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

ID PMID Title PublicationDate abstract
3789477 [Characterization and determination of collagen antibodies by a solid-phase radioimmunolog 1986 The authors have developed a solid phase radioimmunoassay for the detection of antibodies to collagens. They give the technical data of this assay and some results mainly in rheumatic diseases.
3716381 [Changes in the plasma coagulation factors in patients subjected to plasmapheresis]. 1986 Eleven patients with immune-complex diseases were studied, that had been subjected to a total of 96 plasmaphereses during the day. The quantitative changes were followed up that developed in the active factors of coagulation after plasmapheresis. The results revealed that the plasma exchange, applied to the patients studied, induced the following changes: For factor I (fibrinogen)--mean = 2.39 +/- 1.19 g% (p greater than 0.005); for factor II (prothrombin)--mean = 55.5 +/- 20.9% (p less than 0.001); for factor V (proaccelerin)--mean = 97.6 +/- 13.8% (p greater than 0.01); for factor VII (proconvertin)--mean = 106.8 +/- 8.0% (p greater than 0.01); for factor VIII (AHG A)--mean = 64.5 +/- 22.7% (p less than 0.01); for factor IX (AHG B)--mean = 51.58 +/- 26.0% (p less than 0.001); for factor X--mean = 46.4 +/- 18.5% (p less than 0.001) and for factor XII--mean = 27.0 +/- 23.8% (p less than 0.001). That should be given consideration for the indications of the patients and their pretreatment for plasmapheresis.
3350977 Clinical application of new technique that measures C4d for assessment of activation of cl 1988 Feb A new laser nephelometric technique that measures C4d for the assessment of the activation of the classical complement pathway was developed. C4d was isolated from other larger C4 related molecules at a final concentration of polyethylene glycol of 12% and then quantitated by laser nephelometry using a commercially available antiserum, which reacts with C4d determinants. C4d standard (100%) was produced by exhaustive activation of the classical pathway in pooled normal human serum using heat aggregated human immunoglobulin. Serial dilutions of the standard provided a reference curve against which clinical samples were read. Patients with rheumatoid arthritis showed significantly higher C4d values (mean 53.8%) than controls (21.7%; p less than 0.001). The technique proved accurate, rapid, and suitable for the routine laboratory evaluation of complement activation through the classical pathway, and it may be useful in the management of those conditions in which complement activation has a pathogenic role.
2921324 Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the 1989 Mar Mechanisms governing the normal resolution processes of inflammation are poorly understood, yet their elucidation may lead to a greater understanding of the pathogenesis of chronic inflammation. The removal of neutrophils and their potentially histotoxic contents is one prerequisite of resolution. Engulfment by macrophages is an important disposal route, and changes in the senescent neutrophil that are associated with their recognition by macrophages are the subject of this investigation. Over 24 h in culture an increasing proportion of human neutrophils from peripheral blood or acutely inflamed joints underwent morphological changes characteristic of programmed cell death or apoptosis. Time-related chromatin cleavage in an internucleosomal pattern indicative of the endogenous endonuclease activation associated with programmed cell death was also demonstrated. A close correlation was observed between the increasing properties of apoptosis in neutrophils and the degree of macrophage recognition of the aging neutrophil population, and a direct relationship between these parameters was confirmed within aged neutrophil populations separated by counterflow centrifugation into fractions with varying proportions of apoptosis. Macrophages from acutely inflamed joints preferentially ingested apoptotic neutrophils and histological evidence was presented for occurrence of the process in situ. Programmed cell death is a phenomenon of widespread biological importance and has not previously been described in a cell of the myeloid line. Because it leads to recognition of intact senescent neutrophils that have not necessarily disgorged their granule contents, these processes may represent a mechanism for the removal of neutrophils during inflammation that also serves to limit the degree of tissue injury.
