Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 908228 | Pulmonary nodules and rheumatoid factor in the absence of arthritis. | 1977 Oct | Bilateral pulmonary parenchymal nodules were detected in a 41-year-old woman in 1964. These lesions gradually enlarged over a ten-year period. In 1974, the diagnosis of rheumatoid pulmonary disease was based on her clinical course, the presence of rheumatoid factor in the serum, interpretation of a biopsy of a cutaneous nodule, and review of a lung biopsy performed in 1964. The patient never developed arthritis. | |
| 6159213 | Turnover in humans of beta 2-microglobulin: the constant chain of HLA-antigens. | 1980 Aug | The turnover of beta 2-microglobulin, the common subunit of the HLA antigens, has been examined in normal subjects and in some patients with kidney disorders, multiple myeloma and rheumatoid arthritis. All patients displayed elevated serum levels of beta 2-microglobulin. The plasma disappearance curve of 125I-beta 2-microglobulin demonstrated that the protein has a rapid turnover (t 1/2 = 2.1 h; range 1.1-2.8 h) in normal persons and in patients with a normal glomerular filtration rate. In patients with kidney disorders the impaired renal filtration prolonged the turnover time and led to elevated serum levels of beta 2-microglobulin. Simultaneous measurements of 125I-beta 2-microglobulin in serum and urine allowed estimations of the beta 2-microglobulin net reabsorption in the renal tubuli. Two patients with renal disease reabsorbed 84% and 89%, respectively, of the beta 2-microglobulin filtered in the glomeruli. In normal persons the net reabsorption is close to 100%. In patients with normal kidney function increased serum levels of beta 2-microglobulin seem to be due to an increased synthetic rate of the protein as the elimination rate is normal. HLA antigen heavy chains in serum are present in smaller amounts than beta 2-microglobulin. The present data, therefore, suggest an imbalanced synthesis of the two chains. | |
| 6116956 | Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. | 1981 Oct 17 | In rheumatoid arthritis the synovial membrane has many of the characteristics of a hyperactive, immunologically-stimulated lymphoid organ. The basis of this hyperactivity is poorly understood. Highly specific antisera to human Ia-like (HLA-DR) antigens and monoclonal antibodies (OKT series) to various T-lymphocyte subsets were used to analyse both the normal and the rheumatoid synovium and to compare it with normal lymph nodes. In rheumatoid arthritis the synovium acquires an infiltrate with microanatomical similarities to the paracortical area of the lymph node. Large, very strongly HLA-DR-positive macrophage-like interdigitating cells form close contacts with the OKT4+ (inducer-type) T-cells, while the OKT8+ population (T-cells of suppressor-cytotoxic type) between the macrophage-OKT4+ cell clusters is scanty (T4/T8 ratio = 9:1). By contrast, in the lymph node there are more OKT8 T-cells interspersed between the HLA-DR+ interdigitating cells and OKT4+ cells (T4/T8 ratio = 2:1). The large interdigitating cells and the OKT4+ T-cell population may be mutually stimulatory. In the absence of efficient suppression this stimulation may lead to activation of B-lymphocytes and oligoclonal or polyclonal immunoglobulin synthesis, as is found in the synovial membrane in rheumatoid arthritis. | |
| 451180 | Radiologic features of Reiter disease. | 1979 Jul | The radiologic manifestations of Reiter disease in 56 patients are described. Although the findings are often nonspecific, certain features are distinctive, particularly when present in combination. These include subtle periosteal bone apposition at bony prominences, the infrequency of regional panarthritis and hip and shoulder involvement, the tendency for destructive arthritis to be confined to small joints, particularly in the feet, and a typically "discontinuous" spondylitis characterized by eccentric, laterally positioned vertebral hyperostoses which tend to bridge around the contigous disk. Attention is drawn to similar hyperostoses which occur above the true sacroiliac joints. The significance of these features, particularly in terms of differential diagnosis, is discussed. | |
| 386498 | Cold lymphocytotoxins in connective tissue disorders. | 1979 Jan | Sixty-eight patients with various connective tissue disorders, 5 relatives of patients and 26 members of staff from the Centre for Rheumatic Diseases were studied for the presence in their sera of cold lymphocytotoxic antibodies. Antibodies were found in 71 percent of patients with systemic lupus erythematosus, 27 per cent of patients with rheumatoid arthritis, 0 per cent of the small group of relatives and 3.8 per cent of the controls. Absorption studies did not show T or B specificity of the antibodies. The control group, working in close proximity to the patients or their sera did not show any increased incidence of antibodies as compared to control groups of other studies. Red blood cell anti I or HI was found in the sera of 28 per cent of those with cold lymphocytotoxic antibodies. No correlation was found between the presence of the antibodies and number of blood transfusions or pregnancies, increasing age, R3 titre or antinuclear factor. | |
