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Biomedical subjects

S B Roberts

Publications and source records attributed to S B Roberts.

At least 19 recordsLinked to original sources
PubMed2004

Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor.

gamma-Secretase inhibitors are one promising approach to the development of a therapeutic for Alzheimer's disease (AD). gamma-Secretase inhibitors reduce brain beta-amyloid peptide (Abeta), which is believed to be a major contributor in the etiology of AD. Transgenic mice overexpressing the human beta-amyloid precursor protein (APP) are valuable models to examine the dynamics of Abeta changes with gamma-secretase inhibitors in plaque-free and plaque-bearing animals. BMS-299897 2-[(1R)-1-[[(4-chlorophenyl)sulfony](2,5-difluorophenyl)amino]ethyl]-5-fluorobenzenepropanoic acid, a gamma-secretase inhibitor, showed dose- and time dependent reductions of Abeta in brain, cerebrospinal fluid (CSF), and plasma in young transgenic mice, with a significant correlation between brain and CSF Abeta levels. Because CSF and brain interstitial fluid are distinct compartments in composition and location, this correlation could not be assumed. In contrast, aged transgenic mice with large accumulations of Abeta in plaques showed reductions in CSF Abeta in the absence of measurable changes in plaque Abeta in the brain after up to 2 weeks of treatment. Hence, CSF Abeta levels were a valuable measure of gamma-secretase activity in the central nervous system in either the presence or absence of plaques. Transgenic mice were also used to examine potential side effects due to Notch inhibition. BMS-299897 was 15-fold more effective at preventing the cleavage of APP than of Notch in vitro. No changes in the maturation of CD8(+) thymocytes or of intestinal goblet cells were observed in mice treated with BMS-299897, showing that it is possible for gamma-secretase inhibitors to reduce brain Abeta without causing Notch-mediated toxicity.

Aging↗
PubMed2004

Stunted children gain less lean body mass and more fat mass than their non-stunted counterparts: a prospective study.

The aim of the present study was to analyse the changes in body composition of stunted children during a follow-up period and to test the hypothesis of a tendency to accumulate body fat as a consequence of undernutrition early in life. We selected fifty boys and girls aged 11 to 15, who were residents of slums in Sao Paulo, Brazil. Twenty were stunted (S) and thirty had normal stature (NS). The children's nutritional status and body composition were assessed through anthropometry and dual-energy X-ray absorptiometry, at the beginning of the present study and after 3 years, and changes in lean mass (LM and LM%) and fat mass (FM and FM%) were calculated. Stunted boys accumulated more body fat (FM%: S=1.62%, NS=-3.40%; P=0.003) and gained less lean mass (LM%: S=-1.46, NS=3.21%; P=0.004). Stunted girls gained less lean mass (S=7.87 kg, NS=11.96 kg; P=0.032) and had significantly higher values of FM% at follow-up when compared with their baseline values (P=0.008), whereas non-stunted girls had a non-significant difference in FM% over time (P=0.386). These findings are important to understand the factors involved in the increased prevalence of overweight and obesity among poor populations, which appear to be associated with hunger during infancy and/or childhood.

Adipose Tissue↗
PubMed2004

Acute neurosteroid modulation and subunit isolation of the gamma-aminobutyric acidA receptor in the bullfrog, Rana catesbeiana.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has multiple receptors. In mammals, the GABA(A) receptor subtype is modulated by neurosteroids. However, whether steroid interaction with the GABA(A) receptor is unique to mammals or a conserved feature in vertebrates is unknown. Thus, neurosteroid modulation of the GABA(A) receptor was investigated in the brain of the bullfrog (Rana catesbeiana) using the mammalian GABA(A) receptor agonist [(3)H]muscimol. Two neurosteroids, allopregnanolone and pregnenolone sulfate, affected [(3)H]muscimol specific binding in bullfrog brain membrane preparations. Allopregnanolone significantly increased [(3)H]muscimol specific binding in a dose- and time-dependent manner. The pattern of allopregnanolone modulation supports the hypothesis that the bullfrog brain possesses both high-affinity and low-affinity [(3)H]muscimol binding sites. Unlike allopregnanolone, pregnenolone sulfate showed biphasic modulation with increased [(3)H]muscimol specific binding at low nanomolar concentrations and decreased specific binding at micromolar concentrations. Additionally, three cDNA fragments with significant homology to mammalian GABA(A) receptor subunits were isolated from the bullfrog brain. These fragments belong to the alpha1, beta1, and gamma2 subunit families. In mammals, GABA(A) receptors composed of these specific subunit isoforms are effectively modulated by neurosteroids, including allopregnanolone. Neurosteroid modulation of the amphibian brain GABA(A) receptor is therefore supported by both [(3)H]muscimol binding studies and subunit sequences. Allopregnanolone and pregnenolone sulfate modulation of this receptor may thus represent a significant mechanism for steroid influence on amphibian brain and behavior.

