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Biomedical subjects

L A Vaughan

Publications and source records attributed to L A Vaughan.

7 recordsLinked to original sources

Elevated pentose cycle and glucuronyltransferase in daunorubicin-resistant P388 cells.

Anthracycline resistance of P388 daunorubicin-resistant cells cannot be accounted for merely by differences in drug uptake and retention; protection against intracellular drug was also indicated. Cytotoxicity of daunorubicin may be partially due to the formation of free radicals and reactive oxygen species (hydrogen peroxide, hydroxyl radical, singlet oxygen, and superoxide anion radical). Protection against free radicals and peroxides is largely dependent upon the availability of reduced glutathione, which in turn requires NADPH for its continual regeneration. Pentose phosphate cycle (also called hexose monophosphate shunt) is known to provide NADPH for maintenance of glutathione. Activities of the two NADPH-producing dehydrogenases of the cycle, glucose-6-phosphate and 6-phosphogluconate dehydrogenase, were 40% higher (P less than 0.05) and activity of the cycle in intact cells was 2-fold higher in the resistant than the sensitive cells. The cycle was as active in these cells as it is known to be in macrophages, indicating a very effective protection against oxidative stress, free radicals, and alkylating electrophiles. Elevated activity of the pentose phosphate pathway in drug-resistant cells can represent a mechanism of resistance against multiple structurally unrelated drugs. Efflux of daunorubicin may be aided by further metabolism to glucuronides. Daunorubicinol, a known active metabolite of daunorubicin, can be metabolized to a glucuronide by the cells and eliminated into the surrounding medium. Glucuronidation of daunorubicinol was evidenced by (a) release of daunorubicinol following glucuronidase hydrolysis of media from cell incubations with 1.8 microM daunorubicin and (b) production of radioactive glucuronide when cell homogenates were incubated with UDP-[14C]glucuronic acid plus daunorubicinol. Glucuronyltransferase activity with a broad substrate specificity was found in the cells. Using model substrates, 1-naphthol and o-aminophenol, it was determined that glucuronyltransferase activity was 4 times higher in daunorubicin-resistant than -sensitive P388 cells. Elevated glucuronyltransferase could contribute to daunorubicin and multidrug resistance.

Animals

Contribution of various food groups to dietary vitamin B-6 intake in free-living, low-income elderly persons.

Elderly persons are reported to have low dietary intakes of vitamin B-6. Knowing which foods are the primary contributors of dietary vitamin B-6 may be useful to health professionals working to improve the nutritional status of the elderly. Therefore, we examined the contribution of five food groups--flesh foods (including all meat/fish/poultry), grains/cereals, legumes/nuts, fruits/vegetables, and dairy products/eggs--to dietary vitamin B-6 intake in 198 free-living elderly persons aged 60 years or older. Subjects were primarily Caucasian, low-income non-smokers; their mean age was 72 years. Mean dietary vitamin B-6 intake, determined from 3-day diet records, was 1.6 +/- 0.6 mg/day. The fruit/vegetable group was the largest dietary contributor of vitamin B-6 (0.69 mg/day). Flesh foods and cereals/grains contributed equally to the vitamin B-6 intake (0.35 and 0.34 mg/day, respectively). The lowest contributors were dairy products/eggs and legumes/nuts. Approximately 96% of the vitamin B-6 intake could be accounted for by the five food groups. Twenty percent of the population (no. = 39) consumed less than 66% of the Recommended Dietary Allowance (RDA) for vitamin B-6; their vitamin B-6 intake from fruits/vegetables and grains/cereals was 0.36 and 0.10 mg/day, respectively. Individuals with vitamin B-6 intakes greater than or equal to 100% of the RDA (no. = 69) consumed greater amounts of fruits/vegetables (primarily bananas) and grains/cereals (primarily breakfast cereal) than did persons who consumed less than 66% of the RDA for vitamin B-6; their vitamin B-6 intake from fruits/vegetables and grains/cereals was 0.98 and 0.55 mg/day, respectively. In the elderly population studied, plant foods were the major dietary contributors of vitamin B-6.

