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

ID PMID Title PublicationDate abstract
3085648 Hepatitis and neutropenia secondary to gold thiomalate therapy for rheumatoid arthritis. 1986 Feb A 37 year old female with rheumatoid arthritis developed clinical and biochemical evidence of hepatitis after receiving 80 mg of sodium aurothiomalate. Inadvertent rechallenge with sodium aurothiomalate led to recurrence of the biochemical abnormalities and a profound neutropenia and eosinophilia.
3361531 Effects of synovial fluid and synovial fluid cells on chondrocyte metabolism in short term 1988 Feb Freshly isolated synovial fluid (SF) and plasma samples from 20 patients with rheumatoid arthritis (RA) and 9 patients with joint effusions of other diagnoses (non-RA) were immediately (without fractionation or dilution) used as a culture medium for murine articular cartilage. Both intact SF, and cell depleted SF were tested for the effect on proteoglycan synthesis (35S-incorporation) compared to the patients' plasma or standard tissue culture medium. In addition, the effect on proteoglycan degradation was measured using 35S-prelabeled cartilage. Intact SF and cell depleted SF were found to suppress chondrocyte metabolism both in the RA and non-RA group. In the group with RA a strong correlation was found between the number of cells in SF and the degree of suppression. In the same group, intact SF caused a markedly higher suppression of chondrocyte biosynthesis than in the non-RA group (p less than 0.02). In general, the suppressive effect of SF appeared to be at least partially related to inflammatory activity (number of cells in SF) rather than a specific feature of RA. During the short term exposure, no measurable breakdown of matrix proteoglycan was found, both in complete SF and cell depleted SF. Mechanistic studies suggest that neither hydrogen peroxide generated by polymorphonuclear neutrophil leukocytes nor variations in SF viscosity were responsible for the observed effects.
2048293 [The immunomodulating action of ultrasound and sinusoidal modulated currents]. 1991 Jan Leukocytes of normal donors and rheumatoid arthritis patients were exposed to low-intensity ultrasound or sinusoidal modulated currents. Depending on the initial values, expression of the receptors to sheep erythrocytes on T cells was either inhibited or enhanced. Similar effect was obtained upon a single local exposure to the above factors of the joints affected by rheumatoid arthritis. Lymphocytes from patients with chronic lymphoid leukemia differ from those of the donors by response to ultrasound.
2903922 History of enteric coated sulfasalazine in rheumatoid arthritis. 1988 Sep Sulfasalazine was synthesized almost 50 years ago specifically to treat rheumatoid arthritis. At that time bacterial infection was believed to be an important factor in pathogenesis. The linkage of sulfapyridine and salicylate with an azobond was viewed as a method of combining antibacterial and antiinflammatory actions while minimizing gastric irritation. Early therapeutic results were encouraging, but the drug was discarded as an antirheumatic agent for 30 years, until its serendipitous rediscovery. Subsequent controlled trials have confirmed its efficacy, which may be related to sulfasalazine itself or to the sulfapyridine moiety.
3710562 Influence of plasma proteins on activity of proinflammatory enzyme phospholipase A2. 1986 Jun The influence of plasma proteins on quantitation of the proinflammatory enzyme phospholipase A2 (PLA2) from rheumatoid synovial fluid was studied using two different assays. Human and bovine serum albumins increased the rate of PLA2 hydrolysis of membrane-associated phospholipid substrates. In contrast, albumin profoundly inhibited the PLA2 hydrolysis of synthetic phospholipids in micellar dispersion. Other plasma proteins (alpha, beta and gamma-globulins) had minimal effect on PLA2 activity in either assay system. Since the presence of albumin may compromise estimation of PLA2 and of phospholipase-inhibitory proteins, the appropriate selection of assay conditions is obligatory for the accurate quantitation of their respective activities.
2972666 [Pemphigus herpetiformis following D-penicillamine in a patient with HLA B8]. 1988 Sep A 57-year-old patient with rheumatoid arthritis, who was being treated with D-penicillamine, developed a bullous eruption 2 months after the onset of treatment. On the basis of the clinical, histological and immunofluorescent findings, the diagnosis of herpetiform pemphigus was made. The eruptions disappeared within 2 weeks after the discontinuation of D-penicillamine treatment. During the 16-month follow-up period there was no recurrence. It is noteworthy that a patch test with potassium iodide was positive and that testing for HLA antigens revealed HLA B8, A1, A2, and BW39.
