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

ID PMID Title PublicationDate abstract
8316775 A case of long-standing classical rheumatoid arthritis complicated by serological and clin 1993 A patient with RA who developed anti-Sm antibodies, a false positive serological test for syphilis (FPSTS), pericardial effusion, and leukopenia, 19-year after the onset of classical RA, is described. This case indicates a possible clinical association between the development of specific autoantibodies and clinical symptoms of SLE.
8855135 [Successful treatment of interstitial pneumonitis with cyclosporin A in a patient with rhe 1996 Jan A 49-year-old male was admitted to our hospital because of acute renal failure. He had been treated by a local doctor for rheumatoid arthritis (RA) during the past eight years. We treated him with steroid pulse therapy, because of suspected acute interstitial nephritis. We confirmed this diagnosis by renal biopsy and steroid pulse therapy markedly improved his renal dysfunction. Immunohistochemical studies revealed that interstitial infiltrating leukocytes consisted mainly of polymorphonuclear leukocytes (PMNs), macrophages and B lymphocytes, while T lymphocytes were less predominant. ELAM-1 and GMP-140 were expressed in the peritubular capillaries. These findings suggest that endothelial activation of the peritubular capillaries may cause interstitial infiltration of PMNs and macrophages, resulting in the development of acute interstitial nephritis. Four months later, he developed severe interstitial pneumonitis, and his symptoms were not improved by high-dose steroid pulse and cyclophosphamide pulse treatment. Eight weeks after the second admission, cyclosporin A (Cy A) was started. Three weeks after starting Cy A, he was free from symptoms and his chest radiograph was normalized. Renal function was also improved by Cy A. These observations suggest that endothelial activation by adhesion molecules may play an important role in RA-related autoimmune diseases and that Cy A might be efficacious in such cases.
1603605 Oxaprozin: a new NSAID. 1992 May Oxaprozin, a propionic acid derivative, is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its spectrum of anti-inflammatory activity has been demonstrated in both in vitro and in vivo models.1 The majority of published clinical trials have focused on the use of oxaprozin (from Searle) in the treatment of osteoarthritis and rheumatoid arthritis.
8239764 Stress fractures of the pubic rami in rheumatoid arthritis. 1993 Sep OBJECTIVE: To draw attention to and detail the features of stress fractures of the pubic rami in patients with rheumatoid arthritis (RA). METHODS: Twenty two cases were collected prospectively over a four year period from patients undergoing active rheumatological surveillance in Leeds. Both old and new fractures were included. Information was obtained from the patients, clinical notes, and radiological investigations. RESULTS: All patients were women (mean age 68.1 years) with longstanding (mean disease duration 24.2 years) seropositive RA. Nineteen (86%) were receiving regular prednisolone treatment and all patients had radiological evidence of osteoporosis, with vertebral crush fractures in 10 (63%) of the 16 who had vertebral x ray examination. There was no biochemical evidence of osteomalacia. Nineteen (86%) presented with pain in the low back, groin, or hip and three were asymptomatic. Pain developed gradually in seven with an acute onset in the remainder. Six gave a history of a fall but only seven were x rayed at the onset of symptoms and initial radiographs were negative in five of these. In eighteen the fracture had either minimal or no effect on their mobility. Fractures affected all four pubic rami and in four all four were fractured. All but one patient (who had multiple fractures) made an uneventful recovery over two to four weeks with conservative management. CONCLUSIONS: Stress fractures of the pubic rami in RA appear to be more common than had been recognised. The low grade nature of symptoms, the minimal effect on mobility, and the absence of significant trauma are typical features and suggest that many more stress fractures may go unrecognised.
7803792 CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor V beta genes. 1995 Jan 1 CD3+ large granular lymphocyte (LGL) leukemia is a disease of unknown etiology characterized by clonal proliferation of T cells that usually express T-cell receptor (TCR) alpha beta heterodimers. The purpose of this study was to identify the variable (V), joining (J), and diversity (D) region TCR beta-chain genes expressed by CD3+ LGL leukemic cells in an attempt to gain insights into the etiology of this disorder. Twelve patients with LGL leukemia were studied, including seven with both LGL leukemia and rheumatoid arthritis (RA). RA is also a disease of unknown etiology that occurs frequently in patients with LGL leukemia. Clonally expanded T cells that express specific TCR V beta genes have been identified in fluid and tissue specimens from the joints of patients with RA. In this study, V beta expression was determined by PCR using a panel of 22 unique V beta primers to amplify cDNA prepared from peripheral blood mononuclear cells (PBMC). A dominant V beta gene product was readily apparent in all patients. To confirm that the dominant V beta gene originated from a clonal expansion, DNA fragments corresponding to the dominant V beta genes were subcloned into plasmids and independently isolated recombinants were sequenced. V-D-J region sequences that occurred repeatedly indicated clonality. The V beta and J beta genes expressed by the leukemic cells showed a pattern of distribution that followed the frequency with which these genes are represented in the peripheral blood. The residues corresponding to the third complementarity-determining region of the TCR beta chain were different in all cases. A specific pattern of VDJ usage was not identified for those patients with both LGL leukemia and RA; however, utilization of V beta-6 by LGL clones (N = 3) was observed only in the setting of RA. These data suggest that leukemic CD3+ LGL cells have been clonally transformed in a random fashion with respect to the TCR beta chain.
