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Biomedical subjects

S M Watkins

Publications and source records attributed to S M Watkins.

At least 19 recordsLinked to original sources
PubMed2004

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on fatty acid availability and neural tube formation in cynomolgus macaque, Macaca fascicularis.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to alter carbohydrate utilization and specific steps in lipid metabolism. TCDD interacts with estradiol in mobilizing specific fatty acids in chickens that may be a cause of cranial/beak malformations in this species. This study was designed to test the hypothesis that TCDD simultaneously alters critical fatty acid mobilization during early pregnancy and determine if those changes correlate to morphological defects of the developing neural tube in the nonhuman primate. Cynomolgus macaques were treated with a single dose of 4 microg/kg body weight (BW) TCDD on gestational day 15 or 20. Pregnancies were terminated by hysterectomy on gestational day 24-26 and embryos were examined to determine morphology of the developing neural tube. Maternal blood samples were used for fatty acid quantification. Embryos exhibited cellular changes, mainly increased cell death, and intercellular spaces in the neural tube, suggestive of an adverse effect on the developing nervous system. Significant decreases on fatty acid composition were found on some of the eight classes of lipids analyzed. Particularly, a decrease was observed in the n-3 (40-60%) and n-6 (47-75%) essential fatty acids in treated pregnancies compared to untreated controls. These data demonstrate the effect of TCDD in decreasing maternal levels of n-3 and n-6 fatty acids that are considered necessary for normal development in mammals. Since neural tube development is dependent, in part, on n-3 and n-6 fatty acids, it is possible that the limitation of these essential fatty acids in plasma resulted in the observed detrimental effects on early brain development.

Animals↗
PubMed2001

Unique phospholipid metabolism in mouse heart in response to dietary docosahexaenoic or alpha-linolenic acids.

Diet and fatty acid metabolism interact in yet unknown ways to modulate membrane fatty acid composition and certain cellular functions. For example, dietary precursors or metabolic products of n-3 fatty acid metabolism differ in their ability to modify specific membrane components. In the present study, the effect of dietary 22:6n-3 or its metabolic precursor, 18:3n-3, on the selective accumulation of 22:6n-3 by heart was investigated. The mass and fatty acid compositions of individual phospholipids (PL) in heart and liver were quantified in mice fed either 22:6n-3 (from crocodile oil) or 18:3n-3 (from soybean oil) for 13 wk. This study was conducted to determine if the selective accumulation of 22:6n-3 in heart was due to the incorporation of 22:6n-3 into cardiolipin (CL), a PL most prevalent in heart and known to accumulate 22:6n-3. Although heart was significantly enriched with 22:6n-3 relative to liver, the accumulation of 22:6n-3 by CL in heart could not quantitatively account for this difference. CL from heart did accumulate 22:6n-3, but only in mice fed preformed 22:6n-3. Diets rich in non-22:6n-3 fatty acids result in a fatty acid composition of phosphatidylcholine (PC) in heart that is unusually enriched with 22:6n-3. In this study, the mass of PC in heart was positively correlated with the enrichment of 22:6n-3 into PC. The increased mass of PC was coincident with a decrease in the mass of phosphatidylethanolamine, suggesting that 22:6n-3 induced PC synthesis by increasing phosphatidylethanolamine-N-methyltransferase activity in the heart.

Alligators and Crocodiles↗
PubMed2001

Individual metabolism should guide agriculture toward foods for improved health and nutrition.

Genomics and bioinformatics have the vast potential to identify genes that cause disease by investigating whole-genome databases. Comparison of an individual's geno-type with a genomic database will allow the prescription of drugs to be tailored to an individual's genotype. This same bioinformatic approach, applied to the study of human metabolites, has the potential to identify and validate targets to improve personalized nutritional health and thus serve to define the added value for the next generation of foods and crops. Advances in high-throughput analytic chemistry and computing technologies make the creation of a vast database of metabolites possible for several subsets of metabolites, including lipids and organic acids. In creating integrative databases of metabolites for bioinformatic investigation, the current concept of measuring single biomarkers must be expanded to 3 dimensions to 1) include a highly comprehensive set of metabolite measurements (a profile) by multiparallel analyses, 2) measure the metabolic profile of individuals over time rather than simply in the fasted state, and 3) integrate these metabolic profiles with genomic, expression, and proteomic databases. Application of the knowledge of individual metabolism will revolutionize the ability of nutrition to deliver health benefits through food in the same way that knowledge of genomics will revolutionize individual treatment of dis-ease with pharmaceuticals.

