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

ID PMID Title PublicationDate abstract
3559589 A clinical and radiographic analysis of loosening of total knee arthroplasty components us 1986 Patients undergoing bilateral, simultaneous total knee replacement provide a unique opportunity to study the role of operative techniques in the development of radiolucent lines because variables such as age, sex, weight, diagnosis, and bone quality are internally matched when the result on one side is compared with that of the other. This allows more conclusive examination of operative factors, such as component alignment, level of tibial bone resection, and cement handling. With this as the objective, the clinical and radiographic results of the first 50 bilateral total knee replacements performed by the senior author were studied. Postoperative alignment was found to influence significantly the incidence of tibial radiolucent lines. Use of cement to reconstruct defects in the proximal tibia resulting from preoperative deformity consistently led to the development of radiolucent lines in the area of the defect. There was also indirect evidence that failure to achieve an intimate microinterlock at the bone-cement interface may play a major role in the development of tibial radiolucent lines.
1690683 Antibodies to type II collagen in SLE: a role in the pathogenesis of deforming arthritis? 1990 Feb The role of autoimmunity to type II collagen in the arthritis of systemic lupus erythematosus (SLE) has been assessed by ELISA and by Western blotting cyanogen bromide cleavage fragments separated on SDS-PAGE. The results show that antibodies to both native and heat-denatured collagen are quite common in SLE when measured by ELISA. Of particular interest is the demonstration of an association between antibodies to the CB 11 peptide and deforming arthritis in SLE. This is the arthritogenic peptide in murine models of collagen II-induced autoimmune arthritis and the results presented here suggest a potential pathogenetic role in the deforming arthritis of SLE for this specific subset of antibodies to type II collagen.
1996201 [Secondary membranous glomerulonephritis]. 1991 Jan 20 Following 689 percutaneous renal biopsies, membranous glomerulonephritis was proved in 68 patients. In 16 (23.5%) an underlying primary disease was verified, and thus the glomerulonephritis the secondary form. The primary disease was SLE in 5 cases, diabetes mellitus in 5 cases, rheumatoid arthritis in 3 cases, chronic active hepatitis in 2 cases, an ulcerative colitis and eosinophilic angiolymphoid hyperplasia in 1 patient. As initial sign, nephrotic syndrome emerged in 87.5% of the 16 cases. Microscopic haematuria was observed in half of the patients, as was hypertension, while acute renal failure presented in only 1 case. Histologically, in 13 cases the predominance of early glomerular alterations was characteristic, while in 9 cases the picture proved to be equivocal and accompanied by some degree of interstitial alterations. During combined treatment, remission was achieved in 75%. Two patients with SLE died, but not as a consequence of renal failure. Transient side-effects of the treatment were registered in 5 cases. The principal pathogenetic and clinical differences between the individual secondary nephritis forms, and the difficulty of their differentiation from the idiopathic cases, even on repeated examination, are emphasized. In 3 patients the possibility of secondary renal processes was suggested by the histological picture, and this was proved by the detailed clinical findings.
1978639 Thrombocytopenia due to aurothioglucose, sulphasalazine, and hydroxychloroquine. 1990 Oct A 56 year old woman with rheumatoid arthritis developed relapsing thrombocytopenia during successive treatments with aurothioglucose, sulphasalazine, and hydroxychloroquine. The presence of IgM or IgG antibodies or immune complexes reactive with autologous platelets could not be shown. Relapsing thrombocytopenia may indicate a genetically determined HLA-DR3 and B8 aberrant immunological response to stimuli such as certain second line drugs.