3120655 Comparative studies of serum and synovial fluid C reactive protein concentrations. 1987 Oct The relation between serum and synovial fluid (SF) C reactive protein (CRP) concentrations was investigated in a variety of arthritides, including rheumatoid arthritis (RA), psoriatic arthritis, reactive arthritis, and osteoarthritis. SF CRP levels were significantly reduced compared with serum levels in the inflammatory arthritides, but there was good correlation between serum and SF values. SF CRP values were all at the lower limit of the detectable range in osteoarthritis. In patients with RA or psoriatic arthritis followed up serially through an exacerbation of arthritis, changes in SF CRP reflected closely changes in serum CRP. In patients with RA SF/serum ratios of proteins of different molecular weight were used to derive a regression equation between SF/serum ratio and molecular mass. SF/serum values for CRP were significantly less than predicted from its molecular weight, suggesting that CRP is either being selectively bound in synovium or specifically consumed in SF and may be playing an important part in the inflammatory process in RA.
3803929 Neck pain in the elderly: a management review. Part I. 1987 Jan Degenerative disease of the cervical spine is a common cause of neck pain in the elderly. This article reviews the pathogenesis, clinical features, and management of cervical spondylitic radiculopathy and myelopathy in the elderly.
3263771 Evaluation of a nonconstrained total shoulder prosthesis. 1988 Dec We reviewed the radiographs and medical records of 76 patients with 98 nonconstrained total shoulder prostheses: 68 were inserted for rheumatoid arthritis, 25 for osteoarthritis, and five for avascular necrosis. The radiographic follow-up averaged 36 months. Radiographic evidence of postoperative complications was noted in 37 (38%) of 98 shoulders: dislocation of the humeral head (six), upward migration of the humerus (24), loosening of the glenoid compartment (15), loosening of the humeral component (five), subsidence of the humeral component (seven), and heterotopic bone formation (six). Patients with a dislocated prosthesis had limitation of motion, poor function, and residual pain. No increase in pain was associated with proximal subluxation of the humerus. No correlations were found between any of the radiographic findings (the presence of radiolucent lines about the glenoid or humeral components, humeral subsidence, or ectopic ossification) and any of the clinical findings (pain relief, range of motion, motor power, or functional improvement).
2706820 Preliminary criteria for primary fibromyalgia syndrome (PFS): multivariate analysis of a c 1989 Jan Primary fibromyalgia syndrome (PFS) is a common form of nonarticular rheumatism with chronic and generalized musculoskeletal aching and stiffness, accompanied by tender points at characteristic sites in the absence of an underlying condition. No satisfactory criteria for its diagnosis, based on appropriate controlled studies, have yet been proposed. We undertook such a study which included a consecutive series of clinically diagnosed PFS and compared them with 3 control groups--mild rheumatoid arthritis, localized fibromyalgia secondary to trauma and normal controls. Multivariate statistical analysis plus clinical judgement identified 6 historical features and 7 pairs of tender points that best discriminated PFS from the control groups. The criteria, derived from a combination of these historical features and tender points, provided greater than 90% sensitivity and specificity. In an independent and consecutive sample of 45 PFS patients, the criteria yielded a sensitivity of 89%. The present study indicates that a combination of historical features and TP's will likely provide effective PFS criteria.
3378125 Acute changes in calcium and bone metabolism during methylprednisolone pulse therapy in rh 1988 Jun Corticosteroids (CS) decrease bone formation and enhance bone resorption and this can lead to osteopenia. Bone metabolism was studied during the administration of huge amounts of CS (1000 mg methylprednisolone) over a short period of time in 10 patients with persistently active rheumatoid arthritis. The effects could be divided into those occurring within 24 h: (a) a decrease in bone resorption (urinary excretion of calcium and hydroxyproline) and bone formation (alkaline phosphatase); (b) a decrease in renal excretion of calcium; (c) an increase in concentration of serum 1,25-dihydroxy-cholecalciferol and those secondary effects arising after 24 h; (d) a decrease in serum calcium due to the decrease in intestinal Ca absorption and the decrease in renal tubular reabsorption of Ca; (e) an increase in serum PTH concentrations. In a previous study it was found that these changes normalized within a few days after completion of the CS treatment.
