Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2441456 | Patient-specific heterogeneity of antinuclear antibodies as revealed by an isoelectric foc | 1987 Jul | Ninety-nine sera from patients with different rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and mixed and unidifferentiated connective tissue disease) were applied to a newly developed isoelectric focusing (IEF) immunoblot system for the demonstration of antinuclear antibodies. Nucleoproteins were separated according to their isoelectric points (pI) and immobilized onto nitrocellulose, and binding of serum antibodies was determined by an alkaline phosphatase labelled second antibody. 89.8% of all sera positive in indirect immunofluorescence assays with Hep 2 as substrate showed positive reactivity in IEF immunoblot. Furthermore, 88% of patients' sera negative on Hep 2 cells gave a positive reaction in IEF immunoblot. The predominant antibody banding pattern observed showed parallel bands in the acidic as well as the neutral pH ranges. Antibody specificities found in the IEF immunoblot system turned out to be patient-specific, but no marker antibody for a discrete disease entity was obtained. Even when monoclonal antibodies or WHO standard sera were applied to nuclear antigen they exhibited heterogeneity in their binding pattern. Bands with the same pI were observed using sera from patients with different rheumatic disease entities. Immunodeletion experiments suggest the recognition of identical antigenic proteins by the different patients' sera. | |
| 3450546 | A monoclonal antibody to a novel differentiation antigen on human macrophages associated w | 1987 | A monoclonal antibody (RM3/1), raised by immunizing mice with human monocytes, is described which detects a surface antigen on about 20% of freshly isolated peripheral blood monocytes and is increasingly expressed upon cultivation, reaching a maximum between day 2 and 3. By incubation of monocytes with interferon-gamma, 12-O-tetradecanoylphorbol-13-acetate and lipopolysaccharide, antigen expression is decreased but strongly enhanced after incubation with dexamethasone. In cryostat sections of normal tissue, the antibody detects histiocytes in the skin, Kupffer cells in the liver, few alveolar macrophages in the lung, macrophages in the red pulp of the spleen and in the cortex of the thymus, and many macrophages in the placenta. In acute inflammatory tissue, e.g. gingivitis, the antigen is preferentially expressed by macrophages appearing late in the inflammatory process. In chronic inflammation, e.g. BCG granulomas and rheumatoid arthritis, RM3/1-positive macrophages are seen to varying degrees. Double-staining experiments with the antigen 25F9, specific for resting mature macrophages, revealed that RM3/1 and 25F9 are expressed by distinct populations in normal and acute inflammatory tissues. From this it is concluded that the antibody RM3/1 specifically detects a macrophage phenotype which seems to be associated with the healing phase of the inflammatory process. | |
| 3430160 | Radiographic study of Kinematic total knee arthroplasty. | 1987 | One thousand sixty-nine consecutive cemented Kinematic Condylar total knee arthroplasties performed by one group of orthopaedists were studied. The maximum follow-up period was 7 years. Most patients had rheumatoid arthritis or osteoarthritis, and the average patient age was 67 years (range, 12-90 years). Aseptic revisions for loosening were required for only one tibial component and six patella components. Average postoperative flexion was 2.5-107 degrees. The preoperative to postoperative change in range of flexion was not affected by the tilt angle of the tibial component in the sagittal plane. With the use of external alignment guides, the average postoperative alignment was ideal but the standard deviation was high; the standard deviation and the extremes were lower when intramedullary guides were used. There was a 14% incidence of femoral radiolucency and a 30% incidence of tibial radiolucency, which increased only slightly with time. Most radiolucencies on the tibial side were small and restricted to the extreme edges; rarely did radiolucency occur around the central peg. More than one half of the thicker radiolucencies occurred adjacent to wedge-shaped bone defects that were filled with cement. | |
