Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
1677166 [Fatal liver cell necrosis following administration of glafenine]. 1991 Jun 15 The case is described of a patient with fulminant hepatic failure attributed to intake of glafenine 400 mg daily for 15 days. The first symptoms appeared two weeks after discontinuation of glafenine. Other causes of hepatic necrosis could be excluded. Approximately five weeks after the onset of symptoms the patient died of hepatic failure. At autopsy massive hepatic necrosis and massive pancreatic necrosis were demonstrated.
2111123 Genes associated with rheumatoid arthritis and mild inflammatory arthritis. I. Major histo 1990 Apr Patients with mild inflammatory arthritis (IA) were compared with patients with definite rheumatoid arthritis (RA) for abnormal frequencies of major histocompatibility complex (MHC) antigens and haplotypes to determine whether a genetic predisposition either to RA or to mild self-limiting arthritis/arthralgia was present in the patients with IA. In general the MHC antigens with abnormal frequencies found in patients with IA differed from those in patients with RA and were mainly at the A and B loci. In patients with IA the frequencies of HLA-A24, A25, B27, and B35 antigens were significantly higher than those of controls and HLA-DR5 and C4A4 were slightly raised. In contrast, in patients with RA abnormal frequencies of the MHC antigens DR4 and DR2 and the extended haplotypes associated with them [B62 BfS C4A3 C4B3 DR4 GLO2] and [B7 BfS C4A3 C4B1 DR2] confirmed the observations reported on other white populations. Thus MHC antigen associations with IA and RA differ sufficiently to suggest a different genetic basis for the two conditions.
3033237 Tetracyclines inhibit human synovial collagenase in vivo and in vitro. 1987 Feb To determine if tetracyclines can inhibit human synovial collagenase from rheumatoid tissue, paired synovial tissue (or synovial fluid) was collected from 7 patients before and after oral administration of minocycline (100 mg BID) for 10 days. With each patient serving as his own control, the postminocycline collagenase activities fell an average of 67% from pretreatment values. Qualitative SDS-PAGE revealed decreased loss of alpha collagen components and reduced formation of alpha A digestion fragments. Addition of minocycline or a chemically modified tetracycline to synovial culture media in vitro profoundly inhibited collagenase activity. Further study of this action of tetracyclines could serve as a probe of the role of collagenase in rheumatoid arthritis and lead to development of agents capable of modifying the tissue destructive actions of collagenase.
1722966 Cross reaction of antibodies to a glycine/alanine repeat sequence of Epstein-Barr virus nu 1991 Nov P62 is a synthetic peptide which corresponds to the glycine/alanine repeat sequence of Epstein-Barr virus nuclear antigen-1. It is the main epitope recognised by anti-rheumatoid arthritis nuclear antigen antibodies. It was shown previously that anti-P62 antibodies were raised fourfold in patients with rheumatoid arthritis compared with controls. To examine the possibility that this increase was due to cross reactive autoantibodies binding to P62, anti-P62 antibodies from serum samples taken from 10 patients with rheumatoid arthritis and five healthy controls were purified by affinity chromatography. Immunoglobulin G anti-P62 antibodies purified from four of 10 serum samples from patients with rheumatoid arthritis also reacted with human epidermal keratin, denatured collagen type II and actin, but not with influenza antigens, as determined by enzyme linked immunosorbent assay (ELISA). Anti-P62 antibodies in serum samples from healthy controls and patients with rheumatoid arthritis reacted with epidermal keratin by immunoblotting. It is suggested that antibodies to the glycine/alanine repeat sequence of Epstein-Barr nuclear antigen-1 recognise homologous epitopes on keratin, actin, and collagen. It is also possible that molecular mimicry between a major epitope on the Epstein-Barr virus and several autoantigens might contribute to the breakdown of tolerance and autoimmunity in patients with rheumatoid arthritis.
2848449 Evidence that human rheumatoid synovial matrix metalloproteinase 3 is an endogenous activa 1988 Nov 15 The treatment of crude culture medium from human rheumatoid synovial cells with 4-aminophenylmercuric acetate (APMA) or trypsin results in the activation of procollagenase. This process was shown to be dependent on the presence of matrix metalloproteinase 3 (MMP-3). MMP-3 can directly activate procollagenase without changing the apparent molecular weight of procollagenase. This activity was accelerated in the presence of APMA. We propose that MMP-3 plays an important role in connective tissue destruction through the activation of procollagenase in addition to its direct action on components of the extracellular matrix.
