Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2290090 | Tissue response in relation to type of wear particles around failed hip arthroplasties. | 1990 Dec | To establish the types of wear particles and associated tissue response around human prostheses the periprosthetic tissues around 50 hip arthroplasties revised for aseptic loosening of one or more components were examined by light microscopy, transmission electron microscopy, and energy-dispersing x-ray microanalysis. The tissues around cementless metal-on-bone and ceramic-on-ceramic prostheses contained few or no prosthesis wear particles. The tissues around metal-on-metal prostheses contained large numbers of metal particles and large numbers of macrophages, and occasional multinucleate giant cells. The tissues around cemented metal-on-polyethylene prostheses often contained large numbers of small and large polyethylene particles, variable numbers of cement particles, and occasional metal particles. Large numbers of macrophages and multinucleate giant cells were frequently seen in these tissues. Lymphocytes were occasionally seen in association with metal particles. Ultrastructural studies of the periprosthetic tissues confirmed the phagocytosis of submicroscopic wear particles by macrophages. Varying degrees of degenerative change in macrophages were seen in association with phagocytosis of metal particles. Large numbers of cytolysosomes were seen in cells in association with the accumulation of wear particles. | |
| 2836500 | A novel pathway of human T lymphocyte activation. Identification by a monoclonal antibody | 1988 Jun 1 | Substantial evidence indicates that compartmentalized infiltrates of T lymphocytes are central to the pathogenesis of autoimmune diseases such as rheumatoid arthritis, but the mechanisms by which such cells become activated remain unknown. To define surface components of activation pathways important in the function of these cells, we have generated mAb against a rheumatoid synovial T cell line. One such antibody, termed anti-UM4D4, reacts with an Ag, termed UM4D4, which is strongly expressed on most rheumatoid synovial T cell lines and clones, and on a subset of peripheral blood T cells, resting or activated. Anti-UM4D4 is mitogenic in soluble form for PBMC and certain T cell clones, and is comitogenic with the phorbol ester PMA for purified resting T lymphocytes. These functional effects are similar to those previously observed with antibodies to epitopes of CD2 and CD3, surface Ag involved in two well defined pathways of human T cell activation. Binding of anti-UM4D4 to T cells is not, however, blocked by antibodies directed at various epitopes of CD2 and CD3. Moreover, UM4D4 does not comodulate with CD3, and is expressed on a T cell line that lacks CD2, CD3, and CD28. The data, therefore, indicate that anti-UM4D4 identifies a T cell activation pathway, distinct from those previously described, that could play a role in the pathogenesis of T cell-mediated autoimmune diseases. | |
| 1790625 | Clinical analysis in intact erythrocytes using 1H spin echo NMR. | 1991 Sep 14 | A new method of clinical analysis based on 1H spin echo NMR spectroscopy is presented. It is capable of providing information on six metabolites within viable erythrocytes, directly and without any preparative procedures prior to analysis except for cell separation and washing. Erythrocytes from patients with rheumatoid arthritis and Graves' disease are compared with cells obtained from healthy volunteers. The NMR detectable species in the cytosol of the cells are glutathione, ergothioneine, choline, creatine, glycine, lactate and to a lesser extent alanine and valine. Significant differences are observed between the ergothioneine pools in the rheumatoid group (P less than 0.01) compared to the control group. The glutathione: di-glutathione ratio can be assessed from the ratio, g2 to g4, taken from different signals in the glutathione molecule. The total concentration of glutathione present is easily assessed qualitatively but is more difficult to quantitate. | |