2049578 Interleukin-6 activity in paired samples of synovial fluid. Correlation of synovial fluid 1991 Jun Paired synovial fluid (SF) samples obtained from the knees of 12 arthritis patients were studied to establish a relation between parameters of local inflammatory activity and SF interleukin-6 (IL-6) levels. Local disease activity was scored using joint temperature, swelling and pain as clinical parameters of inflammation. SF samples were assayed for laboratory parameters of inflammation such as leucocyte content, the percentage polymorphonuclear cells, the pH, and for immunoglobulin levels (IgG, IgM). SF IL-6 concentrations were determined using the B9-bioassay. Within individual patients the local activity of inflammation as measured using clinical parameters was found to be related to the local SF IL-6 level. When considering the total group of patients, a correlation (P less than 0.001) was found between the clinical parameters of local inflammation and the SF IL-6 levels. Furthermore, IL-6 levels were found to correlate with leucocyte counts (P less than 0.02), the percentage of polymorphonuclear cells (P less than 0.10), the pH value (P less than 0.01), but not with SF IgM and IgG concentrations.
1822334 Serum zinc, copper and selenium in rheumatoid arthritis. 1991 Dec Rheumatoid arthritis (RA) is characterized by low serum Zn and high serum Cu. In multiple linear regression both were explained by disease activity parameters. It is suggested that interleukin-1 causes both changes by 1) increasing the metallothionein-mediated hepatic uptake to serum Zn and 2) upregulating ceruloplasmin (acute phase reactant) gene and synthesis in liver and subsequently the level of ceruloplasmin-Cu complexes in the blood. Cu absorption was diminished by zinc intake. Cu- and Zn-dependent erythrocyte SOD was increased in RA. In contrast to plasma GSHPx serum selenium was low in RA and this was associated with disease activity parameters.
3258384 Association between DR antigens, rheumatoid arthritis with and without extraarticular feat 1988 Jan Seventy-two patients with rheumatoid arthritis (RA) and 18 with systemic lupus erythematosus (SLE) were typed for HLA class I and II antigens. No association was found with any of the antigens tested. However, B8 and DR3 were increased in patients with extraarticular features (EAF), while DR1 was increased in those with RA without EAF. In SLE a trend towards an increased frequency of DR7 was observed. DR5 was the negative marker in both diseases. Our results confirm the peculiar genetic characteristics in our population.
3011666 Oxygen radical production by neutrophils from patients with bacterial infection and rheuma 1986 Jun The production of three kinds of oxygen radicals (superoxide, hydrogen peroxide, and hydroxyl radicals) by neutrophils from patients with bacterial infection or rheumatoid arthritis was measured. The stimulators used in this study were opsonized zymosan (1 mg/ml), phorbol myristate acetate (20 ng/ml), A23187 (1 microM), and platelet activating factor (1 microM). Oxygen radical production by neutrophils from patients with rheumatoid arthritis was not significantly different from that of the control group. Hydrogen peroxide production by the neutrophils from patients with bacterial infection was significantly enhanced by only opsonized zymosan, but the production of the other kinds of oxygen radicals was not. Cytochalasin B reduced the production of hydrogen peroxide induced by opsonized zymosan more markedly than that of any other kind of oxygen radical. The measurement of hydrogen peroxide is suggested to be the most accurate indicator of the enhancement of intracellular production of oxygen radicals by neutrophils during infection.
2968502 Distribution of IgG subclasses among human autoantibodies to Sm, RNP, dsDNA, SS-B and IgG 1988 The IgG subclass distribution of human autoantibodies to Sm, double-stranded DNA (ds-DNA), ribonucleoprotein (RNP), SS-B (La), and IgG rheumatoid factor (RF) have been determined using sensitive ELISA or by indirect immunofluorescence on Crithidia lucilia in sera from patients with systemic lupus erythematosus (SLE), Sjögren's syndrome, and rheumatoid arthritis. For anti-Sm and anti-RNP, IgG1 was the predominant isotype. For anti-ds-DNA and anti-SS-B, IgG1 and a lesser contribution of IgG3 was found. In contrast, IgG1 and IgG4 were the predominant isotypes of human IgG RF. The preponderance of isotypes noted for these autoantibodies did not extend to the IgG subclass distribution for antibodies to trinitrophenol-bovine serum albumin (TNP), tetanus toxoid (Tet. tox.), pneumococcal polysaccharides (Pneumo), and group A streptococcal cell walls (Strep.). The restriction of human humoral responses as well as autoantibodies has both pathogenetic and immunoregulatory implications, and suggests that for these autoantibodies, T-cell-dependent responses, probably driven by antigen, are of importance.
