Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human phosphoribosylpyrophosphate synthetase has been purified 4500-fold to electrophoretic homogeneity from the erythrocytes of normal individuals and of two brothers in whom excessive activity of this enzyme results in excessive rated of purine nucleotide and uric acid synthesis de novo and gouty arthritis. Structural differences between the normal and mutant enzymes are indicated by a lower isoelectric point for the mutant enzyme (pI 4.85) than for the normal enzyme (pI 5.10); decreased electrophoretic mobility of the mutant preparation on cellulose acetate gel at low inorganic phosphate concentrations; increased (2.4-fold) inactivation of the mutant enzyme activity relative to the normal by identical amounts of a specific antiserum which precipitates identical quantities of normal and mutant enzyme; increased thermal lability of the mutant enzyme at 55 degrees; and an increased (2.2-fold) specific enzyme activity for the mutant enzyme despite the comparable purity of the preparations. Antibody inactivation, quantitative precipitin, and immunodiffusion studies as well as the disparity in specific enzyme activities during the course of purification suggest that a structural alteration in the mutant enzyme leads to increased catalytic activity per enzyme molecule, either from a primary alteration in the structural gene(s) for phosphoribosylpyrophosphate synthetase or from a post-transcriptional alteration in the enzyme. Purified preparations of normal and mutant enzymes showed nearly identical affinity constants for magnesium and the substrates, ATP and ribose 5-phosphate, as well as similar inhibition constants for the products, PP-ribose-P and AMP, and the inhibitors ADP, GDP, and 2,3-diphosphoglycerate. An increased maximal velocity of the reaction was, thus, the sole kinetic difference identified. The increased velocity of the mutant enzyme reaction was constant over a range of inorganic phosphate concentrations from 0.1 to 100 mM. Subunit molecular weights of the enzyme preparations, estimated by sodium dodecyl sulfate-polyacrylamide electrophoresis, were identical (32,000), although the undenatured mutant enzyme showed a greater proportion of stainable protein in the smaller of two molecular weight forms (both greater than 500,000) of the enzyme demonstrated on polyacrylamide gel electrophoresis in the presence of 1 mM sodium phosphate.
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PMID:Human phosphoribosylpyrophosphate synthetase. Comparison of purified normal and mutant enzymes. 16 59

Salsalate in a non-acetylated salicylate with activity as an antirheumatic agent. The hemostatic effects of this agent were studied in twelve healthy subjects and nine patients with hemophilia A. Healthy subjects showed no change in bleeding time, platelet aggregation response to adenosine diphosphate (ADP) or collagen, or adenosine triphosphate (ATP) release in response to arachidonic acid as measured in an impedance whole blood lumi-aggregometer. The patients with hemophilia A showed no bleeding time prolongation nor an effect on ADP or collagen induced platelet aggregation in platelet rich plasma. It is concluded that this agent may be useful in the treatment of arthritis in patients with hereditary coagulation disorders.
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PMID:Hemostatic effects of salsalate in normal subjects and patients with hemophilia A. 202 Sep 37

Systemic lupus erythematosus (SLE) can produce profound disturbances in the central nervous system, characterized by encephalopathy, focal neurologic deficits, cerebral infarction, psychosis, and seizures. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine the in vivo levels of high-energy phosphates in the central nervous system of 10 patients with SLE and 10 age-matched normal controls. 31P NMR spectroscopy was performed on a 1.5-Tesla unit equipped with a dual-tuned 1H-31P surface coil and a software-directed DRESS (depth resolved surface coil spectroscopy) pulse sequence. This procedure detected ADP, ATP, sugar phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and phosphodiesters in the brain tissue of all study subjects. Levels of ATP in the deep white matter of 10 SLE patients were significantly decreased compared with the levels in 10 normal controls, as quantitated by the ratio of ATP:ATP + ADP (mean +/- SD 0.81 +/- 0.11 versus 0.91 +/- 0.05; P less than 0.02). In a subgroup of 4 patients, PCr levels were decreased to a greater extent than the ATP levels. NMR spectroscopic alterations were not related to obvious anatomic lesions, as determined by standard cranial proton magnetic resonance imaging. In 4 SLE patients with markedly abnormal 31P NMR spectra, treatment with prednisone (80 mg/day) normalized the levels of ATP and PCr. Restoration of a normal 31P profile was accompanied by an obvious improvement in the patients' mental status and clinical symptoms. 31P NMR spectroscopy is a powerful new technique for monitoring high-energy phosphate metabolism, and may be particularly useful for characterizing central nervous system disease in patients with neuropsychiatric SLE.
Arthritis Rheum 1990 Jun
PMID:Depletion of high-energy phosphates in the central nervous system of patients with systemic lupus erythematosus, as determined by phosphorus-31 nuclear magnetic resonance spectroscopy. 236 38

