Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synovial fibroblast cell strains derived from the synovial membranes of 7 patients with rheumatoid arthritis were examined for the presence of viruses, in particular leucoviruses. Seven similar synovial strains derived from patients with other arthritic conditions were used as a control group. Evidence of the presence of a virus or a viral genome was looked for by several methods of induction followed by 3H-uridine labelling of the cultures. In addition, the culture supernatant, after induction and after the synovial strains had been co-cultivated with a variety of cell lines from several species, was assayed for the presence of viral RNA-dependent DNA polymerase activity. The DNA-polymerase activity of the synovial cells themselves was also determined. No evidence was found by any of these techniques to indicate the presence of virus or viral information within the synovial fibroblasts.
 ...
PMID:Attempts to identify viruses in rheumatoid synovial cells. 6 87

Auranofin (AF) is a new orally absorbed coordinated gold compound currently undergoing Phase I studies for its use in the treatment of rheumatoid arthritis. Our investigations with RAJI lymphoma, HeLa carcinoma, and EBV-transformed cells indicate AF exerts an inhibitory effect on DNA, RNA, and protein synthesis as assessed by 3H-thymidine, 3H-uridine, and 3H-leucine uptake, respectively. A rapid and persistent dose dependent inhibition of 3H-thymidine uptake was observed at gold concentrations of 50-100 microgram/dl while all parameters were inhibited after a 24 hr exposure to 100 microgram/dl. Reductions in viability and surface morphological changes were also observed. These results suggest AF exerts a significant inhibitory effect on essential biological processes and functions.
 ...
PMID:Cellular antiproliferative action exerted by auranofin. 22 2

Synovial fluid lymphocytes from patients with rheumatoid arthritis have been examined for evidence of a productive infection with retroviruses by electron microscopy, labelling with 3H-uredine, growth in soft agar, and culturing in conditioned medium. No such viruses were detected. In addition, the synovial lymphocytes were activated before fusion and cocultivation with several cell lines which have proved permissive for primate retroviruses. Monitoring these cultures subsequently by reverse transcriptase assay, labelling with 3H-uridine, and membrane immunofluorescence gave no indication that retroviruses were present.
 ...
PMID:Viruses and lymphocytes in rheumatoid arthritis. I. Studies on cultured rheumatoid lymphocytes. 53 43

Synthesis of protein, RNA and DNA was studied in skin fibroblast cultures of healthy donors and patients with systemic scleroderma (SSD) and in those with rheumatoid arthritis (RA) with the use of 14C-protein hydrolyzate, 14C-uridine and 14C-thymidine, respectively. A study was also made of the stimulation of 14C-proline incorporation in protein fibroblasts upon addition to serum-free media of 5% bovine embryonic serum. The stability of RNA in fibroblasts was tested. It was shown that the rate of protein synthesis was 11 times higher in fibroblasts of RA patients and 6 times higher in those of SSD patients as compared to the rate of protein synthesis in fibroblasts of normal subjects. The rate of DNA synthesis in skin fibroblasts of RA patients was 15 times higher and in those of SSD patients 4 times higher than normal. In both RA and SSD patients, the synthesis of short-labeled RNA was 2-3 times higher than normal. The addition of embryonic serum increased 2-3 times the incorporation of 14C-proline in protein skin fibroblasts of SSD patients. It was found that all RNA in skin fibroblasts was represented by long-living molecules and that 30-40% of short-labeled RNA in skin fibroblasts of healthy donors and SSD patients underwent degradation within 1-2 hours. The data obtained indicate that fibroblasts of the two pathologies under study are characterized by considerable differences in the synthesis of DNA and the activity of the protein-synthesizing system.
 ...
PMID:[Protein, RNA and DNA synthesis in skin fibroblast cultures from healthy donors and patients with rheumatic diseases]. 257 33

