Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2507329 | Interleukin-1 potentiates bradykinin- and TNF alpha-induced PGE2 release. | 1989 Jul 18 | The ability of interleukin-1 (IL-1 alpha), IL-1 beta, tumour necrosis factor alpha (TNF alpha) and bradykinin to cause prostaglandin E2 (PGE2) release from human synovial cells was examined. IL-1 alpha and IL-beta proved equipotent in their effect, and were up to four orders of magnitude more potent than TNF alpha after incubation for 24 h. Bradykinin proved the weakest of all the agonists examined. When the cells were pretreated with IL-1 alpha or IL-1 beta for 24 h, their ability to release PGE2 in response to a short incubation (1 h) with bradykinin, TNF alpha or a second dose of IL-1 was potentiated. In addition, TNF alpha and bradykinin were shown to increase the level of free arachidonic acid (AA) in the cells. Furthermore, a similar potentiation in the response of pretreated cells was observed with exogenous AA. It is already known that pretreatment with IL-1 for 24 h results in an induction of cyclo-oxygenase (CO). It seems likely, therefore, that activation of phospholipase A2 which occurs during a short incubation with IL-1, TNF alpha or bradykinin releases substrate, AA, which is more rapidly converted to PGE2 by cells in which CO has been induced. The result of these events might indicate a sustained release of PGE2 at sites of inflammation where such mediators are released. | |
| 3315461 | Aspects of the structure, function, and applications of superoxide dismutase. | 1987 | The current status of superoxide dismutase (SOD) is that it is an enzyme with diverse ramifications. This review attempts an understanding of SOD as a structural, functional, and biological entity. Accordingly, the review is in three parts. The first part discusses SOD in terms of protein structure, proceeding from primary to secondary and three-dimensional structure for the three forms of SOD: copper/zinc SOD, manganese SOD, and iron SOD. This is the order of structural knowledge of the enzyme. Iron SOD is an enzyme of prokaryotes and some higher plants. Manganese SOD is an enzyme of prokaryotes and eukaryotes. Copper/zinc SOD is an enzyme of eukaryotes and certain prokaryotes. The evolutionary relationships of the three forms of SOD, the status of the copper/zinc SOD gene in prokaryotes, and the cloning and sequencing of SOD genes are discussed. The second part of the review deals with the catalytic mechanism of SOD in the three forms of the enzyme. Structural and mechanistic conclusions from various spectroscopic studies are critically considered. A detailed picture is given of the active site of copper/zinc SOD. The third part is a review of SOD in the general context of oxygen toxicity. After consideration of the question of superoxide toxicity and superoxide pathology, several areas in which SOD has been investigated or used as a tool in a biochemical, pharmacological, or clinical context are discussed, including population genetics; trisomy 21; development and senescence; the nutritional copper, zinc, and manganese status; hemolysis and anemia; oxygen toxicity in the lung and nervous system; inflammation, autoimmune disease and chromosome breakage, ischemia and degenerative changes; radiation damage; and malignancy. A comprehensive picture is given of measurements of SOD activity in disease states, and the question of superoxide-related disease is considered at several points. | |
| 2116773 | Does steroid pulsing influence the efficacy and toxicity of chrysotherapy? A double blind, | 1990 Jun | To test the hypothesis that early steroid pulsing augments the efficacy and decreases the toxicity of chrysotherapy 40 patients with rheumatoid arthritis were studied in a double blind, placebo controlled study. During the first three months of gold treatment group 1 received monthly intravenous methylprednisolone pulsing (steroid group) while group 2 received placebo (placebo group). All patients were assessed clinically and serologically over a 24 week period. Twelve patients were withdrawn before completion of the study and all but one of the remaining 28 patients reported clinical and serological improvements. Two patients in the steroid group were withdrawn owing to gold induced side effects while four were withdrawn in the placebo group. These small numbers were not significantly different. Minor side effects occurred more commonly in the placebo group. The clinical response was clearly better in the steroid group with statistical significance almost being achieved. In an endeavour to obtain a significant conclusion further patients will now be entered into this study. | |