| 3522745 | Measurement of spontaneous and stimulated anti-microsomal antibody synthesis in vitro by a | 1986 Jul 11 | The spontaneous and stimulated anti-microsomal (anti-Mic) antibody synthesis in vitro by peripheral blood lymphocytes (PBL) from patients with Hashimoto's thyroiditis (HT) was studied by a highly sensitive and thyroid microsome-specific enzyme immunoassay using an avidin-biotin system (A-B EIA). Since the amount of the synthesized anti-Mic antibody by PBL in vitro is very small, it is difficult to study its kinetics and response to mitogens or the specific antigen by conventional assay systems. We applied the avidin-biotin system to conventional indirect EIA and established an assay system which was about four times as sensitive as indirect EIA. PBL from patients with HT synthesized significant amount of IgG anti-Mic antibody spontaneously but those from normal individuals and patients with rheumatoid arthritis did not. IgG anti-Mic antibody synthesis with pokeweed mitogen stimulation was increased in all HT patients and that with thyroid microsome stimulation was increased in three out of five patients. These results indicate that A-B EIA is a useful system to study the mechanism of anti-Mic antibody synthesis in vitro. | |
| 1753955 | [Use of the polymerase chain reaction for typing allelic variants of the human HLA-DQA1 by | 1991 Sep | Class II HLA molecules are the most useful markers for susceptibility to different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM) and rheumatoid arthritis (RA). Polymerase chain reaction and hybridization with a set of allele-specific oligonucleotide have been used for analysis of allelic sequence variation. The analysis of frequencies of HLA-DQA1 alleles among 10 patients of the russian population revealed a uneven distribution. We have developed a method for preparing non-radioactive oligonucleotide probes with terminal deoxynucleotidyl transferase and Bio-11-dUTP. Comparison of biotinylated and 32P-labeled hybridization probes gave the same sensitivity for HLA-DQA1 typing of amplified DNA. Amplification of the HLA-DQA1 gene has been successful on 10 pg of total DNA. This amount of DNA is close to the amount of DNA in a single cell. Alternatively, HLA-DQA1 typing could be based on the analysis of buccal cells of saliva that would avoid the problem of individuals who object to giving blood samples. | |
| 1674424 | Diagnostic significance of angiographically observed visceral aneurysms with regard to pol | 1991 Mar | During a 10-year period, intraparenchymal aneurysms were found in 38 of 748 patients at selective abdominal angiography with magnification technique. According to strict criteria, 17 patients were classified as suffering from necrotizing vasculitis of the polyarteritis nodosa group (PAN), 7 from severe arterial hypertension, and 3 from rheumatoid arthritis. The diagnoses of 5 patients remained to be confirmed, and each of the remaining 6 patients suffered from various other diseases. PAN was diagnosed histopathologically in 2 patients without angiographic aneurysms. Based on the 156 patients in whom the indication for angiography was suspicion of arteritis, the angiographic diagnosis of PAN had a sensitivity of 89 percent and a specificity of 90 percent, a positive predictive value of 55 percent and a negative predictive value of 98 percent. The mean number of both renal and hepatic aneurysms was higher in patients with PAN than in the other patients (p less than 0.01 and p less than 0.05, respectively). Five PAN patients had numerous and large aneurysms, whereas the aneurysms of the other 12 PAN patients did not differ from those of patients with other diseases. Patients with PAN had renal infarcts more often than the other patients (p less than 0.05). Our findings suggest that visceral angiography is useful in establishing the diagnosis of PAN, but the angiographic finding of aneurysms is not pathognomonic. | |
| 2014738 | Registration of arthroplasties in Finland. A nationwide prospective project. | 1991 | Data on hip and knee arthroplasties have been compiled on a nationwide basis in Finland since 1980. Forty-five major departments contribute to the study providing data on the type of operation, the implant used, the diagnosis, and the 1-year clinical results. In the case of revision, new data are sent to the register, enabling survivorship analysis. Between 1980 and 1988, 25,966 operations were reported. Fifty-six percent had been made for primary osteoarthrosis, 22 percent for rheumatoid arthritis, 6.3 percent for secondary arthrosis, and 0.5 percent for CDH. In 1988, the total number of arthroplasties was 4,628: about two thirds hip and one third knee replacements. The annual incidence of primary total hip arthroplasties in 1988 was 58 per 100,000 inhabitants and that for the knees 25 per 100,000 inhabitants. More than 40 percent of the patients were under 65 years of age. In the whole series, primary thromboembolic complications occurred in 1.4 percent, luxations in 1.4 percent, infection in 0.9 percent, and evacuated hematoma in 0.6 percent. The annual frequency of re-arthroplasty increased between 1980 and 1988 from 9.8 to 13.6 percent, indicating an increasing orthopedic work load in the future. | |