| 1700673 | Synovial fluid concentration of five different cytokines in rheumatic diseases. | 1990 Sep | Interleukin-1 beta, interleukin-2, tumour necrosis factor alpha, and the interferons, alfa and gamma, were measured concurrently in synovial fluid samples from 68 patients with rheumatic diseases. Mean interleukin-1 beta concentrations (130.3 (SD 22) pg/ml) were higher in synovial fluids from patients with rheumatoid arthritis (RA) than in those from patients with osteoarthritis (27.8(4.5)pg/ml), while measurements in synovial fluids from patients with seronegative spondarthritis were intermediate (72.7 (32) pg/ml). Interleukin-2 and tumour necrosis factor alpha concentrations were lower in the inflammatory arthropathies (RA: 4.5 (0.6) U/ml, 0.39 (0.04) ng/ml; seronegative spondarthritis: 3.1 (0.3) U/ml, 0.33 (0.03) ng/ml respectively) than those in patients with osteoarthritis (5.2 (0.6) U/ml; 0.05 (0.04) ng/ml). Interleukin-2 and tumour necrosis factor alpha concentrations correlated in all groups (r = 0.7), as did the interferons alfa and gamma (r = 0.7). There was no relation between interleukin-1 beta and either interleukin-2 or tumour necrosis factor alpha, or between the interferons and any other cytokine. Several distinct cytokine patterns were noted. Synovial fluids from two non-arthritic subjects were also examined: interleukin-1 beta concentrations were low, but concentrations of the other cytokines were higher than those seen in most arthritic fluids. | |
| 1747947 | Detection of IL-2 at mRNA and protein levels in synovial infiltrates from inflammatory art | 1991 Dec | A non-radioactive in situ hybridization method for IL-2 mRNA detection based on the use of four biotinylated oligonucleotide probes, plus appropriate positive and negative control probes was developed and applied to synovial surgical and needle biopsies from rheumatoid arthritis (RA), spondyloarthropathy (SpA), psoriatic arthritis (PsA) and juvenile chronic arthritis (JCA) patients. In eight surgical biopsies (six RA, one SpA, one PsA) this non-radioactive system showed similar sensitivity to that of a previously described 32P-labelled probe system, and in addition detected IL-2 mRNA in five out of seven biopsies from SpA and PsA patients and in two out of two JCA needle biopsies. IL-2 mRNA was found in the absence of IL-2 protein in RA biopsies (six surgical, 12 needle), but variable amounts of IL-2 protein were detected in six out of seven needle biopsies from SpA, PsA and JCA patients, where CD3+ lymphoid infiltrates were present. These data suggest differences in IL-2 regulation and expression in RA and non-RA inflammatory arthropathies. | |
| 1756584 | Adult-onset Still's disease. | 1991 Aug | Adult onset Still's disease seems to be the adult form of Still's disease in children. The key symptoms of the disease are high spiking fever, arthritis and a macular or maculopapular, salmon-pink evanescent rash, almost always accompanied by neutrophilic leukocytosis and frequently by sore throat, intense myalgias, lymphadenopathy, splenomegaly and signs of serositis. Tests for IgM rheumatoid factor and antinuclear antibody are characteristically negative. With respect to haematologic abnormalities, the disease may give rise to several problems. First, there is a neutrophilic leukocytosis, which currently is unexplained, and often a normocytic normochromic anaemia, that may be profound. The anaemia has the characteristics of anaemia of chronic inflammatory disease. Both abnormalities disappear after effective treatment of the disease or at spontaneous remission. Secondly, there might be a problem to differentiate AOSD from malignant haematological disorders, including malignant lymphoma and leukaemia, especially when the picture is dominated by lymphadenopathy, splenomegaly, fever and leukocytosis. Although in rare cases the differential diagnosis is extremely difficult, diagnosis can mostly be made or excluded by peripheral blood smear staining, bone marrow biopsies and occasionally lymph node biopsy. Finally, like the juvenile counterpart, AOSD is occasionally complicated by sometimes life-threatening diffuse intravascular coagulation. Factors that might be important in the development of this complication include severe disease activity, liver abnormalities and particular drugs including salicylates, other NSAIDs and some slow-acting antirheumatic drugs. Prompt therapy, including withdrawal of the drug, corticosteroids and sometimes anticoagulant therapy have been successfully applied to most patients. | |
