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BACKGROUND: Serum lipid responses to dietary modification are partly determined by genetic factors. OBJECTIVE: We tested whether plasma lipoprotein and lipid responsiveness to a modification in the dietary ratio of polyunsaturated to saturated fatty acids (P:S) is influenced by the peroxisome proliferator-activated receptor alpha (PPARalpha) Leu162Val polymorphism in healthy men. DESIGN: Ten carriers of the V162 allele and 10 L162 homozygotes were matched according to age and body mass index (BMI). During the protocol, all subjects followed the National Cholesterol Education Program Step I diet, but intake of saturated and polyunsaturated fatty acids was adjusted to obtain a P:S of 0.3 for the first 4-wk period (low-P:S diet) and a P:S of 1.0 for the next 4-wk period (high-P:S diet). RESULTS: At screening, the PPARalpha Leu162Val polymorphism was not associated with anthropometric indexes or plasma lipoprotein and lipid concentrations. After the high-P:S diet, a significant gene-by-diet interaction was observed for changes in plasma total cholesterol, apolipoprotein (apo) A-I, and cholesterol concentrations in small LDL particles (P

BACKGROUND: Obesity is frequently associated with eating disorders, and evidence indicates that both conditions are influenced by genetic factors. However, little is known about the genes influencing eating behaviors. OBJECTIVE: The objective was to identify genes associated with eating behaviors. DESIGN: Three eating behaviors were assessed in 660 adults from the Quebec Family Study with the use of the Three-Factor Eating Questionnaire. A genome-wide scan was conducted with a total of 471 genetic markers spanning the 22 autosomes to identify quantitative trait loci for eating behaviors. Body composition and macronutrient and energy intakes were also measured. RESULTS: Four quantitative trait loci were identified for disinhibition and susceptibility to hunger. Of these, the best evidence of linkage was found between a locus on chromosome 15q24-q25 and disinhibition (P <0.0058) and susceptibility to hunger (P <0.0001). After fine-mapping, the peak linkage was found between markers D15S206 and D15S201 surrounding the neuromedin beta (NMB) gene. A missense mutation (p.P73T) located within the NMB gene showed significant associations with eating behaviors and obesity phenotypes. The T73T homozygotes were 2 times as likely to exhibit high levels of disinhibition (odds ratio: 1.8; 95% CI: 1.07, 2.89; P=0.03) and susceptibility to hunger (odds ratio: 1.9; 95% CI: 1.15, 3.06; P=0.01) as were the P73 allele carriers. Six-year follow-up data showed that the amount of body fat gain over time in T73T subjects was >2 times that than in P73P homozygotes (3.6 compared with 1.5 kg; P <0.05). CONCLUSION: The results suggest that NMB is a very strong candidate gene of eating behaviors and predisposition to obesity. Copyright © 2004 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

The reason for the 3- to 4-h delay between a rise in plasma free fatty acid (FFA) levels and the development of insulin resistance remains unknown. In the current study, we have tested the hypothesis that the delay may be caused by the need for plasma FFAs to first enter muscle cells and to be re-esterified there before causing insulin resistance. To this end, we have determined intramyocellular triglyceride (IMCL-TG) content with proton nuclear magnetic resonance ((1)H-NMR) spectroscopy in healthy volunteers before and 4 h after lowering of plasma FFAs (with euglycemic-hyperinsulinemic clamping) or after increasing plasma FFAs (with lipid plus heparin infusions). Increasing plasma FFAs (from 516 to 1,207 micromol/l or from 464 to 1,857 micromol/l, respectively) was associated with acute increases in IMCL-TG from 100 to 109 +/- 5% (P < 0.05) or to 133 +/- 11% (P < 0.01), respectively, and with a significant increase in insulin resistance (P < 0.05 after 3.5 h). Lowering of plasma FFAs from 560 to 41 micromol/l was associated with a tendency for IMCL-TG to decrease (from 100 to 95 +/- 3%). Changes in plasma FFAs correlated linearly with IMCL-TG (r = 0.74, P < 0.003). The demonstration that acute changes in plasma FFAs were accompanied by corresponding changes in IMCL-TG and with the development of insulin resistance, taken together with previous reports of a close correlation between IMCL-TG and insulin resistance, supported the notion that accumulation of IMCL-TG is a step in the development of FFA-induced insulin resistance. [ABSTRACT FROM AUTHOR]

