Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1693065 | Randomised, double blind, placebo controlled trial of inosine pranobex in rheumatoid arthr | 1990 May | In a randomised, placebo controlled, double blind study inosine pranobex was assessed as a possible second line drug in rheumatoid arthritis. Twenty four patients received inosine pranobex (3 g/day) and 26 patients received placebo for up to 24 weeks. Morning stiffness, articular index, grip strength, pain score, erythrocyte sedimentation rate, C reactive protein, IgG, IgM, and serum urate were assessed at weeks 0, 12, and 24. Baseline characteristics were similar except for a significantly higher C reactive protein in the placebo group. No significant improvement occurred in any variable: (a) when comparing week 0 with week 12 or week 24 for either group, (b) comparing active drug with placebo at week 12 or 24, or (c) taking all 50 patients as one group. Withdrawal from the study for lack of response or side effects was similar in both groups. Serum urate increased transiently but significantly with inosine pranobex (a recognised side effect). It is concluded that inosine pranobex has no second line activity in rheumatoid arthritis. Further, 50 patients effectively given placebo showed no spontaneous improvement in their disease activity. | |
| 3449308 | Low dose pulse methotrexate in rheumatoid arthritis: an 8-year experience with hepatotoxic | 1987 Dec | The clinical utility of standard liver function tests for monitoring low dose pulse methotrexate therapy is reviewed in 163 rheumatoid arthritis patients over an eight-year period. Abnormalities of hepatic enzymes were seen in 58% of patients but led to cessation of therapy in only 5%. Moderate alcohol intake did not affect the frequency of liver test abnormalities. Abnormalities were seen more frequently in patients with longer duration of methotrexate therapy and in those with higher total dose. There was no correlation between liver test abnormalities and day of serum sampling relative to day of methotrexate dosing, nor was a correlation seen between liver test abnormalities and total weekly dose of methotrexate. Methotrexate has been demonstrated to be an effective drug in the treatment of rheumatoid arthritis. The clinical utility of standard liver tests to predict the potential for hepatotoxicity is questionable. | |
| 1715605 | Expression of the CD2 activation epitope T11-3 (CD2R) on T cells in rheumatoid arthritis, | 1991 Sep | CD2R is an activation-associated epitope unmasked by a conformational change of the CD2 cell-surface glycoprotein. In spite of elaborate studies on the role of CD2 and CD2R in adhesion and stimulation of T cells in vitro, no instances of CD2R expression in vivo were known to date. We report high levels of CD2R observed on blood and synovial fluid T cells in rheumatoid arthritis and on peripheral blood T cells in juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease. In vivo, expression of CD2R was restricted to T cells, not limited to a particular T-cell subset and not correlated with the expression of p55 interleukin 2R (IL-2R) (CD25) or major histocompatibility complex (MHC) class II molecules. When stimulated to proliferation via CD2 or CD3, ex vivo CD2R+ T cells showed the same basic activation requirements as CD2R-T cells. | |
| 1747693 | Outcome of parenteral gold therapy in RA patients: a comparison between two periods using | 1991 Dec | Tolerance and outcome of parenteral gold therapy were compared using life-table analysis and ARA remission criteria between 151 rheumatoid arthritis (RA) patients treated in 1983 and in 210 patients treated in 1985. The total risk of termination of therapy was significantly higher in patients treated in 1983 than those treated in 1985. The most common causes were mucocutaneous reactions (41 and 25% in 1983 and 1985, respectively), unsatisfactory effect (15 and 25%) and practical problems (14 and 26%). The outcome regarding all ARA remission criteria except for fatigue (not systematically registered) was significantly more favourable in patients treated in 1985 than in those treated in 1983. | |
| 2789438 | [Efficacy of polyvinylpyrrolidone solutions of various concentrations in patients with rhe | 1989 | Twenty-six experimental animals, 93 patients with osteoarthrosis (OA) and 30 patients with rheumatoid arthritis (RA) were examined. Intraarticular injection of both 15% and 20% polyvinylpyrrolidone (PVP) solutions suppressed the development of experimental arthrosis in rabbits, which manifested in a decrease of the degenerative changes in the cartilaginous tissue of the joints. The clinical examination has demonstrated that the use of different concentrations of PVP produces an equally marked effect in OA. In the group of RA and OA patients given placebo the time-course of changes in the clinical data was pronounced less powerfully. PVP turned out to be effective in secondary synovitis, to influence the immunologic responses occurring in synovitis, and to exert a beneficial action on the rheological properties of the synovial fluid. The drug is completely eliminated from the articular cavity and the body during 5 days. | |