3426924 Elevated levels of abnormally-fucosylated haptoglobins in cancer sera. 1987 Nov Cancer sera have higher levels of serum protein-bound fucose than sera from healthy individuals. In an attempt to identify the cause of this increase, fucoproteins were extracted from the sera of cancer patients and healthy individuals using a fucose-specific lectin (lotus tetragonolobus) coupled to Sepharose, and were analysed by polyacrylamide gel electrophoresis and silver staining. Of the several consistent changes observed for the cancer sera, the most striking was a large increase in a component of 40-45 Kdaltons. The expression of this component in the cancer sera was related to the elevation in serum fucose levels. Two dimensional (2D) electrophoretic analysis of lectin extracts showed that this component had a similar isoelectric point to the beta chains of haptoglobin. Its identity as haptoglobin was confirmed using Western blotting and an anti-haptoglobin antibody. Fucosylated haptoglobins (FHp) were also isolated from some rheumatoid arthritis sera, but there was no correlation between serum fucose levels and the FHp expression. The FHp in cancer sera was of higher molecular weight than that found in rheumatoid sera. Serial specimens from two ovarian cancer patients undergoing chemotherapy had elevated FHp associated with increased amounts of tumour. To the best of our knowledge this is the first time a molecule of this type has been reported in cancer sera and because of its uniqueness it deserves further investigation as a potential cancer marker.
3168322 Measurement and characterisation of circulating anti-endothelial cell IgG in connective ti 1988 Jun We have detected circulating IgG antibodies that bind with high affinity to human umbilical vein endothelial cells in 74% of patients with systemic lupus erythematosus (SLE), 30% of those with scleroderma and 28% of those with rheumatoid arthritis. IgG binding was F(ab) mediated, and did not involve immune complexes. Anti-endothelial IgG were apparently unrelated to other circulating autoantibodies, including anti-cardiolipin or antiDNA IgG. Bound IgG from SLE or scleroderma patients was displaced by IgG from certain unrelated patients whereas others were ineffective. Anti-endothelial cell IgG from all sera tested were adsorbed by human dermal fibroblasts; erythrocytes and leucocytes each adsorbed a fraction of the activity. Purified IgG did not induce complement-mediated cytotoxicity. We conclude that a discrete group of IgG antibodies is common in connective tissue disease patients, reacts predominantly with endothelial cells and dermal fibroblasts, and may be important in the pathogenesis of vascular damage.
3750404 [Frequency of acrocentric chromosome associations in a long-term human lymphocyte culture] 1986 May The frequency of acrocentric chromosome associations (ACA) in the long-term culture of lymphocytes progressively decreases by 25% (on the average) for one mitotic cycle. As a result proliferous lymphocytes after 3-4 divisions contain either no associations or not more than 2 associating acrocentrics. The diversity of the peripheral blood lymphocytes as to the frequency of ACA in the first mitosis is connected with their different proliferative activity in the organism.
2181674 Does the acetyl group of aspirin contribute to the antiinflammatory efficacy of salicylic 1990 Feb In a multicenter, double-blind, parallel-group study, 233 patients with classical or definite RA who demonstrated disease flare during a prestudy washout period were randomized to 12 weeks of treatment with either the nonacetylated salicylate, salsalate (salicylsalicylic acid), or aspirin. Of the 150 patients who completed the study, 83 received salsalate and 67 were treated with aspirin. Doses of the two drugs were calculated to provide equal amounts of bioavailable salicylic acid. The efficacy of salsalate and aspirin, as measured by all the usual variables, was equivalent but aspirin-treated patients had a higher incidence of severe gastrointestinal problems. Thus, this study demonstrated that the acetyl group of aspirin does not enhance the anti-inflammatory efficacy of salicylic acid in RA.
2973648 [Expression of pain in rheumatic disease. Exploratory study]. 1988 Oct An investigation done in 34 rheumatology departments on 259 patients in order to analyse their perception of pain and its repercussions on daily living. The main three diseases justifying hospitalization are: rheumatoid arthritis, lumbosciatica and bone neoplasia. In these patients, pain occurs daily in 75 p. cent of them and continuous in 32 p. cent; the intensity of the pain varies according to the time. There are repercussions on work (63 p. cent), walking (81 p. cent), but also on leisure (74 p. cent), friendly interelations (42 p. cent) and disposition which is disturbed in 62 p. cent of patients. Behavioral analysis in the presence of pain brings up differences depending on the patients: the elder the patient, the least they are able to respond to the handicap caused by pain. Analysis of the pain vocabulary suggest that if the terms expressing the experience of the patient are different according to the diseases, the usual description of painful phenomena are common to patients and the diseases in question.
3101622 CD5 positive B cells in patients with rheumatoid arthritis: phorbol ester mediated enhance 1987 Jan CD5 molecules present on human T cells are detectable but weakly expressed on some human B cells. We have increased the sensitivity of their detection by treating the B enriched cells with phorbol myristic acetate (PMA), a tumour promoting agent. The numbers of CD5+ B cells in the blood of patients with rheumatoid arthritis (RA) were higher than in control blood, and after PMA treatment this was statistically significant. CD5+ B cells were also increased in tonsils, lymph nodes, and spleens after PMA activation. There were no significant differences between the percentages of B cells carrying chi or lambda light chains in their expression of CD5 molecules in patients with RA.