| 2297575 | Antibodies to actin in autoimmune neutropenia. | 1990 Feb 1 | In an effort to characterize the cellular antigens recognized by anti-neutrophil antibodies in autoimmune neutropenia, we studied sera, purified immunoglobulin G (IgG) and isolated F(ab')2 from 70 neutropenic patients suspected of this diagnosis. Anti-neutrophil antibodies were found in the sera of 36 of these patients by either 125I-staph A binding or immunofluorescence cytometric techniques that detected increased binding of patients' IgG to normal neutrophils. Anti-neutrophil antibody positive sera were then evaluated for specific binding to electrophoretically separated neutrophil membrane-associated proteins by immunoblotting. A 43-Kd protein was consistently identified by eight anti-neutrophil antibody positive sera. The specificity of binding to this protein was confirmed with affinity purified IgG and F(ab')2 fragments prepared from these sera. Sera from 20 healthy normal controls and from 22 non-neutropenic, anti-neutrophil antibody negative rheumatoid arthritis patients failed to bind this protein. Separate studies identified the 43-Kd protein as actin. Purified Acanthamoeba actin comigrated with the protein and was specifically bound by anti-neutrophil antibody positive IgG. Moreover, two actin-specific monoclonal antibodies bound to the 43-Kd membrane-associated protein in immunoblots. In addition, a rabbit anti-actin antiserum not only bound to this same 43-Kd protein but also expressed anti-neutrophil antibody activity against normal human neutrophils, as did purified human anti-actin IgG prepared by affinity chromatography from the serum of one of the index patients. These studies indicate that the anti-neutrophil antibodies of certain patients with autoimmune neutropenia include autoantibodies specific for actin. The molecules on the surface of neutrophils, which have actin-like antigenic epitopes and are recognized by these anti-actin antibodies, remain to be characterized. | |
| 3118455 | [Antinuclear antibodies: the classical and the new]. | 1987 Aug 22 | A brief overview is presented of the different antinuclear autoantibodies most frequently mentioned in the literature at the present time. The relationship between these autoantibodies and collagen diseases is described in terms of their usefulness in diagnosis and follow-up. Lupus anticoagulant is also mentioned in view of its possible relationship with anti-DNA autoantibodies. | |
| 3522897 | The clinical application of an ELISA technique for the detection of antihistone antibodies | 1986 Apr | A rapid reproducible technique for measuring antihistone antibodies is described in which unfractioned nuclear histones covalently bonded to plastic discs are employed in an ELISA system. All 20 patients with drug induced lupus erythematosus had antihistone antibodies, usually at high titer. In contrast, 22% of 18 asymptomatic patients with drug induced antinuclear antibodies (ANA), 15% of 20 patients with seropositive RA and 42% of 60 patients with systemic lupus erythematosus (SLE) had detectable antihistone antibodies. High titers of antihistone antibodies were not seen in drug induced ANA or RA. This assay differentiates between patients with drug induced lupus and drug induced ANA (p less than 0.01) and drug induced lupus erythematosus and SLE (p less than 0.01). In patients with SLE antihistone antibodies had no association with disease activity. | |
| 3017244 | Cytotoxic mechanisms in vitro against Epstein-Barr virus infected lymphoblastoid cell line | 1986 Jul | Impaired regulation of latent infection with Epstein-Barr virus (EBV) may contribute to the pathogenesis of rheumatoid arthritis (RA) by allowing uncontrolled polyclonal B cell activation. The control of EBV infection in vitro is dependent on several cytotoxic lymphoid cell populations. The present report examines the suppression of early lymphoblastoid outgrowth by natural killer (NK) like cells and the ability to form cytotoxic T lymphocytes (CTLs) specific for EBV in vitro. The latter was measured by a regression assay of EBV induced lymphoblastoid transformation. In this assay the regression of B cell outgrowth at four and six weeks is due to the generation of CTLs specific for EBV. Patients with RA were defective in this ability to generate CTLs. Eight out of nine patients with RA had a geometric mean at the 50% regression end point equal to or greater than 20 X 10(5) cells/ml. In contrast, the geometric mean for all control donors was less than 4 X 10(5) cell/ml. NK