| 3318421 | Review of the experience with nabumetone in clinical trials outside of the United States. | 1987 Oct 30 | Nabumetone, a new nonsteroidal anti-inflammatory agent, has undergone extensive clinical evaluation in a number of countries. There have been over 4,000 patients treated, including nearly 1,000 elderly patients and over 1,100 patients who have received nabumetone for more than one year. A total of 2,400 of these patients with a variety of rheumatic disorders have been investigated in studies outside of the United States. Studies in rheumatoid arthritis and osteoarthritis have demonstrated that nabumetone is effective in the treatment of these conditions and that this effectiveness is maintained in many patients in the long term. Nabumetone appears to be well tolerated and there is no evidence from patients receiving treatment for 12 months or more of any clinically significant adverse effects on hematologic or biochemical parameters. Thus, these studies support the use of nabumetone in the treatment of rheumatoid arthritis and osteoarthritis. | |
| 3548985 | Comparison of diflunisal and aspirin in long-term treatment of patients with rheumatoid ar | 1986 | A multicenter, open-label clinical trial evaluated the efficacy and tolerability of diflunisal given twice daily and aspirin given four times daily in the long-term treatment of patients with rheumatoid arthritis. Patients who successfully completed a 12-week, double-blind, parallel study comparing diflunisal (500 to 750 mg daily) with aspirin (2.6 to 3.9 gm daily) continued on the same medication in a 40-week, open-label segment of the study. The dosage of diflunisal could be increased to a maximum of 1 gm daily during the open-label phase. Both regimens were effective during the 40-week study. Diflunisal was better tolerated than aspirin as judged by the overall incidence of clinical adverse experiences. Patients treated with diflunisal had significantly fewer adverse experiences involving the digestive system and organs of special sense than did those treated with aspirin. | |
| 3768059 | Rheumatoid nodulosis: report of a case with evidence of intraosseous rheumatoid granuloma. | 1986 Oct | We describe a patient who had multiple subcutaneous rheumatoid nodules associated with episodes of acute intermittent arthritis and subchondral cystic lesions of the small bones of the hands and feet; this condition is termed "rheumatoid nodulosis." The patient had a cystic lesion in communication with the joint cavity, rheumatoid granulomas, and evidence of a central zone of necrosis opening toward the joint space. His case is compared with 8 previously reported cases, and possible etiologies of the subchondral bone cyst formation in rheumatoid nodulosis are discussed. | |
| 2438861 | [Controversial and so-called alternative therapeutic approaches]. | 1987 Jan | In spite of intensive research, it has not yet been possible to produce a complete explanation of the aetiology and pathology of rheumatoid arthritis (R.A.). Therapeutic measures are possible in many phases of the pathogenetic concept, and often produce good, modifying results, improving the course of the disease. No causal therapy of R.A. exists--we do not know the aetiology of this disease. Frustration with conventional medicine on the one side, and the predominating spirit of the times on the other--back to biological methods and the old forms of therapy--are the reasons why chronic polyarthritics drift into the sphere of para-medicine. In the judgement of para-medical methods, "risk/benefit relationship", "superfluous and no longer up-to-date", "controversial--absence of scientific evidence", "controversial", and "controversial--not scientifically acceptable" present some of the decision criteria. Treatment with mussel extracts, beta-sitosterins, THX, and substitution with various substances, as well as anthroposophically-oriented high-potency homeopathy, are to be allocated to the "controversial--not scientifically acceptable" category. If one weighs up the "risk/benefit relationship" of cell therapy, this treatment concept also cannot be supported. Moreover, precisely documented scientific results of this form of therapy do not exist. Methods standing on scientifically-hypothetically interesting ground, but which were tested on too small a group and cannot yet be accepted as sufficiently proven, are therapy with Vitamin E, the use of Thymopoietin, in which, for example, dose-finding and mode of application are not yet firmly established, and therapy with enzyme mixtures. Interferon results, initially extolled in the lay press, have not been confirmed in the most recent studies. Thymopoietin treatments, via the laborious road to the correct application (oral, subcutaneous, intramuscular, intravenous as bolus, intravenous--fractionated), show encouraging successes. As tissue-localized immune complexes (which sort?) play a role in the pathogenesis of R.A., but enzyme mixtures, apart from the problems of absorption, only influence circulating immune complexes, and moreover, in many diseases neither the aetiology nor the pathogenesis is connected with the immune complexes, this therapy concept can be regarded neither as causal nor as scientifically guaranteed. In summary: from the start-point that healing is the ideal aim, it has been forgotten that there are many human sufferings which medicine can ease and ameliorate, but not yet cure.