| 3501097 | Acute and chronic pain in hemophilia. | 1987 Dec | The present study compared acute vs. chronic pain in hemophiliac subjects who suffer both types of pain. Characteristics of the acute pain produced by a hemorrhage into a joint and the chronic arthritic pain that results from repeated bleeding episodes were assessed with the McGill Pain Questionnaire and a visual analogue pain intensity scale. The results showed a high degree of similarity in the sensory, affective and evaluative properties of the two types of pain. The main difference between the acute and chronic pains was one of overall intensity, with the acute pain generally being described as more intense. A comparison of the arthritic pain in hemophilia with the pain of other arthritic disorders revealed no major differences. Sources of inter-individual variability were also explored and the results showed that the pain scores in hemophiliac subjects were largely unrelated to demographic and pain history variables. However, significant differences were observed in the way French- and English-speaking subjects described and rated their pain. Irrespective of the origin of their pain, French-speaking subjects characteristically rated their pain as more intense and more affectively laden than the English group. These results demonstrate that ethnocultural factors associated with language affiliation may contribute to inter-individual variation in pain perception. | |
| 1967122 | Mechanisms of immune injury in rheumatoid arthritis: evidence for the involvement of T cel | 1990 Dec | Evidence for the involvement of T cells, especially CD4+ T cells, in the pathogenesis of RA is substantial and includes 1) the correlation between prolonged CD4+ T-cell depletion and improvement in joint disease in the absence of observable changes in the levels of autoantibodies (rheumatoid factors) in the blood and joints, 2) the infiltration of the inflamed synovial tissues with T cells and, 3) the increased susceptibility of individuals to RA with certain HLA-DR haplotypes. The most direct evidence for the involvement of CD4+ T cells is provided by recent studies which demonstrate rapid improvement in the joint disease manifestations of RA following the infusion of anti-CD4 monoclonal antibodies (Herzog et al. 1989, Walker et al. 1989). It is unlikely that T cells alone are responsible for the joint injury in RA. Autoantibodies (rheumatoid factors) in the joint which contribute to the release of complement breakdown products, and to the secretion of cytokines such as IL-1 by macrophages must also play an important role. Indeed, depletion of CD4+ cells after TLI or therapy with monoclonal antibody reduces, but does not eliminate, joint disease activity. The residual joint disease activity is probably influenced by the continued contribution of autoantibodies to joint injury. Production of these autoantibodies may not be dependent on help from CD4+ cells, since little change is observed in autoantibody levels after CD4+ cell depletion. The mechanisms by which T cells mediate to the joint disease in RA are not clear. Little or no direct evidence of cytotoxic effects of T cells on autologous joint cells has been reported. Considerable evidence suggests that at least some T-cell cytokines (i.e., TNF alpha, IL-6) can contribute to the proliferation of synovial lining cells which results in the marked build-up of inflammatory tissue (pannus) in the joints of patients with RA (Firestein et al. 1990). In addition, T cells may recruit other joint cells, such as macrophages, to secrete cytokines (i.e., IL-1) which both contribute to synovial cell proliferation, and cartilage and bone degeneration. The marked reduction in the spontaneous secretion of IL-1 by synovial biopsies, and improvement in disease activity after TLI support this notion. Interestingly, the CD4+ T-cell lymphokines, IL-2 and IFN-gamma, were not spontaneously secreted in detectable quantities by synovial biopsies. This suggests that the pattern of lymphokines secreted by T cells in the joint in RA are not typical of that in delayed-type hypersensitivity reactions.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 1959292 | Primary total knee arthroplasty in patients with fixed valgus deformity. | 1991 Dec | Ninety-nine knees in 81 patients evaluated from two to ten years and having enough valgus deformity to require specific soft-tissue release were studied. They were also compared to a control group of 40 knees in 31 patients with no angular deformity greater than 5 degrees, who were matched for age and diagnosis. All procedures were performed using a minimally constrained, posterior-cruciate-ligament-sparing prosthesis. Pre- and postoperative axial alignment was measured on weight-bearing long-standing roentgenographs. Analysis included examination for lucent lines in postoperative fluoroscopically positioned roentgenographs and clinical data summarized using the 100-point scoring systems developed by The Knee Society. Knees were classified as having Type I, II, or III valgus deformities: Type I was defined as valgus deformity secondary to bone loss in the lateral compartment and soft-tissue contracture with medial soft tissues intact; Type II was defined as obvious attenuation