1746167 [Musculoskeletal manifestations in patients after bone marrow transplantation. Initial cli 1991 Jul From January 1986 through January 1989 69 adult patients received bone marrow transplants--20 with autologous, and 49 with allogeneic bone marrow. Ten patients after autologous and 33 patients after allogeneic transplantation (TX) could be examined for rheumatological complaints. None of the patients after autologous TX displayed rheumatological manifestations; 8/33 patients after allogeneic TX developed bone necrosis and they had to be treated for several months with high daily doses of prednisolon (mean: 55 mg/day). In 18/33 patients an oligoarthropathy of large joints could be observed after a significant reduction of prednisolon dosage over a period of 5 months. In addition 15/18 of these patients later developed a chronic g-v-h-disease. The TX arthropathy may be induced by cortico-steroid therapy (resp. reduction), but most important, it is a clinical sign for an imminent chronic g-v-h-disease.
3213261 Stimulated chemiluminescence of polymorphonuclear leukocytes in rheumatoid arthritis: in v 1988 May The aim of the study was to investigate the interaction of opsonized zymosan with polymorphonuclear leukocytes (PMNLs) from 26 rheumatoid arthritis patients (six males and 20 females; mean age, 51.88 +/- 11.15 years; range, 33-72 years) and 11 control subjects (two males and nine females; mean age, 56.54 +/- 12.1 years; range, 33-75 years) using a luminol-amplified chemiluminescence (CL). The data obtained suggest that the opsonized zymosan stimulated CL is decreased in untreated rheumatoid patients compared with control subjects. The decreased stimulated CL may be the result of a physico-chemical alteration of the membrane (including decreased membrane fluidity and translocation of receptor sites) induced by free radicals of oxygen and/or by multiple exposures to chemotaxins. Auranofin enhances stimulated CL although the mechanism is not clear. Auranofin could interact with membrane lipids, induce changes in membrane surface charges and increase membrane fluidity. Our results are difficult to compare with those of previous studies, since different assays, and chemoattractants were applied. In addition, the disease activity and medication were also different.
1660155 Limited T-cell receptor beta-chain heterogeneity among interleukin 2 receptor-positive syn 1991 Dec 1 Rheumatoid arthritis (RA) is a disease affecting the synovial membranes of articulating joints that is thought to result from T-cell-mediated autoimmune phenomena. T cells responsible for the pathogenesis of RA are likely present in that fraction of synovial T cells that expresses the interleukin 2 receptor (IL-2R), one marker of T-cell activation. We report herein an analysis of T-cell receptor (TCR) beta-chain gene expression by IL-2R-positive synovial T cells. These T cells were isolated from uncultured synovial tissue specimens by using IL-2R-specific monoclonal antibodies and magnetic beads, and TCR beta-chain transcription was analyzed by PCR-catalyzed amplification using a panel of primers specific for the human TCR beta-chain variable region (V beta). Multiple V beta gene families were found to be transcribed in these patients samples; however, three gene families, V beta 3, V beta 14, and V beta 17, were found in a majority of the five synovial samples analyzed, suggesting that T cells bearing these V beta s had been selectively retained in the synovial microenvironment. In many instances, the V beta 3, V beta 14, or V beta 17 repertoires amplified from an individual patient were dominated by a single rearrangement, indicative of clonal expansion in the synovium and supportive of a role for these T cells in RA. Of note is a high sequence similarity between V beta 3, V beta 14, and V beta 17 polypeptides, particularly in the fourth complementarity-determining region (CDR). Given that binding sites for superantigens have been mapped to the CDR4s of TCR beta chains, the synovial localization of T cells bearing V beta s with significant CDR4 homology indicates that V beta-specific T-cell activation by superantigen may play a role in RA.