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 2605216 | Cloning of the genes for human stromelysin and stromelysin 2: differential expression in r | 1989 Oct 31 | Stromelysin is a member of a gene family of metalloproteinases involved in extracellular matrix remodeling in normal and diseased processes. Primary cultures of rheumatoid synovial cells produce large amounts of metalloproteinase mRNA and proteins. We cloned a cDNA for human stromelysin from a rheumatoid synovial cell cDNA library, and we used the cDNA to isolate the gene for human stromelysin and a related gene, stromelysin 2. We sequenced parts of the genes and found that both are contained on approximately 14 kilobase pairs of DNA. Using an exon-containing fragment of the stromelysin 2 genomic clone as a specific probe in Northern blot analysis, we demonstrate the differential expression of stromelysin and stromelysin 2 in rheumatoid synovial cells, human foreskin fibroblasts, and rabbit synovial fibroblasts. In addition, using chimeric constructs of the stromelysin promoter linked to the bacterial gene chloramphenicol acetyltransferase (CAT), we show that the elements required for the tumor promoter phorbol myristate acetate (PMA), epidermal growth factor (EGF), and interleukin 1 beta (IL-1 beta) induction are contained on a 307 base pair fragment which includes approximately 270 base pairs (bp) of 5'-flanking DNA. The cloning of the human stromelysin and stromelysin 2 genes, the documentation of their differential expression, and the identification of transcriptional regulatory regions in the stromelysin gene will facilitate the study of metalloproteinase gene expression in normal processes and in diseases such as rheumatoid arthritis. | |
| 2436279 | [Alizarin red staining of articular fluids. Comparison of the results with electron micros | 1987 Feb | Coloration of articular fluids with alizarin S red has been proposed as a method of sensitive detection of calcium microcrystals, especially apatite crystals. We are reporting the results of a study of 230 non-selected fluids. The results of the coloration were quantified into negative, slightly positive, moderately positive and strongly positive. Study of X-Rays of the tapped joint and of the hospital file was done in 199 patients. Electron microscope study, of 44 fluid samples, shows that the coloration with alizarin red permits a reliable detection of calcium microcrystals in the articular fluid, only if the strongly positive results are taken into account. But the coloration is not specific for apatite: 5 strongly positive fluids out of 14 contain only, in electron microscopy, crystals of dihydrated calcium pyrophosphate. 10.8% of the stained fluids give a strongly positive result. In two cases, it concerns destructive arthropathies of the shoulder with periarticular calcifications. The other strongly positive results are found in chondrocalcinosis (52 p. cent), in arthrosis (17 p. cent) and in rheumatoid polyarthritis (15 p. cent). As a whole, the results are correlated with age and the degree of radiological destruction. The similar percentage of strongly positive fluids observed in arthrosis and rheumatoid polyarthritis, is not in favor of a specific role of apatite microcrystals in the pathogenesis of arthrosis. Since the majority of strongly positive fluids come from joints which are very destroyed, regardless of the arthropathy concerned (rheumatoid polyarthritis, chondrocalcinosis or arthrosis), it is possible to think that it is mostly the destruction of the sub-chondral bone which explains these results. | |
| 1720108 | Investigating the HLA component in rheumatoid arthritis: an additive (dominant) mode of in | 1991 | We examined the mode of inheritance of rheumatoid arthritis (RA) and estimated the genetic contribution of the HLA-linked locus to the development of RA using data from 111 multiplex families (54 London, 57 Cleveland), and 43 randomly ascertained patients (Seattle). HLA-DR4 was present in 78 multiplex probands (70%); a further 16 probands who were negative for DR4 were positive for DR1. Both DR4 and DR1 were significantly in excess when compared to control population frequencies (P less than 0.001); an additional finding was an excess of DR7, although the numbers of probands with DR7 were small. Despite the well-established HLA association with RA, neither recessive nor additive (dominant) modes of inheritance, nor any intermediate models have been ruled out using affected sib-pair and antigen genotype frequency among patients (AGFAP) methods. However, in our study the AGFAP data for HLA-DR4 and DR1 were close to recessive expectations (P = ns) while an additive (dominant) mode of inheritance was rejected (P less than 0.001). The same results were obtained by an independent method which considered HLA-DR transmission from affected parents to their affected children. The affected sib-pair haplotype sharing method showed deviation from random expectations but did not allow discrimination between recessive and additive (dominant) modes. The effect of the HLA-linked locus on familiarity accounted for only a 1.61-fold increased risk to sibs over the population prevalence, compared to an observed value of 3.90. This indicated that there could be at least one other non-HLA locus predisposing to RA with a weight that is slightly greater than that of HLA. | |