of the medial capsular ligament complex; and Type III was defined as severe valgus deformity with valgus malpositioning of the proximal tibial joint line after overcorrected proximal tibial osteotomy. Only cases of Type I and Type II were represented in the 99 knees reported. Type I patients were treated with lateral soft-tissue release, and Type II patients were treated with medial capsular ligament tightening (i.e., ligament reconstruction procedures on the medial side). The Knee Society postoperative knee score was 87.6 (+/- 10.6) and mean postoperative functional score was 52.3. Alignment was well corrected and knee scores for the Type I and II groups were almost identical as were the functional scores. The results were grouped as 72% excellent, 18% good, 7% fair, and 2% poor. Notably, the control group was 39 of 40 patients excellent, and only one poor. Ligament stability was satisfactorily established by lateral release in Type I and with the combined medial plication in the Type II patients. The ligament-tightening procedures were on the average 40 minutes longer than those for the Type I or the control groups. The controversial nature of the simultaneous ligament reconstruction method is recognized, but good experience is reported. | |
| 2129494 | Recognition of self class II major histocompatibility complex antigens by CD8+ T cell clon | 1990 | T cells from rheumatoid synovium have been expanded in vitro as lines and clones using autologous Epstein-Barr virus-transformed stimulator cells. Both lines and clones recognized autologous class II MHC antigens in the absence of defined exogenous antigens i.e. the equivalent of the autologous mixed lymphocyte response. Surprisingly, despite their MHC specificity, several clones expressed CD8 rather than CD4, but were not cytotoxic. The function of CD8+ T cells within synovium has not previously been defined; in view of their unusual phenotype, they may exert an immuno-modulating role upon the inflammatory response within the joint, by responding to the high density of class II MHC antigens expressed in the rheumatoid synovium. | |
| 3128244 | The effect of granulocyte factor (GF) on the production of interleukins and Tac antigen ex | 1987 | In the course of adherence granulocytes secrete the granulocyte factor (GF) which modifies lymphocyte functions in vitro. GF augments the interleukins production and diminishes mitogen induced Tac antigen expression in vitro, which may result in diminished IL-2 utilization. Consequently, such cells probably do not absorb IL-2 and do not exert their "inhibitory" potency measured in two step culture. The presented data show a relative deficit in interleukin generation in RA patients and have suggested the role of granulocytes in immunoregulation presumably in the course of diseases accompanied by inflammatory processes. | |
| 2254884 | Phenotypic characteristics of dissociated mononuclear cells from rheumatoid synovial membr | 1990 Oct | The phenotypic characteristics of enzymatically dissociated synovial membrane mononuclear cells from 8 patients (14 samples) with rheumatoid arthritis (RA) were assessed by fluorescence activated flow cytometry and compared to peripheral blood (PB) mononuclear cells from 18 patients with RA and 14 normal controls. There was no significant difference between the percentage of CD4+ and CD8+ lymphocytes in synovial membrane compared to RA and normal PB. Double labelling experiments revealed similar percentages of CD4+ CDw29+ (helper-inducer) and CD4+ CD45R+ (suppressor-inducer) cells in RA and normal PB. In contrast, SM CD4+ CDw29+ cells were present in significantly higher proportions than in RA and normal PB (p less than 0.001). Conversely, synovial membrane CD4+ CD45R+ cells were present in significantly lower proportions than in RA and normal PB (p less than 0.001). A similar pattern of CDw29 and CD45R antigen expression was noted on CD8+ lymphocytes reflecting increased killer-effector (p less than 0.001) and decreased suppressor-effector (p less than 0.001) cells, respectively. Other experiments revealed a significant increase in the percentage of synovial membrane CD20+ cells (B lymphocytes) and HLA-DR+ cells compared to RA PB (p less than 0.02 and p less than 0.001) and normal PB (p less than 0.01 and p less than 0.005), and similar proportions of CD14+ cells (monocytes/macrophages). Our results suggest that RA synovial membrane contains populations of T and B lymphocytes that differ quantitatively and qualitatively from those in PB. These may account for some of the abnormalities in intraarticular humoral and cellular immune responses in patients with RA. | |
