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Biomedical subjects

S Grant

Publications and source records attributed to S Grant.

At least 307 records · Page 17Linked to original sources

Characterization of compounds shed from the surface of human leukemic myeloblasts in vitro.

Human leukemic myeloblasts shed glycoproteins from the cell surface during short-term in vitro culture. Shed surface glycoproteins yield a characteristic profile when studied by gel chromatography, isoelectric focusing, immune precipitation, and polyacrylamide gel electrophoresis. Isolation of immunologically active material yields a compound to approximately 75,000--80,000 daltons, with an isoelectric point of 7.6 to 7.9. Various morphological subtypes of acute myelogenous leukemia shed these compounds, but they are most easily obtained from the more differentiated M2 and M4 types as compared to the undifferentiated M1 type. The shed compounds appear to be quantitatively and qualitatively different from compounds shed by other leukemic cells or nonleukemic cells.

Cells, Cultured↗

Differential effect of N-(phosphonacetyl)-L-aspartate on 1-beta-D-arabinofuranosylcytosine metabolism and cytotoxicity in human leukemia and normal bone marrow progenitors.

The effect of N-[phosphonacetyl]-L-aspartate (PALA) on the metabolism and cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) was studied in the human promyelocytic leukemic cell line, HL-60, and in normal human bone marrow. HL-60 cells exposed to 0.1 mM PALA for 12 hr accumulated 58.7 pmol ara-C per 10(6) cells after a 45-min exposure to 1 microM ara-C, compared to 27.8 pmol ara-C per 10(6) cells in untreated control cells. This PALA concentration and exposure interval was associated with a greater than 2-fold increase in both the 45-min generation and 4-hr retention of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate compared to untreated control HL-60 cells. Exposure of HL-60 cells to PALA followed by ara-C produced greater than additive effects on the inhibition of DNA synthesis, the inhibition of cell growth, and clonogenicity. In contrast, exposure of normal human bone marrow to the same PALA-ara-C schedule was not associated with a synergistic inhibition of colony-forming units in soft agar. If these perturbations also occur in vivo, an improvement in the therapeutic index of ara-C in patients with acute leukemia might result.

Antimetabolites, Antineoplastic↗

Cognitive profiles in reading disability.

A group of 35 reading disable (RD) boys and 35 matched controls were studied over a two-year period in order to evaluate the validity of traditional hypotheses about the cause of serious reading impairment in preadolescent boys for whom the common disadvantages of economic privation, bilingualism, and emotional instability were absent. The popular hypothesis of perceptual deficit was not supported by the data, although the finding that most RD boys have a short-term memory deficit was affirmed. The most important new finding was that about one-fourth of the RD boys had serious difficulty in maintaining an efficient set to process and/or evaluate information, especially when that information was contained in oral speech.

Child↗

Abnormal gastric emptying in primary anorexia nervosa.

The gastric emptying rate was measured in 10 female patients with primary anorexia nervosa and 12 healthy volunteers, using a scinti-scanning technique for the simultaneous study of the liquid and solid components of a test meal. The emptying rate of both the liquid and the solid phase components of the meal was significantly slower in patients with anorexia nervosa. The aetiological and therapeutic implications of this finding are discussed.

Adolescent↗

Effect of N-(phosphonacetyl)-L-aspartate on 5-azacytidine metabolism in P388 and L1210 cells.