3396215 Deficient repair of O6-methylguanine in lymphocytes from rheumatoid arthritis families may 1988 Apr Deficient repair of the premutagenic DNA lesion O6-methylguanine (O6-MeGua) has been reported in lymphocytes from patients with autoimmune diseases. This was confirmed in the present study of probands with rheumatoid arthritis (RA) and their families. We also noted a significant deficiency in 9/19 spouses (P less than 0.05) and a statistically non-significant deficiency of repair of O6-MeGua in 14/42 first and second degree relatives in comparison with healthy and non-autoimmune disease controls, respectively. A significant correlation of the repair status of O6-MeGua in DNA between individual probands with RA and respective spouses (P less than 0.01) and probands and respective family members (P less than 0.001) supported the idea that an environmental, transmissible agent could influence the expression of the protein, O6-methylguanine-DNA-transferase (O6-MT), involved in the repair of O6-MeGua. The present results, however, cannot entirely exclude an additional hereditary influence.
3264773 Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonge 1988 Sep In rheumatoid arthritis there is a chronic immune and inflammatory reaction which can lead to the destruction of the diseased joint. Cytokine gene expression was studied in synovial cells using cDNA probes specific for human interleukin 1 (IL-1), -alpha and IL-1 beta, tumour necrosis factor (TNF), -alpha and TNF beta (lymphotoxin); protein molecules which induce cartilage degradation and bone resorption. In all cases studied, IL-1 mRNA was present in freshly isolated synovial cells from fluid or membrane. Compared to levels of IL-1 mRNA found in optimally activated normal blood mononuclear cells, the levels of IL-1 alpha mRNA were high in seven of the nine patients studied, whereas IL-1 beta mRNA, the dominant form in blood, was relatively lower. TNF alpha and TNF beta mRNA were also detected. Rheumatoid synovial cells, cultured without any stimulus, continued to express high levels of IL-1 alpha mRNA for up to 5 days, compared to the 24 h response of activated blood cells; IL-1 beta mRNA in culture was also prolonged. Cultures of rheumatoid joint cells produced IL-1 bioactivity, with roughly equal amounts of IL-1 alpha and beta, as assessed using neutralizing antibodies. TNF bioactivity was also detected which may be of importance as TNF induces the production of IL-1. The finding of these mediators produced in large amounts in active rheumatoid synovial cells suggests that mutually stimulatory cell interactions, mediated by these molecules, may be important in the chronic inflammation and tissue destruction in rheumatoid arthritis.
2238240 [The Swanson silicone implant for wrists in rheumatoid arthritis]. 1990 Nov 12 The Swanson silastic implant was employed in 16 wrists in 13 patients who were followed up for a median of 59 months. At follow up examination, pain had decreased in ten wrists while three remained unchanged. Ten patients were satisfied with the total result. Only few complications occurred. Prosthetic fracture occurred in two wrists (14%). The authors consider that the Swanson silastic wrists implant can produce favourable results in patients with rheumatoid arthritis with moderate to severe radiological destruction.
1969384 Characterization of genomic polymorphism of an activation-associated antigen, Blast-1. 1990 Blast-1 is a human activation-associated glycoprotein expressed on the surface of mononuclear cells, and a possible genetic marker for the manifestation of rheumatoid arthritis. In the present study, genomic polymorphism of the Blast-1 gene was analyzed using 100 healthy subjects. Restriction fragment length polymorphism (RFLP) of the Blast-1 gene was recognized only by Bam HI digestion among 46 restriction enzymes tested. The sizes of polymorphic fragments were 2.4 kilobase (kb) on the L band, and 1.9 kb on the S band. A family study demonstrated that the two alleles of the Blast-1 gene were inherited in a co-dominant Mendelian fashion. The genotype frequencies of homozygosity for the L and S bands were 47% and 42%, respectively, while the frequency of heterozygosity was 11%. The allele frequencies of the L and S bands were 0.68 and 0.32, respectively. The distribution of the Blast-1 genotypes in the present study was concordant with Hardy-Weinberg equilibrium (p greater than 0.7), which indicates that the frequency of the Blast-1 gene in the population is derived from random mating in preceding generations. The results of the present study may provide useful information in disease associations with the Blast-1 gene.
2706825 Gold-induced hypersensitivity pneumonitis in a patient with rheumatoid arthritis. 1989 Jan A case of gold-induced hypersensitivity pneumonitis in a patient with rheumatoid arthritis is reported. Its differentiation from interstitial pulmonary fibrosis associated with rheumatoid arthritis is discussed and the low T4/T8 ratio in the bronchoalveolar lavage fluid of these patients is highlighted.
