Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2949912 | Defective IL2 production in active rheumatoid arthritis. Regulation by radiosensitive supp | 1986 Dec | The production of interleukin 1 (IL1) and interleukin 2 (IL2) by mononuclear cells (MNC) from untreated rheumatoid arthritis (RA) patients or healthy subjects were examined. After PHA stimulation, patient MNC or T cells produced varying amounts of IL2 that were related to the disease activity: patients suffering from active disease showed a scant production of IL2 while those who had a quiescent disease were high producers. The prior irradiation of unfractionated MNC induced a marked increase of the PHA-stimulated IL2 production in both active and quiescent patients compared to the moderate augmentation observed for controls. On the other hand, irradiation of enriched T cells had an enhancing effect only in the active RA patient group. Concurrently, we found that non T cells from active or quiescent RA patients were fully competent to produce IL1 upon LPS activation. Taken together, these findings suggest that the suppressive activity evidenced by irradiation could be mediated by non T cells in quiescent disease or in absence of illness. On the other hand, both radiosensitive suppressor T and non T cells may interfere in IL2 production by active RA patient lymphocytes. | |
| 2499524 | [The dynamics of the analgesic effect of non-steroidal antirheumatic drugs. Ibuprofenlysin | 1989 Apr 20 | In a double-blind clinical study, the analgesic effects of ibuprofen-lysinsalt and diclofenac were compared in 59 patients with rheumatoid arthritis. In the first phase, the patients were given either 1,000 mg ibuprofen-lysinsalt or 50 mg diclofenac at 8.00 a.m. Pain intensity was assessed by the patient with the aid of the visual analog scale (VAS) and a sliding numerical scale. With respect to the rate of onset of the effect and the course of the pain, no statistically significant differences were seen between the two drugs. In a second phase, in which the already mentioned doses of the drugs were administered 3 times a day for 7 days, there was again no significant difference in pain. Drug tolerance was considered very good by 90% of the ibuprofen-lysinsalt group, and 67% of the diclofenac group. Ibuprofen-lysinsalt is a universal, well-tolerated analgetic which can also be used to combat arthritic pain. The somewhat better analgesic effect of ibuprofen-lysinsalt was too small to be statistically significant. | |
| 3230567 | Serum antibodies against chondrocyte cell surface proteins in osteoarthritis and rheumatoi | 1988 Dec | Serum autoantibodies to cartilage cell surface proteins have been detected in the blood from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). As tested by ELISA using plasma membrane vesicles as a substrate, patients with RA exhibited significantly elevated antibody titers, whereas titers were somewhat lower in OA, and only marginal in controls. The antibodies did not crossreact with plasma membranes from fibroblasts or epithelial cells, but showed interspecies crossreactivity towards chicken and rat cartilage cell surface proteins. A group of at least 9 distinct immunoreactive polypeptides could be characterized by Western blot analysis. These peptides had molecular weights of Mr28, 30, 38, 42, 66, 76, 78, 116, and 155 kD. The patients each expressed an individual pattern of reactive antibodies against these proteins. Autoantibody reactivity to cell surface associated collagen type II was also observed. | |
| 2942685 | Alpha 2-plasmin inhibitor-plasmin complexes in synovial fluid. | 1986 Jun | The role of the fibrinolytic enzyme system in inflammatory joint disease has been addressed by several experimental approaches. In our study we examined synovial fluid (SF) in several different diseases for alpha 2-plasmin inhibitor-plasmin complexes by an enzyme linked immunosorbent assay (ELISA). These complexes are present in both rheumatoid and nonrheumatoid SF, with highest levels seen in septic arthritis. Thus the plasminogen system is intact in inflammatory SF, and plasmin may play a role in the local inflammatory process. | |
| 2444935 | Intra-hisian block associated with unusual etiologies. | 1987 Sep | One hundred and sixty-nine patients underwent electrophysiologic study for atrioventricular block. Forty-five (27%) had intra-Hisian block. Four of these 45 patients had unusual etiologies: rheumatoid arthritis, cysticercosis cellulosae, Behcet's disease, and Takayasu aorto-arteritis. Their clinical and electrophysiologic features are described in detail. | |
