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Biomedical subjects

V R Young

Publications and source records attributed to V R Young.

At least 109 records · Page 6Linked to original sources
PubMed1993

Determination of the isotope enrichment of one or a mixture of two stable labelled tracers of the same compound using the complete isotopomer distribution of an ion fragment; theory and application to in vivo human tracer studies.

Calculations of flux rates for stable isotope tracer studies are based upon enrichment values of an infused tracer. We propose the determination of enrichment values by gas chromatography/mass spectrometry, which is based on tracer mole fraction and mass spectrometer signals, normalized over the total signal of an ion fragment isotopomer distribution. The method accounts for overlap of the signals of one or two tracers and the tracee, high tracer mole fraction and incomplete labelling of the (infused) tracer. For the single and multiple tracer case a linear relationship between tracer mole fraction (from zero to one) and all normalized mass spectrometer signals is derived. This linearity over the entire range is demonstrated with a single (1-13C)glucose tracer and for mixtures of (1-13C)- and (3,3-2H2)tyrosine tracers. The linearity allows determination of the tracer mole fraction for two tracers, using multiple linear regression. The corresponding calibration can rely on measurements of the pure tracer and tracee compound, without weighing or check for chemical purity. This is compared with a calibration based on tracer/tracee mixtures. Estimates for the tracer mole fraction are slightly better if based on a calibration, using standard mixtures. In all cases the tracer mole fraction can be determined with high precision (coefficient of variation smaller than 5%) and high accuracy. For tyrosine it is demonstrated that the measurement of seven channels rather than three, for the main isotopomers, does not reduce the precision in the prediction of the tracer mole fraction. Equations are also derived to use the tracer mole fraction to estimate the endogenous production of the tracee under study conditions, assuming a steady state of the host metabolism.

Carbon Dioxide↗
PubMed1993

Variation in total energy expenditure in young healthy free-living men.

Interindividual and intraindividual variation in total energy expenditure (TEE) were examined in 17 healthy, free-living men (weight, 56.4 to 82.4 kg; age, 18 to 30 years). TEE over 14 days, resting metabolic rate (RMR), and body composition were measured two or three times during 77 days of fixed caloric intake using doubly labeled water, respiratory gas analysis, and isotope dilution, respectively. When individual data were averaged, TEE was most significantly related to fat-free mass ([FFM] r = .73, P = .001), body mass (r = .70, P = .002), and RMR (r = .63, P = .006). After adjusting TEE for BM, a significant inverse relation with age was found (partial r = -.52, P = .032). Stepwise regression analysis showed that 69% of individual variation in TEE was explained by BM, age, and fasting respiratory exchange ratio (RER). TEE/RMR averaged 1.73 +/- 0.25 (range, 1.38 to 2.32), and was independent of age and body composition. In 10 subjects in whom triplicate observations of TEE were performed, the average experimental variation for TEE was +/- 11.9% (range, 6.1% to 19.6%) compared with a theoretical estimate of precision of +/- 5.9% based on the reported isotope dose and analytical uncertainty. The difference between theoretical estimates of precision and observed experimental variation suggests that inherent random variation in free-living TEE is +/- 10% (ie, square root of 12(2)-6(2)) in subjects maintained on fixed caloric intake. We conclude that in young free living men (1) BM, age, and RER are important determinants of TEE; and (2) intraindividual variation in TEE is approximately +/- 10% due to fluctuations in physical activity levels within individuals over time.

Adolescent↗
PubMed1993

Phenylalanine conversion to tyrosine: comparative determination with L-[ring-2H5]phenylalanine and L-[1-13C]phenylalanine as tracers in man.

The in vivo rate of conversion of phenylalanine to tyrosine (PheOH) can be estimated using combinations of stable isotope-labeled phenylalanine and tyrosine. We have compared in four healthy adult men the rates of phenylalanine conversion to tyrosine based on the following pairs of primed, continuous tracer infusions administered simultaneously: (1) L-[ring-2H5]phenylalanine and 2H2-tyrosine with a 2H4-tyrosine prime, and (2) L-[1-13C]phenylalanine and 2H2-tyrosine with a 1-13C-tyrosine prime. Phenylalanine oxidation was determined from measurement of 13CO2 excretion in expired air. Tracers were given for 8 hours, with subjects being in the postabsorptive state during the first 3 hours and in the fed state during the remaining 5 hours. Mean (+/- SD) rates (mumol.kg-1.h-1) of phenylalanine conversion to tyrosine for fasted and fed states, respectively, were 5.1 +/- 2.9 and 6.8 +/- 3.4 with 2H5-phenylalanine and significantly higher (P < .05) at 11.1 +/- 5.6 and 12.7 +/- 7.7 with 13C-phenylalanine as tracer. Phenylalanine oxidation was 9.9 +/- 2.0 and 13.5 +/- 2.6, respectively, for fasted and fed states, and these mean values did not differ (P > .1) from the rate of phenylalanine conversion to tyrosine determined using 13C-phenylalanine. These results indicate the need for caution in interpreting kinetic aspects of phenylalanine metabolism when based on isotopic data from multideuterated phenylalanine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Dysprosium as a nonabsorbable marker for studies of mineral absorption with stable isotope tracers in human subjects.

