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A Luke

Publications and source records attributed to A Luke.

51 records · Page 3Linked to original sources
PubMed1992

Inhibitory action of orotate, 2-thioorotate and isoorotate on nucleotide metabolism and nucleic acid synthesis in hepatoma cells.

1. The specificity of the action of orotate on hepatoma cells was investigated. 2. Orotic acid and its methyl ester had similar inhibitory effects on the incorporation of [3H]thymidine into DNA of hepatoma cells. 3. In contrast to previous studies in vivo, incubation of rat kidney cells with orotate caused an increase in the ratio of UTP/ATP concentrations that was similar to effects on hepatic cells. 4. Inhibitory effects of 2-thioorotate and isoorotate on metabolism were found to be less selective and required higher concentrations than with orotate.

Animals↗
PubMed1992

Basal metabolic rate, fat-free mass, and body cell mass during energy restriction.

Basal metabolic rate (BMR) has been reported to decrease during semistarvation and during hypocaloric treatment of obesity. However, it remains controversial whether the decrease is due to change in body composition, or if it represents a downregulation in cellular metabolism. To examine this relationship, we reviewed studies of BMR in children, adolescents, adults, semistarved non-obese, anorexics, and weight-reducing obese. The relationship between BMR and fat-free mass (FFM) of children, lean adolescents, and lean and obese adults consuming sufficient energy could be described by a single line, BMR (MJ/d) = 2.44 + 0.084 FFM (SEE = 0.63, R2 = .80). Obese adolescents demonstrated BMRs greater than predicted and semistarved lean individuals demonstrated BMRs less than predicted by this relationship. Obese individuals demonstrated a reduced BMR during underfeeding, but less so than semistarved lean individuals. The reduction in BMR relative to FFM in semistarved lean individuals could not be explained by disproportionate reductions in body cell mass (BCM).

Adipose Tissue↗
PubMed1990

Inhibitory effects of orotate on precursor incorporation into nucleic acids.

The influence of orotic acid on the incorporation of precursors into nucleic acids was studied in mice and rats and in isolated cells. In vivo, orotate levels were modified by two diets which are known to increase the rate of pyrimidine nucleotide synthesis in rat liver. Of these diets, a 1% orotate diet had greater inhibitory effects than an arginine-deficient diet on the incorporation of [3H]orotate into RNA of mouse kidney than mouse liver. This contrasted with the situation in the rat where there was a greater effect in the liver than the kidney. The situation in the rat was more readily interpreted than in the mouse in terms of previously established effects of these diets on ribonucleotide pool sizes. However, studies using [3H]adenosine as a precursor for incorporation into RNA suggested that even in the mouse the effects of orotate were on pool sizes rather than an inhibitory effect on RNA synthesis. The incorporation of [3H]thymidine into DNA was inhibited by orotate to a similar degree in cultured HTC hepatoma cells and a line of rat liver epithelial cells. An effect on DNA synthesis rather than solely on pool sizes was suggested by the observation that the pool size of dTTP was not increased by 5 mM orotate under conditions in which there was a four-fold increase in the level of UTP in HTC cells. An inhibitory effect of orotate on DNA synthesis was further supported by an observation of decreased incorporation of [3H]deoxyadenosine into DNA and a lower rate of cellular proliferation.

Animals↗
PubMed1989

Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

Animals↗
PubMed1988

pH-related effects of sodium cyanate on macromolecular synthesis and tumor cell division.