| 2247701 | [Diet and autoimmunity]. | 1990 Jul | New data emphasize the importance of nutritional factors in autoimmune diseases. Dietary alterations can be linked to autoimmune disorders as a specific pathogenetic mechanism and also for the malnutrition conditions frequently documented in these patients. The precise function of different nutrients is not completely known as they can be primary pathogenetic agents or causes of acute reacerbations or, finally, simply accompanying phenomena. It is also difficult to modify the intake of a single dietary component and to clarify its metabolic importance for the complexity of metabolic events in the human body and for the possible appearance of cascade-mechanisms. In lipid metabolism the multiple interactions between fatty acids, prostaglandins and leukotrienes are linked to alterations in inflammatory parameters. The exact role of modifications of proteins or of a single amino acid on immune function, also for the possible interference in protein restricted diet of the caloric component, is still unknown. Trace elements and vitamins are certainly important for the control of inflammation and of susceptibility in infections, albeit their role is not clear. More studies are necessary to clarify the link between dietary component and autoimmune diseases. However, study in experimental models and in human Systemic Lupus Erythematosus and Rheumatoid Arthritis demonstrated that a good nutritional homeostasis can contribute to decrease the severity of these disorders and to modify the clinical course with a physiological treatment that is free of side effects. | |
| 2202585 | Naproxen. A reappraisal of its pharmacology, and therapeutic use in rheumatic diseases and | 1990 Jul | Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain nonrheumatic conditions. It may be administered orally or rectally using a convenient once or twice daily regimen. Dosage adjustments are not usually required in the elderly or those with mild renal or hepatic impairment although it is probably prudent to start treatment at a low dosage and titrate upwards in such groups of patients. Numerous clinical trials have confirmed that the analgesic and anti-inflammatory efficacy of naproxen is equivalent to that of the many newer and established NSAIDs with which it has been compared. The drug is effective in many rheumatic diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and nonarticular rheumatism, in acute traumatic injury, and in the treatment of and prophylaxis against acute pain such as migraine, tension headache, postoperative pain, postpartum pain and pain associated with a variety of gynaecological procedures. Naproxen is also effective in treating the pain and associated symptoms of primary or secondary dysmenorrhoea, and decreases excessive blood loss in patients with menorrhagia. The adverse effect profile of naproxen is well established, particularly compared with that of many newer NSAIDs, and the drug is well tolerated. Thus, the efficacy and tolerability of naproxen have been clearly established over many years of clinical use, and it can therefore be considered as a first-line treatment for rheumatic diseases and various pain states. | |
| 2135825 | Epidermal nuclear immunoglobulin deposition in connective tissue diseases. | 1990 Jul | Epidermal nuclear deposition of immunoglobulins (in vivo ANA) was observed in 45 out of 252 skin biopsies (17.8%). It occurred in 19% of cases with systemic lupus erythematosus, in 32% of the mixed connective tissue disease, in 22% of the scleroderma, in 20% of the cutaneous vasculitis, in 18% of the polymyositis, in 33% of the Sjogren's syndrome, but it was absent in cases with rheumatoid arthritis. The in vivo ANA showed a significant association with serum antibodies to an extractable nuclear antigen (ENA), with speckled pattern of immunofluorescent antinuclear antibody (FANA) and with antibody to a fraction of ENA sensitive to ribonuclease termed ribonucleoprotein (RNP). Indirect evidence was obtained suggesting that the epidermal nuclear deposition of immunoglobulins is a true in vivo phenomenon: some patients with serum antibodies to ENA do not display in vivo ANA and contrariwise, no difference was detected between diseased and normal skin for the occurrence of in vivo ANA and also no association was observed between this phenomenon with immune deposits at dermoepidermal junction or in subepidermal vessels. | |
