double blind controlled trial of parenteral methotrexate or gold for RA were followed up two years later. Fifty percent had remained on the original medication, 13/20 on MTX and 7/20 on gold. Only 5 and 3 of them respectively had no active joint swelling. No major differences between the two groups were seen.
3495241 Clinical implications of ribonucleoprotein antibody. 1987 May Out of 97 patients with circulating ribonucleoprotein antibodies, 44 (45%) satisfied the criteria for systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyositis, or rheumatoid arthritis. Forty-two (43%) of the 97 patients whose cases did not fulfill these criteria had at least two of the following three clinical manifestations: arthritis, Raynaud's phenomenon, and swollen or sclerotic fingers. A fifth of the latter group of patients had chronic, restrictive pulmonary disease or myopathy and two thirds had hypergammaglobulinemia, IgM rheumatoid factor, and sensitized epidermal nuclei. Few patients had hypocomplementemia. One patient had nephropathy. Most patients had an unchanged, benign disease course for, on the average, nine years. It is suggested that the term mixed connective tissue disease (MCTD) be reserved for such patients, and that the acronym MCTD be changed to SRA (swollen fingers, Raynaud's phenomenon, and arthritis). Treatment with glucocorticoids is necessary for only a minority of patients.
2962714 Radiologic manifestations of arthritides involving the foot. 1988 Jan This article has discussed the radiographic manifestations of several of the more common articular disorders affecting the foot. An organized, thoughtful approach to radiographic analysis in patients with articular diseases of the foot generally ensures accurate diagnosis. This approach requires knowledge of the classic morphologic features of each articular disease as well as its typical distribution in the foot. Using knowledge of radiologic-pathologic correlation and the target area approach to disease, the physician can make an accurate diagnosis in most instances.
2148643 T gamma delta cells in juvenile rheumatoid arthritis and rheumatoid arthritis. In the juve 1990 Dec Using the anti-TcR gamma/delta-1 monoclonal antibody and flow cytometry, we examined the number of T gamma delta cells in paired samples of peripheral blood and synovial fluid or tissue from 24 children with juvenile rheumatoid arthritis (JRA), five adult patients with JRA, and 14 patients with rheumatoid arthritis (RA). No significant difference was found in the synovial compartment T gamma delta values compared with the blood in JRA, adult JRA, or RA patients. Nor was any significant difference found in the peripheral blood or synovial compartment T gamma delta values in any of the three patient groups compared with the peripheral blood of normal controls. However, seven of the children with JRA had very high T gamma delta values in the synovial compartment while none of the normal children had high T gamma delta values in the blood (P = 0.02, Fisher's exact test). This may indicate a possible separate JRA patient group with high T gamma delta levels in the synovial compartment. In six JRA patients further analysed for T gamma delta subpopulations, a significant predominance of V delta 1+ cells was found in the synovial compartment compared with the corresponding peripheral blood samples (P less than 0.05, Wilcoxon's signed test) and with peripheral blood of child controls (P less than 0.05, Mann-Whitney U test). In these six patients, the T gamma delta-cell expression of the very early activation antigen CD69 were significantly higher (P less than 0.05, Wilcoxon's signed test) in the synovial compartment compared with the peripheral blood. Synovial T gamma delta cells expressing HLA-DR and interleukin 2 receptors could also be detected, in contrast to the peripheral blood in which no T gamma delta cells expressing these antigens could be found. These data suggest that the synovial T gamma delta cells had been activated in vivo.
3135129 Interaction between fibronectin and C1q in rheumatoid synovial fluid and normal plasma. 1988 Apr The interaction between fibronectin and C1q was studied in the presence of normal human plasma and rheumatoid synovial fluid by solid phase binding assay. Fibronectin-C1q binding occurred in the presence of rheumatoid synovial fluid but not in the presence of normal plasma. Binding was strongest at 4 degrees C and in the presence of EDTA. Fibronectin-C1q binding could be induced in the presence of normal plasma by hypotonicity, augmentation of the concentration of solution-phase fibronectin or by the addition of heat-aggregated IgG. The C1q present in rheumatoid synovial fluid bound to both aminoterminal collagen-binding and carboxyterminal noncollagen binding fibronectin fragments although binding to the aminoterminal fragment was stronger. The interaction between fibronectin and C1q in rheumatoid synovial fluid may modulate immune-complex deposition and complement activation in the inflamed joint.
3496056 Vitamin D metabolites in synovial fluid. 1987 May This study has shown that it is possible to measure vitamin D metabolites and vitamin D binding protein (DBP) in synovial fluid as well as serum. Significant amounts of 25-OHD, 24,25-(OH)2D, and DBP are present in synovial fluid. The 25-OHD and DBP maintain a serum:synovial fluid ratio of approximately 2:1 irrespective of the type of joint disease, whereas no such relationship was detected for 24,25-(OH)2D. The possible reasons for these findings are diffusion of the metabolites into synovial fluid or local production from suitable precursors, or both.