activity was measured by a conventional 51Cr release assay with K562 targets. Patients with RA did not have significantly different activity from that of controls (RA patients, n = 4, 45.6 +/- 19.7% (means +/- SD) at 50:1, effector:target; normals, n = 5, 56.6 +/- 5.7%). No spontaneous NK activity was detected against allogeneic or autologous EBV infected B cell targets. When peripheral mononuclear cells from patients were incubated for six days with interleukin-2, lysis of EBV infected targets was seen. No difference in this activity was seen between RA and control studies. Overall, these studies show that patients with RA are defective in their ability to generate CTLs specific for EBV in vitro. | |
| 2303312 | Differences in sodium salicylate protein binding in serum and synovial fluid from patients | 1990 Jan | Protein binding of sodium salicylate in synovial fluid and in serum from 23 inpatients with rheumatic diseases were studied, ex vivo, by equilibrium dialysis. Scatchard model with two classes of sites was used as a mathematical tool. At therapeutic concentrations, protein binding of sodium salicylate was significantly higher in serum than in synovial fluid. The ratio of areas under the curves for bound concentrations for synovial fluid to that for serum was 0.867. This difference was attributed to the hypoalbuminemia observed in the synovial fluid; for a given molar ratio of drug to albumin, or in other words, for the same amount of available drug per mole of albumin. The number of sites occupied was the same in the two biological media. | |
| 2793747 | Bronchoalveolar lavage in interstitial lung disease: effect of volume of fluid infused. | 1989 Oct | To evaluate the effect of varying infusate volume on the results of bronchoalveolar lavage (BAL) in patients with interstitial lung disease, 55 patients underwent 58 BAL during which both a 100- and 250-ml lavage was performed in the same lobe of the lung. Although the percent of the fluid that was returned and the total numbers of cells were greater in the 250- vs. the 100-ml lavage, there were no significant differences in cell differentials or numbers of cells per milliliter between the 100- and 250-ml BAL. We conclude that infusate volume does not affect cell differentials or numbers of cells per milliliter of bronchoalveolar lavage fluid in patients with interstitial lung disease. | |
| 3521952 | Serum calcium status in health and disease: a comparison of measured and derived parameter | 1986 Jun 15 | The relationship of serum ionised calcium to total calcium was investigated in three series of experiments, each using different ion-selective electrodes. In the first, total and ionised calcium were measured in healthy and patient groups to compare the predictive value of each estimation. In the second and third studies, measured ionised calcium was compared with ionised calcium calculated using 5 different formulae, and with total calcium, both uncorrected, and adjusted for varying protein content using eight formulae. In 144 of 149 healthy subjects, serum ionised calcium and total calcium were normal. There were discrepancies between serum ionised calcium and total calcium in 135 of 572 patients with conditions associated with abnormal calcium metabolism. Correction of total calcium, or calculation of ionised calcium did not significantly improve this figure. Thus, corrected or derived calcium values will not substitute for ionised calcium determination in patients with abnormal calcium metabolism. | |
| 1694047 | Whipple's disease with axial and peripheral joint destruction. | 1990 Jun | A seropositive white man had follow-up for 16 years with a diagnosis of palindromic rheumatism. Treatment had included parenteral gold, methotrexate, prednisone, hydroxychloroquine sulfate, and penicillamine before diarrhea led to a biopsy-proven diagnosis of Whipple's disease. Clinical and radiographic criteria for ankylosing spondylitis were met. In addition to classic Whipple's arthropathy, he had the combined but singular findings of pancarpal destruction and cervical apophyseal fusion. HLA typing revealed the B7 antigen. This case illustrates the pitfalls in diagnosis of a chronic polyarthritis that has, as a typical feature, a long latency before manifesting its more specific signs and symptoms (ie, diarrhea, malabsorption, and hyperpigmentation). Care should be taken during evaluation of any disease with atypical and nonspecific features (eg, positive rheumatoid factor in a patient with polyarthritis) and one should continue to reevaluate the original impression while confirmatory evidence is lacking. Moreover, the roentgenographic findings of pancarpal narrowing, apophyseal fusion, and advanced iliofemoral joint disease, in addition to sacroiliitis and syndesmophyte formation, challenge the generally held notion that Whipple's arthropathy is a nondestructive joint disease. | |