| 2809196 | IL-3 induces differentiation of bone marrow precursor cells to osteoclast-like cells. | 1989 Nov 15 | IL-3, a cytokine with hematopoietic differentiating capability, induced murine bone marrow cells to differentiate into cells resembling osteoclasts. The cells resulting from treatment with IL-3 were multi-nucleated and demonstrated tartrate-resistant acid-phosphatase activity, as do resident osteoclasts found in bone. IL-3-induced osteoclast-like cell development in the absence of serum-derived vitamin D metabolites, and a mAb that inhibited IL-3-induced proliferation of an addicted cell line also inhibited the development of osteoclasts in the presence of IL-3. The same Ab had no effect on 1 alpha, 25-dihydroxyvitamin D3-induced differentiation of osteoclasts. This newly described function of IL-3 may indicate a role for activated T cells in the bone resorption seen with rheumatoid arthritis. | |
| 2539060 | Inhibition of human neutrophils by auranofin: chemotaxis and metabolism of arachidonate vi | 1989 Feb | The effect of auranofin on human neutrophil (PMN) 5-lipoxygenase activity and leucotriene B4 (LTB4) chemotaxis was investigated. [1-14C]Arachidonic acid was incorporated into the purified cells until steady state conditions were obtained. After preincubations with serial dilutions of auranofin arachidonic acid release and metabolism were stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thin layer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxis of PMNs towards LTB4 was measured in a modified Boyden chamber. Auranofin showed dose dependent inhibition of both the 5-lipoxygenase pathway (IC50 17.4 X 10(-6) mol/l) and of chemotaxis (IC50 45 X 10(-6) mol/l). The release of arachidonic acid from phospholipids was unaffected in the concentration range tested (1-1000 mumol/l). Inhibition of both neutrophil motility and cellular synthesis of proinflammatory eicosanoids may thus contribute to the beneficial clinical effects of auranofin in rheumatoid arthritis. | |
| 3403066 | Immunolocalization of an angiogenic factor (HAF) in normal, inflammatory and tumor tissues | 1988 Aug 15 | The distribution of a novel human angiogenic factor (HAF) (Schulze Osthoff et al., 1987) has been investigated on various human cell lines, isolated blood cells as well as in normal, inflammatory and tumor tissues. Localization was performed by using the monoclonal antibody (MAb) 5F4 directed against HAF. It was found that 30% of freshly isolated human monocytes expressed the 5F4 antigen. The number of positive cells increased to 75-90% on day 4 to 7 upon culture and then decreased. Twenty percent of freshly isolated human lymphocytes also stained positively, whereas granulocytes and platelets were negative. In cryostat sections of normal human tissue (skin, lung, liver, spleen, placenta) 5F4 is positive with capillary endothelial cells and few macrophages. In inflammatory tissue derived from gingivitis and rheumatoid arthritis, more macrophages than in normal tissues and less endothelial cells were positive. In tumor tissues some endothelial cells and a subset of tumor-infiltrating macrophages expressed the antigen. Tumor cells were positive in advanced melanomas, but only occasionally in stomach carcinomas. We conclude that the angiogenic factor is produced mainly by a subset of inflammatory macrophages which appear to be the principal source of HAF in regenerating or growing tissues. | |
| 3266707 | Neutrophil elastase and cathepsin G: structure, function, and biological control. | 1988 | When neutrophils invade inflamed areas of the body to remove either dead or foreign components they inadvertently release potent enzymes which can, if not properly controlled, cause severe damage to healthy tissue. This can lead to a myriad of diseases including emphysema, rheumatoid arthritis, and glomuerlopnephritis, all of which are really problems of abnormal connective tissue turnover due to uncontrolled protelysis by neutrophil elastase and cathepsin G. An important step in elucidating the functions of both elastase and cathepsin G has been made by virtue of the fact that the amino acid sequence of each has been determined. Furthermore, the crystal structure of one, neutrophil elastase, is now understood. With this knowledge in mind and with the potential for a similar understanding of the mechanism of action of cathepsin G, it should soon be possible to produce synthetic inhibitors of each enzyme which can act as adjunct inhibitors to those naturally circulating in the blood or present in other tissues. As a result there is great hope for reducing the severity of injury produced by these enzymes and, therefore, in decreasing the risk for development of the debilitating diseases associated with abnormal proteolysis by neutrophil proteinases. | |