Amino Acid Sequence↗
PubMed2003

Relative influence of diet and physical activity on cardiovascular risk factors in urban Chinese adults.

OBJECTIVE: The relative influence of dietary factors vs physical activity on cardiovascular risk factors are poorly understood. We investigated these factors in a population whose traditional diet may have both positive (high plant-based) and negative (high refined carbohydrate) aspects, and whose physical activity levels (PALs) vary widely. DESIGN: Cross-sectional study. SUBJECTS: A total of 130 weight stable adults aged 35-49 y (BMI 18-35 kg/m(2)) living in urban Beijing, China. MEASUREMENTS: Dietary intake (by food frequency questionnaire), PAL as the ratio of predicted total to resting energy expenditure), percent body fat (by deuterium oxide dilution), and central adiposity (waist circumference and waist to hip ratio) were assessed. Biochemical parameters (total cholesterol, low- and high-density lipoprotein cholesterol (LDL-C; HDL-C), triglyceride (TG), apolipoproteins A-I and B, glucose, insulin, and homocysteine and its related vitamins), blood pressure and presence of the metabolic syndrome (having >/=3 risk factors of central adiposity, HDL-C, TG, glucose, blood pressure) were also examined. RESULTS: Mean values for cardiovascular risk factors were relatively low, but 19% of subjects had the metabolic syndrome. Using validated methods for measuring food intake and energy expenditure, we found that an adverse cardiovascular risk profile was associated with a diet high in carbohydrate, low in polyunsaturated fat, and low in fruit and vegetables, independent of body fatness and its distribution. While dietary factors predicted individual cardiovascular risk factors more consistently than PAL, avoidance of low PAL reduced the risk of having the metabolic syndrome. CONCLUSION: These results suggest that, regardless of total body fatness and fat distribution, multiple unfavorable dietary factors and low physical activity independently increase the risk for cardiovascular disease. Avoidance of a sedentary lifestyle additionally reduces the risk of developing the metabolic syndrome.

Adult↗
PubMed2002

Energy requirements of urban Chinese adults with manual or sedentary occupations, determined using the doubly labeled water method.

OBJECTIVE: To examine total energy expenditure (TEE) in relation to occupation and reported leisure time activities in free-living Chinese adults, and to determine whether measured TEE values differ from current international dietary energy recommendations. SETTING AND SUBJECTS: Seventy three weight-maintaining adults aged 35-49 y, leading unrestricted lives in urban Beijing, with a wide variety of occupations. DESIGN AND METHODS: A cross-sectional study in which TEE was determined by doubly labeled water, body composition by deuterium oxide ((2)H(2)O) dilution, resting energy expenditure (pREE) by prediction equations, and occupational and leisure time activities by questionnaire. RESULTS: For men and women respectively, TEE averaged 12.10+/-0.32 and 9.53+/-0.23 MJ/day (P<0.001), and physical activity level (PAL=TEE/pREE) was 1.77+/-0.04 and 1.66+/-0.02 (P<0.05). Fat-free mass (FFM) was the single best predictor of TEE (adjusted r(2)=0.71, P<0.001). Occupational category (light, moderate and heavy) further predicted TEE, independent of FFM (adjusted multiple r(2)=0.82, P<0.001). Both TEE adjusted for weight and PAL increased with occupational category. Measured TEE was slightly but significantly higher than the 1985 FAO/WHO/UNU estimates for women with light occupations, but did not differ from estimates for men with light occupations, or for adults with moderate or heavy occupations. CONCLUSION: Level of occupational activity, but not duration or type of leisure activity, significantly predicted TEE in free-living urban Chinese adults. Current energy requirement recommendations slightly underestimated the energy needs of women with light occupations but were accurate for men and women with moderate and heavy occupations. SPONSORSHIP: NIH grants DK53404 and F32-DK09747.

