PubMed HealthSearch

Biomedical subjects

R Gibson

Publications and source records attributed to R Gibson.

At least 19 recordsLinked to original sources

Are long-chain polyunsaturated fatty acids essential nutrients in infancy?

We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil, a source of docosahexaenoic acid (DHA, 22:6 omega 3), to infant formula. Healthy, term infants were randomised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed. Breastfed term infants were enrolled as a reference group. Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6, 16, and 30 weeks of age. Visual evoked potential (VEP) acuity was determined at 16 and 30 weeks. VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age (p < 0.001 and p < 0.01). Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants (p < 0.001). Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested. A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods (< 16 weeks) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula. Erythrocyte arachidonic acid (20:4 omega 6) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks (p < 0.001), although no adverse effects were noted, with growth of all infants being similar. DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity. Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be elucidated.

Adult

Phosphorylation modulates catalytic function and regulation in the cAMP-dependent protein kinase.

Site-directed mutagenesis was used to remove a critical phosphorylation site, Thr-197, near the active site of the catalytic subunit of cAMP-dependent protein kinase. This residue is present in a number of protein kinases, and its phosphorylation largely influences catalytic activity. We changed Thr-197 to aspartic acid and alanine and measured the effects of these substitutions on the kinetic mechanism and inhibitor affinities. The mutants were expressed as the free catalytic subunit and as soluble fusion proteins of glutathione-S-transferase. The values for KATP and Kpeptide for all three mutants are raised by approximately 2 orders of magnitude relative to the wild-type enzyme. Viscosometric measurements indicate that elevations in Kpeptide are the result of reduced rates for phosphoryl transfer and not reduced substrate affinities. This implies that the loop that contains the phosphothreonine, the activation loop, does not reduce access to the substrate site as proposed for the inactive forms of cdk2 kinase [DeBont, H. L., et al. (1993) Nature 363, 595-602] and MAP kinase [Zhang, F., et al. (1994) Nature 367, 704-711]. The mutants associate slowly with the wild-type regulatory subunit, although the cAMP-free wild-type regulatory subunit inhibits the mutants stoichiometrically. A mutant regulatory subunit that binds cAMP poorly and rapidly inhibits the wild-type catalytic subunit does not inhibit the mutant proteins. These data suggest that the phosphothreonine region serves as a docking surface for the regulatory subunit in the holoenzyme complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Biochemical folate, B12, and iron status of a group of pregnant adolescents accessed through the public health system in southern Ontario.

PURPOSE: This study was designed to estimate the prevalence of biochemical iron, folate, and vitamin B12 depletion among a group of Canadian pregnant adolescents accessed through the Public Health system. Further, the impact of prenatal supplement use, chronologic age, gynecologic age, living arrangement, main source of income, postpartum custody plan, time of entry into prenatal care, and cigarette smoking on laboratory indices of the three nutrients were determined. METHODS: Fifty-eight adolescents (14.5-19.0 years) were interviewed and blood samples were collected at 36 +/- 2 wk gestation. RESULTS: Thirteen (22%) of the pregnant adolescents had anemia (hemoglobin < 110 g/L) and forty-five (78%) had depleted iron stores (plasma ferritin < 26.6 pmol/L or 12.0 micrograms/L). Twenty-five subjects had plasma B12 values in the sub-optimal range (< 148 pmol/L). Five of the 16 adolescents who infrequently or never consumed a folate-containing supplement had suboptimal erythrocyte folate values. Twenty-four percent of the subjects had hypersegmented neutrophils and of these, all and 71% of subjects had plasma ferritin and B12 concentrations in the suboptimal range, respectively. Self-reported folic acid and B12 supplement intakes were correlated with the corresponding blood values for these nutrients. In contrast, supplement iron use was only weakly, or not at all associated with biochemical indices of iron status. CONCLUSIONS: Data from the present study indicate that plasma B12 and ferritin levels are low in a group of pregnant adolescents. These low values appear to be associated with a high prevalence of hypersegmented neutrophils. Prenatal supplement use appears to reduce the risk of low folate and B12 blood values but not biochemical iron status.