1696992 Anti-F(ab')2 antibody response to the injection of anticlass II HLA alloantibodies in pati 1990 Jun Placenta eluted gamma globulins (PEGG) contain antibodies against class II HLA antigens and have been used for treating patients with rheumatoid arthritis (RA). In view of the potential use of antibodies to class II HLA for treating autoimmune diseases we looked for the immunobiological effects of PEGG injections in patients. No modulation of class II HLA was seen at the surface of circulating mononuclear cells after one week of daily PEGG injections. In some patients, antibodies to F(ab')2 fragments of PEGG-IgG were produced. These antibodies reacted against F(ab')2 of any IgG as well and did not prevent anticlass II HLA antibodies from binding to class II HLA, thus showing no characteristics of classical antiidiotypic antibodies. The appearance of anti-F(ab')2 antibodies was not correlated with the clinical course of the disease. Their significance is discussed.
1959286 Total knee arthroplasty in valgus knees. 1991 Dec One hundred thirty-four total knee arthroplasties in 98 patients with a valgus alignment were analyzed. Knees with a preoperative alignment of 10 degrees or greater anatomic valgus were believed suitable for inclusion. The average follow-up period in these patients was 4.5 years (range, two to ten years). One hundred eighteen knees were implanted with a posterior stabilized prosthesis, eight knees with a constrained implant design, four knees with a total condylar prosthesis, and four knees with a cruciate-retaining design. All components in all knees were cemented. A lateral retinacular release was necessary in 76% of the arthroplasties secondary to intraoperative lateral subluxation of the patella. The ligamentous release for balancing these valgus-deformed knees was done from the femur. There were 95 knees (71%) rated as excellent, 27 knees (20%) as good, eight knees (6%) as fair, and four knees (3%) as poor. Postoperatively, 76% of the knees had a tibiofemoral alignment between 5 degrees and 9 degrees valgus with an overall average of 7 degrees valgus (range, 3 degrees varus to 15 degrees valgus). Total knee arthroplasty is a reliable and durable procedure in the treatment of valgus knee arthritis. However, valgus-deformed knees represent a greater challenge than their varus counterparts to the implant surgeon in terms of the intraoperative balancing required. This may be a function of the greater difficulty in achieving ligamentous equilibrium and the relative rarity of valgus-deformed knees.
3945590 Septic arthritis. Clinical approach to the 'hot joint'. 1986 Feb 1 Joint space infections continue to be among the most common forms of arthritis. Diagnosis can be difficult, particularly in the presence of underlying joint disease. Septic arthritis should be suspected in all patients who present with an acutely swollen joint. Immediate joint aspiration with Gram's stain and culture of the synovial fluid is essential. Intensive, long-term antibiotic therapy is necessary to prevent a high rate of morbidity and, possibly, death.
2239824 Antinuclear matrix antibody. Hidden antinuclear antibody in patients with connective tissu 1990 Nov A total of 435 serum samples from patients with different rheumatic diseases were screened for the presence of autoantibody to nuclear matrix components by indirect immunofluorescence on 0.1 mol/L HCl extracted HEp-2 cell and WiL2 cell substrates. A total of 28 specimens were positive in this assay. Eighteen of them were from patients with systemic lupus erythematosus (18 of 250), 2 from patients with rheumatoid arthritis (2 of 115), and 8 from patients with mixed connective tissue disease (8 of 10). Antigenic material for this antibody is resistant to DNase, partially sensitive to RNase, and sensitive to trypsin. This indicates that the antigen is composed of protein and possibly RNA. In immunoblot analysis, sera positive for this antibody in indirect immunofluorescence assay recognized different peptides. This suggests that protein peptides are the major antigenic material.
2786788 Clinical, serological, and HLA phenotype subsets in Sjögren's syndrome. 1989 Mar The clinical and laboratory features of 89 patients with Sjögren's syndrome (SS) have been reviewed. Forty-eight of the patients had primary SS, of whom 27 had antibodies to Ro and/or La. The anti-Ro/La antibody positive patients showed a higher frequency of systemic clinical features, as well as high IgG levels and rheumatoid factors compared to those without the antibodies. Patients with SS-SLE developed symptoms of SS at the same age as those with primary SS but facial rashes, photosensitivity, and serositis were more common. Otherwise the clinical and laboratory features were indistinguishable from primary SS with anti-Ro/La. The frequency of HLA DR3 and HLA DRW 52 in European Caucasians with primary SS was 67% and 82% (92% in those with anti-Ro/La) respectively. DRW 53 occurred in 94% of all patients with SS-RA.