| 1112844 | The use of spinal anesthesia for total hip-replacement arthroplasty. | 1975 Mar | Two hundred and thirty-four total hip replacements in 199 patients performed by one surgeon were reviewed to compare the effects of spinal and general anesthesia. The amount of total blood loss was reduced an average of 600 milliliters in patients under spinal anesthesia. The amounts of operative blood loss, postoperative suction drainage, and blood replacement were also reduced very significantly (p smaller than 0.001). The patients in the two anesthesia groups were similar as to sex, age, body weight, pre-existing medical disease, preoperative medications administered, hip disease, type of prosthesis used, position during surgery, and anticoagulation regimen. The postoperative complications were fewer in the spinal anesthesia group. It is concluded from this study that spinal anesthesia is to be preferred over general anesthesia in patients undergoing total hip replacement. | |
| 6253525 | Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic | 1980 Nov | The predominant lipoxygenase products of arachidonic acid were extracted and purified from synovial fluid and sonicates of synovial tissue of patients with rheumatoid arthritis (RA), spondyloarthritis (SA), or a noninflammatory arthropathy (NIA). The concentration of 5(S),12(R)-dihydroxy-6,8,10-(trans/trans/cis)-14-cis-eicosatetraenoic acid (leukotriene B4) in synovial fluid was elevated significantly in patients with RA and a positive latex test for rheumatoid factor (P < 0.05, n = 14) and in patients with SA (P < 0.05, n = 10), compared with that of subjects with NIA (n = 9). The content of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), but not of leukotriene B4, was elevated significantly in synovial tissue of seven patients with RA in comparison with that of four subjects with NIA (P < 0.05). A single intra-articular injection of corticosteroid significantly lowered the synovial fluid level of leukotriene B4 in six patients with RA. These data suggest an involvement of the potent chemotactic factors 5-HETE and leukotriene B4 in human inflammatory disease. | |
| 6374899 | Osteopenia in rheumatology practice: pathogenesis and therapy. | 1984 May | Postmenopausal osteoporosis has a multifactorial pathogenesis related to decreases in bone mass, calcium intake, and circulating estrogen levels. Therapy with supplemental calcium, estrogen, fluoride, anabolic steroids, and calcitonin is discussed. Corticosteroid-induced osteopenia is in part related to a decrease in intestinal calcium absorption and therapy with supplemental vitamin D and calcium may favorably alter the outcome. The osteopenia of rheumatoid arthritis appears to be a diffuse process, with increased metabolic bone activity at sites that are remote from the areas of active synovitis. | |
| 2934806 | Prevalence of symptoms and signs of joint impairment at age 79. | 1985 | The prevalence of back and joint impairments was studied in a representative subsample of 77 women and 57 men aged 79. Forty-six per cent of the subjects had no history of back or joint complaints. Thirty-two per cent reported current back pains while 50% stated they never experienced such pains. Back pains (past or present) were localized in the lumbar region predominantly (40%), and were almost constantly present in 8% of the subjects. The spinal mobility remained acceptable for function of the activities of daily living (ADL) in the majority of the subjects. Thirty-six per cent of the subjects had past or present complaints from the joints of the extremities, predominantly of the knee, shoulder or hip joints. Physical signs of joint disorders as deformities, swelling or tenderness were rare except for enlargement of distal interphalangeal joints (right hand: females 38%, males 14%). Restricted range of motion (ROM) in one or several joints was found in one fifth (i.e., knee joints) to two thirds (i.e., hip joints). No significant gender differences were observed with the exception of the thoracolumbar ROM that was more frequently restricted in males. Severe restriction of separate movements (to less than 50% of ROM) was, generally, infrequent (0-8% of the subjects) although advanced impairment of hip inward rotation was found in 14% of the subjects. Restricted ROM associated with joint complaints was found in 2-11% of the subjects (i.e., knee joints 2%, shoulder joints 9%, hip joints 11%). A considerable proportion of 79-year-olds, thus, had some--though usually limited--restriction of joint ROM. | |