| 3148994 | Depressed PPD and tetanus toxoid presentation by monocytes to T lymphocytes in patients wi | 1988 | A diminished antigen presentation of blood monocytes to autologous T cells has been recently described in patients with rheumatoid arthritis (RA). In this study the defective presentation of common recall antigens by blood monocytes revealed it to be a monocyte dysfunction specific for RA which could not be found in other chronic inflammatory rheumatic or non-rheumatic diseases and which could be restored by recombinant human interferon gamma. In addition, RA monocytes in blood exhibited a strongly reduced expression of HLA-DR determinants on the cell surface. T cells from RA patients produced almost normal interleukin-2 (IL-2) levels and showed a normal IL-2 sensitivity after phytohemagglutinin (PHA) stimulation. Several reasons may be responsible for this altered monocyte function in RA. Among these an in vivo "preactivation" of monocytes associated with a reduced antigen-presenting capacity or an impaired regulation of monocyte/macrophage differentiation are discussed. | |
| 3769195 | Studies of intestinal permeability in inflammatory diseases using polyethylene glycol 400. | 1986 Oct | It has been proposed that increased bowel permeability might play a role in the pathogenesis of inflammatory disease. Intestinal permeation was investigated by measuring the 6-hour urinary excretion of polyethylene glycol (PEG) 400 in 40 adult volunteer controls and in patients with inflammatory disease. Of the patients, 15 had Crohn's disease; 7, ulcerative colitis; 2, celiac disease; and 7, rheumatoid arthritis. No significant difference in total urinary excretion over a 6-hour period was found between controls and patients with ulcerative colitis. Patients with Crohn's disease, celiac disease, or with rheumatoid arthritis were found to have significantly decreased urinary excretion of PEG 400. The results of this study indicate that there is no identifiable increase in intestinal permeation as measured by PEG 400 excretion during periods of active inflammatory disease. | |
| 1708827 | Production of platelet derived growth factor B chain (PDGF-B/c-sis) mRNA and immunoreactiv | 1991 Jan | We present evidence supporting the hypothesis that locally produced platelet derived growth factor (PDGF) B-like polypeptides, as well as heparin binding growth factor-1 (HBGF-1), are involved in stimulating the pronounced hyperplasia of rheumatoid synovial stromal fibroblastlike cells. Explanted rheumatoid synovial tissues in vitro spontaneously secreted, in a time dependent manner, mitogenic activity for rheumatoid synoviocytes that was neutralizable by anti-PDGF antibody. PDGF B/c-sis mRNA transcripts were detected in synovium from patients with rheumatoid arthritis (RA) (n = 5). Spontaneous PDGF B-like synthesis was detected by immunoprecipitation of radiolabeled PDGF B-like polypeptides secreted by explanted tissues. Furthermore, rheumatoid synovial tissues, particularly macrophage-like cells, immunostained specifically with anti-PDGF B chain. The extent and intensity of staining and mononuclear cell infiltration were highly correlated. Immunostaining of osteoarthritic and normal synovial tissues was significantly less than RA synovium. PDGF-B immunostaining of synovial specimens previously characterized for expression of HBGF-1, the precursor of acidic fibroblast growth factor (aFGF), revealed that the extent and intensity of expression of HBGF-1 and PDGF-B were highly correlated. | |
| 1691568 | [Polyclonal activated circulating B-lymphocytes in patients with rheumatoid arthritis]. | 1990 Jan | Peripheral B lymphocytes were studied to investigate the role of polyclonal B-cell activation in the pathogenesis of rheumatoid arthritis (RA). Proliferative responses to anti-mu antibodies coupled to sepharose used as a B-cell-specific mitogen were reduced as compared to healthy controls. When cell surface antigens were studied by flow cytometry employing monoclonal antibodies, B cells from patients with RA showed enhanced expression of Interleukin-2 (IL-2) receptor. In-vivo-activated, in-vitro spontaneously proliferating Epstein-Barr virus transformed B cells positive for immunoglobulin M, G, and A were obtained from patients with RA. In summary, our findings suggest the presence of polyclonal activated B cells in the peripheral blood of patients with RA, and a close relationship of polyclonal activated B cells and the activity of the disease process. | |
| 3127482 | Oral biopsy and fine needle aspiration biopsy from subcutaneous fat in diagnosis of second | 1988 Feb | The reliability of oral biopsy (OB) and fine needle aspiration biopsy from subcutaneous fat (FNAB) in the diagnosis of secondary amyloidosis was compared using the specimens taken from 124 patients, 107 adults and 17 children, suffering from long lasting rheumatoid diseases. 41 of the patients (33.0%) were shown to be positive for amyloidosis with one or both methods. OB was positive in 28, FNAB in 33, and both methods in 20 patients. In addition, rectal biopsy (RB) was positive in 14 out of 43 cases, where it had been taken. In 3 patients, this method was positive for amyloidosis, although OB and FNAB were negative. Thus, the total number of patients positive for amyloidosis in this study was 44 (35.5%). The mean duration time of the disease was significantly longer in the adult and child patient groups with amyloidosis than in those without amyloidosis. The diagnostic sensitivity of OB was 64%, and that of FNAB 75%. The results speak for the use of FNAB as the first choice method in the diagnosis of secondary amyloidosis. | |