Aged

Plasma pyridoxal 5'-phosphate concentration and dietary vitamin B-6 intake in free-living, low-income elderly people.

Free-living, elderly persons (aged greater than or equal to 60 y, n = 198) were recruited to determine the effects of age, sex, health status, dietary vitamin B-6 intakes, and B-6 supplement use on plasma pyridoxal 5'-phosphate (PLP). Vitamin B-6 intakes were determined from 3-d diet records; supplementation was based on self-reported brand and frequency data. Fasting blood samples were analyzed for PLP. Subjects were primarily low-income Caucasians. There was no linear relationship between dietary vitamin B-6 intake, age, sex or health status, and PLP while accounting for supplemental vitamin B-6 use. PLP, however, was negatively correlated with age (p less than 0.001) in individuals with PLP values between 32 and 90 nmol/L. Vitamin B-6 status was low (PLP less than 32 nmol/L) in 32% of this elderly population (n = 198) and could be attributed to low dietary vitamin B-6 intakes and/or the presence of health problems reported to alter vitamin B-6 status. This research suggests that low vitamin B-6 status is prevalent in low-income, elderly persons, especially those with multiple health problems.

Aged

Development and testing of a statistical and graphics-enhanced nutrient analysis program.

The authors have developed and tested a nutrient analysis program that will compute and present graphically summary statistics of population and population subgroup nutrient intakes. The program analyzes for 44 nutrients from 5,800 separate food items. Capabilities of the program include: storage of large numbers of diet records and evaluations of their nutrients; calculation of nutrient means and standard deviations; data sorting based on subject characteristics, such as age, sex, and supplement use; and generation of bar graphs and line plots for individual and/or group data. To test this computerized nutrient analysis program, two sets of 3-day diet records from 200 elderly individuals were analyzed. The program was then used to generate means, differences between means, and distribution frequencies of designated nutrients for various population subgroups (e.g., men greater than or equal to 65 years vs. men greater than or equal to 80 years) as well as comparisons with individual files (e.g., Mr. Smith vs. all men greater than or equal to 65 years). The statistical and graphics capabilities also function within the context of recipe analysis and menu planning, which enhances the application of this program in institutional and community nutrition settings.

Aged

Bacterial safety of a closed-administration system for enteral nutrition solutions.

The purpose of this study was to investigate the bacterial integrity of a newly designed closed-administration system for enteral formula delivery. Three clinical simulations, designated Phases I, II, and III, were tested: dispersal of (I) 3 L formula over a 24-hour period, (II) 2 L formula over a 24-hour period, and (III) 2 L formula over a 48-hour period. Within each 24- or 48-hour simulation phase, a single administration set was used. Samples were withdrawn for bacterial analysis at 4- or 8-hour intervals. Simulations and samplings were completed under controlled, but not aseptic, conditions. Results indicated that bacterial growth was insignificant across all three simulation phases. Re-utilization of the administration set did not introduce bacterial contamination into subsequent liters of formula. Alcohol cleansing of the administration set was not found to be necessary for maintenance of bacterial closed integrity. Even when administered over a 24- or 48-hour period, the formula dispersed through this closed system did not develop any significant degree of bacterial growth. Results of this study suggest that this newly designed system for the administration of enteral formula significantly minimizes the risk of bacterial contamination.

Bacteria

Longitudinal changes in the mineral content of human milk.

Thirty-eight lactating women, from 1 to 31 months postpartum, provided monthly milk samples for determination of calcium, magnesium, manganese, copper, iron, and zinc. Subjects remained in the study an average of 4 consecutive months, with a maximum participation of 9 months. Subject variation accounted for the majority of variance in the raw data. After statistically controlling subject effect, copper, iron, and zinc levels were shown to be significantly related to duration of lactation. Prediction equations for these three minerals were developed, making it possible to calculate, on an individual basis, the copper, iron, and zinc levels of milk to be produced in future months. Data were also collected to determine possible correlations between breast milk mineral levels and the maternal dietary intake, serum levels, or hair concentration of these same minerals. No significant correlation was found between the milk mineral content and any of the three parameters under study.

Adult