2944308 [Cutaneous side effects of gold therapy. Clinical and histologic results]. 1986 May Based on our own observations in 40 patients and a review of the literature the clinical and histological aspects of dermatitis caused by gold therapy are discussed. There is a broad spectrum of cutaneous side effects following gold therapy. In most of the patients a nonspecific dermatitis can be observed. The skin lesions may also mimic lichen planus, pityriasis rosea or various forms of eczema, obscuring early diagnosis. Histologically four types of reactions can be differentiated including a dermatitis type, vasculitis type, a lichenoid and an urticarial type.
1959733 [The experimental induction of rheumatoid factors of low affinity and cross reactivity wit 1991 Jan The study of the anti-nuclear cross reactivity of rheumatoid factors has shown differences between patients with rheumatoid arthritis and healthy seropositive subjects. This paper describes the finding, of a subpopulation of rheumatoid factor molecules which show a cross reactive idiotype and show high affinity for IgG and cross reactivity against histones in rheumatoid arthritis patients but not in healthy subjects. These molecules, in turn, were able to induce, experimentally, heterogeneous rheumatoid factor molecules that show a low affinity for IgG and cross-reactivity against nucleoproteins other than histones, most likely through idiotypic networks. The mechanism could be responsible for the diversification of serum autoantibodies found in rheumatoid arthritis.
3492837 [Epidemiologic aspects of disability caused by rheumatic diseases in the Gera district, Ea 1986 Sep In the period 1968-1977, the mean annual invalidization rates due to rheumatic diseases in the district of Gera are 36.6 for the female insured population, 19.3 for the male one, per 10(5) persons. After the age of 40, invalidization rates are rising steeply. Degenerative arthropathies (osteoarthroses and displacements of the intervertebral disk or vertebrogenic pain syndromes) constitute more than four fifths of all first-time invalidizations. First-time invalidization was done, on average, 7 years before reaching the age-limit provided by law for old-age pension, in one third temporally limited. The longitudinal monitoring of the invalidzation rates supports the hypothesis that clinical manifestations of degenerative arthropathies are increasing.
2637465 [The interleukin-1 activity in rheumatoid arthritis patients]. 1989 Oct In 25 healthy subjects and 47 patients with RA production of interleukin-1 was studied. Increase in the production of interleukin-1 in the supernatants of nonstimulated monocyte cultures was observed in RA patients and more frequently in patients with high activity of the inflammatory process.
3264162 Prostaglandin E2 modulation of rheumatoid factor synthesis. 1988 Dec We examined the influence of prostaglandin E2 (PGE2) on the in vitro synthesis of rheumatoid factor (RF) by purified human B and T lymphocytes stimulated with Staphylococcus aureus Cowan 1 or pokeweed mitogen (PWM). Supernatants were assayed for total IgM and RF. PGE2 at concentrations of 10(-7) M to 10(-9) M significantly inhibited RF and IgM secretion stimulated by S aureus Cowan 1, a cross-linker of B cell surface Ig. The magnitude of inhibition of RF production was significantly greater than that of total IgM at low PGE2 concentrations (P less than 0.05). In contrast, PWM-stimulated cultures were only minimally inhibited by PGE2 at all concentrations tested. Since cross-linking of surface Ig renders B cells more susceptible to inhibition by PGE2, heat-aggregated IgG (HAIgG) was added to the PWM-stimulated cultures in an attempt to increase the sensitivity of precursors of RF-secreting cells to the inhibitory effects of PGE2. Addition of HAIgG markedly increased PGE2-mediated inhibition of RF synthesis without significantly affecting IgM production. Inhibition could not be overcome by the addition of soluble T helper cell factors, indicating that PGE2-mediated suppression was not the result of an inhibitory action of T helper cells. When lymphocytes from patients with rheumatoid arthritis were examined, HAIgG was found to be unable to induce sensitivity to PGE2-mediated inhibition of responsiveness. These results suggest that down-regulation of RF synthesis requires both cross-linking of surface Ig and the influence of PGE2. Abnormalities in this immunoregulatory mechanism may explain the ongoing production of RF in patients with rheumatoid arthritis.
3964311 Enhanced phospholipase activity in peripheral blood monocytes from patients with rheumatoi 1986 Mar Peripheral blood monocytes (PBM) from patients with rheumatoid arthritis (RA) produce greater amounts of prostaglandins (PG) than do control cells. To further explore the reasons for the increased PG production, we assessed the phospholipase activities in these cells. We found that PBM from patients with severe RA expressed greater phospholipase A2 (PLA2) and phospholipase C (PLC) activities than did the control cells. Enhanced PLA2 activities were observed in RA patient cells when phosphatidylcholine (PC) or phosphatidylethanolamine (PE) were used as substrates. Enhanced PLC activities also were seen when PC, PE, and phosphatidylinositol (PI) were used as labeled substrates. Increased PLC activity was observed whether linoleic acid or arachidonic acid was esterified to the 2 position of the phospholipid substrate used. Because all patients with RA were treated with nonsteroidal antiinflammatory drugs, we examined the effects of aspirin ingestion on phospholipase activities. Aspirin had no consistent effect on PLA2 activities but markedly inhibited PLC activities against PC, PI, and PE with arachidonic acid in the R2 position. That aspirin enhanced PLC activities against PC and PI with linoleic acid in the R2 position, suggests that PLC activity may be regulated in part by the R2 fatty acid. Our results indicate that increased phospholipase activities exhibited by PBM from RA patients may help explain the increased PG production by these cells. The increased phospholipase activities in PBM from RA patients do not appear to be due solely to nonsteroidal antiinflammatory drug therapy.
