Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2187494 | Cytokines and growth regulation of synoviocytes from patients with rheumatoid arthritis an | 1990 | Paracrine growth factors probably stimulate the pathologic proliferation of synovial fibroblast-like cells (synoviocytes) in rheumatoid arthritis (RA), but the relative importance of various factors is highly controversial. To address this problem, we compared the effects of highly purified or recombinant cytokines, in serum-free medium, on the in vitro long-term growth of synoviocytes from patients with RA and rats with streptococcal cell wall (SCW) arthritis. Of the factors tested (PDGF, aFGF, bFGF, EGF, TGF-beta, IL-1-alpha, TNF-alpha and IFN-gamma), PDGF, was clearly the most potent stimulant of long-term growth of both rat and human synoviocytes. The strong mitogenic activity of rheumatoid synovial fluids was significantly inhibited by neutralizing anti-PDGF antibody, thus confirming the importance of PDGF. EGF, TGF-beta, IL-1-alpha, TNF-alpha, and IFN-gamma had minimal effects. Similar to the effects on anchorage-independent growth, TGF-beta 1 and 2, inhibited serum- or PDGF-stimulated anchorage-dependent growth. Considered in the context of other reports, these data support the view that cytokines such as PDGF, and possibly aFGF and bFGF, play major roles in stimulating synoviocyte hyperplasia in RA and SCW arthritis, whereas TGF-beta may inhibit synoviocyte growth. | |
| 2830657 | Collagen antibodies in Ross River virus disease (epidemic polyarthritis). | 1987 | Antibody activity against collagen was measured in 53 samples of serum from 48 patients with active signs of epidemic polyarthritis (EPA) following infection with Ross River virus. Activity was higher against denatured collagen than against native collagen, but was within the normal range for each. Determination of HLA phenotypes permitted a search for any relationship between HLA type and differences in collagen antibody levels within the normal range. No relationship was detected with HLA antigens predominating in EPA or with HLA antigens that are associated with high collagen-antibody levels in rheumatoid arthritis (RA), which suggests that the latter associations may represent failure to control collagen antibody levels after the onset of RA. The findings also provide evidence against a role for nonspecific enhancement of humoral immune responses in the pathogenesis of EPA, and constitute a further point of distinction between EPA and RA. | |
| 3309545 | Impaired glucose handling in active rheumatoid arthritis: relationship to the secretion of | 1987 Oct | An intravenous glucose tolerance test was performed in 45 untreated patients with active inflammatory rheumatoid arthritis and in age- and sex-matched healthy subjects. The mean k value in the patients, which correlated to the inflammatory activity, was 1.0 +/- 0.05 (SEM), which was significantly lower (P less than .001) than in the controls (1.8 +/- 0.09). The basal serum insulin concentration and the maximum insulin response to glucose loading were significantly higher (P less than .001 and P less than .01, respectively) in the patient group. The patients had a normal basal concentration of growth hormone in the serum, but during glucose infusion the concentration increased. The plasma glucagon level was significantly lower than in the controls (P less than .001). The urinary output of cortisol and catecholamines was normal. It is concluded that impaired glucose handling in active chronic inflammatory disease cannot be explained as a stress reaction but may be due to peripheral insulin resistance mediated by the inflammatory process. A paradoxical increase in growth hormone secretion during glucose infusion may suggest that this hormone is one factor that influences glucose handling in chronic inflammation. The pathophysiologic relevance of altered glucose metabolism and enhanced insulin secretion is uncertain but may reflect a possible link with the proposedly increased risk of atherosclerotic cardiovascular disease in rheumatoid arthritis. | |
| 2325282 | [CT of gold pneumonitis]. | 1990 Feb | We experienced five cases of gold pneumonitis. CT findings of four cases and pathological findings of an autopsy case were discussed. CT findings of gold pneumonitis could be classified as follow; (1) high density shadow of subpleural zone-BOOP suspected- (2) high density shadow along the broncho-vascular bundle (3) small cystic shadow of subpleural zone-UIP. Histological findings of an autopsy case revealed the fibrosis along the broncho-vascular bandle. A variety of radiologic and pathologic feature on the gold pneumonitis were seen. | |
| 3166806 | The significance of 3H-thymidine degradation in cell culture experiments with special refe | 1988 Sep | The degradation of 3H-thymidine under various cell culture conditions was analysed. It was found that a half of 3H-thymidine was degraded to 3H-thymine during 24 hours in PHA stimulation of blood lymphocytes. A control culture in which PHA was not added also caused 3H-thymidine degradation. 3H-thymidine degradation was prevented by adding 5-nitrouracil to the incubation medium at a concentration of 0.577 mg/ml. At the same time 5-NU increased 3H-thymidine incorporation into lymphocytes by 47%. 5-NU also eliminated the inhibitory effect of rheumatoid arthritis synovial tissue eluate on PHA stimulation. In addition 5-NU and nonradioactive thymine increased the 3H-thymidine labelling index of fresh rheumatoid arthritis synovial membrane biopsies, and also more of the isotope was accumulated in the individual cells of the membrane. These studies demonstrate that 3H-thymidine degradation is an important phenomenon in cell cultures and that it can be prevented effectively by using 5-nitrouracil with 3H-thymidine. | |