Adjuvant arthritis in rats is a T-cell dependent "autoimmune" disease with close similarities to several forms of human arthritis. Injection of mycobacterial adjuvant leads to T-cell activation and proliferation, processes in which the de novo expression of the interleukin 2 (IL-2) receptor plays a pivotal role. The subsequent massive mononuclear cell infiltration of the joints ultimately results in complete joint destruction. Because activation of the helper/inducer subset of T lymphocytes is critical to the establishment of disease, we reasoned that IL2-PE40, a cytotoxic IL-2-Pseudomonas exotoxin fusion protein that targets the membrane-penetration and ADP-ribosylation domains of the toxin to cells bearing the IL-2 receptor, would be an effective and specific therapy. Adjuvant-injected rats were randomized to treatment with IL2-PE40, phosphate-buffered saline, or either of two control proteins related to IL2-PE40 but lacking either the receptor-binding moiety or an enzymatically active toxin domain and previously demonstrated to lack cytotoxicity in vitro. Intraperitoneal IL2-PE40 given before the establishment of overt clinical disease proved an effective and specific modifier of adjuvant arthritis by clinical, histological, and radiographic criteria. Our data suggest that IL2-PE40 may be effective in those diseases in which activated T-cells play an important role.
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PMID:Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats. 249 2

Extracellular generation of inorganic pyrophosphate (PPi) in cartilage organ culture is markedly augmented by ATP.ATP, not an ATP metabolite (ADP, AMP, adenosine) is necessary for this augmentation. Excess PPi production is effectively blocked by known inhibitors of nucleoside triphosphate (NTP) pyrophosphohydrolase (EDTA, EGTA, dithiothreitol). Excess 32P-PPi is generated directly from gamma 32P-ATP by cartilage, as substrate and product have similar specific activities. These findings strongly favor ecto-NTP pyrophosphohydrolase as the source of extracellular PPi generation in the presence of NTP. Additionally, active nucleotide and nucleoside catabolism is demonstrated in these cartilage organ cultures.
Arthritis Rheum 1985 Apr
PMID:Cartilage nucleoside triphosphate pyrophosphohydrolase. II. Role in extracellular pyrophosphate generation and nucleotide metabolism. 298 90

Methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones (MHSK and PHSK, resp.) upon oral administration displayed marked antiinflammatory activity in a variety of acute tests viz. carrageenan, histamine, 5-hydroxytryptamine, dextran, bradykinin and prostaglandin (PG) induced oedema in rats and carrageenan evoked swelling in mice; the activity was not altered by adrenalectomy. In subacute test of formaldehyde arthritis, they showed significant reduction in paw swelling but were less effective in granuloma tests. In chronic tests, they produced marked antiarthritic effect both in developing and established adjuvant arthritis. The compounds prevented the inflammation induced increase in serum transaminase levels and leucocyte counts. They inhibited the passive cutaneous anaphylaxis and produced reduction in ADP induced platelet aggregation. The compounds showed weaker antipyretic activity than acetylsalicylic acid in pyretic animals. MHSK showed analgesic activity using the tail clip method and antagonised acetic acid induced writhing syndrome. The compounds lacked any local anaesthetic activity. The low ulcerogenic potential of these compounds in animal models may be related to their relative inability to inhibit PG synthetase.
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PMID:Antiinflammatory actions of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones. 349 90

Muscle energy metabolism was studied by chemical analysis of biopsy samples from: 1) trigger points in the trapezius muscle from 15 patients with primary fibromyalgia (PF), 2) nonpainful, anterior tibial muscle from 6 patients with PF, and 3) the trapezius muscle from 8 healthy controls. We found a decrease in the levels of adenosine triphosphate, adenosine diphosphate, and phosphoryl creatine, and an increase in the levels of adenosine monophosphate and creatine, in the trapezius muscles from the patients. These findings support the notion that the pain in patients with PF is of muscular origin.
Arthritis Rheum 1986 Jul
PMID:Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia. 374 98