| 6480788 | High-performance liquid chromatographic determination of bupivacaine in human serum. | 1984 Aug 10 | A selective high-performance liquid chromatographic method for the determination of bupivacaine in human serum is described. The technique is based on a single extraction of the drug from alkalinized serum with a mixture of hexane-isopropanol-chloroform. Desmethyldoxepin is used as internal standard. The chromatographic system consists of a home-packed Nucleosil C8 (10 microns) column; the mobile phase is acetonitrile--0.05 M potassium phosphate buffer (pH 3.3) (28:72, v/v). The method can accurately measure serum bupivacaine concentrations down to 20 micrograms/l using 500 microliters of sample. The coefficient of variation for intra-assay variability of bupivacaine is 2.1% (n = 13) and for inter-assay variability of bupivacaine 5.7% (n = 11) at 1.00 mg/l. The calibration graph is linear over the range 0.02-5.00 mg/l and the extraction efficiency is 91.8 +/- 3.8% (+/- S.D., n = 7). The method is accurate and sensitive for both clinical and pharmacokinetic studies on bupivacaine in man. The method is applied to the analysis of serum samples obtained from orthopaedic patients during both spinal and epidural analgesia. | |
| 3877768 | A rapid and reproducible method for the analysis of immune complexes using affinity chroma | 1985 Nov 28 | A new procedure which couples different analytical techniques in a format permitting the rapid analysis of immune complex components is described. Complexes obtained from sera by polyethylene glycol (PEG) precipitation were resuspended and then added, using a batch method, to antibody coupled to Sepharose beads. Antibody directed against either human C1q or human C3c were used in the present study. Bound immune complexes were washed and then eluted from the Sepharose by sodium dodecyl sulphate (SDS) treatment and simultaneously reduced with dithiothreitol. Individual components were separated by SDS gradient polyacrylamide gel electrophoresis and then transferred to nitrocellulose by Western blotting. Individual strips of nitrocellulose were investigated using specific antisera and a radiolabelled probe. Immune complexes (IC) isolated from the sera of 7 rheumatoid arthritis (RA) patients were analysed using this method and the results obtained for both affinity adsorbents compared. | |
| 6362945 | The role of cellular interactions in joint erosions. | 1984 Jan | Maintenance of the normal integrity of articular cartilage is due to a balance between the synthesis and degradation of the extracellular matrix. This balance is maintained as a result of the anabolic and catabolic activities of the indigenous cells, the chondrocytes. It is becoming understood that the metabolic activity of the chondrocytes can be modified by certain intercellular messengers. To date, two such intercellular messengers have been recognized and partially characterized: the interleukins and the catabolins. These messengers are probably part of a much wider family of proteins that function in the control of connective tissue structure in general. In terms of the arthritic diseases, the catabolins seem likely to play a role in the early stages of chondrocyte-mediated matrix degradation in osteoarthritis, (OA), while in rheumatoid arthritis (RA) the catabolins, probably coming from the fibroblastic cells of the synovium, and the interleukins, probably originating from the inflammatory cells of the pannus, may work in association with extrinsic proteinases secreted by a number of component cells of the inflammatory synovium. Recognition of the role of intercellular messengers in both the physiology and pathology of articular tissues provides new and exciting possibilities in pharmacodynamic systems for prevention of joint damage. | |
| 7416061 | Lipoproteins and cholesterol esterification rate in plasma during a 10-day modified fast i | 1980 Sep | The influence of a 10-day modified fast on the concentrations of lipids and lipoproteins and the rate of cholesterol esterification in plasma was studied in 12 subjects with rheumatoid arthritis. The subjects were randomized and seven patients completed the period of fasting while the others served as controls. During the withdrawal of nutrients a rich supply of fluids, at least 2.7 to 3 liter/day containing around 200 kcal was given as fruit or vegetable juices and teas. After 10 days of fasting the concentrations of cholesterol and phospholipids in plasma were reduced by a mean of 21 and 11%, respectively, based on a 27% mean reduction of these lipids in the low density lipoprotein fraction. In all fasting subjects but one there was a reduction of the triglyceride concentration in the very low density lipoprotein fraction. The high density lipoprotein fraction was unchanged. The molar and fractional cholesterol esterification rates in plasma were reduced by a mean of 27 and 8.5%, respectively, after 10 days of fasting compared to the prefasting levels. The rate of cholesterol esterification in plasma is believed to reflect the turnover of cholesteryl esters in plasma, which therefore seemed to be reduced during fasting. The present findings might be explained by deprivation of specific nutrients or by a generally reduced metabolic rate during energy deprivation. | |
