Search PubMed⌕ Search

Biomedical subjects

P A Simkin

Publications and source records attributed to P A Simkin.

At least 73 records · Page 4Linked to original sources
PubMed1982

Gout with superactive phosphoribosylpyrophosphate synthetase due to increased enzyme catalytic rate.

We have studied families C and A in which superactivity of PRPP synthetase (E.C. 2.7.6.1) is associated with gout and uric acid overproduction in affected hemizygous males. PRPP synthetase catalyzes synthesis of PRPP, a regulatory substrate in purine synthesis de novo. Activities of the enzyme in erythrocyte and fibroblast extracts from the male index cases, T.C. and R.A., were nearly threefold greater than normal at each Pi concentration tested. PRPP synthetase superactivity was accompanied by increased intracellular PRPP concentration and generation in erythrocytes and fibroblasts from these patients, and enhanced rates of PRPP-dependent purine synthesis reactions, including purine synthesis de novo, were demonstrable in their fibroblasts. These findings suggested that increased intracellular synthesis dut to enzyme superactivity underlay purine nucleotide and uric acid overproduction in these patients. Similar studies in cells from the sister of T.C. and the mother of R.A. showed increased values that were, however, intermediate between normal values and those of the affected males, indicating that these women are heterozygous carriers of the traits for enzyme superactivity. The enzymatic basis for increased PRPP synthetase activity in both families was investigated. Immunochemical studies in dialyzed erythrocyte lysates and highly purified erythrocyte enzyme preparations provided evidence for increased enzyme activity per molecule of immunoreactive enzyme. In addition, purified T.C. and R.A. PRPP synthetases showed 3.1- and 2.8-fold greater enzyme specific activities, respectively, than comparably purified normal enzymes. Kinetic constants of purified T.C. and R.A. PRPP synthetases for substrates, activators, and inhibitors were indistinguishable from normal, and increased maximal reaction velocity alone appeared to account for enzyme superactivity. Despite an apparently similar kinetic mechanism for superactivity, the diminished electrophoretic mobility of T.C. PRPP synthetase and increased thermal lability of R.A. PRPP synthetase suggested distinct structural alterations leading to enzyme superactivity in families C and A.

Adult↗
PubMed1981

Urate spherulites in gouty synovia.

We have identified urate crystals in gouty synovial fluid in a spherulite form. Studies in vitro established these "beachball" structures as chemically identical to classic "needles" of monosodium urate monohydrate, the prime factor in gouty arthritis. Previously described in the 1890s by a German scientist, these structures have not been recognized by clinicians examining fluid from arthritic joints. We suggest an identification scheme for beach ball-like" structures in synovial fluid.

Acute Disease↗
PubMed1980

Urate metabolism in a mongrel dog.

(1) We have performed short-term turnover studies in a trained mongrel dog, and found remarkably linear turnover curves for both urate and its principle metabolic product, allantoin. (2) Infusions of Pyrazinamide, Probenecid, and Sodium Salicylate had no apparent effect on urate metabolism. (3) The "uricolytic index" for endogenous urate is consistenely lower than that of infused, isotopic urate. This finding suggests renal synthesis and direct excretion of unlabelled urate. (4) The renal clearance of labelled urate is higher than that of endogenous urate despite apparent renal synthesis. This finding suggests that urate may exist in more than one molecular form.

Allantoin↗
PubMed1979

Synovial permeability in rheumatoid arthritis.

In patients with rheumatoid arthritis, as well as in persons with other kinds of synovitis, proteins enter the knee joint more rapidly than in normal individuals (P less than 0.001). The rheumatoid synovium, however, is less permeable to small molecules (tritiated water, P less than 0.02; urate, P less than 0.05; and glucose, P less than 0.002) than is the normal joint lining. This difference is explained if rheumatoid microvascular changes enhance synovial permeability to proteins while coexisting interstitial changes diminish synovial permeability to smaller molecules.

Arthritis, Rheumatoid↗
PubMed1979

Management of gout.

The diagnosis of gout depends on showing urate crystals in synovial effusions or, with less certainty, recognizing a characteristic clinical presentation. The management of gout has four phases: control of inflammation, diagnostic evaluation, education of the patient, and treatment for the hyperuricemia. Sound logical principles guide each aspect. Careful attention to these four phases of management should lead to highly satisfactory control of the syndrome of gout.

Adrenal Cortex Hormones↗
PubMed1979

Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples.

Uric acid excretion can be measured in milligrams of urinary uric acid per decilitre of glomerular filtrate by obtaining the product of urinary uric acid and serum creatinine concentrations and dividing by the urine creatinine (all concentrations in mg/dL). In 29 normal adult men, the excretion rate in spot, midmorning samples was 0.4 +/- 0.1 (SD) mg of uric acid per decilitre of glomerular filtrate. Eight of 36 untreated gouty men excreted acid at a rate more than three standard deviations above normal. Excretion of uric acid is conveniently and physiologically assessed by this simple method.

Gout↗
PubMed1977

The pathogenesis of podagra.

Precipitation of crystals from solution is a relatively simple phenomenon that should be explained by changes in concentration, temperature, pH, or other local factors. Which of these factors determines the preferential precipitation of urate crystals at the base of the big toe? Podagra correlates with degenerative joint disease of the toe, often follows abuse of the feet, and classically occurs in the middle of the night. These characteristics suggest that crystals may form in resolving synovial effusions. The urate concentration must transiently rise in such an effusion because water will leave the joint space twice as fast as urate. If the local concentration surpasses the solubility of urate, crystals will form that may than induce acute podagra.

Adult↗
PubMed1976

Oral zinc sulphate in rheumatoid arthritis.

A preliminary trial of oral zinc supplementation was conducted in twenty-four patients with chronic, refractory rheumatoid arthritis. Zinc sulphate (220 mg three times daily) or placebo capsules of identical appearance were added to pre-existing therapy for 12 wk. This double-blind trial was followed by an open 12-wk period when all subjects took zinc. During the double-blind phase, zinc-treated patients fared better than controls with regard to joint swelling, morning stiffness, walking time, and the patient's own impression of overall disease activity. The indices and joint tenderness also improved with zinc treatment in both groups of subjects during the second 12-wk period. These encouraging results indicate that oral zinc sulphate deserves futher study in patients with active rheumatoid arthritis.

Administration, Oral↗