2279417 Our experience in occipito-cervical fusion. 1990 Apr Occipito-cervical fusion for congenital and post-traumatic anomalies of the axis was used to treat 5 patients; the results obtained are analyzed. The authors also discuss the advantages of using autoplastic bone graft which remains stable in time, without creating disabling sequelae in the patient.
3113811 Production of prostanoids by rheumatic synovial cells in vitro: effects of anti-inflammato 1987 Jun To evaluate the role of prostanoids in rheumatoid arthritis the effects of anti-inflammatory drugs on prostanoid concentrations and their ratios were studied in a primary culture of adherent synovial cells from patients with rheumatoid arthritis. Cells from rheumatoid synovium have a great capacity for prostanoid production. PGE2 is the main prostanoid but synovial cells are also capable of producing 6-keto-PGF1 alpha and PGF2 alpha. There were also very low TxB2 concentrations in the culture medium after incubation. All nonsteroidal anti-inflammatory drugs used (diclofenac, indomethacin and tolfenamic acid) reduced markedly, in concentrations achieved therapeutically (greater than or equal to 0.13 mumol/l), the production of all the prostanoids from endogenous substrate. There were no differences in the efficacity of the drugs. Hydrocortisone was needed for higher concentrations to inhibit PGE2, 6-keto-PGF1 alpha and PGF2 alpha production. TxB2 formation remained almost unaltered. After the drug incubation there were also clear alterations in the ratios between these prostanoids, which may have therapeutic importance. It is suggested that this kind of synovial cell culture can be used for testing the effects and mechanisms of different anti-inflammatory drugs in standardized cell culture conditions.
2946328 [Antilymphocytic antibodies in human diseases as a factor decreasing the functional activi 1986 Nov 157 sera from adults and children with rheumatoid arthritis, rheumatic fever, myocarditis, neurodermatitis, bronchial asthma, wound infections, second degree obesity without symptoms of diabetes were examined. 60% of sera contained high concentrations of antibodies possessing cytotoxicity against thymus cells, but not against bone marrow cells. Sera of healthy children and adults contained no cytotoxic antibodies. Sera cytotoxic against mouse thymus cells inhibited the suppressing activity of mouse splenocytes in experiments on syngeneic transfer, reducing the ability of human lymphocytes to form T-RFC. The latter phenomenon is associated with the decline in the number of T-theophylline-sensitive lymphocytes, known as T-suppressors.
3325903 [Physiopathology of the mechanism of activation of neutrophils: a future pathway?]. 1987 Dec Numerous agonists such as chemotactic factors, phorbol esters, calcium ionophores, arachidonic acid or particles induce a cascade of events associated to oxygen reduction, the oxidative burst, in phagocytes and specially in neutrophils. Diverse transductional pathways involved in the oxidative burst were described. Moreover, various pathologies of the transductional pathways in different cell systems were recently observed. We think that the study of neutrophils constitutes first an excellent model of Cell Biology and second a putative model of the physiopathology of the transductional pathways.
1851410 Activation of the neutrophil myeloperoxidase-H2O2 system by synovial fluid isolated from p 1991 Apr Synovial fluid isolated from 16 patients with rheumatoid arthritis activated luminol dependent chemiluminescence in bloodstream neutrophils, and the maximal activity stimulated varied over a 50-fold range. In contrast, these same fluids only activated a much lower range (two- to threefold) of maximal rates of lucigenin dependent chemiluminescence and cytochrome c reduction, two assays which only measure oxidant secretion which is independent of myeloperoxidase. Over 95% of the luminol dependent chemiluminescence activated by all samples was inhibited by azide (indicating its dependence upon myeloperoxidase), but anti-(myeloperoxidase) IgG (which specifically inhibits only the extracellular activity of this enzyme) only inhibited the response stimulated by some samples: those fluids which activated the highest luminol dependent chemiluminescence also stimulated the greatest activity of an extracellular myeloperoxidase-H2O2 system. A clear correlation was shown to exist between the activity of myeloperoxidase already present in the fluids (after its secretion from neutrophils in situ within the rheumatoid joint) and the ability of the fluid to activate luminol dependent chemiluminescence. It is concluded, therefore, that all synovial fluid samples tested possess almost equivalent levels of a factor(s) which activated O2-/H2O2 secretion and that the variations in the measured activity of the extracellular myeloperoxidase-H2O2 system are dependent upon the level of degranulation which had occurred within the joint.