| 2446798 | Characteristics of antibodies adsorbed on the DNA immunoadsorbent, agarose poly-L-lysine-D | 1987 | Agarose-poly-L-lysine (Ag-(lys)n-DNA) has been used to bind DNA for assay of anti-DNA antibodies (ab). In this work, an algorithmic approach has been used to classify antinuclear ab (ANA) as being directed against native DNA (dsDNA), denatured DNA (ssDNA), DNA-protein complexes (deoxyribonucleoprotein; DNP), and against antigens which are independent of DNA (iDNA). These ab were subjected to Ag-(lys)n-DNA, and the selectivity of this adsorbent for the various specificities of ab was determined. The DNA on the columns was left untreated or treated with S1 nuclease, this being effected either by treating the DNA prior to introducing it onto the columns or by adding S1 nuclease to the columns after the DNA was bound. Ag-(lys)n-DNA adsorbs ab directed against ssDNA and DNP as well as ab to dsDNA; iDNA ab are not adsorbed. S1 nuclease treatment does not effectively remove ssDNA regions from the Ag-(lys)n-DNA, but it does result in the abolition of the adsorption of a population of ab which are in the anti-DNP sera and contribute to the total ANA load. While anti-iDNA ab are not adsorbed onto the columns, they do contribute to the ANA titer, unlike anti-ssDNA ab which are adsorbed onto the Ag-(lys)n-DNA but do not contribute to the ANA titer. We conclude that Ag-(lys)n-DNA bears antigenic sites for dsDNA, ssDNA, and DNP ab and suggest that our understanding of the characteristic ab-binding profile of this versatile immunoadsorbent may have applications in the study of autoimmune diseases. | |
| 3048922 | Mechanical strength of trabecular bone at the knee. | 1988 Aug | Interest in the biomechanical properties of trabecular bone has expanded in response to the problems related to total and partial joint replacement with the knee joint constituting a main focus of attention. This relatively recent development has left a number of fundamental problems unanswered, especially related to the machining, storage and testing of trabecular bone specimens. Nevertheless, these studies have contributed to the understanding of the mechanical function of trabecular bone. Regarding the role of trabecular bone at the knee joint, the following conclusions may be emphasized (conclusions drawn from the author's previous studies (I-X) are shown in italics): (1) Trabecular bone is almost exclusively responsible for the transmission of load at the proximal tibial epiphysis from the knee joint to the metaphysis. The peripheral shell surrounding the epiphysis is not composed of cortical bone and plays a negligible role in load transmission. (2) The compressive strength and stiffness of trabecular bone is primarily dependent upon the apparent density, trabecular architecture and the strength of the bone material. Direct and indirect sources suggest that the true material strength of trabecular bone is less than that of cortical bone. The epiphyseal trabecular architecture, featuring a marked polarity with alignment of primary trabeculae at right angles to the joint surface, is responsible for functional anisotropy which points to the axial compressive properties as the more important mechanical parameters. (3) Tensile and shear properties are of special relevance to mechanical loosening of implants. These properties may be derived from the apparent density, and a close empirical relation to the axial compressive strength and stiffness is suggested. (4) The foam-like structure of trabecular bone is the basis for the large energy absorptive capacity. (5) The pattern of axial compressive stiffness and strength at the normal proximal tibia differs little among individuals. Supporting the medial tibial plateau is a large high strength area with maximal strength centrally and slightly anteriorly, while laterally there is a restricted area of relatively high strength posteriorly with a lower maximal value than medially. Bone strength is significantly reduced within ten millimeters of the subchondral bone plate, and this reduction continues distally at the lateral condyle. At both condyles strength is reduced towards the periphery with very low values being obtained at the margins of the condyles and at the intercondylar region. Absolute bone strength values are influenced by the level of physical activity.