| 2187926 | Transforming growth factor-beta and cellular immune responses in synovial fluids. | 1990 Jun 1 | Mononuclear cells in synovial fluids (SF) from patients with rheumatoid arthritis and other arthropathies are characterized by functional and phenotypic changes, including impaired mitogen responsiveness and inverted ratios of CD4+/CD8+ T lymphocytes. This is related to previously described activities in synovial fluids that inhibit proliferation of lymphocytes induced by mitogens and cytokines. The present study examines the relationship of these activities and transforming growth factor beta (TGF-beta), which is now known as the most potent endogenous inhibitor of lymphocyte function. It is shown that most of the activity in SF that inhibits IL-1-induced thymocyte or T cell proliferation is neutralized by a specific antibody to TGF-beta. Analysis of the SF in the CCL64 assay, a standard test for TGF-beta, showed a close correlation between the levels of immunosuppressive activity and TGF-beta. SF contain spontaneously active inhibitors of T cell function and this is caused by the presence of active TGF-beta. Higher titers are found after transient acidification, which is known to activate the latent form of TGF-beta. Characterization of the TGF-beta isoforms showed that most of the material in SF is TGF-beta 2. Analysis of TGF-beta effects on T cell subsets demonstrated that it completely inhibits proliferation of CD4+ cells whereas at the same concentrations of purified or rTGF-beta CD8+ cells are only inhibited by maximally 31.1%. SF also preferentially inhibit CD4+ Th cell proliferation and this effect is neutralized by antibody to TGF-beta. Collectively these results indicate that the presence of TGF-beta accounts for most of the immunosuppressive activities in SF and that this factor may be responsible for functional and phenotypic changes of SF lymphocytes. | |
| 3134689 | [Tiopronin in 69 cases of rheumatoid polyarthritis treated earlier with D-penicillamine]. | 1988 Apr 30 | This study concerns 69 patients with rheumatoid arthritis (RA) and having received successively D-penicillamine (DP) then, after a mean period of 2 years, tiopronin (TP) at a daily dose of 1,500 mg. TP demonstrated an as frequent, as marked, and as prolonged effectiveness as that of DP. 28 patients are still under TP treatment, with a mean length of treatment of 43.7 months. The rate of effectiveness of TP was similar, whether or not the response to DP was favorable: 64.1 and 64.3 p. cent respectively; 72.4 p. cent of the 29 cases which did not respond to DP, responded favorably to TP. The manifestations of intolerance to TP were similar in nature (including the first reported case of obstructive bronchiolitis) and frequency to those observed with DP. There were only a few manifestations of crossed intolerance: the rate of TP discontinuation because of intolerance was the same, whether the DP was well tolerated (29.6%) or discontinued because of poor tolerance (30%). The same undesirable effect was only observed in 4 cases: one case of pemphigus, another case of toxic dermatitis, 2 proteinurias. This study confirms that TP represents a new, major long-term treatment of RA and demonstrates that this very product is an excellent take over medication. | |
| 1796656 | [Kidney function in therapy with non-steroidal antiphlogistic drugs. A double-blind cross- | 1991 Nov | The effect of piroxicam (1 x 20 mg daily), diclofenac (2 x 50 mg daily) and indomethacin (3 x 25 mg daily) on renal function was compared in a double-blind cross-over study of 33 patients with various rheumatologic diseases. Individuals with preexisting renal impairment were excluded. In 16 patients piroxicam was compared with diclofenac. In another group of 17 patients piroxicam was compared with indomethacin. Each drug was given for 28 days. The mean inhibition of renal prostaglandin E2 by the three drugs was comparable. There was no significant alteration of the renal function parameters in any of the drugs. These results confirm that nonsteroidal antiinflammatory drugs with short (diclofenac, indomethacin) but also with long half life (piroxicam) do not decrease renal function in individuals without renal impairment. | |