The effect of N-phosphonacetyl-L-aspartate (PALA) pretreatment on the metabolism and cytotoxicity of 5-azacytidine (5-aza-Cyd) was studied in two murine leukemic cell lines. Exposure of P388 and L1210 cells to 3 mM PALA for 3 hr before adding 5-aza-Cyd at 75 microM was accompanied by a two-fold increment in acid-soluble and 3-fold increment in acid-insoluble incorporation of 5-aza-Cyd in both cell lines. RNA incorporation of 5-aza-Cyd increased from 97.5 +/- 3.4 pmol 5-aza-Cyd per microgram D-ribose in control cells to 299.2 +/- 4.2 pmol 5-aza-Cyd per microgram D-ribose in PALA-treated cells; a smaller increment in DNA incorporation of 5-aza-Cyd was also noted. Sequential treatment of cells with PALA and 5-aza-Cyd was associated with a 40% reduction in protein synthesis compared to only a 2 and 8% reduction, respectively, produced by the drugs given alone. Sequential administration of PALA and 5-aza-Cyd resulted in greater than additive cytotoxicity as measured by both growth inhibition and in vitro soft-agar cloning assays. Exposure of both cell lines to 3 mM PALA for 3 hr produced 50 and 65% reductions in intracellular levels of cytidine triphosphate and uridine triphosphate; intracellular accumulation of 5-azacytidine triphosphate, the lethal metabolite of 5-aza-Cyd, increased from 43.4 +/- 2.1 pmol/10(6) cells to 92.4 +/- 3.3 pmol/10(6) cells in PALA-treated cells. PALA was able to augment the metabolism and cytotoxicity of 5-aza-Cyd in a uridine-cytidine kinase-mutant 5-aza-Cyd-resistant L5178Y subline. This sequential drug combination has a rational biochemical basis and may offer significant advantages over either drug when administered alone, especially in cells which are resistant to 5-aza-Cyd.

Animals↗

Probenecid and intraocular methicillin.

Probenecid was given intravenously to rabbits in an effort to extend the intraocular longevity of intravitreal methicillin. With relatively high levels of probenecid, an insignificant elevation of half-life was obtained. Aqueous levels of methicillin were measured after intravitreal injection and were found to be adequate to inhibit penicillinase-producing S. aureus for approximately 20 hours.

Animals↗

Vitreous cylinders.

Vitreous cylinders, a rarely discussed ophthalmologic entity, were studied in two clinical cases and in five enucleated eyes. The cylinders were found in four cases of ocular toxoplasmosis, one case of vitreous hemorrhage complicating a malignant melanoma, and one case of pars planitis and one of uveitis, both of unknown causes. Results of scanning electron microscopy in one specimen suggested that cylinders are formed by condensation of vitreous collagen fibers. We emphasize the nonspecific nature of this interesting vitreous finding.

Aged↗

Altered 5-azacytidine metabolism following 3-deazauridine treatment of L5178Y and human myeloblasts.

The effect of 3-deazauridine pretreatment on 5-azacytidine metabolism was studied in suspension cultures of L5178Y murine leukemia. A 3-hr exposure to 2 microM 3-deazauridine followed by a 1-hr exposure to 5 microM [14C]-5-azacytidine resulted in a 2-fold increase in total intracellular 5-azacytidine accumulation compared to untreated controls. Under the same conditions, incorporation of 5-azacytidine into the acid precipitable fraction of L5178Y cells was increased 3-fold. Incorporation of 5-azacytidine into RNA increased 85% following 3-deazauridine pretreatment, but 5-azacytidine incorporation into DNA did not change significantly. In cells pretreated with 3-deazauridine, there was an 80% reduction of intracellular cytidine triphosphate, the natural feedback inhibitor of uridine-cytidine kinase, the rate-limiting enzyme in the phosphorylation of 5-azacytidine. Intracellular levels of 5-azacytidine triphosphate, the presumed lethal metabolite of 5-azacytidine, increased from 28.8 pmol/10(6) cells in control cells to 56.4 pmol/10(6) cells following 3-deazauridine treatment. The sequence of 3-deazauridine followed by 5-azacytidine demonstrated synergistic cell killing when measured by an in vitro soft-agar cloning assay. Similar biochemical alterations were also seen in human leukemic myeloblasts. It appears that 3-deazauridine-induced alterations in 5-azacytidine metabolism may account for the enhanced cytotoxicity of this drug sequence.

3-Deazauridine↗

Bacillus cereus endogenous panophthalmitis.

A case of severe suppurative endogenous panophthalmitis caused by Bacillus cereus resulted from intravenously administered medications. This is the first, to our knowledge, well-documented case of endogenous endophthalmitis associated with this organism. It is recommended that if on Gram's stain of the anterior chamber fluid, Gram-positive rods are seen, chloramphenicol should be administered in addition to penicillin because of the possibility of B cereus infection.

Adult↗

Take two young men.

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Health Occupations↗