2737038 [Comparative study of diagnostic criteria of rheumatoid arthritis in Chinese patients]. 1989 Feb The ARA 1958 and 1987 revised classification criteria of RA are tested in 111 consecutive patients with RA and 54 cases of non-RA connective tissue diseases from three hospitals of tertiary level in Beijing. Comparing the two criteria, the specificity was the same as 88%, whereas the sensitivity changed from 94% of 1958 criteria to 91% of 1987 criteria. Factors affecting the sensitivity of 1987 criteria were mainly the morning stiffness which became to be more than 1 hour and increasing of number of swelling joints from one to three.
1677490 [Clinicopathological study of nephropathy in patients with rheumatoid arthritis]. 1991 Feb We carried out a retrospective study to investigate the clinical and pathological findings in 31 patients with rheumatoid arthritis (RA). In clinical findings, 17 patients showed nephrotic syndrome, five had isolated proteinuria, two had proteinuria and hematuria and seven had renal failure. In pathological findings, there were 16 patients with membranous nephropathy (MN), two with proliferative glomerulonephritis (DPGN), two with minor glomerular abnormality (MGA), six with amyloidosis, 2 with tubulointerstitial nephritis, and three patients had accompanying lupus nephritis. Eleven of 16 with MGN had been treated with gold, bucillamine or D-penicillamine, so they were diagnosed as drug induced MGN. In the other five patients, we could not decide which drugs induced the nephropathy. The 2 cases of MGA were associated with nephrotic syndrome and acute renal failure, which were caused by non-steroidal antiinflammatory drugs. There were two cases of non-Ig A DPGN, which was regarded as the native nephropathy in RA. The three cases with lupus nephritis were diagnosed as systemic lupus erythematosus by the criteria of the American Rheumatism Association (ARA). In conclusion, the nephropathy in patients with RA was varied and renal biopsy was a useful examination.
3519094 A comparison of plasma and synovial fluid profiles of standard and controlled-release form 1986 The plasma and synovial fluid profiles of standard and controlled-release formulations of ketoprofen were compared in 8 patients with rheumatoid arthritis. During chronic dosing with both forms of ketoprofen, peak drug concentrations were lower and occurred later in the synovial fluid than in the plasma. These findings were more pronounced in the case of the controlled-release formulation. The apparent elimination half-life of standard ketoprofen in synovial fluid was prolonged compared to its half-life in plasma, a finding which has not been previously documented. This may explain the clinical observation that, despite a very short plasma elimination half-life, standard ketoprofen exerts a satisfactory therapeutic effect when given twice daily. There was no accumulation of ketoprofen from either formulation in synovial fluid after steady state had been achieved. It is suggested that future pharmacological studies with anti-inflammatory agents should include both synovial fluid and plasma concentration data.
1838534 Analysis of T cell receptor V alpha and V beta gene usage in synovia of patients with rheu 1991 Oct T cells are thought to play a fundamental role in the pathogenesis of rheumatoid arthritis (RA). Activated T cells expressing alpha/beta T cell receptor (Tcr) infiltrate the rheumatoid synovium and could potentially initiate a local inflammatory response directed against joint constituents. A Tcr repertoire with restricted heterogeneity may reflect a selective expansion of T cells reactive to a few antigenic determinants within the synovium. To determine whether predominant V alpha and/or V beta gene usage of the expressed alpha/beta Tcr repertoire is a feature of synovial T cells in patients with RA, the polymerase chain reaction (PCR) was used to amplify Tcr-alpha and Tcr-beta chain transcripts. The peripheral blood and synovia of five patients with adult RA were examined and no evidence of preferential use of 19 Tcr V alpha gene families was found. Similarly, most of the 18 Tcr V beta gene families could be detected in RA synovia although there were quantitative differences in Tcr V beta gene expression when compared to peripheral blood. This report shows that when the extremely sensitive assay of oligonucleotide hybridization of PCR amplified Tcr transcripts is used, permitting identification of specific V gene families, the alpha/beta Tcr repertoire in the rheumatoid synovium is more diverse than was previously thought. Therefore, in patients with RA of long duration, the synovial T cell response is most likely to be polyclonal.