3720217 Low-dose weekly oral methotrexate therapy for inflammatory arthritis. 1986 Jun The efficacy and toxicity of low-dose, weekly oral methotrexate (MTX) therapy for inflammatory arthritis was evaluated. Fifty-nine patients with a diagnosis of inflammatory arthritis who had failed to respond to or developed toxicity to gold, penicillamine, or hydroxychloroquine therapy were treated with MTX 10-20 mg administered orally or intravenously once a week in divided doses. Various tests to assess arthritis were performed upon each patient's entrance into the study and at specified intervals throughout the 24-month study period. The mean duration of methotrexate therapy was 15.5 months. Patients showed significant improvement in number of swollen joints, duration of morning stiffness, amount of pain, and amount of activity during the study period. Of the 35 patients who had had roentgenographic studies of their hands performed initially and after one year of MTX therapy, 23 had no evidence of new joint erosions after one year. Biopsies of hepatic tissue from 20 patients showed no progressive changes when compared with pretreatment biopsies. Gastrointestinal symptoms, mucocutaneous lesions, or small increases in liver enzyme concentrations were observed in 31 patients; three patients developed pulmonary toxicity and had to be withdrawn from the study. MTX is an effective agent for the treatment of inflammatory arthritis in patients who do not respond to therapy with nonsteroidal anti-inflammatory drugs or slow-acting antirheumatic drugs. Short-term weekly oral MTX therapy does not appear to result in clinically important liver disease.
3027129 Molecular cloning of human synovial cell collagenase and selection of a single gene from g 1987 Feb We used a subclone of a rabbit genomic clone for collagenase that cross-hybridizes with human synovial cell messenger RNA (mRNA) to identify a human collagenase complementary DNA (cDNA) clone. The human cDNA clone is 2.1 kilobases (kb) and selects a mRNA transcript of approximately the same size from primary cultures of rheumatoid synovial cells that produce collagenase, but no mRNA is selected from control (nonproducing) synovial fibroblasts. Restriction enzyme analysis and DNA sequence data indicate that our cDNA clone is full length and that it is identical to that recently described for human skin fibroblast collagenase. The cDNA clone identified a single collagenase gene of approximately 17 kb from blots of human genomic DNA. The identity of human skin and synovial cell collagenase and the ubiquity of this enzyme and of its substrates, the interstitial collagens types I, II, and III, imply that common mechanisms controlling collagenolysis throughout the human body may be operative in both normal and disease states.
2505778 Cytokines in chronic inflammatory arthritis. III. Rheumatoid arthritis monocytes are not u 1989 Sep Macrophages present in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) express large amounts of HLA-DR molecules on their surface, despite low levels of gamma-interferon (gamma-IFN) in the joint. To determine whether this apparent paradox is the result of increased sensitivity to gamma-IFN in RA, we compared concentrations of gamma-IFN that induced HLA-DR and DQ on peripheral blood monocytes of RA patients and normal donors, using fluorescence-activated cell sorter analysis. Among normal donors, highly variable sensitivity to gamma-IFN was observed. Higher amounts of gamma-IFN were required to induce class II major histocompatibility complex molecules on RA monocytes versus normal monocytes. The maximum amount of HLA-DR that could be induced on RA and normal monocytes was similar; however, peak levels of HLA-DQ were significantly less in RA. Monocytes from patients with other forms of chronic inflammatory arthritis had intermediate HLA-DQ expression after gamma-IFN treatment. These data suggest that an increased sensitivity to gamma-IFN in RA does not account for the high level of HLA-DR expression in the joint. Also, a defect in HLA-DQ and HLA-DR induction by gamma-IFN was observed.
2924461 Threaded cup acetabuloplasty. Early clinical experience. 1989 Apr Loosening of the acetabular cup component in total hip arthroplasty (THA) remains a source of ongoing concern. Threaded cup acetabuloplasty (TCA) utilizes torque and compression to gain purchase of the acetabular cup into the bony margin of the acetabulum. In an earlier study of 121 patients who had THA with TCA, patient assessments and roentgenograms were examined at an average of 30 months after surgery. Twenty percent of the cases were carried out for failed arthroplasty and 20% of the procedures required bone-graft reconstruction. A 22% incidence of moderate to severe postoperative pain, a 3% incidence of cup dislodgement, and a 24% incidence of radiolucencies between 1-2 mm were observed. The four cup dislodgements occurred in patients with severe osteopenia or in those requiring extensive bone-graft acetabular reconstruction. Good clinical results were obtained for osteoarthritic patients treated with primary THA. These early findings suggest that there is no advantage, but there are possible disadvantages, to threaded cup acetabuloplasty when compared to cup fixation with cement.