8753124 [Pneumonia caused by varicella-zoster virus in a patient with rheumatoid arthritis]. 1996 May A 56-year-old woman suffering from rheumatoid arthritis, was admitted to our hospital for evaluation of fever and dyspnea. A month before admission, she had been given a diagnosis of herpes zoster and was treated with an antiviral agent. However, a perineal eruption persisted. A chest X-ray film and a chest CT scan showed many diffuse nodular shadows in both lung fields. With conservative treatment, the shadows regressed along with the skin eruption and other symptoms. Pneumonia caused by varicella-zoster virus was diagnosed from the clinical course, chest roentgenographic and CT scan findings, and serological data. The risk of mortality in varicella-zoster pneumonia is high in adults, especially in immunosuppressed patients. Early diagnosis and effective treatment are, therefore, essential in the management of this disease. Though varicella-zoster pneumonia is rare, chest roentgenographic and CT scan findings are characteristic and suggestive. This case may serve as a reminder of the features of varicella-zoster pneumonia: many nodular shadows on the chest X-ray film and CT scan.
8346983 Lack of association of increased antibody levels to mycobacterial hsp65 with rheumatoid ar 1993 Jul OBJECTIVES: To investigate the role of humoral immunity to mycobacterial hsp65 in the aetiology of rheumatoid arthritis. METHODS: Levels of IgG antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples of 152 twin pairs discordant for RA and in serum samples from 62 normal blood donors. RESULTS: No significant differences between antibody levels in the subjects with RA compared either with their unaffected twins or with a group of normal blood donors was observed. In the monozygotic twins there was a strong but negative association between levels of antibody to hsp65 and disease status. Zygosity, sex, and HLA status did not significantly affect levels of antibody to hsp65. CONCLUSION: Previous reports of an association between hsp65 and RA were not confirmed.
8409448 IL-4 inhibits growth factor-stimulated rheumatoid synoviocyte proliferation by blocking th 1993 Nov 1 A major feature of rheumatoid arthritis is an uncontrolled proliferation of synoviocytes. This is consistent with the active production of factors such as platelet-derived growth factor (PDGF) and IL-1 by the synovitis, which act in vivo as well as in vitro as potent synoviocyte growth factors. We have previously shown that IL-4 is able to inhibit growth factor production in an ex vivo model of synovitis. Herein, we show that IL-4 strongly inhibited PDGF and IL-1 beta stimulated rheumatoid arthritis synoviocyte proliferation in a dose-dependent manner and through its 130 kDa receptor. This antiproliferative effect of IL-4 directly correlated with a blockade of the synoviocyte cell cycle at the G0 + G1 phases. We also observed that IL-4 induced striking morphologic changes in IL-1 beta or PDGF-stimulated synoviocytes, including increased volume and granulosity. These changes led to major perturbations of the cell monolayer, associated with a marked decrease of synoviocyte viability. Taken together, these data indicate that IL-4 inhibits growth factor-induced proliferation of synoviocytes by interfering with the cell cycle, and by decreasing cell survival.
1555050 Effects of tiaprofenic acid on plasminogen activators and inhibitors in human OA and RA sy 1992 The effect of therapeutic and pharmacological concentrations of tiaprofenic acid, a non-steroidal anti-inflammatory drug (NSAID), on the synthesis of the plasminogen activators, urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), and the plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2), by human synovial membranes isolated from osteoarthritis (OA) and rheumatoid arthritis (RA) sufferers was evaluated. Both forms of plasminogen activator (PA) and PA inhibitor (PAI) were synthesized by the arthritic synovium. PAI-1 and PAI-2 were both synthesized in greater amounts than the plasminogen activators. Tiaprofenic acid induced a dose-dependent decrease in uPA synthesis in both OA and RA, particularly in OA synovium, but had no true effect on tPA. Tiaprofenic acid also exerted a suppressive effect on the synthesis of PAI-1 in both OA and RA synovial membranes, and on the release of PAI-2 in RA synovium. The results of this study indicate that a decrease in uPA synthesis may be one of the mechanisms by which tiaprofenic acid could exert its effects on the arthritic process. The suppressive action of tiaprofenic acid on PAI is not likely to have a significant impact on the balance of plasminogen activators and plasminogen activator inhibitors, as plasminogen activator inhibitors are synthesized in greater amounts than plasminogen activators.