| 3236305 | Persistent synovial lymphocyte responses to mumps and adenovirus antigens. | 1988 Nov | A man in his 50s with rheumatoid arthritis showed maximal synovial lymphocyte reactivity to mumps antigen on 9 of 10 testings over a period of 6 years; peripheral blood lymphocytes showed no significant responses to mumps antigen in 5 testings over 5 years. A boy of 15 with recurrent arthritis of the right knee showed maximal synovial lymphocyte reactivity to adenovirus antigen. This reactivity was again present during a subsequent episode more than 3 years later; peripheral blood lymphocytes showed no such response to adenovirus antigen. | |
| 2181672 | Neutrophil activation: an alternative to prostaglandin inhibition as the mechanism of acti | 1990 Feb | Experimental findings suggest that inhibition of neutrophil activation rather than suppression of prostaglandin formation may represent the principal mechanism of action of antiinflammatory drugs. This theory would account for the effectiveness of prostaglandin preserving agents, such as the nonacetylated salicylate salsalate, in the treatment of rheumatic disease. Results of the controlled clinical trials described in other papers contained in this supplement indicate that salsalate is equally effective as aspirin and the newer NSAID naproxen in relieving the signs and symptoms of rheumatoid arthritis. The damage to the gastric mucosa associated with NSAID use is believed to be attributable to impairment of mucosal defense mechanisms resulting from the inhibition of gastroprotective prostaglandins. Confirmation of neutrophil activation as the mechanism of action of NSAIDs would explain the efficacy of salsalate in light of its lower incidence of gastrointestinal side effects in controlled clinical trials with aspirin and naproxen. Establishment of such a mechanism would also suggest that the other adverse effects related to prostaglandin inhibition, such as hypersensitivity reactions, platelet dysfunction, and a reduction in renal function, are not necessary correlates of effective antiinflammatory therapy. | |
| 3124265 | Modes of action of second-line agents. | 1987 | The slow acting anti-rheumatic drugs (SARDS) are a chemically heterogeneous group. They produce a more profound effect on clinical and biochemical aspects of rheumatoid arthritis than do the aspirin-like non steroidals. The similarities in their clinical effects suggest that they have a common mode of action. Review of the known activity of SARDs on different cell types at various anatomical sites suggest that in fact different SARD drugs act in differing and sometimes conflicting ways. The site of action of SARDs within the body--whether at the level of synovial inflammation or of the systemic immune response--is largely undetermined. The effects produced by a single agent in vivo and in vitro are not always the same so a single mode of action, for example through possession of a thiol group, cannot explain the effects of all SARDs. Indeed a single agent such as aurothiomalate may show multiple effects and the same is now shown to be true for the newer agent sulphasalazine. A unifying hypothesis is put forward to explain the clinical similarities but different cellular effects. It is proposed that all SARDs act on some aspect of the central reaction in the ongoing immune response where antigen presentation to T helper cells results in interleukin 2 production and the generation of activated T cells. The precise site affected in this cell to cell/monokine reaction will vary between drugs, but the overall effect of blocking this will be similar for all drugs, both in short term clinical benefit and in the problem of disease flares after withdrawal of therapy. | |
| 1909213 | Gamma/delta T cell receptor positive T cells in the inflammatory joint: lack of associatio | 1991 Oct 1 | In patients with inflammatory synovitis, the proliferative response by lymphocytes from synovial fluid to soluble mycobacterial antigens is enhanced relative to those from peripheral blood. Earlier studies suggested that gamma/delta T cell receptor positive (TCR+) T lymphocytes may significantly contribute to the mycobacterial-specific synovial fluid response. We therefore examined the relationship of the T cell proliferative response to Mycobacterium tuberculosis antigens and the presence of gamma/delta TCR+ T cells employing several monoclonal antibodies. No consistent increase of gamma/delta TCR+ T cells was noted in inflammatory synovial fluids or tissues. Nonetheless, lymphocytes from the majority of the synovial fluids proliferated vigorously in response to water-soluble M. tuberculosis antigens. There was no relationship between the percentage of gamma/delta TCR+ T lymphocytes and the intensity of the proliferative response. In contrast, stimulation with whole mycobacterial organisms was capable of enriching the gamma/delta TCR+ cell population obtained from the peripheral blood of tuberculosis skin test positive normal controls and from some inflammatory synovial fluids. These observations do not support a role for mycobacteria reactive gamma/delta TCR+ synovial T lymphocytes in response to soluble mycobacterial antigens or in the local pathogenesis of inflammatory synovitis. | |