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 3944162 | Deep sepsis following total knee arthroplasty. Ten-year experience at the University of Ca | 1986 Feb | Between September 1971 and May 1982, at the University of California at Los Angeles Medical Center, 821 total knee arthroplasties were performed in 604 patients, all of whom received perioperative antibiotics. Deep sepsis, proved by a positive culture of a specimen obtained by postoperative arthrocentesis, developed fourteen times in thirteen knees of twelve patients, an incidence of 1.71 per cent. In one of these patients, who had systemic lupus erythematosus and bilateral knee replacement, the right knee became infected with two distinct organisms on two different occasions (separated by ten months). The first infection was probably hematogenous while the second, developing after a dental procedure, definitely was. Over-all, five infections were hematogenous with an identified source and one other was suspected of having a hematogenous origin. The time from operation to the diagnosis of sepsis averaged 8.3 months over-all, but five of the fourteen infections were recognized less than two months after arthroplasty. For the six infections that were assumed to be hematogenous, the time from operation to the diagnosis of sepsis averaged 16.4 months. The major presenting symptom was pain in thirteen of the fourteen infections. The initial treatments of the fourteen infections consisted of intravenous antibiotics in all of them, primary removal of the prosthesis and so-called exchange arthroplasty after five days in one, removal of the prosthesis and fusion in one, arthrotomy and débridement in six, arthroscopic irrigation in three, and antibiotics alone in three (of which one was treated with an exchange arthroplasty after three weeks). At last follow-up, only four of the thirteen prostheses had been salvaged.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1718099 | [Effect of different media on long-term cultivation of human synovial macrophages]. | 1991 May | Cells of rheumatoid synovial tissue were bred in dispersion culture. In order to investigate the influence of three different culture media on the maturation and vitality of synovio-macrophages, Ham F10 (+fetal calf serum) and RPMI 1640 (+pooled AB Rh+ human serum) were compared with the serum- and cytokin-free solution AIM V. Combining light microscopic, transmission electron, and scanning electron microscopic methods (backscatter-mode), the enzyme and antibody features of synoviocytes were detected. The ratio of macrophages were determined in the light microscope by marking with CD 14. The functional maturation was shown by the amboceptor test. This study demonstrates that RPMI 1640 (+AB Rh+ human serum) is favorable for cultivating human synoviomacrophages. Under serum-free conditions AIM V is especially appropriate. | |
| 2205906 | Immunohistopathologic findings in synovial biopsies before and after synovectomy in patien | 1990 | Synovial biopsies were obtained from 28 patients with various kinds of chronic arthritis, at synovectomy and 6 and 12 months later. The tissues were examined by immunofluorescence technique, recording the quantities of cells and extracellular deposits staining with polyclonal antisera to IgG, IgA, IgM, C3c, fibrinogen, and chi and lambda light chains, and monoclonal antibodies to CD3, CD5, CD11b, HLA DR, and TCC (Terminal Complement Complex). These parameters were compared with scores obtained by arthroscopy and clinical evaluation (Colorado Knee Score) performed at the same time. Taken as a group, the immunological parameters showed reduction in activity 6 months after synovectomy (p less than 0.01), and a tendency to revert to base-line values after 12 months. A similar reduction in activity after 6 months was also found by arthroscopic and clinical evaluation. Thus, this longitudinal study demonstrated a relationship between changes in immunologic activity, arthroscopic findings and clinical activity after synovectomy in patients with chronic arthritis. This is consistent with an immunological pathogenesis for the inflammation in these joints. | |
| 3728210 | Action of histamine on PHA chemiluminescence response of blood mononuclear cells in autoim | 1986 Apr | Peripheral blood mononuclear cells (PBMs) of patients suffering from autoimmune diseases showed significantly lower chemiluminescence response to PHA than the controls. High doses of histamine (10(-5) M) inhibited the chemiluminescence while low doses caused a mild enhancement in all groups of patients. The preformed histamine content of the PBMs was not significantly higher in the patients than in the controls. Individually, a reverse correlation was found between the activity of the disease and the sensitivity of the cells to histamine. In very active cases, virtually no inhibition by histamine was found. | |