1825059 T cell receptor delta diversity of freshly isolated T lymphocytes in rheumatoid synovitis. 1991 Jan In some patients with rheumatoid synovitis the distribution of V delta gene families used by freshly isolated T lymphocytes from the synovial fluid and peripheral blood is different: peripheral blood T lymphocytes preferentially use the V delta 2 gene segment, whereas the majority of synovial fluid T lymphocytes use the V delta 1. The antigenic diversity of T cell receptor gamma/delta is mainly dependent upon base sequences in the V-J junction. In the present study we investigated whether the synovial fluid T lymphocytes expressing the V delta 1 gene segment were derived from a polyclonal or monoclonal expansion. The sequences encoding the V-J junctions of 11 cDNA clones derived from the synovium of two patients with chronic arthritis were determined. Our data demonstrate that the V delta 1 cDNA clones have different V-J junction sequences. This indicates that the V delta 1-expressing T cells found in the synovial compartment are polyclonally expanded.
3489009 Specific bioactivities of monocyte-derived interleukin 1 alpha and interleukin 1 beta are 1986 Sep In this report we compare the bioactivities of pure, human monocyte-derived interleukin 1 (IL-1) alpha and beta in the standard murine thymocyte proliferation assay, a human dermal fibroblast proliferation assay, and in an assay measuring stimulation of prostaglandin E2 (PGE2) release from human rheumatoid synoviocytes. In each case the different species of IL-1 produced saturable stimulation and gave similar dose response curves. Half-maximal stimulation was observed at average IL-1 concentrations of 29 pM in the thymocyte assay, 2 pM in the dermal fibroblast proliferation assay, and 5 pM in the synovial cell assay. Our results show that native, monocyte-derived IL-1 alpha and IL-1 beta are both potent stimulators of connective tissue cells and that the specific bioactivities of these molecules are similar to each other in tests on human connective tissue cells, as well as on murine lymphoid cells.
2792744 Affective, substance use, and anxiety disorders in persons with arthritis, diabetes, heart 1989 Sep The authors estimated the sex- and age-adjusted prevalence of affective, substance use, and anxiety disorders in persons in a general population sample who identified themselves as having arthritis, diabetes, heart disease, high blood pressure, chronic lung disease, or no chronic medical conditions. Persons who reported ever having arthritis, heart disease, chronic lung disease, or high blood pressure had a significantly increased adjusted prevalence of each of the three groups of lifetime psychiatric disorders, relative to a no-chronic conditions comparison group (each p less than 0.05). Persons who ever had diabetes had an increased adjusted prevalence of lifetime affective and anxiety but not substance use disorder. Persons with current (i.e., active) arthritis, heart disease, or high blood pressure had a significantly increased adjusted prevalence of recent (6-month) anxiety disorder, whereas those with current chronic lung disease had an increased adjusted prevalence of recent affective and substance use but not anxiety disorder.
2925731 Deep vein thrombosis after total hip replacement. A comparison between spinal and general 1989 Mar The effect of hypobaric spinal anaesthesia or narcotic-halothane-relaxant general anaesthesia on the incidence of postoperative deep vein thrombosis was studied in 140 elective total hip replacements in a prospective randomised manner. Deep vein thrombosis was diagnosed using impedance plethysmography and the 125I fibrinogen uptake test, combined, in selected cases, with ascending contrast venography. The overall incidence of deep vein thrombosis was 20%. Nine patients (13%) developed deep vein thrombosis in the spinal group and nineteen (27%) in the general anaesthetic group (p less than 0.05). The incidences of proximal thrombosis and of bilateral thrombi were also less with spinal anaesthesia than with general anaesthesia. It is concluded that spinal anaesthesia reduces the risks of postoperative thromboembolism in hip replacement surgery. The presence of varicose veins, being a non-smoker and having a low body mass index were associated with an increased incidence of deep vein thrombosis.