We investigated the diagnostic significance of UDP-D-xylose : proteoglycan core protein beta-D-xylosyltransferase (EC 2.4.2.26) in different chronic joint diseases. This enzyme is located almost exclusively within chondrocytes, where it initiates the formation of chondroitin sulphate during the biosynthesis of proteoglycans and from which it is easily released after damage of articular cartilage. Xylosyltransferase activity was determined in synovial fluid and serum by a radiochemical method, based on the incorporation of [14C]xylose from UDP-[14C]xylose into an exogenous acceptor protein. Serum has been shown to be the appropriate material for the determination of xylosyltransferase activity in blood, since in plasma fibrinogen causes an inhibition of enzyme activity of about 50%. The catalytic concentrations of xylosyltransferase in synovial fluids and sera of patients with chronic joint diseases (n = 131) ranged from 0.5 to 22.0 mU/l and from 0.8 to 5.6 mU/l, respectively. On most cases we found higher xylosyltransferase activities in synovial fluids than in the corresponding sera. The highest catalytic concentrations of the enzyme were observed in the synovial fluids of patients suffering from rheumatoid arthritis (median value: 5.56 mU/l, 90%-range: 3.2-22.0 mU/l). Synovial fluids of patients with arthritis urica, however, showing a comparable high degree of inflammation, contained lower enzyme catalytic concentrations (median value: 2.38 mU/l, 90%-range: 0.7-5.2 mU/l), which were in the range of those in osteoarthrosis (median value: 2.50 mU/l, 90%-range: 0.8-4.8 mU/l). The higher xylosyltransferase activities in rheumatoid synovial fluids seem to be attributed to an increased cartilage destruction during the course of this disease.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:UDP-D-xylose: proteoglycan core protein beta-D-xylosyltransferase: a new marker of cartilage destruction in chronic joint diseases. 312 82

1. Nucleosides and bases in physiological fluids result from metabolism of nucleic acids and nucleotides and from dietary sources. As nucleotide catabolism increases during tissue injury, nucleosides and bases could serve as useful biochemical markers in arthritis. 2. We have quantified nucleosides and bases in synovial fluid and plasma by high-performance liquid chromatography in order to examine whether nucleotide metabolism is increased in patients with rheumatoid arthritis and osteoarthritis. 3. At least ten u.v.-absorbing compounds were detected in plasma and synovial fluid; only urate, creatinine, hypoxanthine and uridine were present in identifiable and quantifiable amounts. 4. In synovial fluid from patients with rheumatoid arthritis the concentration of hypoxanthine was increased and that of urate decreased compared with osteoarthritis. 5. These data suggest that there is an increase in purine metabolism in the rheumatoid arthritis joint and that hypoxanthine is a potential marker of synovitis.
 ...
PMID:Nucleosides and bases in synovial fluid from patients with rheumatoid arthritis and osteoarthritis. 333 57

In defining host resistance factors in uremia, experiments were designed to assess the effect of renal failure serum upon the reactivity of normal human lymphocytes to phytohemagglutinin in vitro. Normal buffy coat cells were resuspended in sera obtained from normal subjects and from 14 patients with renal failure, then stimulated with phytohemagglutinin M and the cellular response measured by the increase in thymidine or uridine uptake. The mean thymidine uptake by stimulated cells in normal sera was 14,389 +/-1695 (SEM) cpm per 2 x 10(6) lymphocytes. Uridine uptake under the same conditions was 12,540 +/-1887 cpm. Compared to these are a mean thymidine uptake of 2740 +/-457 cpm and uridine uptake of 3928 +/-667 cpm in renal failure sera. Both differences are significant at P<0.01 level. For controls representing "chronic illnesses," sera from patients with pneumococcal meningitis, cirrhosis of the liver without jaundice, rheumatoid arthritis, and paraplegia with urinary tract infection did not cause suppression. No single drug had been taken by all the renal failure patients; three patients were taking no drugs. The serum from one patient with acute renal failure suppressed thymidine uptake while her serum obtained after recovery from her illness supported a normal lymphocyte response. Improvement of lymphocyte response was also noted in 9 of 10 sera obtained from patients immediately after hemodialysis. These observations plus the inhibition of stimulated cells by normal serum mixed with renal failure serum indicate the presence of a dialyzable inhibitory factor rather than the absence of a supporting factor in the renal failure sera. Lymphocytes preincubated for 24 hr in renal failure serum responded normally when transferred to normal serum and stimulated. Cells stimulated in normal serum and transferred to renal failure serum within the initial 24 hr of incubation demonstrated depressed thymidine uptake. Also, cell survival for 72 hr incubation as judged by trypan blue exclusion and chromium-51 release was similar in normal and renal failure sera. Thus, the suppressive effect of renal failure serum does not depend upon the initial phytohemagglutinin-cell interaction nor upon a significant cytotoxic effect. These studies demonstrate that a dialyzable factor(s) in the serum of patients with renal failure can greatly suppress one parameter by which an immune function of circulating lymphocytes is assessed and provides at least, a partial explanation for delayed homograft rejections in renal failure as well as the susceptibility of such patients to various infections.
 ...
PMID:Defective cellular immunity in renal failure: depression of reactivity of lymphocytes to phytohemagglutinin by renal failure serum. 557 33