| 1917593 | Autocrine stimulation of interleukin 1 in human adherent synovial lining cells: down regul | 1991 Aug | Interleukin 1 (IL-1) exerts biological properties on various immune and nonimmune cell types and tissues and thus may play an important role during chronic inflammatory processes. Here we have examined the IL-1 biosynthesis in adherent synovial lining cell (ASLC) cultures obtained from patients with rheumatoid arthritis (RA). We report that ASLCs in culture showed heterogeneous endogenous levels of IL-1 alpha and beta expression. Recombinant interleukin 1 (rIL-1) alpha or beta induced increases of IL-1 alpha and beta mRNA and proteins levels in ASLCs. Although IL-1 synthesis is enhanced by rIL-1 treatment, no soluble IL-1 alpha or beta could be detected by specific enzyme-linked immunosorbent assays. A pretreatment with recombinant IFN gamma (rIFN gamma) down-regulated the effect of rIL-1 on IL-1 synthesis in ASLCs. Actinomycin D suppressed the endogeneous and rIL-1-induced IL-1 mRNA expression Indomethacin, in the presence of rIL-1 alpha or beta, up-regulates the level of expression of IL-1 beta in ASLCs pretreated with rIFN gamma, but has the opposite effect in non-pretreated cells. The increase of IL-1 gene expression by rIL-1 in human ASLCs from RA patients may contribute as an amplification of the disease progress. These studies may also explain the beneficial effects of IFN gamma in experimental models of IL-1-induced bone and cartilage degradation and in patients with diseases involving IL-1. | |
| 1778090 | Clinical efficacy and tolerability of tenoxicam in African patients with osteoarthritis, r | 1991 | An open clinical evaluation was carried out in 736 African out-patients suffering from rheumatic and inflammatory disorders to assess the efficacy and tolerability of tenoxicam in relieving the signs and symptoms of their condition. On entry, all previous treatment was discontinued and patients received a simple daily dose of 20 mg tenoxicam orally for 15 days in the case of those with rheumatoid arthritis or tendinitis, or for 30 days in those with osteoarthritis. Paracetamol was allowed as a rescue analgesic. Subjective verbal scale assessments were used to determine levels of pain at rest, on movement and at night, sleep disturbance and functional incapacity, on entry and during treatment. At the end of the study period, both physicians and patients gave an overall opinion of the clinical response to tenoxicam, and patients were asked how their current compared with their previous treatment. The results showed that approximately 90% of patients had an excellent or good response to tenoxicam with marked improvement in all the signs and symptoms evaluated. Moreover, tenoxicam proved to be well tolerated, only a small number of patients reporting adverse events, mainly gastro-intestinal. | |
| 2551105 | Modulation of the migration and chemotaxis of PMN cells by hyaluronic acid. | 1989 May | Hyaluronic acid (HA) has a dose-related inhibiting effect on the migration and chemotaxis of polymorphonuclear leucocytes (PMN) in vitro. These effects were measured with a new indirect quantitative assay. On average 1 mg HA/ml causes an inhibition to about 80% of the control (spontaneous migration). This effect increased progressively with an increasing HA concentration, and with 4 mg HA/ml only about 19% of the PMN were able to migrate in the in vitro system. Similar results were obtained in the presence of a potent chemotactic factor (leukotriene B4 [LTB4]). In the mean 1 ng LTB4/ml alone stimulated the chemotaxis of PMN by a factor of 3 compared to the spontaneous migration. The highest HA concentration (4 mg/ml) reduced the number of migrating PMN cells to about 17%. From these experiments it may be concluded that the HA in the synovial fluid of the healthy joint has a protective effect against the invasion of PMN cells. This functions is disturbed in inflamed joints by the decrease in the HA concentration and possibly by its depolymerization. The intraarticular application of high molecular weight HA might be an important therapeutic regimen to restore the natural barrier against PMN migration, also in the presence of chemotactic factors and could therefore be helpful for interrupting the inflammatory cascade. |