Adolescent

Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30 wk of lactation.

The fatty acid composition of breast milk from 23 breast-feeding women was serially assessed by capillary gas chromatography from the 6th to the 30th wk of lactation. The proportions of total n-3 and n-6 fatty acids were unchanged with time, although some significant differences were noted for individual polyunsaturated fatty acids (PUFAs). Of the n-3 PUFAs, only docosahexaenoic acid (DHA, 22:6n-3) concentrations changed, decreasing between 6 and 16 wk from 0.26 +/- 0.13% to 0.21 +/- 0.13% of total fatty acids but remaining at this proportion until 30 wk. Of the n-6 PUFAs, 18:3, 20:3, 20:4, and 22:5 all showed reductions with time. Compared with concentrations observed in a 1981 study, linoleic acid was higher (14% compared with 11% of total fatty acids), whereas the concentration of DHA was lower (0.21% compared with 0.32% of total fatty acids), possibly reflecting a general change in the diets of Australian women.

Adult

Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil.

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.

Adolescent

How appropriate are commercially available human milk fortifiers?

A preliminary investigation was made into the effectiveness of two breastmilk fortifiers on the Australian market (FM-85 [Nestlé, Vevey, Switzerland] and Enfamil Human Milk Fortifier [EHMF; Mead Johnson, Evansville, IN, USA]). Infants < 1800 g and < 34 weeks gestation at birth, who were receiving breast milk, were randomized to receive either of the fortifiers (n = 14 for FM-85, n = 10 for EHMF), until a weight of 2 kg was reached. Infants not receiving breast milk (n = 9) were fed a preterm formula (Prenan, Nestlé). The two fortifier groups were similar in most parameters examined: (i) weight gain (17.9 +/- 3.0 vs 17.4 +/- 3.5 g/kg per day); (ii) head circumference growth (1.02 +/- 0.28 vs 1.03 +/- 0.25 cm/week); (iii) arm muscle area growth (32.6 +/- 20.0 vs 33.5 +/- 13.7 mm2/week); (iv) arm fat area growth (14.0 +/- 8.7 mm2/week); (v) plasma calcium (2.52 +/- 0.08 vs 2.58 +/- 0.15 mmol/L); (vi) plasma phosphate (2.02 +/- 0.21 vs 2.13 +/- 0.32 mmol/L); (vii) plasma copper (5.28 +/- 2.83 vs 5.66 +/- 3.07 mumol/L); and (vii) plasma zinc (13.3 +/- 5.5 vs 15.8 +/- 9.2 mumol/L). The FM-85 group had a higher alkaline phosphatase level (355 +/- 110 vs 231 +/- 70 iu/L) than the EHMF group; however, no values were outside the normal range. The Prenan group had a higher rate of weight gain (23.6 +/- 3.3 g/kg per day) and higher arm fat area growth rate (25.2 +/- 7.6 mm2/week) than the fortifier groups while all other parameters were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Effects of diabetes on the activity and content of the branched-chain alpha-ketoacid dehydrogenase complex in liver.

Severe ketotic diabetes induced in rats by streptozotocin resulted in a reduction in activity of the hepatic branched-chain alpha-ketoacid dehydrogenase complex, regardless of whether activity was expressed on the basis of liver wet weight, total liver, liver protein, or liver DNA. A decrease in enzyme specific activity (units of enzyme activity per mg of enzyme protein) was found responsible for the reduction in measurable enzyme activity of the complex. Insulin treatment reversed the decrease in enzyme specific activity. Treatment of tissue extracts with phosphoprotein phosphatase had no effect, indicating that activity of the complex was decreased by some mechanism other than reversible phosphorylation. Specific protein components of the complex were also not found reduced by the diabetic state. Induction of severe ketotic diabetes in rats previously fed a low-protein diet resulted in activation of the enzyme as a consequence of dephosphorylation. Nevertheless, the specific activity of the dephosphorylated enzyme of diabetic, low-protein-fed rats was decreased relative to that of control, low-protein-fed animals. Reconstitution studies with tissue extracts fortified with the purified E1 component indicate that severe diabetes induces a defect in this component of the hepatic branched-chain alpha-ketoacid dehydrogenase complex.