| 2785012 | Radio-immunological study of the regulation of interleukin-2 production in peripheral bloo | 1989 Jan | A radio-immunoassay for human T cell growth factor, also called Interleukin-2 (IL-2), has been carried out using a recombinant IL-2 preparation as tracer and a polyclonal rabbit antiserum. The assay is highly specific for IL-2: there is no cross-reaction with either type I and II interferons, epidermal growth factor or tumor necrosis factor alpha. Using the sequential saturation procedure the limit of sensitivity was 0.5 U/ml. Intra- and between-assay coefficients of variation were 8 and 11%, respectively. With this assay, IL-2 recovery in serum and peripheral blood mononuclear cell culture (P.B.M.C.) medium was 79 and 95%, respectively. In serum of 109 normal subjects and 102 rheumatoid arthritis patients mean IL-2 concentrations (+/- SD) were 1.5 +/- 0.5 U/ml and 1.4 +/- 0.4 U/ml respectively. The IL-2 production by P.B.M.C. in vitro was also studied. In unstimulated cultures, IL-2 release remained undetectable, i.e. below 0.5 U/ml. After stimulation of mononuclear cells from 36 normal subjects with increasing amounts of phytohemagglutinin (PHA), the 3H-thymidine incorporation followed a bell-shaped curve, the maximum response being observed at a 2.5 micrograms/ml PHA concentration. After a 72-hr mononuclear cell stimulation, IL-2 release increases with PHA concentrations ranging from 0 to 10 micrograms/ml. In patients with rheumatoid arthritis (R.A.), P.B.M.C. incorporated 3H-thymidine as in normal subjects. In contrast, mean +/- SEM IL-2 production by P.B.M.C. from patients with inactive RA (5 +/- 0.9) and active disease (1 +/- 0.5) was significantly lower than that from normal subjects (12 +/- 0.7 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3532786 | Auranofin therapy and quality of life in patients with rheumatoid arthritis. Results of a | 1986 Oct | In a six-month, randomized, double-blind study at 14 centers, auranofin (3 mg twice daily) was compared with placebo in the treatment of patients with classic or definite rheumatoid arthritis. All patients had unremitting disease for at least the previous six months and at least three months of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, oral steroids, and analgesics were allowed throughout the trial. Efficacy was analyzed in 154 patients who received auranofin and 149 who received placebo. To reflect an expanded view of outcome assessment, the measures used included some 20 nontraditional measures of functional performance, pain, global impression, and utility (worth or value) in addition to five standard clinical measures of rheumatoid synovitis (e.g., number of tender joints). The nontraditional measures were mainly in the form of structured questionnaires administered by trained interviewers. To minimize the statistical problem of multiple comparisons, most of the measures were grouped into four composites--clinical (standard measures), functional, global, and pain--and the treatment effect for each composite was tested at the 0.0125 level of significance. Auranofin was superior to placebo in the clinical (p = 0.003), functional (p = 0.001), and global (p = 0.007) composites and trended similarly in the pain composite (p = 0.021). Individual measures within the composites consistently favored auranofin. Other measures, not part of the composites, also favored auranofin, including a patient utility measure designed for this study, the PUMS (p = 0.002). Results confirm the hypothesis that the favorable effect of auranofin on clinical synovitis is accompanied by improvements across a range of outcomes relevant to the patient's quality of life. | |
| 3335087 | Alignment and long-term clinical results of a semiconstrained knee prosthesis. | 1988 Jan | In knee arthroplasty, component malpositioning seems to be a fundamental cause for failure. The degree of malpositioning is important. To investigate this degree, 86 of 137 knee arthroplasties performed with the Townley semiconstrained bicondylar prosthesis were examined after a mean follow-up period of 6.5 years (range, 5.0-8.5 years). Five arthroplasties were excluded because of aseptic loosening, but none of these showed malalignment in postoperative roentgenograms. Clinical results and the patients' reports on deterioration of prosthetic function were correlated with positioning of the prosthetic components. Total alignment between 6 degrees of varus and 7 degrees of valgus was associated with good clinical results. Total alignment of more than 7 degrees of valgus, anterior tilting of the tibial component, or positioning of the femoral component in more than 12 degrees of valgus correlated with relatively poor clinical results. | |
