Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3046757 | Renal biochemistry in rheumatic disease. | 1988 Apr | In patients with osteo-arthritis, renal disease will almost invariably be the consequence of unrelated coincidental renal pathology. In polyarthritic rheumatoid arthritis and ankylosing spondylitis, renal disease can arise as part of the pathology of a systemic disease, or more likely its treatment. As a rule amyloidosis is the most important complication in terms of progressive irreversible loss of renal function. By contrast, SLE, polyarteritis and Sjögren's disease carry a much higher risk of renal involvement. The regular evaluation of renal function in such patients can enable the kidney damage to be assessed at an early stage and allow treatment to be instituted early. | |
| 2041892 | Diffuse infiltrative lymphocytosis syndrome in human immunodeficiency virus infection--a S | 1991 Feb | Certain adults and children with human immunodeficiency virus (HIV) infection develop a syndrome characterized by marked parotid gland enlargement, sicca symptoms and pulmonary insufficiency. Lymphocytic tissue infiltration is accompanied by circulating CD8 lymphocytosis, and autoantibodies are infrequently observed. Progressive lymphocytic visceral involvement may necessitate the careful use of immunosuppressive therapy, in addition to antiretroviral agents. Specific associations with particular MHC class I and II gene products suggest that this disorder may represent a distinctive host immune response to HIV. Infection with HIV should be considered in all high-risk individuals presenting with the sicca syndrome. Similarly, it should be considered in individuals in whom Sjögren's disease is a diagnostic possibility but where atypical features are present. | |
| 3035352 | Epstein-Barr virus as an etiological agent in primary Sjögren's syndrome. | 1987 Apr | It is proposed that the initiating event in primary Sjögren's syndrome is infection with Epstein-Barr virus (EBV), and that the autoimmune exocrinopathy that progresses to keratoconjunctivitis sicca and xerostomia is a sequel to this. Our hypothesis is based on the findings that the antinuclear antibody, anti-La(SS-B), is a marker of primary Sjögren's syndrome, and that anti-La reacts with a ribonucleoprotein, the La autoantigen, to which bind not only all cellular RNAs transcribed by RNA polymerase III, but also the viral RNAs, EBER 1 and EBER 2, encoded by the Epstein-Barr virus (EBV). It is proposed that during EBV infection, there are multiple copies of the EBERs available to bind to the La ribonucleoprotein and when infection occurs in subjects who have an impaired T cell-mediated response to EBV, and who are genetically predisposed to autoimmunity, there is loss of immunological tolerance to La with production of anti-La (SS-B). Thus the inflammatory process in exocrine glands which culminates in the sicca syndrome is due to the combined effects of chronic EBV infection and autoimmunity. Two patients are briefly described in whom primary Sjögren's syndrome appeared to be a direct consequence of EBV infection. The hypothesis engages the question of the respective roles of virus infection, specific immunodeficiency to virus, immunogenetic constitutive influences and an autoimmune response to a ribonucleoprotein antigen in the genesis of a particular organ-specific inflammatory reaction. | |
| 1940783 | Misoprostol-induced urinary incontinence. | 1991 Nov | In a young woman with rheumatoid arthritis misoprostol induced urinary incontinence. The urodynamic study described here revealed a deficiency in urethral resistance which may explain the phenomenon. This side-effect may be more common than expected, and misoprostol should be administered with caution to patients suffering from urinary stress incontinence. | |
| 3338420 | Lingual seizures. | 1988 Jan | A 73-year-old patient with hyperglycemia and rheumatoid arthritis presented with attacks of involuntary lingual movements that were associated with pain at the base of the tongue, often followed by aversion of head and eyes to the left with clonic contractions of the left corner of the mouth. Seizures could be induced by a combination of specific movement and somesthetic stimuli. Ictal EEG recording revealed a focal epileptiform discharge in the right centrofrontal area, thus confirming that the patient had lingual seizures, an extremely unusual manifestation. | |