In past work, the selective effects of sodium cyanate on macromolecular synthesis in tumors have not been seen with cells in culture. We have explored the possibility that differences in the response of tumor cells to cyanate in vivo and in vitro may be related to the pH in the environment to which cells are exposed. When rat hepatoma (HTC) cells were incubated with sodium cyanate (0.25 mg/ml), there was a greater inhibition of precursor incorporation into RNA and DNA with a decrease in pH from 7.4 to 6.6. At pH 7.4 there was no significant effect of sodium cyanate on the incorporation of [3H]leucine into protein of rat hepatocytes and HTC cells, but at pH 6.6 there were decreases of 50% or greater. The time of response and the reversibility of the inhibitory effects of sodium cyanate were not those anticipated from carbamoylation of amino groups but were compatible with modification of sulfhydryl groups. The uptake of [14C]sodium cyanate in HTC cells and human colon cancer (HT29) cells was greater at pH 6.6 than at 7.4. Over a period of 4 days there was a slower rate of cell division by HTC and HT29 at pH 6.6 than at pH 7.4. The addition of sodium cyanate caused a further reduction in the rate of proliferation, and at a concentration of 0.25 mg sodium cyanate/ml there were decreases in cell numbers. The data suggested that a lower interstitial pH in tumors than normal tissues would result in greater sensitivity to inhibitory effects of sodium cyanate on macromolecular synthesis.

Animals↗
PubMed1988

Selective modulation of nucleotide levels in rat liver and hepatomas by high-orotate or arginine-deficient diets and by carbamoylating agents.

Transplanted Morris hepatomas in Buffalo-strain rats were found to be resistant to the changes in ribonucleotide levels in rat liver caused by a high-orotate diet or an arginine-deficient diet. The increase in UTP levels and decrease in ATP levels seen in the livers of rats on a 1%-orotate diet were less marked in the livers of BUB- and DBA-strain mice on this diet. Although the changes were less than in rat liver, there was a 2-3-fold increase in UTP concentration in the livers of mice on the high-orotate diet. However, there was a similar response in nucleotide levels in the two species when the animals were maintained on an arginine-deficient diet, and there was a greater than 10-fold increase in the UTP level in the livers of both rats and mice. These diets had much less effect on the levels of deoxyribonucleotides than of ribonucleotides. In contrast to the insensitivity of hepatomas to dietary modulation of nucleotide levels, treatment of hepatoma-bearing rats with carbamoylating agents (sodium cyanate and 2-chloroethyl isocyanate) caused decreases in the levels of nucleotides in the tumors which were generally greater than in host livers. For example, 2-chloroethyl isocyanate depressed ATP levels in the Morris hepatomas 5123C and 20 under conditions in which there was no significant effect on host liver ATP. The data revealed selective modulation of nucleotide levels in normal and neoplastic liver which may be achieved by either dietary modification or drug treatment.

Animals↗
PubMed1987

Action of carbamoylating agents on the uptake of metabolites in hepatomas and liver.

The effects of 2-chloroethylisocyanate, ethylisocyanate and sodium cyanate on the uptake of isotope-labeled thymidine, leucine and H2O were compared in rat liver and hepatomas. The data suggested that carbamoylating agents may have a common property of inhibiting uptake of compounds in hepatomas under conditions in which there is a smaller effect or no action in the liver of tumor-bearing rats. The distinction between tissues may have been mediated, in part, through effects on tumor circulation and was less apparent when isolated cells were studied in vitro. Preferential inhibitory effects of carbamoylating agents on the uptake of leucine and H2O were also observed with a murine hepatoma, but they were not as great as with rat hepatomas.

Animals↗
PubMed1987

Orotate uptake and metabolism in normal and neoplastic tissues.

The uptake of [3H]orotate was greater in mouse liver than in hepatoma but the difference was less marked than in the rat. Of the tissues examined, a high uptake of [3H]orotate was restricted to the liver and kidney in rat, mouse and guinea-pig. We confirmed that a high orotate diet greatly increases the ratio of UTP to ATP concentration in rat liver but we observed that there is little change of this nucleotide ratio in kidney. Evidence was obtained for a different pattern of orotate metabolism in rat liver and kidney.

Animals↗
PubMed1987

Effects of carbamoylation with alkyl isocyanates on the assay of proteins by dye binding.