2721541 Influence of renal failure, rheumatoid arthritis and old age on the pharmacokinetics of di 1989 The single-dose plasma kinetics of diflunisal was studied in healthy young and old subjects, in patients with rheumatoid arthritis, and in patients with renal failure. The plasma and urine kinetics of the glucuronidated metabolites of diflunisal were studied in the healthy elderly subjects and in the patients with renal failure. In addition, the multiple-dose plasma kinetics of diflunisal was assessed in healthy volunteers and in patients with rheumatoid arthritis. After a single dose of diflunisal the terminal plasma half-life, mean residence time and apparent volume of distribution were higher in elderly subjects than in young adults. No difference was observed in any pharmacokinetic parameter between age-matched healthy subjects and patients with rheumatoid arthritis. The elimination half-life of unchanged diflunisal was correlated with the creatinine clearance (r = +0.89) and its apparent total body clearance exhibited linear dependence on creatinine clearance (r = +0.78). In patients with renal failure, the terminal plasma half-life and mean residence time of diflunisal were prolonged. The renal and apparent total body clearances were lower, the mean apparent volume of distribution was higher and the mean area under the concentration-time curve extrapolated to infinity (AUC) was greater in the renal failure patients than in controls. The plasma concentration of the glucuronidated metabolites rapidly rose to levels above those of unchanged drug in renal patients, whereas they were lower than those of unchanged diflunisal in controls. The AUC (0-96 h) of diflunisal glucuronides in the patients was four-times that in controls, and the terminal elimination half-life of the glucuronides was prolonged in them. The renal excretion and clearance of diflunisal glucuronides were reduced when renal function was impaired. After multiple dosing, the pre-dose steady-state plasma-concentration increased with decreasing creatinine clearance (r = -0.79). When the plasma concentration exceeded 200 mumols.l-1, the elimination half-life was doubled, due to partial saturation of diflunisal conjugation. This finding suggests that lower doses could be used in long-term treatment. Thus, old age and arthritic disease appear to have little influence on the kinetics of diflunisal in the absence of renal functional impairment. Ordinary doses can be given for short term treatment of elderly patients with or without RA. In patients with renal failure, however, reduced doses of diflunisal are recommended.
3238351 Molecular mimicries between human IgG, IgM rheumatoid factor and streptococcal IgG Fc rece 1988 A monoclonal IgM rheumatoid factor (RF) from a patient with mixed essential cryoglobulinaemia was found to bind to type M15 group A streptococci with high affinity. The reaction was exerted via the antibody combining sites since it was inhibited by F(ab')2 fragments of anti-idiotypic (Id) antibodies but not by F(ab')2 of anti-IgMFc or normal rabbit IgG. The streptococcal strain also possessed receptors for the Fc part of IgG. IgMRF and IgG attached to different sites on the streptococcal surface, since e.g. anti-Id did not inhibit the IgG Fc-receptor binding. Furthermore, it was found that the interaction between the streptococcal IgG Fc receptor and IgG--like the RF/IgG interaction--took place in the interface between C gamma 2 and C gamma 3 and that histidine 435, tyrosine 436 and/or one both of histidine 433 and 310 were involved.