| 3578339 | Pyoderma gangrenosum with myelofibrosis. | 1987 May | Pyoderma gangrenosum is a papulovesicular skin disorder commonly associated with underlying systemic disease, but rarely with the myeloproliferative syndromes. A case of rapidly progressive pyoderma is cited in a 77-year-old white man who had no other evidence of disease aside from macrocytic anemia. Bone marrow biopsy revealed proliferation of fibroblasts and a dense reticulin network consistent with myelofibrosis. Response of the pyoderma to steroid therapy was dramatic. Although pyoderma gangrenosum is more commonly associated with inflammatory bowel disease and rheumatoid arthritis, this is the fifth reported case of its coexistence with idiopathic myelofibrosis. | |
| 3698395 | Management of infected total knee arthroplasty. | 1986 Apr | A retrospective study of the Mayo Clinic experience with the management of 61 infected total knee arthroplasties treated between 1970 and 1980 revealed rheumatoid arthritis as an underlying diagnosis in 47%. Previous operations had been performed in 58%. Arthrodesis was the most frequently utilized salvage technique and was successful in 83%. Reimplantation of a new prosthesis was successful in 63%. Debridement alone was successful in six knees when performed early for acute infections. | |
| 3741515 | Development of criteria for the classification and reporting of osteoarthritis. Classifica | 1986 Aug | For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms. | |
| 3004515 | Alterations in macrophage collagenase secretion induced by gold sodium thiomalate. | 1986 Jan | The effects of gold sodium thiomalate (GST) on the production of specific collagenase by thioglycolate-elicited macrophages was investigated. Our studies demonstrated that GST administration can significantly decrease collagenase production in a dose-dependent manner. These effects were observed with levels of GST attainable in serum or synovial tissue during routine chrysotherapy. In addition, GST altered lysozyme secretion by activated macrophages in a pattern distinct from that of collagenase alteration. These effects of enzyme secretion were not secondary effects of GST on viability, general protein secretion, or the specific assay procedures utilized, and were not attributable to the thiomalate moiety. Thus, GST may exert its therapeutic effect in rheumatoid arthritis through interference with the production of degradative proteolytic enzymes, which are important effector molecules mediating tissue destruction. | |
| 2689006 | Genetic epidemiology of Greenland. | 1989 Nov | The Inuit (Eskimo) gene pool is in many respects similar to that of East Asian populations. Some polymorphisms imply frequent occurrence of disorders comparatively rare in Western Europe (e.g. lactose and sucrose malabsorptions). Low frequencies of alleles for slow isoniazid acetylation and sparteine/debrisoquine oxidation indicate slow elimination of a multitude of drugs. Autoimmune disorders (e.g. rheumatoid arthritis, insulin-dependent diabetes mellitus, Graves' disease and psoriasis) are rare, possibly explained by the associations of these disorders with HLA-alleles rare in the Inuit (e.g. HLA-B8). A correspondingly high incidence of reactive arthritis may be explained by a frequent HLA-B27 allele. The prevalence of disorders due to instability of mesenchymal tissues (e.g. spondylolisthesis, osteoarthrosis, hernia, heart block) still requires a biochemical explanation. Attention is drawn to the urgency of genetic studies in the Arctic because of the accelerating hybridization of the Inuit in all circumpolar areas. | |
| 2883843 | [Origin, diagnosis and treatment of sternoclavicular joint dislocation]. | 1987 Feb | Traumatic dislocation of the sternoclavicular joint is very uncommon (1,5% of all dislocation, 10% of all dislocations in clavicular joints; ratio acromioclavicular dislocations: sternoclavicular dislocations = 5-10:1). The functional importance of this joint requires open reduction with reconstruction of its ruptured ligaments and the disc. The sternoclavicular joint can be dislocated in association with congential, developmental, degenerative and inflammatory processes (M. Friedrich, rheumatoid arthritis). Epiphyseal separations or fractures of the medial end of the clavicle can usually be treated conservatively, but interposition of the joint capsule between the fragments may cause the dislocation to be irreducible. In addition to clinical examination and anteroposterior of oblique posteroanterior X-rays, tomography, computed tomography and arthrography can be of help in diagnosis. Additional special X-ray pictures as suggested by Heinig, Hobbs and Kattan are very helpful in determining the degree of dislocation (Allman). If open reduction is necessary, the functional importance of the disc and the angle of inclination of the joint socket must be taken into consideration. | |