The disposition and effect on hemostasis of a single 150 mg dose of sulindac was studied in young healthy subjects and in older patients with arthritis. Older patients were restudied after 2 weeks of sulindac, 150 mg b.i.d. The only difference in disposition of the first dose was a reduced plasma sulfone metabolite concentration in the elderly patients with arthritis. Chronic sulindac dosing resulted in accumulation of the drug and its sulfone and sulfide metabolites in plasma to a greater extent than previously reported for young subjects. No differences in renal clearance of sulindac and its sulfone metabolite related to age or chronic drug dosing were observed. No renal excretion of the active sulfide metabolite was detected. Bleeding time in the elderly patients was shorter than in the young healthy subjects before sulindac dosing, but was prolonged in the elderly patients after 2 weeks of dosing to values similar to control data from the young healthy subjects. This change correlated weakly with plasma sulfide metabolite concentrations. Differences in bleeding time were not reflected in changes in platelet aggregation induced by adenosine diphosphate either with respect to age or chronic drug dosing. Our data provide no justification for lowering the recommended dose of sulindac for patients older than 65 years of age.
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PMID:Effects of age and disease on the pharmacokinetics and pharmacodynamics of sulindac. 401 23

Prostaglandins are analogs of the parent 20 carbon prostanoic acid. They are divided into 4 series: PGE; PGF; PGA; PGB, according to the presence of functionalities in the cyclopentane structure. Biosynthesis of prostaglandins were first independently reported by Bergstrom et.al. and van Dorp et.al. who showed that certain w-6-unsaturated fatty acids were biological precursors of prostaglandins. Later, various investigators reported the biosynthesis of prostaglandins of the different series. The 2 most widely used routes of prostaglandins synthesis are 1) the Corey cyclopentyl-lactone route, and 2) the bicyclohexane route. The synthesis is divided into 1) naturally occuring primary prostaglandins and 2) the prostaglandin analogs and derived prostaglandins. Because of the general instability of natural prostaglandins in the basic and acidic milieu, various preparations of prostaglandins and chemically stable dosage forms have been developed. Various methods used in analyzing prostaglandins include: 1) TLC; 2) GLC; 3) spectral methods; 4) radioimmunoassay; and 5) enzymatic assay. In vitro and in vivo studies on the metabolism and catabolism of various prostaglandins showed that they are rapidly metabolized in various animal systems and humans. The major routes for this metabolic transformation are: 1) oxidation of the secondary C15 hydroxy group; 2) reduction of the C13 double bond; 3) B-oxidation; 4) w-hydroxylation; and 5) w-oxidation. Prostaglandins produce a wide range of biological effects on animal and human systems (the reproductive; gastrointestinal; respiratory; and cardiovascular systems). The biological actions of prostaglandins on animal and human reproductive tissue vary depending on the particular prostaglandin studied and hormonal state of the tissue. Certain prostaglandins can decrease the tonus, frequency, and amplitude of spontaneous contractions of human uterine strips while other prostaglandins can cause contraction of isolated myometrial strips. Prostaglandins are widely used in labor induction; induction of therapeutic abortion; and fertility control. Prostaglandins have also been found to either increase or decrease cyclic AMP; inhibit ADP-induced platelet aggregation; lower blood pressure in animals; affect lipid and carbohydrate metabolism, and prevent adjuvant arthritis.
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PMID:Prostaglandins. 456 72

Native (n) but not single stranded (ss) DNA was found to induce release of 3H-serotonin (5-HT) from platelets of the majority of normal individuals. However, ssDNA markedly enhanced 5-HT release induced by heat-aggregated IgG (aggIgG), while less enhancement was seen using nDNA. Similar enhancement was produced by polyinosinic acid but not by polyinosinic:polycytidylic acid. The ability of ssDNA to potentiate aggIgG-induced 5-HT release seemed specific for aggIgG, since no effect on ADP or epinephrine-induced release was observed and thrombin-induced release was inhibited. In contrast, nDNA in high concentrations (100 micrograms/ml) potentiated ADP, epinephrine, and thrombin-induced 5-HT release. These results suggest that ss-and nDNA may interact with platelets by different mechanisms and provide a means by which DNA, released at sites of tissue injury, could modulate the role of platelets in the inflammatory response. The ability of DNA to enhance the aggIgG-induced platelet release reaction may be important in immune complex diseases such as systemic lupus erythematosus.
Arthritis Rheum 1983 Feb
PMID:The effect of native and single stranded DNA on the platelet release reaction. Enhancement of aggregated IgG-induced serotonin release. 682 15


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