3-Hydroxybutyric Acid

Effects of a fish oil rich diet on hyperoxic lung damage in mice.

Mice were fed a chow diet plus 10% cellulose, 10% fish oil or 10% sunflower oil for 3 weeks, then exposed to 100% oxygen for 75 h. Large changes in lung fatty acid composition occurred, but this did not affect hyperoxic lung damage nor levels of thiobarbituric acid reactive substances or myeloperoxidase in lungs of mice following exposure to hyperoxia. Thus there is no evidence that the ingestion of large quantities of fish oil increased the susceptibility to the oxidative stress induced by hyperoxia.

Animals

A single administration of LFA-1 antibody confers prolonged allograft survival.

C57BL/6 (B6) thyroid gland transplanted to the left kidney capsule of an allogeneic (BALB/c) host was typically rejected in 14 days. A single administration of 500 micrograms of an antibody to the adhesion molecule, leucocyte function-associated antigen (LFA-1, CD11a), prevented all thyroid allograft rejection for at least 70 days. Fifty percent of the treated recipients retained intact allografts for 470 days. However, the same treatment with anti-CD11a could not protect a sensitized BALB/c mouse from rejecting a second B6 thyroid allograft. Production of donor-specific alloantibodies elicited by allograft rejection was also inhibited in this system. In this transplant model, the Ab therapy is more efficacious than that of FK506, administered daily for 14 days at 15 mg/kg. These results demonstrate the remarkable effect of an anti-LFA-1 antibody in promotion of allograft survival.

Animals

Linking the Computerized Severity Index (CSI) to coded patient findings in the HELP system patient database.

The Computerized Severity Index (CSI) is a commercially available scoring system for hospital inpatients. Trained abstractors review the patient's paper medical record and enter the diagnoses and relevant physiological facts. The HELP (Health Evaluation Through Logical Processing) System at LDS Hospital stores patient data in discrete codes. We believe that HELP's coded patient database may drive an automatic version of CSI without the need for manual input. This descriptive study examines the nature and depth of the HELP System patient findings needed to implement an automatic CSI.

Databases, Factual

Comments on occupational and environmental factors in the origin of non-Hodgkin's lymphoma.

The review of the literature regarding non-Hodgkin's lymphoma and occupational and environmental factors presented at this workshop suggested associations with viruses, solvents, and hair dyes. A population-based case-control study among men from Iowa and Minnesota notes similar associations. Workers engaged in metal working, hair care, painting, and dry cleaning experienced nonsignificant excesses. Risks from specific exposures showed some variation by histological type. Both follicular and diffuse non-Hodgkin's lymphoma were associated with benzene. The diffuse type was linked to solvents other than benzene and formaldehyde, while the follicular was excessive among workers exposed to oils and greases.

Adult

Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among men in Iowa and Minnesota.

Data from an in-person interview study of 622 white men with newly diagnosed non-Hodgkin's lymphoma and 1245 population-based controls in Iowa and Minnesota were used to measure the risk associated with farming occupation and specific agricultural exposures. Men who ever farmed were at slightly elevated risk of non-Hodgkin's lymphoma (odds ratio = 1.2, 95% confidence interval = 1.0-1.5) that was not linked to specific crops or particular animals. Elevated risks were found, with odds ratio generally 1.5-fold or greater, for personal handling, mixing, or application of several pesticide groups and for individual insecticides, including carbaryl, chlordane, dichlorodiphenyltrichloroethane, diazinon, dichlorvos, lindane, malathion, nicotine, and toxaphene. Associations were generally stronger for first use prior to 1965 than more recently, and when protective clothing or equipment was not used. Small risks were associated with the use of the phenoxyacetic acid herbicide 2,4-dichlorophenoxyacetic acid, but the risks did not increase with latency or failure to use protective equipment. Exposure to numerous pesticides poses problems of interpreting risk associated with a particular chemical, and multiple comparisons increase the chances of false-positive findings. In contrast, nondifferential exposure misclassification due to inaccurate recall can bias risk estimates toward the null and mask positive associations. In the face of these methodological and statistical issues, the consistency of several findings, both within this study and with observations of others, suggests an important role for several insecticides in the etiology of non-Hodgkin's lymphoma among farmers.