2312372 Chronic neutropenia following gold therapy. 1990 Jan We describe the first case of chronic neutropenia of 17 years' duration following gold therapy in a 53-year-old woman given a 1-g course of gold therapy in 1965 for treatment of seropositive rheumatoid arthritis. Although she had a good response to the gold therapy, her originally normal leukocyte count fell to 1.2 x 10(9)/L. Over the subsequent 17 years, she required multiple hospitalizations for recurrent skin, mouth, and respiratory tract infections. Serial leukocyte counts failed to show a cyclical nature to the chronic neutropenia. Normal results of a technetium Tc 99m spleen scan and lack of increased bone marrow leukocyte precursors rendered a diagnosis of Felty's syndrome unlikely. A bone marrow biopsy specimen revealed an isolated reduction in the number of myeloid precursors, which is consistent with gold-induced bone marrow toxicity. This patient's relative freedom from serious life-threatening infections remains enigmatic, but is undoubtedly related to her ability to augment another phagocytic cell line, and the remarkable phagocytic activity of her monocytes appears to have well compensated for her neutropenia. This activity was most likely responsible for her long-term survival.
1650841 Synovial fluid ATP: a potential substrate for the production of inorganic pyrophosphate. 1991 May The enzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH) is present in all joint fluids and on intraarticular cells. It generates inorganic pyrophosphate (PPi) from nucleoside triphosphate substrate, thus serving as a potential source of the PPi which forms in the cartilages of patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition. NTPPPH is also important in matrix vesicle induced calcification with basic calcium phosphate (BCP) crystals. An articular substrate for this enzyme was sought. ATP was measured in the joint fluids from 107 patients with various forms of arthritis. Synovial fluid ATP levels were higher in patients with CPPD deposits than in osteoarthritis (p less than 0.02) or rheumatoid arthritis (p less than 0.002). ATP also correlated with PPi concentration (p less than 0.05) and with the presence of BCP crystals (p less than 0.05), but not with cellularity of the fluid, NTPPPH activity, or age of the donor. This substrate for NTPPPH may contribute to CPPD crystal deposition by generating PPi and may stimulate matrix vesicle induced formation of BCP crystals in several forms of arthritis.
1979687 Sensitivity of a Dutch Health Assessment Questionnaire in a trial comparing hydroxychloroq 1990 To measure health status in Dutch rheumatoid arthritis patients, we have translated and revised the Health Assessment Questionnaire (HAQ) and added questions about psychosocial status from the Arthritis Impact Measurement Scales (AIMS). The resultant questionnaire turned out to be reproducible and valid. In a double-blind trial comparing Hydroxychloroquine and Sulphasalazine, after 48 weeks the Physical Disability score showed a significant difference in favour of the Sulphasalazine group, reflecting the smaller deterioration in radiographic damage in this group. Thus the Physical Disability part of the questionnaire is sensitive to difference between two slow-acting anti-rheumatic drugs.
3238359 An ELISA for IgA-IgG and IgM-RF measurement. II. RF in several disease and control groups 1988 The before introduced solid phase ELISA was employed for the RF determination in the sera of RA patients and controls. The threshold values for positive results (calculated as the 95% distribution percentile of healthy donors) were 8, 3, and 3 U/ml for IgA, IgG, and IgM-RF, respectively. The results confirm the validity of the assay with clear negative results in several negative control groups (healthy donors, patients of the oto-, rhino-, laryngeal ambulance, diabetes mellitus, degenerative arthropathies; n = 111, median IgA, IgG and IgM-RF values of less than or equal to 2, less than or equal to 2 and less than or equal to 1 U/ml, respectively; 25-75% distribution percentiles within the median value) and positive results in the positive control group (seropositive RA; n = 20, median IgA, IgG and IgM-RF values of 324, 479 and 170 U/ml, respectively). 16/24 patients with so-called seronegative RA (negative Latex Fixation Test or Waaler Rose Test) had positive results in the ELISA, two of them had rheumatoid nodules clinically. The IgG-RF activity in the ELISA appears to be a good parameter for the course control of RA under gold therapy. 10 RA patients with clinical improvement of disease (declining ESR, CRP, joint index) after six months of gold therapy (= 0.6 g total gold amount) had a decline of total RF activity of 70% in median, whereas 10 patients with no clear effect on disease activity had only a decline of 20% in median.