| 2538840 | Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective | 1989 Apr | Inbred Lewis (LEW/N) female rats develop an arthritis in response to group A streptococcal cell wall peptidoglycan polysaccharide (SCW), which mimics human rheumatoid arthritis. Histocompatible Fischer (F344/N) rats do not develop arthritis in response to the same SCW stimulus. To evaluate this difference in inflammatory reactivity, we examined the function of the hypothalamic-pituitary-adrenal (HPA) axis and its ability to modulate the development of the inflammatory response in LEW/N and F344/N rats. We have found that, in contrast to F344/N rats, LEW/N rats had markedly impaired plasma corticotropin and corticosterone responses to SCW, recombinant human interleukin 1 alpha, the serotonin agonist quipazine, and synthetic rat/human corticotropin-releasing hormone. LEW/N rats also had smaller adrenal glands and larger thymuses. Replacement doses of dexamethasone decreased the severity of LEW/N rats' SCW-induced arthritis. Conversely, treatment of F344/N rats with the glucocorticoid receptor antagonist RU 486 or the serotonin antagonist LY53857 was associated with development of severe inflammatory disease, including arthritis, in response to SCW. These findings support the concept that susceptibility of LEW/N rats to SCW arthritis is related to defective HPA axis responsiveness to inflammatory and other stress mediators and that resistance of F344/N rats to SCW arthritis is regulated by an intact HPA axis-immune system feedback loop. | |
| 1725166 | Protective effects of human recombinant MnSOD in adjuvant arthritis and bleomycin-induced | 1991 | We have previously shown that human recombinant methionyl manganese superoxide dismutase (MnSOD) is more efficient than CuZnSOD as an anti-inflammatory agent in a model of acute inflammation (Carrageenan-induced paw edema). This effect was attributed to the prolonged half-life of MnSOD in blood (t1/2 = 6 h vs. 10 min, respectively). In the present study, the two enzymes were compared in terms of their effectiveness in two systems: (1) Adjuvant-induced arthritis in rats, which is considered to be a model for the chronic situation of rheumatoid arthritis and (2) Bleomycin-induced lung fibrosis, which is a chronic situation believed to be mediated by oxygen free radicals. Rats inflicted with adjuvant arthritis were treated during the period of maximal joint swelling (Days 15-21 after adjuvant injection) with MnSOD or CuZnSOD (12 to 50 mg/kg, i.p. daily). MnSOD administration resulted in a 50-75% reduction of paw swelling, as well as inhibition of the elevation of serum globulins. A similar treatment with CuZnSOD gave merely marginal effects. In the second system, lung fibrosis was induced in rats by intratracheal administration of bleomycin. MnSOD (50 mg/kg, s.c.), administered 2 h before and then 2 and 4 days after bleomycin, markedly inhibited lung fibrosis, as evident from lung weight and collagen content measured by the 3rd week. By contrast, CuZnSOD administration did not give a significant effect. The results indicate that MnSOD is superior to CuZnSOD in the treatment of chronic inflammatory processes. In addition, they lend further support to the involvement of oxygen free radicals in bleomycin toxicity. | |
| 3175547 | Individually adapted lightweight walking aids with moulded handles for patients with sever | 1988 | Patients with severely deforming rheumatoid arthritis and impaired function of the upper extremity are often unable to use conventional walking aids. This report describes 42 such patients who were equipped with altogether 75 individually manufactured, lightweight walking aids (12 crutches, 12 forearm-crutches, 39 crutch-sticks and 12 sticks). A plaster cast of the patient's grip as well as analysis of the integrated function of the shoulder-elbow-wrist was used when preparing the walking aid. It was thereby possible to produce suitable walking aids for all but one patient. At follow-up after 12-18 months, of use, most patients belonging to functional classes II and III were satisfied with their walking aid(s) and 22 considered it/them indispensable. However, in 4 patients, progressive disease with increased disease activity/deteriorating hand function and in 3 patients increasing shoulder pain reduced their usability. Lack of motivation was one reason for low use intensity. Follow-up demonstrated that most patients were able to use these walking aids without detectable negative effects on the upper extremity. The durability of the walking aid was satisfactory. Thus an individually moulded handle on an adapted lightweight walking aid is important helping patients with severely deforming arthritis to maintain independent ambulation, and should be made more widely obtainable. | |