| 2591111 | Evidence of neuromuscular hyperexcitability features in patients with primary fibromyalgia | 1989 Jul | The presence of clinical and electromyographic (EMG) features of neuromuscular hyperexcitability (NMHE) and of the commonly associated neurovegetative disturbances (NVD) were investigated in 49 patients with primary fibromyalgia (PF) and in a control group of 33 patients with rheumatoid arthritis (RA). At least two clinical features of NMHE were present in 39%, and at least three NVD in 63% of PF patients. In contrast, only 1 RA control had two NMHE features (p greater than 0.005) and three NVD (p less than 0.001). Moreover, a significant post-ischemic spontaneous EMG hyperactivity was observed in 11 PF patients, and in only 1 control with RA (p less than 0.05). Finally, in patients with PF the number of tender points were correlated with psychological tests for depression (p less than 0.02), and the number of NVD. The present study shows that in patients with PF there is a large prevalence of NMHE complaints and NVD. The potential underlying pathogenetic mechanisms are also discussed. | |
| 3654692 | Resection arthroplasty as a salvage procedure for a knee with infection after a total arth | 1987 Sep | Between 1970 and 1983, resection arthroplasty was done as a salvage procedure for twenty-eight knees (twenty-six patients) with infection after total arthroplasty. Eleven patients had multiarticular rheumatoid arthritis; fourteen, osteoarthritis; and one, multiarticular neuropathic arthropathy. Systemic signs of infection were eliminated in all patients and local signs, in 89 per cent of the patients. After resection arthroplasty alone, fifteen patients were able to walk independently. Six patients with monoarticular osteoarthritis who found the resection arthroplasty to be unacceptable had a successful secondary arthrodesis. In three patients a spontaneous bone fusion developed after the resection, with the knee in a good position. Two patients who were unable to walk before the resection arthroplasty were still unable to do so postoperatively. Neither the patient's disease nor the type of prosthesis that had been used was a reliable predictor of success of the resection arthroplasty. The patients who had had the most severe disability before the total knee arthroplasty were most likely to be satisfied. Patients who had had less disability were more likely to find the results of resection arthroplasty to be unsatisfactory. | |
| 3771599 | Trapeziometacarpal total joint replacement using the Steffee prosthesis. | 1986 Oct | The first forty-five Steffee trapeziometacarpal total joint replacements that were used to treat severe trapeziometacarpal arthritis in thirty-eight patients were analyzed retrospectively. The length of follow-up ranged from two through six and one-half years. Forty-two of the arthroplasties resulted in relief of pain, and the restoration of strength and motion was highly satisfactory. Although radiographs showed a high incidence of asymptomatic radiolucent lines at the bone-cement interface of the trapezial component, only three patients had symptomatic loosening. We concluded that trapeziometacarpal total joint replacement can provide good relief of pain and restore function of the thumb to patients with severe trapeziometacarpal arthritis, although further study is necessary to assess the long-term results of the procedure. | |
| 2464266 | Pathogenesis of rheumatoid arthritis. | 1988 | This report gives a review on recent results of investigations of cellular aspects of inflammation. The role of macrophages and T-helper-cells with particular focus to the effects of the various mediators on their target cells will be discussed. Interleukin 1, Tumor Necrosis Factor, Interleukin 2, and Interferon as well as arachidonic acid metabolites contribute to the clinical findings of inflammation. We have to admit that the whole process of inflammation in rheumatic arthritis (RA) is not yet clear. For example we do not know in detail why RA is self perpetuating, why and when rheumatoid pannus occurs or under which circumstances immune complexes may cause the various organ manifestations. Recent findings are discussed. | |
| 3577479 | The spectrum of organ and systems pathology in human Lyme disease. | 1986 Dec | Lymphocytes, plasma cells, and mononuclear phagocytes are frequently found in human tissues infected by the Lyme disease spirochete, Borrelia burgdorferi. Experience has shown that these cells comprise the tissue bed inflammatory infiltrate in Lyme disease affecting the joint synovia, myocardium, and skin. While many differences otherwise exist, Lyme synovitis has lymphoplasmacellular similarities with rheumatoid synovitis, lymphoplasmacellular epimyocarditis similarities with syphilitic myocarditis, and occasionally synovial endarteritis obliterans. Silver staining can demonstrate the spirochete if a careful search is done. | |