7966061 A Canadian survey of current methotrexate prescribing practices in rheumatoid arthritis. 1994 Jul OBJECTIVE: To conduct a cross sectional survey of methotrexate (MTX) prescribing practices of Canadian rheumatologists in their treatment of rheumatoid arthritis (RA). METHODS: A 15-item questionnaire was mailed to 197 rheumatologists with a 79% response rate after 3 mailings. RESULTS: The usual starting dose was 7.5 mg/week (range = 2.5-15.0) and the usual maximum dose prescribed was 15 mg/week (range = 10-50); 81% routinely coadministered MTX and non-steroidal antiinflammatory drugs; 28% routinely used folic acid prophylaxis; 97% of respondents performed regular assessments of liver function. Only 17% requested a liver biopsy after a certain time and 23% after a certain cumulative dose. Sixty-two percent performed pre-MTX liver biopsy on patients with liver function abnormalities. Only 14% of respondents routinely performed pulmonary function tests. Ninety-one percent of respondents noted that 1-50% (mode = 10%) of patients refused to accept MTX therapy after it had been recommended, usually because of fear of side effects. CONCLUSION: Despite potential toxicity, the majority of respondents used MTX in the treatment of adult RA.
8358143 McGill Pain Questionnaire translated into Danish: experimental and clinical findings. 1993 Jun OBJECTIVE: To develop a methodology for translating the McGill Pain Questionnaire (MPQ) into a Danish version, and to make comparisons to studies of patients speaking other languages. DESIGN: Finding suitable Danish adjectives using the same methodology as that in the original MPQ. Comparison of Danish descriptors to the words in the English version of MPQ. Survey in healthy subjects and patients with rheumatoid arthritis (RA) and fibromyalgia (F). SETTING: The general public and hospital outpatients. PATIENTS: A random sample of 186 healthy volunteers, 20 patients with rheumatoid arthritis and 41 patients with fibromyalgia. MAIN OUTCOME MEASURES: Danish words translated as closely as possible to the descriptors in the original McGill Pain Questionnaire. A pain-assessment instrument making international pain description possible. RESULTS: A Danish version of the McGill Pain Questionnaire was developed with scale values of Danish descriptors not differing more than 5 x SEM from the 'patient' words in the English version. The subdivision into classes and subclasses was respected. In the reliability experiment, the same rank values were found in 85% of subclasses. In a study using two experimental pain stimulus intensities, seven of 10 subjects obtained higher MPQ scores following the high-intensity stimulus. In the clinical study, the pain profiles of patients with RA and F in English, Italian, and Danish patients were almost the same. CONCLUSION: The present methodology of translating the McGill Pain Questionnaire permits comparison of studies from English-speaking and non-English-speaking populations, thus facilitating international research exchange.
8523335 Treatment of rheumatoid joint inflammation with intrasynovial triamcinolone hexacetonide. 1995 Sep OBJECTIVE: To determine the effectiveness of intrasynovial triamcinolone hexacetonide coupled with joint rest (3 weeks upper extremity; 6 weeks lower extremity) in the treatment of joint and tendon sheath inflammation in patients with seropositive rheumatoid arthritis (RA). METHODS: The medical records of 169 patients with seropositive RA treated by a single rheumatologist for at least one year between 1974 and 1992 were abstracted. RESULTS: Nine hundred fifty-six injections were given to 140 patients; approximately 75% of injected synovial structures remained in remission during a mean followup 7 years; 218 injections were given into previously treated structures. The injection rate was about 2 per patient in the first year, half of which were given at the time of the first visit. The rate then approximated 0.6 injections per patient-year for the next 15 years. Joints in the right upper extremity were injected significantly (p = 0.01) more frequently than those on the left. CONCLUSION: Intrasynovial triamcinolone hexacetonide followed by rest is a very useful adjunctive modality in the treatment of seropositive rheumatoid arthritis.