| 3072384 | Collagen arthritis in rats, arthritogenic lymphokines and other aspects. | 1988 Sep | This review will mainly highlight data from selected, independent studies which collectively implicate a primary role for T cells in the pathogenesis of collagen arthritis in rats. Conferring insusceptibility to this experimental disease with the use of polyclonal, T cell specific antiserum provided direct initial evidence for this conclusion. Substantiation for the theory of a dominant T cell role in collagen arthritis was afforded by T cell line vaccination; scrutiny showed that the mechanism accounting for this protection was a specific down-regulation of the cellular response to collagen. Additional support came from experiments which showed that as few as 10(3) type II collagen specific T line cells were capable of provoking a sustained proliferative synovitis when instilled into the knee joint cavity of syngeneic naive rats. Further analysis of this phenomenon revealed that the arthritogenic capacity of various collagen-reactive line cells correlated with their ability to release a 65-Kd, collagen-binding lymphokine. This antigen-specific lymphokine was designated arthritogenic factor, based on an arthritogenic activity in the knee joint bioassay similar to that of the cells. A functional and physicochemically identical rat arthritogenic factor has also been identified in the adjuvant model of arthritis. These data support the premise that a major effector mechanism in experimental rat arthritis is the release of arthritogenic factor by expanded clones of autoreactive T cells; they also indicate that substantive efforts should be undertaken to seek to identify arthritogenic factor-like lymphokines in patients with chronic inflammatory synovial disease. As an equally plausible alternative hypothesis, the review will close with a brief discussion of recent findings supporting the possible involvement of cartilage-binding, complement-fixing anti-type II collagen antibodies in the pathogenesis of rheumatoid arthritis. | |
| 3105056 | Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell s | 1987 Apr 3 | B lymphocytes bearing the Leu-1 cell-surface antigen (Leu-1+), the human equivalent of mouse Ly-1+ B lymphocytes, have been detected in human peripheral blood, but there is little information on their frequency and properties. Analysis by fluorescence-activated cell sorter and double immunofluorescence showed that Leu-1+ B cells are consistently present in the peripheral blood and spleens of healthy subjects and constitute 17.0 +/- 5.0% (mean value +/- standard deviation) and 17.3 +/- 3.9%, respectively, of total B cells. When purified Leu-1+ and Leu-1- B lymphocytes were transformed into immunoglobulin-secreting cells by infection with Epstein-Barr virus and the culture fluids were tested for reactivity with self-antigens, at least two important autoantibodies, antibody to the Fc fragment of human immunoglobulin G (rheumatoid factor) and antibody to single-stranded DNA, were found to be made exclusively by Leu-1+ B cells. It is concluded that the Leu-1+ lymphocytes represent a major subset of the normal human B cell repertoire and include the B cells capable of making autoantibodies similar to those found in systemic lupus erythematosus and rheumatoid arthritis. | |
| 2493051 | Genetic diversity of murine rheumatoid factors. | 1989 Mar 1 | Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human and murine rheumatoid arthritis as well as in the regulation of normal immune responses. Their genetic origin, clonal diversity, and inducing agents, and the relatedness between RF associated with disease and those occurring under physiologic conditions are not well understood. In this study, the genetic and clonotypic origin of 34 monoclonal IgM RF-secreting hybridomas from arthritic MRL-lpr/lpr and nonarthritic MRL-+/+ and C57BL/6-lpr/lpr mice was examined by RNA hybridization. For this purpose, we used probes for 10 VH and 13 Vk gene families as well as all JH and Jk gene segments. The majority of hybridomas expressed distinct Ig gene segment patterns and, hence, were clonally unrelated. Overall, a variety of different V and J gene segments were expressed in the hybridoma panel, suggesting that a large number of distinct genetic elements participates in expression of RF-like activity. RF from arthritic mice expressed Vk messages from the overlapping Vk22 and Vk28 gene families more frequently than did those from nonarthritic mice. RF from autoimmune MRL mice, both arthritic MRL-lpr/lpr and nonarthritic MRL-+/+, showed skewed JH4 segment usage, whereas those from C57BL/6-lpr/lpr preferentially expressed JH2. | |