Leflunomide is a novel immunosuppressive compound that is effective in the treatment of animal models of autoimmune disease and human rheumatoid arthritis. The mechanism of action is unknown. Here we show that leflunomide blocked 1) increases in nucleolar size and number, 2) upregulation of the nuclear protein antigens (PCNA and Ki-67), 3) increases in uridine incorporation and total RNA and DNA content, 4) cell cycle progression and 5) proliferation in mitogen-stimulated rat spleen mononuclear cells and human peripheral blood mononuclear cells (HPBMC). Exogenous uridine reversed the leflunomide-dependent inhibition of the normal increase in total RNA and DNA content in mitogen-stimulated HPBMC and rat spleen cells. Uridine reversed the leflunomide-dependent inhibition of cell cycle progression in stimulated rat cell cultures. Either uridine or cytidine, which can be converted to uridine by cytidine deaminase, reversed the antiproliferative effect of leflunomide in HPBMC. Dihydroorotate accumulated in leflunomide-treated human T-lymphoblastoid cells, suggesting that the compound inhibited the fourth enzyme in the pyrimidine biosynthetic pathway, dihydroorotate dehydrogenase. The results support the hypothesis that the in vitro effects of leflunomide on T-lymphocytes are due to inhibition of de novo pyrimidine synthesis.
 ...
PMID:The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis. 747 31

Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4-trifluoromethylphenyl)-4-isoxazole carboximide] is an immunosuppressive agent effective in the treatment of rheumatoid arthritis. In spite of its clinical potential, its mechanism of action has not been elucidated. Recent studies suggest that leflunomide may interfere with the metabolism of pyrimidine nucleotides. In our studies, the active metabolite of leflunomide, RS-61980 (A77 1726, 2-hydroxyethylidene-cyanoacetic acid-4-trifluoromethyl anilide), was cytostatic towards a human T-lymphoblastoma cell line (A3.01). The inhibition of growth could be overcome completely by uridine. The other nucleosides, cytidine, adenosine and guanosine, did not overcome the effect of the compound. Since uridine is a precursor for the salvage synthesis of UMP, we propose that RS-61980 may be inhibiting the de novo pathway of UMP synthesis. Using human cells, the six enzymes catalyzing de novo UMP biosynthesis were tested for their sensitivity towards RS-61980. Only one of the enzymes, dihydroortate dehydrogenase (DHODH, EC 1.3.3.1) was inhibited by RS-61980 with a Ki value of 2.7 +/- 0.7 microM. The other five enzymes were not affected. The inhibition exhibited mixed-type kinetics towards both substrates, dihydroorotic acid and coenzyme Q. These results suggest that the molecular target of leflunomide action is DHODH. The immunomodulating activity may be related to the inhibition of UMP synthesis in proliferating lymphocytes.
 ...
PMID:Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. 757 49

The effect of reactive oxygen species (ROS) generated by a xanthine oxidase hypoxanthine system (mainly H2O2) on proteoglycan (PG) metabolism and structure was investigated in vitro, using cell monolayers of cultured rabbit articular chondrocytes and purified resident and newly synthesized proteoglycans. It was shown that ROS generated in this system frequently stimulate (at low concentrations), and consistently inhibit (at higher concentrations), the incorporation of 35SO4 and 3H-glucosamine into PG molecules synthesized by cultured chondrocytes. The inhibition of isotopes' incorporation at higher enzyme concentrations was suppressed completely by heating xanthine oxidase and allopurinol with superoxide dismutase (SOD) and catalase. ROS at high concentration also inhibited 3H-uridine incorporation but had no effect on 35SO4 and 3H-uridine uptake by the cells. They also alter hyaluronan (HA) and PG monomers by fragmenting the core protein moiety and destroying the hyaluronic acid binding region. Altered PG monomers do not interact with HA to form complexes, but fragmented HA still retain a significant PG monomer-binding capacity. PG-HA complexes are easily and irreversibly destroyed by ROS. These results suggest that ROS may at low fluxes stimulate PG-synthesis under physiological conditions and alter cartilage metabolism and structure in conditions where they are overproduced, such as in rheumatoid arthritis, and in hemochromatosis and other iron storage diseases.
 ...
PMID:Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans. 800 11


1 2 3 4 5 Next >>