Biomarkers↗
PubMed2000

Comprehensive lipid analysis: a powerful metanomic tool for predictive and diagnostic medicine.

The power and accuracy of predictive diagnostics stand to improve dramatically as a result of lipid metanomics. The high definition of data obtained with this approach allows multiple rather than single metabolites to be used in markers for a group. Since as many as 40 fatty acids are quantified from each lipid class, and up to 15 lipid classes can be quantified easily, more than 600 individual lipid metabolites can be measured routinely for each sample. Because these analyses are comprehensive, only the most appropriate and unique metabolites are selected for their predictive value. Thus, comprehensive lipid analysis promises to greatly improve predictive diagnostics for phenotypes that directly or peripherally involve lipids. A broader and possibly more exciting aspect of this technology is the generation of metabolic profiles that are not simply markers for disease, but metabolic maps that can be used to identify specific genes or activities that cause or influence the disease state. Metanomics is, in essence, functional genomics from metabolite analysis. By defining the metabolic basis for phenotype, researchers and clinicians will have an extraordinary opportunity to understand and treat disease. Much in the same way that gene chips allow researchers to observe the complex expression response to a stimulus, metanomics will enable researchers to observe the complex metabolic interplay responsible for defining phenotype. By extending this approach beyond the observation of individual dysregulations, medicine will begin to profile not single diseases, but health. As health is the proper balance of all vital metabolic pathways, comprehensive or metanomic analysis lends itself very well to identifying the metabolite distributions necessary for optimum health. Comprehensive and quantitative analysis of lipids would provide this degree of diagnostic power to researchers and clinicians interested in mining metabolic profiles for biological meaning.

Biomarkers↗
PubMed1999

Butyric acid and tributyrin induce apoptosis in human hepatic tumour cells.

The anti-colon cancer effect of dietary fibre results in part from its fermentation into the short-chain fatty acid butyric acid (BA) by intestinal microflora. BA has potent anti-colon cancer properties owing to its ability to induce apoptosis in colon cancer cells. The colon is not the only location where BA may reach high concentrations, because dietary BA is rapidly absorbed and transported to the liver. We have investigated whether BA could induce apoptosis in transformed human liver (Hep G2) cells. Hep G2 cells treated with BA displayed acetylated histones, increased DNA fragmentation and morphological features consistent with apoptosis. These biochemical features of BA-treated liver cells are identical to those of BA-treated colon cells. In addition, we investigated whether BA present in tributyrin, a triacylglycerol more compatible for inclusion into colloidal lipid structures than BA, could also induce apoptosis in Hep G2 cells. Tributyrin induced DNA fragmentation and morphological features characteristic of apoptotic cells in Hep G2 cells. These results are a significant advance towards delivering BA via colloidal lipid particles to cancerous sites in vivo. This study showed that BA and tributyrin are potent apoptotic agents, and we suggest that sources of dietary BA, such as milk fat, may provide anti-liver cancer properties.

Acetylation↗
PubMed1998

The design of arm pressure covers to alleviate pain in high G maneuvers.

HYPOTHESIS: Arm pain has been noted especially when increased coverage anti-G suits are worn in combination with PBG (pressure breathing during G) in high G centrifuge test runs. Arm pain has forced the termination of test runs and has the potential to cause a serious decrement in a pilot's ability to function effectively during high-G flight. Based on the theory that arm pain is caused by fluid pooling in the arm, four new pressure cover systems for the arm were designed and tested. METHODS: Seven test subjects wore each design in a series of runs in a dynamic flight simulator (DFS). Subjects experienced both gradual and rapid onset rate runs with G levels ranging from +3.0 G to +9.0 G. Data were collected on the maximum G's achieved, pain location, and pain intensity. Subjective responses on the comfort and function of each design and overall arm cover design preferences were also obtained via a questionnaire. RESULTS: Analysis of the DFS data, using a two-factor ANOVA (subjects, designs), revealed that each of the new designs provided significantly better protection from arm pain than the control condition (no protection) and that each of the designs significantly improved the maximum G level attained during rapid onset acceleration in the range of +1 G. CONCLUSION: No positive correlation was found between subject ranking of the four new design concepts at the conclusion of the study in terms of the pain reduction they provided and the pain levels reported during DFS testing.