8061165 Differential B lymphocyte galactosyltransferase activity in the MRL mouse model of rheumat 1994 Oligosaccharides can be of fundamental importance to glycoprotein function. Glycosylation abnormalities are present in rheumatoid arthritis (RA) and may be associated with disease pathogenesis. To determine whether similar disease mechanisms occur in the MRL-1pr/1pr autoimmune arthritic mouse, studies on B lymphocyte galactosyltransferase (GTase) have been carried out. In MRL mice, a significant reduction in peripheral blood lymphocyte (PBL) GTase activity was found when compared to their paired splenic (SP) GTase activity (-69%, p = 0.002) and histocompatible non-autoimmune control CBA/Ca mice (-67%; p = 0.002). The changes in PBL GTase activity are similar to those found in RA and on further analysis, using mixing experiments in the presence of purified human milk GTase, this reduction was shown not to be due to the presence of a soluble intracellular GTase inhibitor. Furthermore when examining MRL derived hybridoma cells producing IgG, significantly reduced GTase activity was detected in the rheumatoid factor (RF) producing hybridoma cells compared to those secreting an irrelevant antibody (-21%, p < 0.05). Together these findings suggest that the glycosylation changes observed in this study, and those reported previously in RA, are tissue-specific, may result from cells trafficking from centres of disease activity and are not the result of direct enzyme inhibition. It is now important to further understand the mechanisms controlling glycosylation and relate disease associated changes with those occurring as part of normal cellular physiology.
8311538 Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoa 1993 Dec OBJECTIVES: To compare, by immunohistochemistry, the cellular and cytokine profile in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial membranes (SMs). Synovium was obtained at knee arthroplasty from 10 patients with RA and 10 with OA. METHODS: Synovial membranes were stained with a panel of monoclonal antibodies (MAb) to assess cytokine expression (IL-1 alpha, IL-1 beta, IL-6, GM-CSF, TNF-alpha and EGF) and the intensity of the mononuclear cellular infiltrate (MNC). RESULTS: Significantly greater percentages of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, GM-CSF and EGF cells were detected in all areas of the rheumatoid SMs when compared with osteoarthritic SMs. Five RA but only one OA SM demonstrated focal lymphoid aggregates. Lining layer thickening was noted in RA SMs only. The intensity of the MNC and number of blood vessels were greater in the RA group. CONCLUSION: The results suggest that the differences in cytokine production by RA and OA SMs are quantitative but that the greater thickness of the synovial lining layer and higher vascularity may be specific to RA.
7686371 Rheumatoid factors from patients with rheumatoid arthritis react with tryptophan 60 and 95 1993 Jul OBJECTIVE: To define precise epitopes on human beta 2-microglobulin (beta 2m) reacting with polyclonal IgM rheumatoid factors (RF) from patients with rheumatoid arthritis (RA). METHODS: Ten polyclonal RF were tested for their human beta 2m epitope-binding specificities using the entire 99-amino acid sequence synthesized as overlapping 7-mers in an enzyme-linked immunosorbent assay. Glycine substitution for each residue within RF-reacting linear regions was employed to define major reactive sites. RESULTS AND CONCLUSION: Major beta 2m residues contributing to RF reactivity were tryptophans at positions 60 and 95, lysine at 58, and arginine at position 97.
8774184 Eosinophils are an insignificant cellular component of rheumatoid synovium in patients wit 1996 Aug OBJECTIVES: To examine the distribution of eosinophils in rheumatoid synovial tissue and to determine whether or not their tissue distribution is related to that of mast cells or macrophages. METHODS: Consecutive tissue sections from 31 specimens of rheumatoid synovial tissue and cartilage-pannus junction were stained for eosinophils, mast cells, and macrophages with monoclonal antibodies and immunolocalisation techniques. RESULTS: Eosinophils were absent in 28 of the 31 specimens; the remaining three showed only the occasional eosinophil. By contrast the mean values for mast cell and macrophage (CD68/KP1 marker) distributions were 24 (SD 22) and 104 (SD 66) per mm2, respectively. CONCLUSION: There are very few eosinophils in inflamed rheumatoid synovial tissue and sites of cartilage erosion despite the presence of appreciable numbers of macrophages and mast cells, the mast cells showing various states of activation. Such findings are at variance with those in allergic inflammation, in which the presence of eosinophils has been reported to be regulated by specific chemokines and adhesion molecules.