Two studies were conducted to determine if dysprosium (Dy) could be used as a quantitative fecal marker for studies of zinc-70 (70Zn), copper-65 (65Cu) and magnesium-26 (26Mg) absorption in humans. In the first experiment, Dy excretion was shown to be complete (104 +/- 9%; mean +/- SD, n = 6) and the kinetics of fecal Dy excretion closely paralleled that of 70Zn but not 65Cu. Because of the similarity in 70Zn and Dy excretion kinetics, a method for estimating 70Zn absorption was developed which used 70Zn and Dy data from only the first two stools passed after isotope administration. Average estimates of 70Zn absorption based on the two-stool (partial pool) vs total pool (5-day composite) method were not different (28.0 +/- 5.2 vs 24.4 +/- 4.1%, respectively; means +/- SEM; p > 0.10). In the second study, the same questions was addressed relative to 26Mg absorption. 26Mg and Dy also exhibited nearly identical excretion patterns. Average estimates of 26Mg absorption based on the partial pool vs total pool method were comparable yielding mean values of 22.7 +/- 3.4 vs 23.2 +/- 2.5% and 26.1 +/- 1.8 vs 24.3 +/- 1.8%, respectively, from magnesium-26 oxide (26MgO) and 26Mg glycinate. Advantages and limitations of the partial pool method for estimating mineral absorption are discussed.

Absorption↗
PubMed1993

An isotopic study of the effect of dietary carbohydrate on the metabolic fate of dietary leucine and phenylalanine.

The fate of dietary leucine and phenylalanine was studied in five healthy, young adult men, by using a dual, stable isotope-tracer infusion approach to estimate amino acid fluxes, splanchnic (Sp) uptake, and dietary of absorbed amino acid to the peripheral circulation. Subject received two, 4-h tracer infusions of [1-13C]leucine and [15N]phenylalanine infused through a feeding tube placed in the duodenum, and [5,5,5-2H3]leucine, [ring-2H5]phenylalanine, and [6,6-2H2]glucose infused simultaneously by vein. In one experiment subjects received an amino acid mixture (83 mg amino acid.kg-1.h-1) via the feeding tube and in the other experiment amino acids were supplied with carbohydrate (CHO) (167 mg.kg-1.h-1). Sp uptake of dietary leucine decreased with added dietary CHO (29% of ingested leucine for amino acids alone vs 20% with CHO; P < 0.05) but was not different for phenylalanine (P > 0.05). Addition of CHO decreased both release of leucine via protein breakdown and leucine oxidation and increased body leucine balance (P < 0.05).

Adult↗
PubMed1993

Requirements for indispensable amino acids in adult humans: longer-term amino acid kinetic study with support for the adequacy of the Massachusetts Institute of Technology amino acid requirement pattern.

Twenty young men received an L-amino acid diet, supplying 140 mg N.kg-1 x d-1 and patterned as in the Egg diet for 1 wk, and then for 3 wk either a pattern based on international recommendations (modified FAO diet; n = 7), our new amino acid requirement pattern (MIT diet; n = 7), or the egg pattern (Egg diet; n = 6). At the end of the initial week, at 1 and 3 wk with the three experimental diets, and after 3 d after return to the Egg diet, an 8-h continuous intravenous infusion with [1-13C]leucine (3 h fast, 5 h fed while subjects received hourly meals supplying the equivalent of one-twelfth the daily intake) was conducted. After 3 wk with the different diets, mean daily leucine balances were lower (P < 0.01) with the FAO diet (-160 mumol.kg-1 x d-1) than with the MIT diet (-15 mumol.kg-1 x d-1). Together with changes in plasma amino acid profiles [eg, methionine increased (P < 0.05) during feeding with the FAO and Egg diets but not with the MIT diet; increased proline concentrations during the fed state (P < 0.05) with the FAO diet but not with the MIT or Egg diets] we interpret these findings to indicate that the FAO diet is not capable of maintaining amino acid homeostasis, as is the case with the MIT and Egg diets.

Adult↗
PubMed1993

Energy expenditure, aging and body composition.