Adult↗
PubMed1998

Docosahexaenoic acid accumulates in cardiolipin and enhances HT-29 cell oxidant production.

The objective of this study was to investigate membrane fatty acids for their effects on mitochondrial function in live cells. Mitochondrial potential and oxidant production were measured in human colonic adenocarcinoma (HT-29) cells with membranes enhanced in either oleic acid, linoleic acid, arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid. Docosahexaenoic acid-enriched cells had increased mitochondrial potential and produced 5-fold more cellular oxidants than did cells enriched with any other fatty acid. Oxidant production in fatty acid-enriched HT-29 cells did not correlate with the degree of unsaturation for total membrane fatty acids. However, there was a strong correlation between the degree of fatty acid unsaturation of cardiolipin, a critical inner-mitochondrial membrane phospholipid, and oxidant production. Cardiolipin acyl composition is known to influence the activity of electron transport complexes, an effect that can increase mitochondrial oxidant production. Docosahexaenoic acid was enriched to 48 mol% of the fatty acids present in HT-29 cell cardiolipin. These results demonstrate the importance of membrane acyl composition to mitochondrial potential and oxidant production in live cells. Additionally, results suggest that docosahexaenoic acid increases cell oxidant production by accumulating in cardiolipin, where its presence alters electron transport efficiency.

Cardiolipins↗
PubMed1995

Elevated blood lead prevalence in Florida two-year-olds.

The prevalence of blood lead values of 10 mcg/dl or higher was estimated in Florida two-year-olds in a population-based random sample survey. Subjects were chosen at random from birth certificates of children born in Florida in mid-1991. Parents were interviewed and children's blood specimens obtained in the summer of 1993. Results are based on 387 subjects. Overall prevalence of elevated blood lead was 3.2% (95% confidence limits 2.2, 4.0), with nine children in the range of 10 to 14 mcg/dl and four of 15 or over. In certain subgroups, prevalence was higher: nonwhite 9.4% (2.9, 15.9); mother not married 8.3% (3.1, 13.5); mother on Medicaid 6.7% (2.5, 10.8); housing built in 1978 or before 7.1% (2.3, 11.8); yard dirt or dirt plus grass 10.8% (4.6, 16.9). In Florida, prevalence is much lower than in the nation as a whole. A screening strategy that concentrates on screening Medicaid-eligible children and those living in homes built before 1978 would appear to be quite efficient and may uncover a prevalence of 7.0% or more.

Adult↗
PubMed1989

Phytohaemagglutinin responsiveness of peripheral lymphocytes and survival in patients with primary breast cancer.

The response of peripheral blood lymphocytes from 153 breast cancer patients to the T-cell mitogen phytohaemagglutinin (PHA) was measured prior to surgery and patients assigned to either high (Hi/PHA) or low (Lo/PHA) PHA response groups. Patients were followed up for between 8 and 12 years, or until death. Clinical characteristics were similar in Hi/PHA and Lo/PHA groups. In the 96 patients who received no postoperative adjuvant therapy, overall and relapse-free survival was significantly longer in Hi/PHA than in Lo/PHA patients (p less than 0.005, and p less than 0.025 respectively); relative risk of death within 12 years was 0.52 and of relapse was 0.64. In 47 patients who were treated with radiotherapy postoperatively, there was no correlation between the PHA response and overall or relapse-free survival. The implications of these findings for the selection of breast cancer patients for adjuvant treatment following surgery are discussed.

Adult↗
PubMed1987

Suppression of in vitro peripheral blood lymphocyte mitogenesis by cytotoxic drugs commonly used in the treatment of breast cancer: a comparative study.

Cultures of normal donor peripheral blood mononuclear cells were tested in vitro for suppression by chemotherapeutic agents or their metabolites. The drugs tested were those commonly used in the treatment of breast cancer, namely, 5-fluorouracil, doxorubicin, vincristine, methotrexate and cyclophosphamide (actually testing its active metabolite, 4-hydroxy-cyclophosphamide). The lymphocytes were stimulated by phytohaemagglutinin (PHA), and the inhibitory effect of the drugs on subsequent DNA synthesis was measured by tritiated thymidine uptake. Drug concentrations used were equivalent to expected in vivo plasma and body fluid levels following i.v. injection of a standard therapeutic dose. Results suggest that the drugs may be ranked for suppression of T-cell function as follows: doxorubicin greater than vincristine = cyclophosphamide greater than 5-fluorouracil greater than methotrexate.

Adult↗