| 2107989 | The effect of gold sodium thiomalate and auranofin on lipopolysaccharide-induced interleuk | 1990 Mar | The anti-rheumatic gold compounds gold sodium thiomalate (GST) and auranofin (AF) have variable and often unpredictable effects in patients treated for arthritis. As inhibition of interleukin-1 (IL-1) production may be an important effect of these drugs, we investigated their effect on IL-1 production by lipopolysaccharide (LPS) stimulated monocytes in a serum-free, non-adherent culture system. A bi-modal effect was observed: low concentrations (GST 10-250 ng/ml and AF 1-100 ng/ml) potentiated IL-1 production, and higher concentrations (GST 200-1000 ng/ml and AF10-500 ng/ml) inhibited it. This bi-modal effect was observed for both secreted and cell-associated IL-1 activity with the exception that GST failed to inhibit cell-associated IL-1 generation. The potentiating effect was dependent on the continuous presence of gold for at least the first few hours after LPS stimulation. The inhibitory effect of GST was dependent on its presence after LPS stimulation while that of AF was evident even if cells were pretreated with AF and washed before exposure to LPS. There was considerable individual variation in IL-1 production in response to LPS as well as in the effects of gold on cells from both healthy individuals and patients with arthritis. There was also some overlap in the range of concentrations of gold that potentiated and inhibited IL-1 production, and there was relative insensitivity to the inhibitory effects of gold in certain individuals. These results may explain some of the variability in the response of patients to chrysotherapy and support further studies to see if these in vitro effects might predict clinical response to gold. | |
| 3707217 | Atypical erosive osteoarthritis and Sjögren's syndrome. | 1986 Apr | An unusual, destructive form of erosive hand arthropathy is described in five postmenopausal women. Although early clinical and radiological findings were most in keeping with a diagnosis of erosive osteoarthritis (EOA), hand involvement progressed to a distribution intermediate between EOA and rheumatoid arthritis (RA). Although asymptomatic, all patients had features of Sjögren's syndrome (SS), including keratoconjunctivitis sicca (KCS) and lymphocytic foci in labial biopsy specimens. These cases, which are clinically unlike either RA or EOA, may represent a unique arthropathy associated with sicca features. | |
| 2625686 | Variation in the effects of mononuclear cell products from different individuals on metall | 1989 Dec | Human articular cartilage in organ culture shows a variable degree of endogenous metalloproteinase secretion depending on the individual from whom it was obtained. Cartilage with low endogenous levels are stimulated by interleukin 1 (IL-1) to levels comparable to the high endogenous group. Total blood mononuclear cell products obtained from different individuals either behave in a manner similar to that seen with IL-1, which results in sustained high levels of enzyme secretion, or show an initial stimulation followed by a subsequent dropoff in enzyme secretion even though incubation is continued in the presence of mononuclear cell products. The factor(s) causing this dropoff can be distinguished from IL-1. Production and regulation of such factors may reflect a mechanism whereby the action of IL-1 can be controlled during the inflammatory response. | |
| 2146965 | IgG and IgA antibodies to the collagen-like region of C1q in rheumatoid vasculitis. | 1990 Nov | We investigated the presence of IgG and IgA antibodies to C1q in serum samples from 80 patients with rheumatoid arthritis (RA), 31 patients with rheumatoid vasculitis, and 80 healthy controls. IgG and IgA antibodies to C1q, as measured by enzyme-linked immunosorbent assay, were found in less than 5% of the sera from RA patients and from healthy controls. In contrast, IgG and IgA antibodies to C1q were found in 29% and 61%, respectively, of the sera from patients with rheumatoid vasculitis. The occurrence of IgA antibodies to C1q has not been previously demonstrated. These results also demonstrate that IgG antibodies to C1q do not occur exclusively in systemic lupus erythematosus patients: Sera of patients with rheumatoid vasculitis frequently contain IgG or IgA antibodies to C1q, which contribute to immune complex formation. | |