| 3262908 | Antibodies to amyloid A protein in rheumatic diseases. | 1988 | Circulating autoantibodies against amyloid A protein (AA) were demonstrated by enzyme immunoassay in 18/62 patients with rheumatoid arthritis (RA) and in 9/27 patients with systemic lupus erythematosus (SLE). In the subset of RA patients who had developed amyloid, the frequency of antibodies to AA was lower than in those without amyloid (P less than 0.05). The antibody levels showed some variation in serial serum samples during follow-up (1-4 years) of patients with amyloidosis or SLE, but did not correlate with disease activity. In contrast to the patients with rheumatic diseases, patients with inflammatory bowel disease and acute bacterial peritonitis had antibody levels within the range of the healthy control subjects. The results show that autoantibodies to protein AA may occur in rheumatic diseases; their occurrence does not, however, identify subjects with tissue amyloid deposits. Absorption experiments suggest that the antibodies may be directed to circulating amyloid A protein. | |
| 3438510 | [Rupture of the anterior cruciate ligament: a frequently unrecognized cause of failure of | 1987 | Out of 386 unicompartmental prostheses inserted in the Orthopaedic Centre in Dracy Le Fort between 1977 and 1986, 79 cases in 68 patients with a follow-up equal to or more than five years and a mean of seven years were able to be reviewed. This study showed that 75 per cent of knees had a satisfactory result and 25 per cent were failures. Apart from well-recognised causes of failure such as rheumatoid arthritis, overcorrection or the use of a six millimetre tibial plateau, the authors discovered a frequent cause not clearly recorded in the literature--that is anterior cruciate laxity. This situation was found retrospectively in the pre-operative weight-bearing radiographs. Out of 15 knees showing a pre-operative laxity equal to or greater than 10 mm in the lateral radiograph, 13 were failures and 10 were operated on again after a mean of three-and-a-half years. An investigation of anterior cruciate laxity should be made systematically by weight-bearing lateral radiographs, if necessary with stress views, before recommending a unicompartmental prosthesis. | |
| 2440743 | The clinical use of intravenous gammaglobulin. | 1987 | The availability of safe and effective preparations of human immune globulin that can be administered intravenously has revolutionized replacement therapy for patients suffering from hypogammaglobulinaemia. Of equal importance and greater interest, however, has been the recognition that super physiological doses of IgG can manipulate an abnormal immune system. Future prospects for the use of immunoglobulin preparations to supply specific antibodies includes the standardization of procedures, whereby patients with acute sepsis may receive antibiotics and immunoglobulin simultaneously. Already there is in vitro evidence that suggests that opsonized bacteria are more readily affected by aminoglycosides. It seems certain that gamma globulin will be used routinely in the management of patients with a number of immunomalignancies, such as chronic lymphatic leukaemia and multiple myeloma that feature hypogammaglobulinaemia, especially when chemotherapy is being administered. Control trials are underway to determine whether gamma globulin given intravenously to premature babies will satisfactorily correct their immuno-deficient state and improve their chances of survival. The immunomanipulative capacity of immunoglobulin is yet to be fully realized. Success in ideopathic thrombocytopenic purpura had led to a trial of gamma globulin in a number of autoimmune conditions. Success has been reported in myasthenia gravis, rheumatoid arthritis, diabetes, patients with circulating antibodies to factor VIII and Kawasaki's disease. The mechanism of action is unknown but almost certainly multifactorial. Two proven mechanisms that will be added to in the future, include blockade of the Fc receptors on cells of the reticulo-endothelial system and manipulation of immunoregulatory T cells by the presence of anti-idiotypic antibodies in the preparation. | |