We investigated the importance of adaptive variations in energy expenditure in the regulation of energy balance in young and elderly men of normal body weight leading unrestricted lives. Changes were measured in total and resting energy expenditure and body composition in response to overeating by approximately 4.2 MJ/d or undereating by 3.3 MJ/d for 21 d in 39 young and elderly men consuming a typical diet. In the young men, an average of 85-90% of the excess energy intake during overeating was deposited. During underfeeding, mobilization of body energy compensated for an average of 65% of the energy deficit in these subjects. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (+0.63 +/- 0.20 MJ/d, P < 0.01) and decreased during underfeeding (-0.42 +/- 0.12 MJ/d), but at least some of these changes were due to the obligatory expenditure associated with nutrient assimilation. There was no significant change in energy expenditure for physical activity or thermoregulation from overfeeding or underfeeding. Preliminary results indicate that aging had no effect on responses to overfeeding or underfeeding. These findings suggest that adaptive variations in energy expenditure are not the major determinant of energy regulation in young adults of normal body weight and that, instead, energy balance is maintained on a day-to-day basis through the control of nutrient intakes.

Adult↗
PubMed1993

A kinetic study of L-2H3-methyl-1-13C-methionine in patients with severe burn injury.

To explore the consequences of severe burn injury on methionine metabolism we carried out tracer studies, using [1-13C, 2H3-methyl] methionine, given by continuous intravenous infusion, in 12 adult patients. Each was studied in the "fasted" and in the fed state while receiving parenteral nutrition. Compared with findings obtained in our previous studies in healthy adults using a similar protocol, the rates of transmethylation (Tm), homocysteine remethylation (Rm), and methionine oxidation (C) were all substantially increased in burn patients. From the relationships between these systems, it appears that there is a relative increase in the recycling of methionine carbon via Rm during the fasted state. This implies active methyl group transfer and utilization in burn patients. Parenteral feeding increased methylmethionine flux (Qm) and the rates of Tm, Rm, and C. However, the Tm/Qm ratio did not change with feeding in the patients, whereas it increased in healthy young adults. This may not necessarily reflect the consequences of burn injury, but may be due to differences in the route of methionine intake or its level relative to requirement, compared with the conditions of study in healthy adults. Further studies on methionine-cysteine interrelationships, using an isotopic approach, in burned patients are needed to evaluate these possibilities.

Adult↗
PubMed1993

Effects of protein restriction and acute refeeding on leucine and lysine kinetics in young men.

To explore the effects of altered protein intake on the uptake and utilization of dietary amino acids in human subjects, six healthy male Massachusetts Institute of Technology students were studied during three dietary periods each of 9 days, with tracer infusion studies conducted on days 8 and 9. During one period the diet provided a generous protein intake (1.5 g.kg-1.day-1) and during the other two a low-protein intake (0.1 g.kg-1.day-1). Tracer infusions (fed state) were given while subjects received either a liquid formula, supplying the prior protein intake or (on day 9) a generous intake. Combinations of [2H3]Leu and [13C]Leu and of [15N]Lys and [2H4]Lys were given via continuous intravenous or intragastric infusion for 4 h to estimate leucine kinetics and the first-pass splanchnic uptake of tracer. Dietary-induced changes in leucine flux and oxidation were similar irrespective of the tracer and/or route of administration and sampled pool (leucine or KIC) used for calculation. Estimates of absolute changes in the rates of leucine disappearance via nonoxidative metabolism (protein synthesis) and of appearance via protein breakdown depended on the route of [13C]Leu administration. However, it appears that both altered rates of protein synthesis and breakdown contribute to the adaptations required in the body nitrogen economy when protein intakes are restricted and subsequently resupplied. From the intragastric [13C]Leu protocol, the first-pass splanchnic uptake of tracer was the same (approximately 30%) for generous, low-protein, and refed conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Dietary arginine uptake by the splanchnic region in adult humans.

To determine the uptake of dietary arginine and leucine by the splanchnic region, two experiments were carried out, each involving four healthy young adult men who received a diet supplying 1 g protein.kg-1.day-1 for 7 and 10 days before conducting a primed constant tracer infusion protocol. In study 1, subjects received for 8 h (3-h fast; 5-h fed state, achieved by a constant intragastric infusion of the diet formula) L-[5,5-2H2; guanidino-15N2]arginine ([M4]Arg), L-[guanidino-13C]arginine ([13C]Arg), and L-[5,5,5-2H3]leucine ([2H3]Leu) simultaneously by an intragastric infusion on day 7 and a repeat of this protocol on day 10 except with tracer administration given by vein. Plasma arginine fluxes were essentially the same for the two arginine tracers but differed significantly with route of administration. In study 2 the subjects received on day 7 a constant intravenous infusion of [13C]Arg and [2H3]Leu and a simultaneous intragastric infusion of [M4]Arg and [1-13C]leucine. On day 10 the routes of administration of these tracer pairs were reversed. During the fed state in study 1, splanchnic uptake of dietary arginine was 31 +/- 10 and 34 +/- 8%, based on the [13C]Arg and [M4]Arg tracers, respectively, and it was significantly higher (P < 0.01) than for leucine, which was 10 +/- 6%. In study 2, splanchnic uptake of dietary arginine, estimated from a series of tracer-protocol combinations for the fed state, was approximately 38% compared with a lower (P < 0.01) value of approximately 15% for leucine.