Adult

Smoking and risk of leukemia.

The relation between tobacco use and leukemia was evaluated in a population-based case-control study of 578 white men with leukemia and 820 controls conducted in Iowa and Minnesota during 1981-1984. Risks were significantly elevated for all leukemia (odds ratio (OR) = 1.4) and chronic lymphocytic leukemia (OR = 1.6) for both tobacco users and cigarette smokers. There were significantly elevated risks for cigarette smokers of longest duration for all leukemia (OR = 1.6), chronic myelogenous leukemia (OR = 3.3), and chronic lymphocytic leukemia (OR = 1.6). Thus, the findings of this study provide additional support for an association between smoking and the risk of several types of leukemia.

Adult

Smoking and risk of non-Hodgkin's lymphoma and multiple myeloma.

Population-based case-control interview studies of 622 White men with non-Hodgkin's lymphoma and 820 controls from Iowa and Minnesota (United States) and 173 White men with multiple myeloma and 452 controls from Iowa offered the opportunity to investigate the relationship of these cancers with smoking. Risks were significantly elevated for all lymphoma (odds ratio [OR] = 1.4), high-grade lymphoma (OR = 2.3), and unclassified lymphoma (OR = 2.8) for cigarette smokers. Dose-response gradients were not seen with intensity of cigarette use, but risks for these subtypes were greatest for cigarette smokers of longest duration. Similar elevations in risks were seen for tobacco users. The risk of multiple myeloma was not significantly elevated for either tobacco users or cigarette smokers. The findings from this study confirm the lack of an association between smoking and multiple myeloma and provide some support for an association between tobacco use and certain subtypes of non-Hodgkin's lymphoma.

Case-Control Studies

Alcohol consumption and risk of leukemia, non-Hodgkin's lymphoma, and multiple myeloma.

Population-based case-control interview studies of white men, 578 with leukemia, 622 with non-Hodgkin's lymphoma, and 820 controls from Iowa and Minnesota and 173 with multiple myeloma and 452 controls from Iowa, offered the opportunity to investigate the relationship of these cancers with alcohol consumption. Although drinkers had non-significantly elevated risks for specific subtypes of leukemia (acute lymphocytic leukemia (OR = 3.0), myelodysplasia (OR = 1.6), and other leukemia (OR = 1.5)) and multiple myeloma (OR = 1.3), there were no statistically significant findings and no dose-response gradients with amount of alcohol consumed. Thus, these data suggest that alcohol is not an important contributor to the etiology of lymphatic and hematopoietic tumors.

Alcohol Drinking

Relative changes in salivary Na+ and K+ concentrations relating to stress induction.

Three independent studies are reported in which periods of "relaxation" (A) and presumed stressors (B) were given to female students in an ABA design. The "stressors" were: (1) obligatory time-wasting activity; (2) a mental "IQ" test; and (3) delivering a speech. Saliva was collected immediately after "relaxation" and "stress" periods. "Stress" and "arousal" state were retrospectively assessed in experiments (1) and (2) by subject self-rating and in experiment 1 also by trained observers for the periods A and B. The molar [K+/Na+] ratio was determined for each saliva sample. The prediction that [K+/Na+] would increase with stress induction was supported by statistically significant results with stressors 1 and 2 (p less than 0.01), but speech delivery (3) resulted in a significant rise of [K+/Na+] after the stressor period. Correlations between [K+/Na+] and "stress" and "arousal" ratings also substantiated the prediction.

Adolescent