| 2294514 | A test of the Self-Help Model: learned response to chronic illness experience. | 1990 Jan | The purpose of this study was to increase understanding of the essential dynamics of learned response to chronic illness experience. A Self-Help Model was tested with 396 subjects with diagnoses of rheumatoid arthritis or arthritis-related conditions. Self-Help Model variables include disease characteristics, background inputs, monitoring, severity of illness, dependency, uncertainty, enabling skill, self-help, and life quality. Severity of illness, disease characteristics, background inputs, and monitoring explained 24% of the variance in dependency and 40% of the variance in uncertainty. Monitoring was the strongest contributor to explanation of enabling skill; however, only a small amount of the variance in enabling skill was explained, adjusted R2 = .15. Enabling skill was the strongest predictor of self-help, beta = .42, minimizing the influence of uncertainty, beta = -.23 and dependency, beta = -.10, on self-help, R2 = .55. Self-help was strongly related to life quality, beta = .62. Self-help and uncertainty explained 49% of the variance in life quality. Results suggest a basis for interventions that reduce dependency and uncertainty and enhance enabling skill. | |
| 2672341 | The metabolism and immunology of bone. | 1989 Aug | Many cells and their cytokines produce a significant effect on bone metabolism. Bone matrix synthesis is a function of the osteoblast (Fig 1), influenced directly by numerous local and systemic factors (Tables 1 and 2). Locally synthesized factors such as SGF, BMP, and BDGF may be particularly important in stimulating new bone formation at sites of bone resorption or following bony injury. Of the systemic factors, GH; somatomedin C (IGF-1); high concentrations of insulin, testosterone, PDGF and TGF beta; and low concentrations of PGE2 and IL-1 appear to stimulate bone formation in vitro. These latter factors may be more important in maintaining skeletal growth and bone mass. Bone resorption by osteoclasts (Figs 2 and 3) is also controlled by the osteoblast, as this cell produces a leukotriene-dependent polypeptide that stimulates osteoclastic bone resorption. Osteoblasts cover the periosteal and endosteal bone-surfaces and limit exposure of the underlying bone to osteoclasts. PTH, vitamin D, PGE2, and other systemic factors interact directly with the osteoblast, not the osteoclast. Surface receptor binding of PTH increases intracellular cAMP and calcium and results in release of the factor that stimulates osteoclastic bone resorption. PGE2 induces osteoblasts to activate osteoclasts and is a major controlling factor in bone metabolism; the osteoblast produces PGE2, which can then modify osteoblastic function by positive feedback. Although low concentrations of PGE2 stimulate bone formation, higher concentrations promote osteoblast-mediated bone resorption. Furthermore, many of the systemic factors stimulate bone resorption via a PGE2-associated mechanism. Immune cytokines also appear to exert a profound influence on bone metabolism. INF-gamma inhibits osteoclastic resorption, whereas IL-1, TNF, and LT strongly stimulate bone resorption. However, low concentrations of IL-1 paradoxically result in stimulation of bone formation. These cytokines, particularly in various combinations, may prove extremely important in understanding and treating the bone loss associated with malignancies, osteoporosis, and rheumatoid arthritis. | |
| 2141550 | Activation of human T cell clones through the UM4D4/CDw60 surface antigen. | 1990 Jul | UM4D4 is a recently defined antigen that is expressed on approximately 25% of peripheral blood T cells, but on the majority of T cells in inflammatory synovial fluid. Anti-UM4D4 activates peripheral blood T cells in the presence of accessory cells and/or phorbol ester. UM4D4 has been assigned to a new antigen cluster termed CDw60. The present study examined the ability of anti-UM4D4 to activate T cell clones derived from the synovial fluid of patients with rheumatoid arthritis. UM4D4 was expressed at varying levels on both lectin-generated and antigen-specific clones, including clones of CD4+, CD8+, and CD4-CD8- phenotypes. Anti-UM4D4 used in soluble form as a single stimulus was typically mitogenic for the CD4+ and some of the CD8+ clones, but not for the CD4-CD8- clones. Phorbol ester boosted the response to anti-UM4D4 in some clones, had no effect in others, and diminished the responses in some cases. In contrast to anti-UM4D4, anti-CD3 was generally not mitogenic in soluble form, although it was mitogenic when conjugated to beads. The data show that T cell clones derived from an inflammatory T cell infiltrate can be readily activated through the UM4D4/CDw60 antigen. |