8991977 Elevation in anti-Proteus antibodies in patients with rheumatoid arthritis from Bermuda an 1995 Oct OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) from Bermuda and England have an increased anti-Proteus antibody titer when compared to healthy Bermudian and English controls, and to ascertain whether any increase in antibody titer is specific by testing 4 other microbes, Escherichia coli and 3 normal anaerobic bowel bacteria. METHODS: Antibody titers were measured by ELISA and indirect immunofluorescence (IIFA) under coded conditions. RESULTS: Elevated titers of anti-Proteus antibodies were demonstrated in 34 patients with active RA from Bermuda when compared to 33 healthy Bermudian controls by ELISA (p < 0.001) and IIFA (p < 0.001). An elevation of anti-Proteus antibodies was also observed in 34 patients with RA from England when compared to 30 healthy English controls again by ELISA (p < 0.001). A similar antibody elevation in 31 patients with RA from England was observed when compared to 30 healthy controls when measured by IIFA (p < 0.001). However, there was no significant elevation in antibody titers against E. coli or the 3 normal bowel flora isolates in the patients with RA from both countries compared to their respective controls, when measured by ELISA. CONCLUSION: A specific elevation in the immune response to Proteus mirabilis has been demonstrated in patients with RA from both Bermuda and England. However, this study cannot distinguish between antibody association with disease per se and association with disease activity. The role of Proteus in RA and the effect of anti-Proteus therapy in patients with RA merits further study.
7504991 Identification of new B cell epitopes in the sera of rheumatoid arthritis patients using a 1993 Dec A random nanopeptide phage library was used to screen a pool of immunoglobulin fractions obtained from rheumatoid arthritis (RA) patients. After three rounds of panning, random individual phages were selected by their capacity to react with individual sera from RA patients. By sequencing the inserts corresponding to the peptides displayed on the surface of the phages, we found that phages displaying particular peptides were overrepresented in the selected libraries. The peptides displayed by these phages were: pep1 = Ala-Asp-Gly-Gly-Ala-Gln-Gly-Thr-Ala; pep2 = Pro-Gly-Pro-Ser-Arg-Ala-His-Phe-Leu; pep3 = Leu-Ser-Ser-Arg-Glu-Pro-Gln-Ala-Arg; pep4 = Arg-Leu-Thr-Arg-Glu-Leu-Tyr-Ala-Gln and pep5 = Tyr-Thr-Gln-Lys-His-Gln-Ala. The percentage of sera positive for pep1 was higher in RA patients as compared to the normal adults (p < 0.0004) and the reacting antibody was mainly of IgG isotype. The specificity of binding to the phage displaying pep1 was confirmed by competition experiments using both isolated phages and a synthetic peptide. Interestingly, a mutated phage displaying only Ala-Asp-Gln-Gly-Thr-Ala had no significant reactivity with the sera, indicating that the amino acids (Gly-Gly-Ala) of pep1 are the vital for the binding. Taken together this study demonstrates that it is possible to select specific ligands from a random phage library using sera from RA patients. In addition, this approach could be useful for identifying peptide antigens that might be part of causitive agents in autoimmune diseases.
8927727 [HRCT of the lung in collagenoses]. 1996 Jul Collagen vascular diseases, representing systemic soft tissue disorders, may cause a broad spectrum of pathologic changes of the respiratory tract. The type and extent of manifestations can vary considerably among individuals and entities. This survey describes the chest radiographic and, in particular, high-resolution computed tomographic (HRCT) findings of individual lesions of the respiratory tract. It includes fibrosing alveolitis (alveolitis, interstitial pneumonia, pulmonary fibrosis) and bronchial (bronchitis/bronchiolitis, bronchiectasis), pleural and vascular manifestations, as well as lymphadenopathy and abnormalities related to therapy. We present typical patterns of changes in progressive systemic sclerosis (PSS, scleroderma), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD, Sharp syndrome), Sjögren syndrome, overlap syndrome and rheumatoid arthritis (RA). Furthermore, we describe findings which are specific for individual entities such as esophageal involvement in PSS, acute pneumonitis and pulmonary hemorrhage in SLE, lymphoproliferative disease in Sjögren syndrome and necrobiotic nodules in RA.
8266026 Meta-analysis of NSAIDs: contribution of drugs, doses, trial designs, and meta-analytic te 1993 To elucidate potential bias sources in meta-analyses, I studied whether the effect of nonsteroidal, anti-inflammatory drugs on joint count in patients with rheumatoid arthritis was related to trial design (active or placebo control), sample size, duration of treatment, drop-out rate, the existence of a wash-in period, drug, dose, and meta-analytic technique. In short-term trials, none of the covariates was related to the effect size. No differences between drugs or doses were found in usual gold standard meta-analyses, comparing drugs within trials before pooling. In a meta-analysis of treatment arms, however, four drugs were either significantly more or less effective than average, but these deviations were spurious. In meta-analyses of NSAIDs, indirect comparisons may allow a preliminary comparison of drugs that have not been compared directly. Treatment arms should be compared within trials before pooling, however.