| 2784965 | Antiproliferative effects of methotrexate on peripheral blood mononuclear cells. | 1989 Apr | Methotrexate was added to cultured mononuclear cells from the peripheral blood of normal individuals and patients with rheumatoid arthritis (RA) to study the drug's effects on mononuclear cell proliferation and antibody synthesis. In the presence of methotrexate, marked antiproliferative effects (to levels less than 15% of baseline) were seen with 3H-deoxyuridine, but not with 3H-thymidine, as the marker of cell division. This difference was not due to altered kinetics of proliferation or the presence of salvage nucleotides in the culture medium. The absence of suppression of antibody production preactivated by pokeweed mitogen in vitro and the low levels of suppression of spontaneous IgM rheumatoid factor production by blood mononuclear cells from RA patients suggested a relative resistance of activated cells to the effects of methotrexate. The effects of methotrexate on both cell proliferation and antibody synthesis were completely reversed by the addition of high concentrations of exogenous folinic acid. The results suggest that methotrexate has effects on immunocompetent cells that may contribute to the efficacy of this drug in the treatment of RA and other autoimmune diseases. | |
| 3735281 | HLA antigens in psoriatic arthritis. | 1986 Jun | HLA antigen frequencies were studied in 158 patients with psoriatic arthritis, and compared to those of 101 patients with uncomplicated psoriasis and 243 healthy controls. The HLA antigens B16, B17, B27, B39 and Cw6 were associated with psoriatic arthritis. No associations between DR antigens and psoriatic arthritis were demonstrated. However, the subset of patients with rheumatoid-like arthritis demonstrated an increase in DR4. Uncomplicated psoriasis patients had higher frequencies of B17, Cw6 and DR7 than patients with psoriatic arthritis, while B7 and B27 correlated with development of arthritis. HLA-B27, Cw2 and DRw52 were associated with back involvement, whereas B38 and B39 were associated with polyarthritis. HLA-B7, B13 and DR7 correlated with milder disease in patients with psoriatic arthritis. | |
| 2593319 | [A study of microproteinuria in patients with collagen disease]. | 1989 Aug | To examine the subclinical renal damage in collagen disease, we analyzed the excretion pattern of microproteinuria. We studied 58 collagen disease patients including 25 RA (rheumatoid arthritis) patients, 15 SLE (systemic lupus erythematosus), 5 PSS (progressive systemic sclerosis), 4 MCTD (mixed connective tissue disease), and 9 others. Urinary protein was not detected by urine dipsticks in all patients. Urinary proteins, which were concentrated to 5 mg/ml, were subjected to linear gradient (4-30%) SDS-PAGE and then transferred to nitrocellulose membrane by electrophoretic blotting method. The membrane was stained with Auro Dye and the blotted proteins were identified by enzyme immunoassay using specific antibodies. The percentages of albumin of whole urinary proteins were 27.2 +/- 13.7% in RA and 25.8 +/- 12.6% in PSS, which were significantly lower than that of controls (42.1 +/- 15.3%). However no significant difference in the percentage of urinary albumin was noted between SLE and controls. The percentages of low molecular weight (MW) proteins (proteins having smaller MW than albumin) were higher in RA and PSS. Especially the bands with MW of 25,200 were prominent and these percentages were 11.3 +/- 6.1% in RA and 14.6 +/- 9.1% in PSS, which were significantly higher than controls (5.1 +/- 3.5%). These bands with MW of 25,200 were demonstrated to be free light chains of immunoglobulins by western blotting method. From the above observations, protein excretion patterns in RA or PSS patients were so-called tubular proteinuria, and especially free light chain excretion was increased. We proposed that tubular dysfunction and abnormal production of free light chain might exist frequently in collagen diseases, especially RA and PSS. |