2948255 Evidence for common antigens on human non-adherent synoviocytes (type A) and peripheral mo 1986 Sep The characterization of a homogeneous non-adherent synoviocyte (Type A) cell population (greater than or equal to 95%) from non-rheumatoid patients by culturing the cells in the presence of forty percent foetal calf serum is reported. These cells were able to phagocyte latex beads, iron particles, fluoresceinated zymosan and yeast. Furthermore, non-adherent synoviocytes were capable of being infected by the obligate intracellular parasite of peripheral monocytes Leishmania donovani. Indirect immunofluorescence experiments with specific anti-human monocyte (OKM1) antibody and specific antisynoviocyte serum, showed the presence of common surface structures between synoviocytes A cells and peripheral monocytes. Fifty five percent of the synoviocytes were also positive for HLA Dr antiserum. Analysis by two dimensional gel electrophoresis showed that peripheral monocytes and synoviocytes secreted identical polypeptides in vitro. These results strongly suggest a relationship between synoviocytes A and mononuclear phagocyte system.
3500825 Follow-up study of Reiter's disease and reactive arthritis. Factors influencing the natura 1987 Sep The acute clinical picture and long-term prognosis of 160 patients with Reiter's disease (RD), and 144 patients with reactive arthritis triggered by yersinia infection (YA), was analysed. Most of the patients with RD were men, while YA was as common among male and female patients. YA manifested in a third of patients as incomplete or complete RD. The long-term prognosis in RD was less favourable than in YA. Recurrent arthritis, development of chronic destructive arthritis and radiologic sacroiliitis were more frequent in RD than in YA. The presence of HLA-B27 was the major factor determining extra-articular inflammatory symptoms and the development of chronic problems.
1862246 Dietary omega-3 fatty acids: effects on lipid mediators of inflammation and rheumatoid art 1991 May Dietary supplementation omega-3 polyunsaturated fatty acids may inhibit (at least partially) three pathways of the synthesis of lipid mediators of inflammation: the platelet-activating factor synthesis pathway, the cyclooxygenase pathway, and the 5-lipoxygenase pathway. In addition, selected cellular functions of polymorphonuclear neutrophils may be modulated by dietary fish oil. The exact mechanism of the effects of dietary supplementation with omega-3 poly-unsaturated fatty acids on these pathways is not completely elucidated; it is quite probable that the effects will vary with the duration, dose, and composition of the omega-3 polyunsaturated fatty acid preparation, with background medical therapy, and the presence of and degree of activity of the underlying inflammatory disease state.
1816217 Double blind, placebo controlled trial on the cytoprotective effect of misoprostol in subj 1991 Dec Ninety arthritic patients were randomly allotted to receive misoprostol 200 micrograms thrice daily or placebo, for 4 weeks, while they were started on various NSAIDs. While upper gastrointestinal symptoms occurred equally in both groups, patients on placebo had significantly more post-therapy abnormal endoscopy findings. Misoprostol was well tolerated without any adverse side effects; it did not interfere with the therapeutic efficacy of the NSAIDs. Arthritic patients requiring long term NSAID therapy appear to benefit from misoprostol because of its cytoprotective effect on the gastrointestinal mucosa.
2820052 Decreased NA+, K+-ATPase activity in erythrocyte membrane from rheumatoid arthritis patien 1987 The activity of the plasma membrane Na+/K+-ATPase and cellular sodium (Nai) and potassium (Ki) content were analysed in RBCs from 15 rheumatoid arthritis (RA) and 30 reference subjects (11 healthy controls, 12 osteoarthritis and 7 gouty patients). Na+/K+-ATPase activity was determined by measuring the inorganic phosphate (Pi) released by incubation in a reaction medium in the presence and absence of K ions or ouabain. Nai and Ki were measured with an ion-selective electrode analyser on the hemolysates, after washing the RBCs in 110 mM MgCl2. The Na/K-ATPase activity was significantly lower in RA patients than in both healthy controls and patients with osteoarthritis or gout. A slight but significant increase in Nai was observed in rheumatoid subjects. It is hypothesized that the decrease in the Na+/K+-ATPase activity in RA may be the result of a defective expression of membrane proteins, which is probably related to the altered cell sensitivity observed.