Adult↗
PubMed1993

Effect of fasting and feeding on measurement of carbon dioxide production using doubly labeled water.

The doubly labeled water method is a noninvasive technique for measurement of rates of CO2 production and total energy expenditure in free-living human subjects. The experimental protocol used in validation studies usually involves prolonged fasting before and after the isotope dose is given to start the study, although it is not clear whether this intrusive aspect of the method is necessary. We investigated this issue in four healthy adults [3 women and 1 man: age 29 +/- 2 (SD) yr, body mass index 22 +/- 2.7 kg.m2] with monitored constant physical activity who underwent two doubly labeled water studies that differed only in the duration of fasting before and after isotope dosing (either 6 h of fasting before and 5 h after dosing or 0.5 h before and 3 h afterward). No significant difference between the two measurements was found in the rate constants for isotope disappearance, the ratio of the dilution spaces of the isotopes, or CO2 production rate. These results indicate that prolonged fasting before and after isotope administration should not be necessary in doubly labeled water studies.

Adult↗
PubMed1993

Effects of dietary protein restriction on the fractional rates of protein synthesis in perfused rat hindlimb.

The effects of dietary protein restriction on protein synthesis were investigated in perfused rat hindlimb. The fractional rate of protein synthesis was measured with [3H]phenylalanine in young adult (7-week-old) rats fed a low protein (5% casein) diet and a protein-free diet for 3 weeks. The low protein diet (LPD) allowed a moderate gain in body weight. The fractional rate of protein synthesis fell to 70% of the control value in LPD group and further fell to less than a half in the protein-free diet (PFD) group. Thus, the protein synthesis rate decreased as the dietary protein content was reduced. The fall of protein synthesis was mainly accompanied by the reduction of RNA activity (mg protein/mg RNA/day) rather than RNA concentration (RNA/protein). The rate of protein breakdown was calculated by subtracting growth rate from protein synthesis rate. The breakdown rate was decreased in LPD group and increased slightly in PFD group. From the low rates of protein synthesis and breakdown, it appears that dietary protein restriction, at least allowing a gain in body weight, makes the turnover rate slow down. The overall changes in protein synthesis obtained in the perfused hindlimb are consistent with the reported results in vivo.

Animals↗
PubMed1992

Phenylalanine and tyrosine kinetics in relation to altered protein and phenylalanine and tyrosine intakes in healthy young men.

Plasma phenylalanine (Phe) and tyrosine (Tyr) turnover and the rate of conversion of phenylalanine to tyrosine (Phehyd) and of phenylalanine oxidation (Pheox) after reduced intakes of Phe and Tyr were determined in a metabolic study involving five healthy young adult men. In a pilot study, six postabsorptive young men received either 12- or 4-h infusions of [2H2]Phe and [1-13C]Tyr or [1-13C]Phe and [2H2]Tyro. From these results a primed 8-h constant infusion of [1-13C]Phe and [2H2]Tyr and [2H3]leucine was used in the metabolic study (first 3 h fasted, the 5 h fed) at the end of 1-wk periods during which subjects received an adequate nitrogen L-amino acid based-diet followed by a restricted intake of Phe and Tyr. This procedure was again repeated after 1 and 3 wk when subjects were given a diet low in both nitrogen and Phe and Tyr. Phe and Tyr fluxes were not significantly affected by diet during the fasted metabolic state but Tyr fluxes were lower when the restricted intakes were given. Compared with the rate during the fasting state, Pheox was significantly higher (P less than 0.01) when the adequate diet was consumed; Pheox and Phehyd for fed and fasted states were similar when Phe and Tyr were restricted.

Adult↗
PubMed1992

Energy requirements in the elderly.

The major components of daily energy expenditure may change during aging. A review of current estimates of energy requirements leads to the conclusion that direct estimates of daily energy expenditure are desirable to confirm the validity of the present recommendations. A more extensive examination of the metabolic and nutritional significance of the major food fuel sources is necessary to further define human energy needs.

Aged↗