| 6421522 | Interleukin 2 deficiencies in rheumatoid arthritis and systemic lupus erythematosus. | 1984 Apr | The ability of peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren's syndrome (SS) to produce interleukin 2 (IL-2) and respond to it in-vitro was examined. Phytohemagglutinin-stimulated lymphocytes from over half of the SLE patients exhibited a decreased ability to produce IL-2 while their concanavalin A-generated blast cells responded normally to exogenous IL-2. Lymphocytes from RA patients not only produced less IL-2 than normals (P less than 0.001), but also responded poorly to exogenous IL-2 (P = 0.011). These abnormalities did not correlate with the patient's age, sex, duration of disease, or disease activity. Production of and response to IL-2 was widely varied among patients with SS and not different from controls. The decreased response of RA lymphocytes to IL-2 may result from a smaller number of cell surface IL-2 receptors since IL-2 adsorption to RA cells was lower than to either SLE or normal cells. These data suggest that IL-2-related abnormalities may play a role in the disordered immunoregulation characteristic of RA and perhaps of SLE. | |
| 6607144 | Evidence for B cell activation in patients with active rheumatoid arthritis. | 1984 Jan | Peripheral blood lymphocytes and in some cases synovial eluate cells from 51 patients with rheumatoid arthritis (RA), were analysed for the percentages of cells bearing surface light chains (total B cells), IgM and IgD. In addition, their capacity to form rosettes with mouse erythrocytes (mRFC)--a property of a B cell subpopulation--was determined. Activity of the disease was assessed by clinical and laboratory criteria and classified as very active, moderately active and inactive. Normal, age and sex matched individuals and a group of patients with a variety of other rheumatological disorders, were used as control populations. Although there was no significant difference in percentages of total B cells in any of the groups compared with normal controls, there was a small but significant increase in the ratio of cells bearing IgM to those bearing IgD in patients with very active disease. This was paralleled by a significant decrease in the mRFC in this disease activity group. Patients with inactive disease showed no change in their proportions of IgM:IgD, but did show a significant increase in mRFC. These results are discussed in terms of the presence of activated B cells in patients with very active RA. | |
| 6360612 | Pirprofen. | 1983 Dec | Pirprofen, a nonsteroidal antiinflammatory drug (NSAID) undergoing Phase III investigation as Rengasil (Ciba-Geigy Corp.), is useful in the management of both rheumatoid arthritis and osteoarthritis and as an analgesic. In doses of 600-800 mg/d, pirprofen has been found to be as effective as, but not superior to, aspirin 3.6 g/d in relieving the more common symptoms of rheumatoid arthritis. Pirprofen is as effective as, but not superior to, other available NSAIDs in terms of efficacy, tolerability, and incidence of adverse effects. The recommended dosage in osteoarthritis is 450-600 mg/d. As with all NSAIDs, including aspirin, the side effects most commonly seen with pirprofen are gastrointestinal in nature. Peptic ulceration and occult gastrointestinal blood loss have been reported in a small percentage of patients receiving pirprofen. Central-nervous-system-related side effects that are frequently associated with high-dose aspirin therapy appear less frequently with pirprofen. Although it does not offer distinct advantages over other NSAIDs, pirprofen offers an effective therapeutic alternative for patients who are unable to tolerate aspirin or other existing compounds. | |
| 6177558 | Adjuvant arthritis: immunopathological and hyperalgesic features. | 1982 Jul | Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human rheumatoid arthritis and, as such, is one of the most widely used models for studying the anti-inflammatory properties of compounds. Adjuvant arthritis can be induced in the rat by the injection of various bacterial cell walls or their components; however, the exact immunogen remains unknown. Recently, an autoantibody response to type II collagen was described not only in the collagen-induced arthritic model but in the adjuvant-induced disease as well. This response thus suggests that shared antigenic determinants exist between type II collagen and the responsible immunogen in the bacterial cell wall components. The contribution of the T lymphocyte to the pathogenesis of adjuvant arthritis is well known. It has now been shown that under specific conditions, adjuvant arthritis can be either enhanced or suppressed with pharmacologic or surgical manipulation, thus suggesting the heterogenicity of T lymphocytes capable of influencing the course of the disease. Levamisole was shown to reverse the augmentation of adjuvant disease seen after adult thymectomy, which suggests that levamisole can restore an aberrant immune response. Monoclonal antibodies are now being developed to evaluate T cell subsets in the rat. The use of these antibodies to study or selectively deplete lymphocyte subpopulations in this disease model promises to reveal immunologic characteristics that may lead to the development of new classes of immunoregulant drugs. Finally, the adjuvant rat has been found useful as a pain model capable of detecting the analgesic properties of both central and the newer peripheral analgesics. The above studies further corroborate the similarities between the immunopathological and hyperalgesic features of human rheumatoid arthritis and adjuvant disease. Recently developed immunologic technology may allow a new look at an old model and may result in the ability to evaluate new classes of immunoregulating agents. | |