2292466 Murine delayed-type hypersensitivity granuloma: an improved model for the identification a 1990 The present study examined the effects of five different classes of anti-inflammatory/immunoregulatory drugs using a mouse model of mBSA-induced delayed-type hypersensitivity granuloma (DTH GRA) to measure immune-mediated chronic inflammatory tissue formation. The compounds were administered orally daily following induction of DTH GRA (days 0 to 4); granulomata were quantitated gravimetrically on day 5. NSAIDs, with the exception of flurbiprofen, showed little activity in comparison with the steroids dexamethasone (1-3 mg/kg/day, orally) and prednisolone (3-10 mg/kg/day, orally), which caused significant suppression of DTH GRA tissue (65-76% and 26-68%, respectively). The "immunoregulatory" compounds levamisole and D(-)penicillamine were inactive, whereas cyclophosphamide (5-50 mg/kg/day, orally) reduced the response by 24-83%. The "interferon alpha-inducers" Tilorone, U-54,461, and U-56,499 were also potent inhibitors of the DTH GRA response; U-54,462, a weak interferon alpha-inducer, was inactive. Cyclosporin A (50-100 mg/kg/day, orally) suppressed DTH GRA most effectively when administered on days 3 and 4 (66% and 97%) of the five-day granuloma response (treatment was ineffective when given on days 1 and 2). We conclude that the DTH GRA response described above may be useful for evaluating different types of unique therapeutic agents that are effective in the treatment of chronic immuno-inflammatory disease such as rheumatoid arthritis.
2210971 Reactive oxygen species and hyaluronate in serum and synovial fluid in arthritis. 1990 Oxygen-derived free radicals (ODFR) depolymerized synovial-fluid (SF) hyaluronic acid (HA) when hypoxanthine/xanthine oxidase (HX/XAO) was used as the radical generator. The molecular-weight distribution of ODFR-induced SF HA degradation products was determined using high performance liquid chromatography (HPLC) with TSK 5000 PW or TSK 6000 PW size-exclusion columns and simultaneously using 125I-labelled hyaluronate-binding protein (125I-HABP) assay. The exposure of SF HA to hydroxyl-radical flux resulted in the formation of a degradation product having a molecular weight of 13.5 X 10(3) daltons, from which no further degradation was achieved. If the iron chelator desferrioxamine and hydroxyl-radical scavenger mannitol were present in the reaction mixture, the HA peak decreased by 30-50%, as a result of reaction with superoxide radical and hydrogen peroxide. These results show that superoxide radical and hydroxyl radical may have different modes of action on SF HA. The molecular-weight distribution of serum HA from patients with rheumatoid arthritis varied in different individuals and ranged between 275 X 10(3) and 650 X 10(3).
3487652 Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole. 1986 Apr A 61-year-old patient with rheumatoid arthritis receiving treatment with methotrexate developed bone marrow hypoplasia after treatment with trimethoprim-sulfamethoxazole. The bone marrow recovered after stopping methotrexate.
3469971 Severe autonomic neuropathy in amyloidosis secondary to rheumatoid arthritis. 1986 Oct Autonomic neuropathy, although reported to occur in 15% of patients with AL primary) amyloidosis, is extremely rare in AA (secondary) amyloidosis. We report a patient with amyloidosis secondary to rheumatoid arthritis in whom autonomic neuropathy resulted in severe and disabling orthostatic hypotension. Extensive amyloid deposits were found throughout the autonomic nervous system.
2896459 Sulfasalazine: II. Some notes on the discovery and development of salazopyrin. 1988 May In summing up: salazopyrin is an effective drug, particularly in ulcerative colitis. Serious adverse effects are remarkably rare. Salazopyrin provoked an improvement in 75-80% of cases of UC. It is excellently adapted for long-term treatment and, in this respect, is clearly superior to corticosteroids. It prevents relapses, particularly if the dosage is increased. The main indication for corticosteroids in UC is for acute attacks early in the course of the disease and to influence allergic symptoms during the disease. For acute swelling of the rectum, local treatment with corticosteroids or salazopyrin is often effective. Adverse effects occur in about 15% of cases treated with salazopyrin. They are due primarily to hypersensitivity to the drug. With very few exceptions, they disappear spontaneously or are controlled by corticosteroids or by some other treatment. The allergic pulmonary changes may give rise to a modest dyspnea, which is not fatal. The cyanotic and the yellow-coloring of the skin are harmless side effects. As to sulfa crystals in the kidneys and the urine, for the most part, they can be avoided by simple treatment. Agranulocytosis is a rare complication in the course of treatment with salazopyrin. During the 35 yr that the drug has been used, only 14 cases have been published in the literature. Of this number, three have died, but the treatment of the agranulocytosis is known in only one of them. Nonpublished cases probably exist, but this number does not seem to be great in my experience. In comparison with many other drugs (certain chemotherapeutics and antibiotics), the frequency of serious side effects caused by salazopyrin is remarkably low.