2321716 An unusual presentation of cardiac tamponade. 1990 Feb A case of pericardial effusion with tamponade that presented as an acute abdomen is described.
2302843 Enhanced cytotoxicity in the rheumatoid joint. 1990 Mar The cytotoxic cytokines, tumor necrosis factor-alpha or cachectin and lymphotoxin (LT), are mediators of bone resorption and of inflammation and may have relevance in rheumatoid arthritis. Using mononuclear cells (MC) isolated from matched peripheral blood (PB) and synovial fluid (SF) of 13 patients with rheumatoid arthritis, we examined the generation of cytotoxic activity in a bioassay capable of detecting both TNF and LT. Synovial fluid mononuclear cells (MC) released significantly more cytotoxic activity than did matched PBMC, both spontaneously and following activation with phytohemagglutinin P (PHA). When PB and SFMC were stimulated with the combination of PHA plus phorbol-12-myristate acetate (PMA), the resulting culture supernatants possessed comparable cytotoxic activity. Neutralization studies employing anti-cytokine antibodies indicated that TNF represented 43 and 59% of the cytotoxic activity in the PHA plus PMA-induced culture supernatants from PB and SF, respectively. Since no inhibition was noted with antibodies to LT, the nature of the remaining approximately 50% of the cytotoxic activity was not determined. In PB and SF culture supernatants, obtained both spontaneously and following PHA activation, the concentration of TNF measured by ELISA significantly correlated with the level of cytotoxicity. As with the cytotoxic activity, the concentration of TNF was greater in the PHA-stimulated supernatants from SF than from PB. These observations suggest that TNF in the SF may contribute to the inflammation and bone destruction observed in rheumatoid arthritis.
1915559 Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: re 1991 Oct Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a growth factor for granulocytes and macrophages, is an activator of cells of the monocyte/macrophage lineage and induces HLA class II expression and cytokine synthesis in these target cells. Macrophage activation and class II expression are prominent features in rheumatoid arthritis (RA) joints, but the mechanism of their stimulation is not understood, since interferon-gamma, the major stimulus of class II expression, is not usually detectable at the protein level in synovial cell culture supernatants. We have, therefore, studied GM-CSF expression in cultures of cells derived from joints affected by RA and osteoarthritis (OA), and show that GM-CSF is produced spontaneously both by RA synovial cells and to a lesser extent by OA synovial cells in the absence of extrinsic stimuli. GM-CSF production continues for the 5-day duration of the culture period. Using neutralizing antibodies to tumor necrosis factor (TNF)-alpha we demonstrated that GM-CSF production in RA synovial cell cultures is dependent on the continued presence of active TNF-alpha. This result supports our concept that continued activation of the cytokine network is a marked feature of RA, and that TNF-alpha plays a pivotal role in this network, by regulating the production of other pro-inflammatory cytokines, such as interleukin 1, as demonstrated previously, and GM-CSF.
3369750 Detection of mycoplasmal antigens in immune complexes from rheumatoid arthritis synovial f 1988 May This study was directed towards the detection of suspected antigenic microbial fragments in the immune complex (IC) fraction from chronic inflammatory disorders of the delayed type allergy. Mycoplasmas as the microbial prototype and joint fluids from the rheumatoid host were investigated. Protein-A affinity chromatography was used to isolate the immunoglobulin complex (IgG-IC) in six synovial fluids obtained from rheumatoid arthritis patients. The IgG-IC was digested with pepsin to further purify and obtain F(ab)2 complexes with greater specificity. The F(ab)2 complexes were dissociated and electrophoresed by SDS-PAGE and analyzed by immunoblotting using affinity purified rabbit antisera to six reference strains of human mycoplasmas. The presence of trace amount of mycoplasma antigens in the immune complex fractions was indicated by specific banding with antisera to M. pneumoniae, M. arthritidis, M. hominis, M. fermantans, and M. salivarium in one or more of the six synovial fluid fractions. The ELISA and immunoblot assays of seroconversion in rabbits immunized with the synovial fluid fractions also indicated the presence of mycoplasmal antigens.