Adult↗
PubMed2001

Differential skeletal muscle expression of myostatin across teleost species, and the isolation of multiple myostatin isoforms.

Two myostatin (MSTN) isoforms were isolated from brook trout with 92% identity in corresponding regions at the nucleotide level. One isoform was isolated from muscle and brain and the second from ovarian tissue. To our knowledge this is the first time two MSTN isoforms have been isolated from a given vertebrate species. Within the brain, MSTN transcripts were localized to the optic lobes, hindbrain, and hypothalamus. In the trout ovary, MSTN transcripts were upregulated at ovulation in several females. MSTN cDNA fragments were also isolated from several other fish species and differential expression of MSTN among muscle fiber types was observed.

Animals↗
PubMed2001

Meal palatability, substrate oxidation and blood glucose in young and older men.

We investigated the effects of food palatability on the thermic effect of feeding (TEF), substrate oxidation and circulating glucose and insulin. Healthy young men (23.4+/-1.0, SD, years, n=10) and older men (69.4+/-1.3, years, n=9) were resident in a metabolic unit for two 2-day study periods. On the second day of each period, they consumed in random order either a palatable test meal containing 2.93 MJ or a nonpalatable control meal containing the same foods in identical amounts but blended and freeze-dried into biscuit form. TEF and respiratory quotient (RQ) were measured over 6 h and blood samples were taken for measurement of glucose and insulin. Age group had no effect on TEF, RQ or circulating glucose other than to delay the time of peak TEF (P<0.002 for both meals). There was no significant effect of meal type on TEF, but RQ and circulating glucose were higher following consumption of the palatable meal (P<0.001 for both parameters). These results suggest that over 6 h postprandial, consumption of palatable foods does not increase TEF, but is instead associated with increased glycemic response and increased carbohydrate oxidation. These changes, combined with previous work on the glycemic index, predict an accelerated return of hunger and increased energy intake at subsequent meals following consumption of palatable vs. control foods. Further studies are needed to examine the possible mechanism for this previously suggested "second meal" effect of diet palatability on energy intake.

Adult↗
PubMed2001

The energy expenditure of postmenopausal women classified as restrained or unrestrained eaters.

OBJECTIVE: Restrained eating is a common dietary practice among individuals who are attempting to prevent weight gain, but little is known about differences in energy physiology and regulation between restrained and unrestrained eaters. We investigated this issue in non-obese free-living postmenopausal women classified as long-term restrained (n=26) or unrestrained (n=34) eaters group matched for body mass index (BMI). MEASUREMENTS: Measurements were made of total energy expenditure (TEE), resting energy expenditure (REE), body composition, reported leisure time activity, maximal aerobic capacity (VO2max) and weight change during the study period. In addition, physical activity level (PAL) and nonexercise activity thermogenesis (NEAT) were calculated from measured variables. RESULTS: There were no significant differences between the groups in body composition, weight change, aerobic capacity or total leisure time activity. Relationships between fat-free mass (FFM) and both REE and TEE, and the relationship between work load and energy expenditure in the test of maximal oxygen consumption, were also not different between groups. However, restrained eaters had a significantly lower PAL (equal to TEE/REE, 1.72+/-0.04 vs 1.84+/-0.04, P<0.05). In addition, in multiple regression models predicting NEAT, NEAT was significantly lower in restrained eaters than unrestrained eaters and there was a positive relationship between NEAT and weight change in unrestrained eaters but no relationship in restrained eaters (P<0.05). CONCLUSIONS: In contrast to a previous report, we found no significant difference in TEE between restrained and unrestrained eaters. PAL was slightly lower in restrained eaters, apparently due to reduced NEAT, and restrained eaters also lacked the positive association between NEAT and body weight change seen in unrestrained eaters. This latter finding, if confirmed in future studies, could help explain an increased susceptibility of restrained eaters to weight gain. SPONSORSHIP: NIH grants AG12829, DK46124 and T32AG00209, and US Cooperative Agreement number 58-1950-9-001.