The effect of carbamoylation with alkyl isocyanate was used both to monitor the stability of the isocyanates and to study the influence of charge modification on protein assay. Carbamoylation of poly (L-lysine) with methyl isocyanate, ethyl isocyanate and 2-chloroethyl isocyanate was observed to decrease binding of methyl orange. The data emphasized the lability of alkyl isocyanates and indicated the importance of preparing aqueous solutions at low temperatures for studies on protein carbamoylation. After carbamoylation of several proteins, there was decreased metachromasia on binding to Coomassie Blue G. Poly (L-lysine) and H1 histone showed anomalous behavior in that with low concentrations of Coomassie Blue G the metachromasia was increased by carbamoylation, but at high concentrations of the dye the metachromasia was decreased by carbamoylation. In contrast to some reports in the literature, the data indicated that there is not always a simple relationship between the positive charge on a protein and the interaction with anionic dyes.

Azo Compounds↗
PubMed1986

Effects of sodium cyanate in mice bearing B16 melanoma.

Sodium cyanate injected IP at a dose level of 200 or 250 mg/kg caused a 90% or greater inhibition of the incorporation of [3H]thymidine into DNA of B16 melanoma transplanted SC in mice. Despite the inhibitory effect of sodium cyanate on precursor incorporation into DNA, no significant effect on host survival was observed when sodium cyanate was administered as a single agent in the diet, in drinking water, or by IP injection to mice that had received IP transplants of B16 melanoma. The action of melphalan and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in prolonging the survival time of melanoma-bearing mice was not enhanced by combined treatment with sodium cyanate. However, combined injections of sodium cyanate and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) increased the survival of tumor-bearing mice significantly more than injections of BCNU alone at a lower dose than the maximum tolerated one. These data and other studies suggest that B16 melanoma may be less responsive to the action of sodium cyanate than are murine leukemic cells or rat hepatomas.

Animals↗
PubMed1986

Influence of carbamoylation on some analytical properties of basic polypeptides.

The effect of carbamoylation on the assay or identification of histones and polylysine was investigated. Incubation with sodium cyanate decreased the positive charge on these polypeptides as judged by changes in the binding of methyl orange or the electrophoretic mobility. Histones in chromatin appeared less accessible to carbamoylation than isolated histones. Carbamoylation of proteins under conditions in which there was little or no effect on the Lowry procedure could affect their assay by methods utilizing metachromasia with Coomassie Blue G. The Bradford assay has low sensitivity for Hl histone and polylysine but this can be increased by preincubation with sodium cyanate. More extensive carbamoylation of polylysine caused decreased sensitivity which was the only response seen with core nucleosomal histones and bovine serum albumin when preincubated with sodium cyanate. It was concluded that the sensitivity for Hl histone and polylysine in assays dependent on metachromasia with Coomassie Blue G may be changed by factors which decrease the positive charge on these polypeptides.

Animals↗
PubMedDate not supplied

Quantitative assessment of recruitment efforts for prevention trials in two diverse black populations.

BACKGROUND: Prevention efforts to reduce the morbidity and mortality disparity between blacks and whites in the United States present a national health priority. However, participation of blacks in prevention trials has been low. The present study reports successful recruitment processes from two economically diverse black populations. METHODS: The two studies were independent projects, but both were part of a nationally funded collaboration on cardiovascular health. "Hip Hop to Health" is a 4-year randomized controlled trial aimed at dietary fat reduction and increased exercise among inner-city black families. The Fat Reduction Intervention Trial in African-Americans project is a 5-year trial to reduce total fat, saturated fat, and cholesterol intake among black families from a working class community. RESULTS: The two populations differed on demographic characteristics. Direct presentation was the most effective recruitment strategy in the "Hip Hop to Health" program. In contrast, telephone recruitment and neighborhood canvassing were the more successful strategies for FRITAA. CONCLUSIONS: Although both populations were black and at comparable cardiovascular disease risk, the differing demographics between the groups made different recruitment strategies necessary. This study documented the labor-intensive quality of successful recruitment, and results suggest that successful recruitment requires strategies tailored to the needs, experiences, and environment of the target group.

Adult↗