| 7131712 | Atherosclerosis of the coronary arteries in collagen disease and allied disorders, with sp | 1982 Nov | To clarify the etiology of atherosclerosis in collagen disease, the prevalence and quality of coronary arterial lesions was examined histopathologically. The materials consisted of 68 autopsy cases, including 10 of rheumatoid arthritis (RA), 28 of systemic lupus erythematosus (SLE), 8 of progressive systemic sclerosis (PSS), 5 of dermatomyositis (DM) and 17 of miscellaneous collagen disease (MD). As a control group (C), 9 age-matched cases of hematologic disorders were chosen. In order to conduct systematic research on coronary arteries, tissue blocks were taken, according to the method proposed by the "Vascular Lesion of Collagen Disease Research Committee" in Japan. To estimate the narrowing of the coronary arterial lumen quantitatively, the coronary stenosis index (CSI), which was the sum of the grade of three main coronary arterial narrowing scores, were used. Significant coronary stenosis (more than 75% occlusion of the lumen) was observed in 8 cases of SLE, one of PSS, 2 of DM and 4 of MD. Stenosis was due to atherosclerosis except in 3 cases of MD. The degree of stenosis expressed by the CSI was higher in MD, SLE and DM than in C (p less than 0.05). Atherosclerotic lesions in collagen disease tended to have a higher population of cellular components than did those in C. There were no statistical correlations between the CSI and some risk factors (age, hypertension, hypercholesterolemia and long-term corticosteroid administration). In the 12 cases with significant stenosis due to atherosclerosis, only 4 patients received corticosteroid hormone for more than one year. Active vasculitis with prominent inflammatory cell infiltration was observed in 2 cases of RA, 3 of SLE and 9 of MD. In cases of vasculitis in SLE examined by the serial section method, luminal narrowing caused by intimal fibrocellular proliferation seemed to have a close relationship with inflammatory cell infiltration in the media and the adventitia. It was concluded that prolonged stimulation of the injured intima by the common risk factors played an important role in the acceleration of coronary atherosclerosis and this intimal change should be reconsidered as a preceding lesion of coronary atherosclerosis. | |
| 3915304 | Therapeutic benefits of oxygen radical scavenger treatments remain unproven. | 1985 | Pharmaceutical firms and practitioners are rushing to test the medical benefits of oxy radical scavengers in a multitude of clinical situations despite the fact that convincing evidence of oxygen radical tissue damage in vivo is lacking and that properly controlled trials have been few and far between. Analysis of the therapeutic literature reveals disturbing discrepancies: unconvincing animal data, disparities between pharmacologic and enzymatic activity, and prolonged clinical improvements reported in situations where none should be expected. The proper control, inactivated scavenging enzyme, has never been used clinically or in animal models. The results of clinical trials with scavengers have a wider interpretation, since benefits are extrapolated to imply pathophysiologic mechanisms. It is especially important, therefore, no matter how hard we would like to believe that oxygen radical scavenging will be a therapeutic breakthrough, that we insist upon tightly designed clinical trials. | |
| 6869409 | Ophthalmologic safety of long-term hydroxychloroquine sulfate treatment. | 1983 Jul 18 | The fear of retinal toxicity has been a major factor limiting the use of chloroquine and hydroxychloroquine. Patients reported to develop retinal toxicity with visual loss usually took daily dosages higher than those currently in use. Toxicity with low dosages (for example, 250 mg per day chloroquine or 400 mg per day hydroxychloroquine) usually reveals pigment abnormalities; associated loss of vision is rare. When 99 patients treated with hydroxychloroquine for more than one year were studied prospectively, four patients showed evidence of retinal toxicity; none developed visual loss, and all abnormalities were completely reversible after drug discontinuation. All persons receiving antimalarials should be evaluated by an ophthalmologist at baseline and every six months thereafter. Funduscopic examinations and visual field testing with a red object must be included. Although this protocol may detect abnormalities that are not drug related, no loss of vision has developed in patients so monitored. |