Basal Metabolism↗
PubMed2001

Effects of a cereal rich in soluble fiber on body composition and dietary compliance during consumption of a hypocaloric diet.

OBJECTIVES: To investigate the effects of oats, a cereal rich in soluble fiber, on body composition changes and dietary compliance during consumption of a weight loss diet. METHODS: Subjects were 41 healthy men and women aged 18 to 78 years. Weight maintenance energy requirements were established over two weeks during consumption of a control diet with low soluble fiber content. Subjects then consumed a hypocaloric diet for six weeks, either consuming a low soluble fiber control diet or a diet containing 45 g/1000 kcal rolled oats, a whole grain cereal rich in soluble fiber (mean energy deficit -895+/-18 kcal/day relative to weight maintenance energy requirements). Changes in body fat and fat-free mass were determined by underwater weighing, and dietary compliance was assessed using the urinary osmolar excretion rate technique. In a final phase of the study, subjects ate ad libitum for six months, and changes in body weight and composition were monitored. RESULTS: There was no significant effect of the oat-containing diet on body weight or composition changes during the hypocaloric regimen or in the subsequent ad libitum period. In addition, fecal energy excretion was not significantly different between groups. However, there were non-significant trends indicating reduced hunger in the oat group compared to controls (frequency of hunger 2.5+/-0.5 vs. 3.6+/-0.4, P=0.1). In addition, fewer oat subjects were non-compliant (four versus seven subjects dropped out or had urinary osmolar excretions greater than 130% of values predicted from dietary intake), but again the difference was not significant. CONCLUSIONS: These results suggest that use of a cereal rich in soluble fiber in a closely monitored hypocaloric feeding regimen does not improve weight loss or dietary compliance. Further studies are needed to examine the possibility that cereals containing soluble fiber may have effects on hunger and dietary compliance that could be important in less tightly controlled protocols than the one described here.

Adult↗
PubMed2001

Metabolic, psychological, and health correlates of dietary restraint in healthy postmenopausal women.

BACKGROUND: Dietary restraint, a term used to describe the intentional control of food intake to prevent weight gain or promote weight loss, is commonly practiced by older adults, but little is known about its effects on physiology and metabolism. METHODS: We therefore compared a wide range of parameters between groups of healthy non-obese postmenopausal women classified psychometrically as unrestrained eaters (body mass index [BMI] 23.8 +/- 0.6 [SEM] kg/m(2), n = 28) or restrained eaters (BMI 24.5 +/- 0.5, n = 39). Measurements were made of reported micronutrient intakes, cardiopulmonary function, hematology, body temperature, skin thickness, bone mass, and immune function; in addition, self-perceived health, mood, and some dimensions of eating behavior were assessed by questionnaire. RESULTS: Macronutrient and micronutrient intakes were not significantly different between restrained and unrestrained eaters reporting energy intake to within 30% of predicted total energy expenditure. Restrained eaters had significantly lower hemoglobin (12.9 +/- 0.1 [SEM] vs 13.2 +/- 0.1 g/dl; p <.05), but values were within the normal range in both groups. In addition, restrained eaters scored significantly higher on the Eating Attitudes Test (p <.01) and drive-for-thinness (p <.001) and maturity fears (p <.05) subscores of the Eating Disorders Inventory, but values were again within the normal range. No other parameter differed significantly between groups. CONCLUSIONS: In this normal-weight population, restrained eating was not associated with detrimental effects in a wide range of physiological, metabolic, and health characteristics. Further work is needed to determine the relevance of these results to the general population.

Attitude to Health↗
PubMed2001

Physiologic effects of lowering caloric intake in nonhuman primates and nonobese humans.

Caloric restriction (CR) reduces the rate of aging and increases life span in all small animal species studied to date, but the effects of CR in humans remain uncertain. This review summarizes current knowledge of the effects of CR in nonhuman primates and humans. The results suggest that CR has a range of beneficial effects in nonhuman primates studied under laboratory conditions, and short-term markers of CR seen in animal models appear to occur in humans subject to CR also. However, the overall benefit of CR in human populations remains to be established, and studies in human populations are needed.

Aging↗
PubMed2001

An oat-containing hypocaloric diet reduces systolic blood pressure and improves lipid profile beyond effects of weight loss in men and women.