| 2257864 | A multiple dose pharmacokinetic and tolerance study of once daily 200 mg sustained-release | 1990 | The pharmacokinetic profile of 200 mg sustained-release flurbiprofen capsules was compared in nine elderly (mean age 84.2 years) and 10 young (mean age 38.1 years) patients with arthritis. After a single capsule, a 48 h plasma concentration profile was performed. The patients then took 1 capsule daily for a further 13 days with plasma levels of the drug being measured pre-dose on alternate days. Following ingestion of the last capsule, a further 48 hour plasma concentration profile was performed. These results were compared with each other and with computer predicted data obtained from dosing with 200 mg conventional flurbiprofen (as 100 mg b.d.). In both young and elderly patients, the two 48 h plasma concentration profiles confirmed the sustained-release characteristics of the capsule. There was no evidence of dose-dumping, although, in one elderly patient with a partial gastrectomy, higher plasma concentrations were observed. Inter- and intra-patient variability was acceptable. A steady-state was achieved within the predicted four days in both groups and there was no evidence of accumulation with the daily dosing interval. A mean steady-state level of approximately 6 micrograms/ml was achieved for both populations. Computer predicted data for 200 mg conventional flurbiprofen (as 100 mg b.d.) showed a pre-dose/peak range of 1-12 micrograms/ml. The pre-dose/peak ranges for the young and old patients were 4-10 micrograms/ml and 4-8 micrograms/ml respectively. One young patient developed a hypersensitivity reaction of moderate severity; one young and four elderly patients developed a low haemoglobin concentration during the study. No other changes in haematological or biochemical parameters were seen. | |
| 2972742 | Dendritic cell-lymphocyte clusters that form spontaneously in rheumatoid arthritis synovia | 1988 Nov | Lymphocytes cluster about dendritic cells (DC) spontaneously in 48 h cultures of rheumatoid arthritis synovial fluid (RA SF) mononuclear cells and in peripheral blood autologous or allogeneic mixed leukocyte reactions. In the latter case, the clusters are predominantly CD4+ T cells (T4/T8 greater than 5) and with time progress in blastic cells that express IL-2 (Tac) and/or transferrin (T9) receptors. In contrast, the clusters in RA SF cultures have a T4/T8 ratio of less than 1 and a majority of the T8 cells coexpress the Leu 7 marker. T cells in these clusters remain inert and with time the clusters disintegrate. Addition of IL-1, IL-2, or IFN-gamma alone or in combination had no effect on RA SF clusters but T cells became blastic when exposed to 10% RA SF. Mixing experiments using RA SF DC with normal T cells and RA T cells with normal DC show that both RA SF DC and T cells are immunofunctional. In addition, clusters of RA SF from a patient with active tuberculosis proliferated vigorously to PPD. Therefore, the unique RA SF cluster profile may reflect the memory nature of the RA SF T cells resulting in a paucity of T cells that are responsive to autologous stimulation. However, an immunosuppressive role for the double-labeled (CD8 and Leu 7) cells has not been excluded. | |
| 2600939 | A longitudinal study of the leukocyte protein L1 as an indicator of disease activity in pa | 1989 Nov | L1 is a major granulocyte and monocyte protein. It is released during leukocyte activation, and the plasma level is thought to reflect the inflammatory activity. Fifteen patients with classical or definite rheumatoid arthritis were examined monthly during one year. The laboratory tests included L1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), orosomucoid, haptoglobin, ceruloplasmin, alpha 1-antitrypsin, immunoglobulins and blood cell counts. The clinical tests included articular index, grip strength, morning stiffness and pain. The L1 protein was found to have highly significant correlations (p less than 0.0001) with orosomucoid (r = 0.86), CRP (r = 0.79), ESR (r = 0.78), haptoglobin (r = 0.75), alpha 1-antitrypsin (r = 0.63) and ceruloplasmin (r = 0.44). Significant correlation was also found between L1 and IgA. None of the laboratory variables showed significant correlation with pain, but when they were correlated with articular index, grip strength and morning stiffness, L1 was found to have the highest average correlation coefficient (p less than 0.0001). | |
| 3548984 | A 12-week, double-blind, multicenter study comparing diflunisal twice daily and ibuprofen | 1986 | Diflunisal, a nonacetylated salicylate preparation with a prolonged duration of action, was compared with ibuprofen for the treatment of rheumatoid arthritis in a multicenter trial comprising 210 patients. Diflunisal was administered twice a day (500 to 750 mg/day) and ibuprofen was administered four times a day (1,600 to 2,400 mg/day). To maintain double-blind conditions, all patients ostensibly followed the same regimen, ingesting their assigned drug and a matching placebo of their nonassigned drug. Disease activity assessments and laboratory tests were done periodically throughout the 12 weeks of the study, and results were compared with pretreatment findings. Efficacy evaluations in 187 patients showed that both treatments were similarly efficacious. Safety and tolerability also were similar in the two groups. Diflunisal, however, offers a more acceptable BID treatment schedule. |