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Biomedical subjects

R M Fox

Publications and source records attributed to R M Fox.

At least 181 records · Page 10Linked to original sources
PubMed1977

Incorporation of deoxynucleotides into DNA by diethylaminoethyldextran-treated lymphocytes.

In the presence of diethylaminoethyldextran cultured human lymphocytes will utilize deoxynucleotides for the synthesis of DNA, whereas in the absence of diethylaminoethyldextran no incorporation of deoxynucleotides is detected. Labeled deoxynucleoside mono-, di-, and triphosphates are incorporated into DNA at approximately the same rate. Deoxynucleotide incorporation is essentially linear for 10 min but continues at a gradually diminishing rate for an additional 20 to 50 min. The initial rate of DNA synthesis is at least 20 to 40% of the in vivo rate, and in those cells that are in S phase 0.7-1.5% of the DNA is synthesized. By the three properties examined (restriction to S phase, semiconservative mode, and initial product in short chains), DNA synthesis in diethylaminoethyldextran-treated cells resembles DNA synthesis in vivo.

Cell Line↗
PubMed1977

Peripheral vascular disease as a mode of presentation of pseudoxanthoma elasticum.

Two men presenting with premature peripheral vascular disease and minimal risk for atherosclerosis were found to have pseudoxanthoma elasticum (PXE). Fluorescein angiography was found to be of potential value in the early recognition of angioid streaks and pseudoxanthoma elasticum. There was evidence of disruption of arterial elastic tissue which may contribute to atherogenesis in PXE. Management is presently limited largely to minimizing risk factors for atherosclerotic vascular disease.

Adult↗
PubMed1976

Anemia of azaribine in the treatment of psoriasis.

Azaribine is an effective agent in the treatment of psoriasis. In this investigation the extent of clinical dermatologic remission appeared to correlate with the degree of metabolic block induced by 6-azauridylic acid, as quantitated by the urinary excretion of orotic acid and orotidine, and the development of anemia. Following azaribine therapy there was a coordinate rise of the specific activities of erythrocyte orotate phosphoribosyltransferase and orotidine-5'-monophosphate decarboxylase. There was no correlation between the pretreatment activity of these enzymes and the clinical response to azaribine. The anemia of azaribine therapy was mile and of a megaloblastic type. Uridine effectively corrected the azaribine-induced anemia, but led to exacerbation of the patients' psoriasis. Following uridine therapy there was a reduction in the urinary excretion of orotic acid and orotidine, presumable reflecting end-product inhibition or repression of the first steps of a repeated pyrimidine biosynthesis.

Adult↗
PubMed1975

Interconversion of different molecular weight forms of human erythrocyte orotidylate decarboxylase.

Orotidylate decarboxylase has been purified approximately 300-fold from human erythrocytes. It was shown to exist in three molecular weight forms, a probable monomer of molecular weight 62,000, a dimer, and a tetramer. Conversion of the monomer to higher molecular weight forms was associated with increased stability to thermal inactivation and was promoted by a number of low molecular weight compounds, including orotic acid and competitive inhibitors of the enzyme. Orotic acid phosphoribosyltransferase co-purified with the decarboxylase but was much more susceptible to inactivation. The partially purified orotidylate decarboxylase showed a triphasic Lineweaver-Burk plot when examined over a wide range of substrate concentrations. The separated molecular weight forms gave linear double reciprocal plots with Km values corresponding to the three values obtained with the erythrocyte enzyme preparation. The values obtained were 25, 3, and 0.6 muM for the monomer, dimer, and tetramer forms, respectively.

Carboxy-Lyases↗
PubMed1975

Nascent DNA from phytohemagglutinin-stimulated human lymphocytes.

DNA synthesis was studied in human peripheral blood lymphocytes that had been stimulated with phytohemagglutinin. DNA pulse-labeled with [3H]thymidine was fractionated by sucrose gradient centrifugation or by chromatography on hydroxylapatite columns. Nascent DNA was identified as a single-stranded species that sedimented at 4-5S in neutral sucrose gradients and appeared to be precursor to chromosomal DNA in pulse-chase experiments. At least two-thirds of the nascent DNA was released as single strands from high molecular weight DNA without employing a denaturation step. It is concluded that synthesis of DNA by phytohemagglutinin-stimulated lymphocytes involves a low molecular weight, single-stranded, short-lived intermediate similar to that described for other eukaryotic cells.

Cell Separation↗
PubMed1971

Studies on the coordinate activity and liability of orotidylate phosphoribosyltransferase and decarboxylase in human erythrocytes, and the effects of allopurinol administration.

A coordinate relationship between the activities of two sequential enzymes in the de novo pyrimidine biosynthetic pathway has been demonstrated in human red cells. The two enzymes, orotidylate phosphoribosyltransferase and decarboxylase are responsible for the conversion of orotic acid to uridine-5'-monophosphate. Fractionation of red cells, on the basis of increase of specific gravity with cell age, has revealed that these two enzymes have a marked but equal degree of lability in the ageing red cell. It is postulated that orotidylate phosphoribosyltransferase and decarboxylase form an enzyme-enzyme complex, and that the sequential deficiency of these two enzymes in hereditary orotic aciduria may reflect a structural abnormality in this complex. In patients receiving allopurinol, the activities of both enzymes are coordinately increased, and this increase appears to be due, at least in part, to stabilization of both orotidylate phosphoribosyltransferase and decarboxylase in the ageing red cell. Allopurinol ribonucleotide is an in vitro inhibitor of orotidine-5'-monophosphate decarboxylase and requires the enzyme hypoxanthineguanine phosphoribosyltransferase for its synthesis. However, the administration of allopurinol to patients lacking this enzyme results in orotidinuria and these patients have elevated orotidylate phosphoribosyltransferase and decarboxylase activities in their erythrocytes. Evidence is presented that the chief metabolite of allopurinol, oxipurinol, with a 2,4-diketo pyrimidine ring is capable of acting as an analogue of orotic acid. It is postulated that the in vivo formation of oxipurinol ribonucleotide, catalyzed by orotidylate phosphoribosyltransferase, after allopurinol administration, leads to inhibition of orotidine-5'-monophosphate decarboxylase. This inhibition results in the urinary excretion of excessive amounts of orotidine and orotic acid, and "pseudo-substrate" stabilization of orotidylate phosphoribosyltransferase and decarboxylase.

Adenine↗
PubMed1970

Orotidinuria induced by allopurinol.

The administration of allopurinol to patients suffering from hyperuricemia and to normal subjects results in increased excretion of the pyrimidine nucleoside orotidine. Evidence is presented for the interference by allopurinol of the de novo biosynthesis of uridine 5'-phosphate in man.

Allopurinol↗