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D Villacorte

Publications and source records attributed to D Villacorte.

6 recordsLinked to original sources
PubMed1982

Effect of L-glutamine antagonists on 5-phosphoribosyl 1-pyrophosphate levels in P388 leukemia and in murine colon adenocarcinomas in vivo.

The intratumoral content of 5-phosphoribosyl 1-pyrophosphate (PRPP) and the activity of the enzymes anabolizing and catabolizing the sugar phosphate were determined following i.p. administration of an LD10 dose of an L-glutamine antagonist or saline to tumor-bearing animals. Elevation of PRPP pool size following administration of L-[alpha S,5S]-alpha-amino-3-chloro-4,5-dihydro-5-isopazoleacetic acid (NSC-163501) (AT-125) was maximal at 8 hr and returned to pretreatment levels by 24 hr. In P388 leukemia, dose for dose, at 4 hr, 6-diazo-5-oxo-L-norleucine (NSC-7365) (DON) was the most potent of the L-glutamine antagonists in elevating basal PRPP pool size (50% above control) followed by AT-125 and azaserine, 300 and 100% above control respectively. Moreover, such augmentation in PRPP pool size preferentially affected P388 tumor rather than the small intestine. Following i.p. administration of LD10 doses of AT-125, DON and azaserine, the specific activities of PRPP anabolizing and catabolizing enzymes were determined. A significant inhibition of PRPP amidotransferase was demonstrated with DON and AT-125 (P less than 0.05), and no inhibition with azaserine. A similar modulation of PRPP pool size demonstrated in vivo following administration of 250 mg/kg of ART-125 in mice bearing colonic adenocarcinoma lines. It was suggested that a significant increase of PRPP pool size might cause the possible synergism of a selected L-glutamine antagonist and 5-fluorouracil as reported after the appropriately scheduled administration of methotrexate and 5-fluorouracil.

Adenocarcinoma↗
PubMed1975

Nonenzymatic conversion of human hexosaminidase A.

Incubation of purified hexosaminidase A with merthiolate, parahydroxymercuribenzoic acid, or silver ions resulted in the formation of an enzyme which was identical, in all respects tested, with hexosaminidase B. Its electrophoretic mobility was identical to hexasaminidase B at three different pH levels. Its chromatographic properties, thermostability, and immunologic reactivity with specific anti-hexosaminidase A and anti-hexosaminidase B antisera were indistinguishable from hexosaminidase B. Conversion could be prevented by GSH but was not reversed by GSH once it had occurred. Conversion of hexosaminidase A to hexosaminindase B was accompanied by the appearance of an electrophoretically rapid, catalytically inactive protein. Hexosaminidase B, itself, was unaltered by incubation with merthiolate. These findings support a previously proposed model of hexosaminidase structure in which hexosaminidase A is (alphabeta)3 and hexosamindase B is (betabeta)2. On treatment of hexosaminidase A with merthiolate and other converting agents alpha and beta subunits are presumably dissociated and they reassociate as (betabeta)3, that is, hexosaminidase B. The expected free or polymerized catalytically inactive, alpha chains are detected on acrylamide gel electrophoresis. We suggest that the catalytic site of human hexosaminidase may be present only on the beta subunit and that the alpha subunit influences the substrate specificity of the enzyme, particularly as directed toward GM2.

Chromatography↗
PubMedDate not supplied

Spectrin extractability in blood storage.

The extractability of spectrin from red blood cell membranes was measured both by dialysis against 1 mM EDTA for 44 hours and by incubation with 1 mM EDTA for 60 minutes. We confirmed that the extractability of spectrin is somewhat impaired when membranes are prepared from metabolically depleted erythrocytes, but the extent of impairment was considerably less than has been previously reported. Red blood cells which had been rendered nonviable by prolonged storage in citrate phosphate dextrose solution manifested normal spectrin extractability. We conclude that the loss of spectrin extractability is an insensitive manifestation of loss of red blood cell viability, and that it is not suitable for the prediction of loss of viability during red blood cell storage.

Blood Glucose↗