| 1793011 | Phosphonate-phospholipid analogues inhibit human phospholipase A2. | 1991 Sep | A phosphonate-containing phospholipid (PL) analogue (Compound 1) designed as a transition-state inhibitor competively inhibits non-human extracellular PLA2 at a mole fraction of 0.003 in the kinetic "scooting mode" (Jain et al., Biochem 28:4135 (1989]. To further profile the activity of Compound 1, we examined its activity with purified human enzyme and in whole cell systems. Compound 1 effectively inhibited a 14 kDa human PLA2 purified from joint synovial fluid of patients with rheumatoid arthritis using 3H-AA labeled E. coli as substrate (IC50 = 1.7 microM) and a high MW PLA2 (110 kDa) isolated from the cytosol of a human monocytic cell line, U-937, which selectively hydrolyzes AA-containing PL (IC50 = 165 microM). It failed to reduce A23187-induced PGE2 or LTC4 production by human adherent monocytes or LTB4 release from human neutrophils which may be due, in part, to poor membrane partitioning. | |
| 2224617 | The role of coronary angioplasty in patients with associated noncardiac medical and surgic | 1990 Sep | Percutaneous transluminal coronary angioplasty was performed in 22 patients with associated significant medical or surgical conditions. It was successful in 22 patients. Two had procedure-related complications: one femoral hematoma and one small myocardial infarction. The patients were divided into a 'medical' group (12 patients) and a 'surgical' group (10 patients). In the medical group, mean coronary artery stenosis decreased from 87 +/- 5% to 20 +/- 13% and mean coronary artery stenosis decreased from 57 +/- 2% to 16 +/- 7%. In the surgical group coronary artery stenosis decreased from 83 +/- 9% to 18 +/- 9% and the gradient from 49 +/- 16 to 16 +/- 6 mmHg. Percutaneous transluminal coronary angioplasty allowed the safe management of underlying conditions in all patients so that medical treatment could be continued and noncardiac surgery performed. | |
| 3070724 | The Gm system. Anti-Gm's: characteristics in rheumatoid arthritis; experimental induction | 1988 | Gm system: Some RFs specifically detect Mendelian markers of human Ig, originally proving that Ig production is gene controlled. The genetic marker systems of human Ig with 17 Gm, 2 Am, 3 Km and 1 Em markers are briefly described. Examples of the usefulness of the Gm system in medicine, immunology and molecular biology are mentioned. CONCLUSIONS: 1. Some RFs have been essential tools in elucidating genetic control mechanisms in Ig production. 2. Knowledge of the Gm system is extensive. Anti-Gm's: High-titered anti-Gm's are common in R.A. The anti-allotypes in R.A. are markedly restricted as to their specificity. They are usually not directed against the individuals own Gm markers. Anti-human-immunoglobulins were observed in 12 of 18 sera from patients with mononucleosis. The majority of these anti-immunoglobulins were inhibitable by native human Ig and showed restricted specificity. CONCLUSIONS: 1. There is a strong stimulus for production of particular anti-Gm's in a majority of R.A. cases. 2. Notions of an autoimmune origin for many anti-Gm's in R.A. are not in obvious agreement with experimental observations. 3. Anti-human-Ig's with restricted specificity are commonly induced in mononucleosis. | |
| 2575936 | Enhancement of the activity of thyroid-stimulating antibodies by anti-human IgG antibodies | 1989 Sep | In an attempt to determine whether or not anti-human IgG antibodies could influence the activity of thyroid-stimulating antibodies (TSAb), we investigated the effects of anti-human Fc antibody (anti-Fc antibody) and IgG from rheumatoid arthritis patients (RA-IgG) on TSAb activity using FRTL-5 cells. It was found that these anti-human IgG antibodies enhanced the TSAb activity in vitro. FRTL-5 cells were first incubated with Graves' disease IgG for 30 min at 37 degrees C, then washed and incubated in Hanks' balanced salt solution with anti-human IgG antibodies for 60 min at 4 degrees C, and then for a further 120 min at 37 degrees C. The level of cAMP accumulated in the medium was determined by RIA. Anti-Fc antibody significantly augmented the cAMP formation stimulated by 16 out of 24 Graves' IgGs, whereas anti-F(ab')2 antibody did not potentiate cAMP accumulation. Three of five RA-IgGs, which are usually defined as specific antibodies for the Fc fragment of human IgG, mimicked these stimulatory effects. Protein A also potentiated the cAMP formation stimulated by Graves' IgGs. Furthermore, there was a significant correlation between the TSAb titres of these Graves' IgGs and the potentiating effects of anti-Fc antibody (r = 0.495, P less than 0.05, n = 21). These results suggest that the interaction of TSH receptor antibody with anti-human IgG antibodies might modulate thyroid function in Graves' disease. |