| 3733799 | Silastic interposition arthroplasty of the shoulder. | 1986 May | We report a series of 12 Silastic interposition arthroplasties of the shoulder. There was a very high incidence of dislocation or fragmentation (50%) leading to early failure of the device in seven patients. Our analysis suggests that the operation should be restricted to rheumatoid arthritic shoulders in which there is no loss of bone or distortion of the humeral head. | |
| 3698396 | The outcome of failed knee arthrodesis following total knee arthroplasty. | 1986 Apr | After failure of total knee arthroplasty, arthrodesis was attempted in 120 cases, and unsuccessful in 25 (21%). Failure of arthrodesis was defined as nonunion persisting one year after arthrodesis or reoperation to obtain union. The number of attempts at arthrodesis ranged from one to four. The most frequent reasons for reoperation were persistent pain and instability. Most failures were caused by poor apposition owing to bone loss. Union was obtained in ten knees (average follow-up period, 44.5 months), but not in 11 (average, 35.3 months). | |
| 2634628 | Cachectin/tumour necrosis factor-alpha in the circulation of patients with rheumatic disea | 1989 | By means of a sensitive double-antibody radioimmunoassay, cachectin/tumour necrosis factor-alpha (TNF) was measured in sera from 51 patients with rheumatic disease. Elevated levels of circulating cachectin/TNF were observed in 46% of patients with rheumatoid arthritis (RA; p less than 0.001 versus blood donors) and in 29% of patients with systemic lupus erythematosus (SLE; p less than 0.05 versus blood donors). Marked elevation of cachectin/TNF occurred in both RA and SLE patients in connection with severe infections. The results show that cachectin/TNF is present in the circulation of certain patients with rheumatic disease, and that although the median cachectin TNF level in SLE patients is lower than that in RA patients, the cachectin/TNF response in SLE patients to severe infections is similar to that in RA patients. | |
| 1675281 | Differential responses of human and rat cartilage to degrading stimuli in-vitro. | 1991 Mar | Human cartilage biopsies incubated for 2 days in-vitro with 15% synovial fluid from rheumatoid arthritis patients contained less glycosaminoglycans (GAG) than control biopsies. Recombinant human (rHu)-interleukin-1 alpha (IL-1 alpha) and IL-1 beta at 10 or 100 ng mL-1 had no effect on human cartilage GAG levels. Similarly, GAG loss from human cartilage biopsies into medium over 5 days was significantly increased by synovial fluid but unaffected by 100 ng mL-1 IL-1 alpha or IL-1 beta compared with controls. However, when rat femoral head cartilage samples were incubated with 100 ng mL-1 rHu-IL-1 alpha or IL-1 beta for 5 days there was a significant increase in GAG loss from the cartilage into medium, whilst human synovial fluid significantly decreased the loss of GAG from rat cartilage into medium, compared with controls. The results demonstrate that human and rat cartilage differ from each other in their responses to degrading stimuli and suggest that animal cartilage may have limited application for the screening of drugs intended for the treatment of human arthritides. | |
| 3592781 | Correlation of immunoglobulin and C reactive protein levels in ankylosing spondylitis and | 1987 Apr | Serum C reactive protein (CRP), IgG, and IgA levels were measured in 22 patients with ankylosing spondylitis (AS) and in 20 patients with rheumatoid arthritis (RA) to study the regulation of these proteins in inflammatory disease states. In both RA and AS the mean CRP, IgG, and IgA levels were raised above normal values. Although IgA and CRP levels showed a significant positive correlation in RA (r = 0.53, p = 0.02), there was no correlation between these values in AS (r = 0.24, p = 0.29). The difference in correlation coefficients between the AS and RA groups was significant at a p = 0.05 level. In RA the raised IgA levels may be another manifestation of the acute phase response, as shown by the good correlation between IgA and CRP in that disease. In AS, however, the IgA levels, although raised, do not correlate with CRP levels, suggesting that the mechanism of increase of IgA in the two diseases is different. Gut mediated immune stimulation has been proposed as a cause of raised IgA levels in AS. | |
| 3265956 | Incidence and management of diarrhea during longterm auranofin therapy. | 1988 Dec | The incidence, severity, and management of diarrhea during longterm administration of auranofin (AF)--up to 33 months--were evaluated prospectively in 137 patients with active rheumatoid arthritis. At least 1 episode of diarrhea was reported in 101 patients (74%), but the rate of occurrence/patient-months of therapy was 24% (569 events/2,370 patient-months of treatment). The monthly prevalence declined from a range of 30-40% during the initial 6 months to about 10% for patients treated for 18-24 months. Most diarrhea was intermittent and mild; only 11 patients (8%) discontinued treatment because of diarrheal symptoms. No intervention was required in 46 of the 101 patients affected. In 44 others, loose stools were successfully managed with antidiarrheal medications, a reduction in dosage, or both. Although diarrhea is a common event during AF administration, particularly early in therapy, for most patients it usually does not significantly interfere with treatment. |