| 2522758 | Immunohistological features of synovitis in ankylosing spondylitis: a comparison with rheu | 1989 Feb | The immunohistological features of the synovial membrane in ankylosing spondylitis, HLA-B27 associated oligoarthritis, and rheumatoid arthritis wer examined with particular reference to T lymphocyte subsets. T helper (CD4+) cells clearly outnumbered T suppressor/cytotoxic (CD8+) cells in rheumatoid arthritis, whereas both cell types were present in equal numbers in ankylosing spondylitis. A reduction of CD4+/CD45R+ suppressor/inducer cells relative to CD4+/UCHL1+ helper/inducer cells was apparent in all diagnostic groups. The observations were suggestive of disease specific inflammatory responses within synovial membrane. | |
| 1653773 | Biochemical perturbations of BW 91Y (3-deazaadenosine) on human neutrophil chemotactic pot | 1991 | The studies reported here were designed to examine the chemotactic potential, arachidonic acid (AA) metabolism and phospholipid transmethylation in peripheral blood neutrophils from patients with rheumatoid arthritis (RA): a) prior to treatment with BW 91Y (3-deazaadenosine), b) after 4 weeks when half the patients were on active medication and half were on placebo, and c) after 4 weeks at which time all patients were on active medication. The authors demonstrate that BW 91Y in vitro at 600 pg/ml caused a decrease in chemotactic potential as measured by the leading front (LF) assay in neutrophils from both normal volunteers (p less than 0.025) and RA patients. They also demonstrate that BW 91Y caused a significant increase in production of [3H]LTB4 (LTB = leukotriene B) in ionophore-stimulated neutrophils from both normal (p less than 0.025) and RA patients (p less than 0.050) as compared to initial values. BW 91Y caused decreased incorporation and percent distribution of [3H]AA into phosphatidylcholine (PC), with a resultant increase in percent distribution into phosphatidylethanolamine (PE). There was also an increased release of [3H]AA from the PE fraction in BW 91Y-treated cells in response to ionophore stimulation. BW 91Y was found to exhibit a dose-dependent (10(-7) to 10(-4) g/ml) inhibition of the uptake and incorporation of L-[methyl-3H]methionine into the cellular lipids, while at low doses (10(-9) to 10(-5) g/ml) it stimulated the significant uptake and incorporation of [methyl-14C]choline chloride into PC. Although the total cellular content and percent composition of PC remained unchanged, it was found that BW 91Y caused a slight decrease in PC plasmalogens and an apparent increase in the 1,2-diacyl-glycerophosphatidylcholine (-GPC). BW 91Y was found, however, to have no effect on the amount or stimulated metabolism of the ether-linked 1-O-alkyl-2-acyl-GPC. As further evidence for this, the authors demonstrate that BW 91Y has no effect on the ionophore-stimulated production of [14C]acetate-labelled 1-O-alkyl-2-acetyl-GPC, or [14C]PAF. | |
| 1913008 | Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroid | 1991 Oct | Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day. Nineteen patients received active therapy (as evening primrose oil 6 g/day) and 21 received placebo (olive oil 6 g/day). No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose. Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil. Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis, olive oil may itself have hitherto unrecognized benefits. | |
| 3365030 | Autoantibodies to type II collagen: occurrence in rheumatoid arthritis, other arthritides, | 1988 Apr | Serum IgG antibodies to native and denatured human type II collagen (Col II) were measured using an enzyme linked immunosorbent assay (ELISA). One hundred and thirty one patients with various forms of arthritis such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PSA). Reiter's Syndrome (RS), osteoarthritis (OA), and gout, 60 with autoimmune connective tissue disease, and 37 with the chronic inflammatory conditions--graft versus host disease and leprosy--were studied. With the exception of RS, PSA, OA, and gout, significant levels of Col II antibodies were detected in each disease group. Blocking studies with types I and II collagen on selected serum samples confirmed the specificity to native Col II, though some cross reactivity was apparent with denatured collagen. The patients with RA who were Col II antibody positive tended to fall into stage III of disease progression. There was, however, no correlation with rheumatoid factor, erythrocyte sedimentation rate, or disease duration and this, together with the finding that Col II antibodies are present in a wide array of diseases, makes their role in the pathogenesis of RA questionable. They may arise as a secondary disease perpetuating mechanism in some patients, or in turn may be an epiphenomenon secondary to generalised disturbed immunoregulation or B cell hyperreactivity, or both, that characterises these clinical conditions. | |