Hypertension, dyslipidemia and overweight contribute substantially to cardiovascular disease risk. One of the most effective methods for improving high blood pressure and lipid profiles is loss of excess weight. Other recommendations for reducing cardiovascular risk include changes in dietary micronutrient, macronutrient and fiber intakes. To better define a diet for reduction in cardiovascular risk, 43 adults (body mass index 26.4 +/- 3.3, range 20.5-33.9 kg/m(2)) participated in an 8-wk study to determine the effects of two diets on weight, blood pressure, lipids and insulin sensitivity. For 2 wk, weight was maintained and all subjects consumed a control diet. For the next 6 wk, subjects consumed one of two hypocaloric diets (maintenance energy minus 4.2 MJ/d): the control diet (n = 21) or a diet containing oats [45 g/(4.2 MJ dietary energy. d), n = 22]. There was no significant difference between groups in changes in weight loss (control -4.0 +/- 1.1 kg, oats -3.9 +/- 1.6 kg, P = 0.8). The oats diet resulted in greater decreases in mean systolic blood pressure (oats -6 +/- 7 mm Hg, control -1 +/- 10 mm Hg, P = 0.026), whereas diastolic blood pressure change did not differ between the two groups (oats -4 +/- 6 mm Hg, control -3 +/- 5 mm Hg, P = 0.8). The oat diet resulted in significantly greater decreases in total cholesterol (oats -0.87 +/- 0.47 mmol/L, control -0.34 +/- 0.5 mmol/L, P = 0.003) and LDL cholesterol (oats -0.6 +/- 0.41 mmol/L, control -0.2 +/- 0.41mmol/L, P = 0.008). In summary, a hypocaloric diet containing oats consumed over 6 wk resulted in greater improvements in systolic blood pressure and lipid profile than did a hypocaloric diet without oats.

Adult↗
PubMed2001

An underfeeding study in healthy men and women provides further evidence of impaired regulation of energy expenditure in old age.

The effect of aging on energy regulation remains controversial. We compared the effects of underfeeding on changes in energy expenditure and respiratory quotient in young normal weight men and women [YNW, age 25.7 +/- 3.2 y(SD), body mass index (BMI) 23.1 +/- 1.6 kg/m(2)], young overweight men and women (YOW, age 26.1 +/- 3.5 y, BMI 27.7 +/- 2.1 kg/m(2)) and older (OLD) men and women (age 68.4 +/- 3.3 y, BMI 27.4 +/- 3.4 kg/m(2)). The thermic effect of feeding (TEF) during weight maintenance, and changes in resting energy expenditure (REE) and respiratory quotient were determined in response to undereating by an average 3.75 MJ/d for 6 wk. In addition, body composition was measured. No significant differences among the groups were observed in TEF, fasting and postprandial respiratory quotient, or the change in fasting respiratory quotient with underfeeding. However, REE adjusted for fat-free mass and fat mass was significantly lower in OLD subjects compared with YNW and YOW subjects (P < 0.05). In addition, the REE response to weight change was significantly attenuated in the OLD subjects (P = 0.023). These data suggest that the responsiveness of energy expenditure to negative energy balance is attenuated in old age, and provide further support for the hypothesis that mechanisms of energy regulation are broadly disregulated in old age.

Adult↗
PubMed2001

Dietary energy density and weight regulation.

Dietary energy density (ED) has been suggested as an important determinant of energy intake and, therefore, energy regulation. This review summarizes published studies on the effects of dietary ED on hunger, satiety, energy intake, and body weight in healthy individuals, and compares the relative effects of ED manipulated by dietary fat only, fat and fiber, water, and type of sweetener. In short-term studies, consumption of low-ED foods promotes satiety, reduces hunger, and decreases energy intake with no marked differences between different dietary manipulations used to change ED. In addition, low-ED diets promote moderate weight loss in long-term studies. In studies lasting longer than 6 months, weight loss was more than three times as great in individuals consuming diets both low in fat and high in fiber compared with diets only low in fat (-3.4 kg versus -1.0 kg). Combined, these studies suggest that diets low in fat and high in fiber may be the most effective low-ED diets for promoting weight loss. Further research is needed on the effects of dietary ED by changing water or sweetener content.

Body Composition↗