| 3246134 | Anteroposterior radiographic view of the knee. An unreliable indicator of bone damage. | 1988 Dec | The clinician and/or radiologist uses standard radiographic views to assess bony changes in the joints of patients with both potential and established arthritis. Using AP (standing) views, we recorded the number of osteophytes and/or subchondral cysts seen on both nonarthritic and arthritic tibial tables and their respective plateaus. These data were compared with the number of osteophytes and/or subchondral cysts observed on "en face" views taken of the same tibial tables after they were resected from the knee joints. Not all of the osteophytes or subchondral cysts present in these tibial tables were detected with the AP view. Narrow osteophytes and those located at extreme anterior or posterior positions on a plateau were missed. Single cysts scattered across a plateau were also not seen. We found that the standard AP view gave an inaccurate measure of the amount of bone damage actually present in the tibial tables of arthritic knees. | |
| 1831836 | Appearance of beta-human atrial natriuretic peptide in collagen disease. | 1991 Jul | To elucidate the circulating forms of human atrial natriuretic peptide (hANP) in collagen disease, we analysed plasma samples obtained from 21 patients with systemic lupus erythematosus, rheumatoid arthritis or progressive systemic sclerosis with no clinical evidence of cardiac involvement. The findings were compared with those obtained from 21 healthy control subjects. Plasma hANP-like immunoreactivity was normal in all but three of the controls and in two patients with the nephrotic syndrome due to lupus nephritis. Reverse-phase high-performance liquid chromatography, gel permeation chromatography and subsequent radioimmunoassay for hANP revealed that the circulating hANP consisted of alpha-hANP, beta-hANP and gamma-hANP in the patients with collagen disease whereas alpha-hANP predominated in the control group. beta-hANP appeared in 18 of the 21 patients but was not observed in the controls. These data suggest that beta-hANP circulates in the plasma of patients with collagen disease even when no myocardial involvement is apparent and that the appearance of beta-hANP is not always associated with an increase in total plasma hANP-like immunoreactivity. Thus the appearance of beta-hANP in plasma is not a phenomenon specific to congestive heart failure. | |
| 2868855 | Isolation and identification of a new major metabolite of diflunisal in man. The sulfate c | 1986 Jan | A new metabolite of diflunisal has been identified in volunteers and patients after multiple dose administration. The metabolite was isolated from human urine by silica gel chromatography and was further purified by reversed phase HPLC. Arylsulfatase from Helix pomatia and from Aerobacter aerogenes completely hydrolyzed the isolated metabolite to diflunisal, although hydrolysis by bacterial arylsulfatase was extremely slow. Electron impact mass spectra for diflunisal and its sulfate conjugate were virtually identical. Negative ion fast atom bombardment mass spectra clearly showed the quasimolecular ion [M-H]- at m/z 329 (base peak) as well as a large fragment ion (90% relative intensity) at m/z 249 corresponding to the loss of the sulfate moiety. Urinary excretion patterns in volunteers and rheumatoid arthritis patients revealed that sulfate conjugation of diflunisal is a minor metabolic pathway after single 500-mg dose administration (less than 10% of the dose), whereas it becomes a major pathway (21.3-44.3% of the dose) following multiple doses (500 mg b.i.d.). In one volunteer, who ingested 500 mg diflunisal b.i.d. for 5 weeks, it was shown that the percentage of the dose excreted as diflunisal sulfate gradually increased during the first week to approximately 30% and stayed virtually unchanged for the remaining 4 weeks of diflunisal intake. These preliminary observations are not compatible with the idea that sulfate conjugation is capacity-limited at lower substrate concentrations than glucuronide conjugation, nor do they suggest that sulfation of diflunisal is rate-limited by depletion of inorganic sulfate body stores. | |
| 3020161 | Reactions of sera from patients with rheumatoid arthritis, systemic lupus erythematosus an | 1986 Oct | P3HR-1 and Ramos cells induced with sodium butyrate and 12-O-tetradecanoylphorbol 13-acetate were used in the protein immunoblot technique to identify Epstein-Barr virus (EBV)-specific antibodies present in sera from clinically normal individuals and patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and infectious mononucleosis (IM). Sixteen EBV-specific polypeptides were detected ranging in mol. wt. from 22,000 (22K) to 140K. Many of the sera contained antibodies to different subsets of these antigens, and a high proportion expressed autoantibodies which reacted with cellular components from an EBV genome-negative cell line. About 50% of the sera from each category reacted with the 44K to 48K and 36K and 38K early antigen (EA) components. A high proportion of the SLE sera (64%) were found to contain anti-EA antibodies, suggesting an association between EBV and SLE. Almost all of the EBV-seropositive sera examined contained antibodies against a 22K late antigen, but none of the sera from IM patients reacted with this polypeptide. |