To identify chromosomal regions harboring genes influencing the propensity to store fat in the abdominal area, a genome-wide scan for abdominal fat was performed in the Quebec Family Study. Cross-sectional areas of the amount of abdominal total fat (ATF) and abdominal visceral fat (AVF) were assessed from a computed tomography scan taken at L4-L5 in 521 adult subjects. Abdominal subcutaneous fat (ASF) was obtained by computing the difference between ATF and AVF. The abdominal fat phenotypes were adjusted for age and sex effects as well as for total amount of body fat (kilogram of fat mass) measured by underwater weighing, and the adjusted phenotypes were used in linkage analyses. A total of 293 microsatellite markers spanning the 22 autosomal chromosomes were typed. The average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were available for single-point (SIBPAL) and 156 families for multipoint variance components (SEGPATH) linkage analyses. The strongest evidence of linkage was found on chromosome 12q24.3 between marker D12S2078 and ASF (logarithm of odds [LOD] = 2.88). Another marker (D12S1045) located within 2 cM of D12S2078 also provided evidence of sib-pair linkage with ASF (P = 0.019), ATF (P = 0.015), and AVF (P = 0.0007). Other regions with highly suggestive evidence (P < 0.0023 or LOD > or =1.75) of multipoint linkage and evidence (P < 0.05) of single-point linkage, all for ASF, included chromosomes 1p11.2, 4q32.1, 9q22.1, 12q22-q23, and 17q21.1. Three of these loci (1p11.2, 9q22.1, and 17q21.1) are close to genes involved in the regulation of sex steroid levels, whereas two others (4q32.1 and 17q21.1) are in the proximity of genes involved in the regulation of food intake. This first genome-wide scan for abdominal fat assessed by computed tomography indicates that there may be several loci determining the propensity to store fat in the abdominal depot and that some of these loci may influence the development of diabetes in obese subjects. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We have previously shown that patients with restricting type anorexia nervosa (AN-R) have low plasma lipid levels, which increase with refeeding. In this study, we investigated plasma lipid levels in patients with eating disorders, distinguishing between individuals with bulimia nervosa (BN) and anorexia nervosa of the binge eating/purging type (AN-B). METHODS: We examined the fasting lipid levels in individuals with BN (n = 10) and AN-B (n = 9), and compared these findings with a group of age-matched normal weight healthy controls (C) (n = 10). RESULTS: The AN-B group had significantly higher concentrations of total plasma cholesterol, apolipoprotein (apo) B, apoA1, and low-density lipoprotein (LDL)-cholesterol than both control and BN groups (p < .05). The AN-B group also had higher plasma triglycerides and intermediate-density lipoprotein (IDL)-apo B levels (p < .05) than controls. DISCUSSION: In conclusion, the issue of hyperlipidemia in patients with eating disorders is a complex one and this study, taken together with the findings of our previous study, demonstrates the importance of carefully distinguishing between the major types of eating disorders (AN-R, BN, and AN-B) when examining plasma lipid levels. [ABSTRACT FROM AUTHOR]

Spleen cells harvested from mice infected intraperitoneally with M. lepraemurium 11-17 weeks prior lo harvest acquired the capacity to inhibit concanavalin A (Con A) induced proliferation of normal spleen cells when precultured for up to 24 h in mitogen-free medium. The in vitro induced suppressor activity correlated with the length of the preculture period, the time post-infection and the infecting dose. These findings were interpreted as an indication that suppressor cell precursors accumulated in the spleen of infected mice during the early phase of the disease. The interaction of infection dependent adherent suppressor cell precursors and infection-independent, non-adherent regulatory cells is necessary for the suppressor activity to develop. Both the cells which transmit the inductive signal and the precursor cells which mature into active suppressor cells are radiosensitive, whereas suppressor activity itself is a function of radioresistant adherent cells. Preculture of cells for a short period before they were cocultured with Con A-stimulated normal spleen cells, allowed the detection of suppressor cells before they were deleterious to the infected host and also turned out to be a relevant in vitro model for characterization of suppressor cell development during M. lepraemurium infection. [ABSTRACT FROM AUTHOR]

The production of interleukin-2 (IL-2) by Con A-activated spleen cells (SC) progressively declined and reached negligible values during the course of infection of C57BL/6 mice with Mycobacterium lepraemurium. In addition, the capacity of cultured SC to utilize IL-2 was highly reduced, as demonstrated by the accumulation of IL-2 activity in culture supernatants at 48 and 72 h after Con A activation. The depressed IL-2 utilization started to be observed about 1 to 2 weeks prior to the onset of the depressed IL-2 production and was not reversed by the addition of exogenous IL-2; thus implying that a lack of IL-2 utilization rather than a lack of IL-2 production could be directly responsible for the inhibition of T-cell proliferative responses to Con A in SC cultures of infected mice. The utilization of IL-2 was found to be down-regulated, at least in part, by splenic suppressor cells since, in mixed-culture experiments, SC from infected mice actively depressed the capacity of normal splenocytes to consume IL-2. Finally, the depressed IL-2 utilization would result from a 2- to 3-fold reduction of either or both the density of high-affinity IL-2 receptors and their affinity for IL-2. [ABSTRACT FROM AUTHOR]

The impairment of cellular immunity in mice infected with Mycobacterium lepraemurium was shown to correlate with the development of suppressor cells. We have previously reported that before suppressor activity is detectable in freshly harvested cell suspensions, suppressor cell precursors accumulate in the spleen of infected mice. Upon overnight culture in the presence of a regulatory cell subset, these precursor cells acquire the capacity to impair the concanavalin A (Con A)-induced proliferation of normal spleen cells. The purpose of this study was to determine the phenotype of the cells involved in this phenomenon. This was done by following the development of suppressor activity in spleen cell suspensions depleted of defined cell subsets of the adherent or the non-adherent cell fractions with selected MoAbs and immunomagnetic beads or by in vivo treatment. Our results indicate [hat the acquisition of suppressor activity requires the interaction of la+CDllb+FcγR+lgG- asialo GMl- adherent cells with Thy-1- CD4-CD8-lgG-Ia-asialo GMl-FcγR+CD1lb+ non-adherent cells. It is also shown that the development of suppressor activity is impaired by preventing cell cell contact between these two cell subsets through coculture in Transwell chambers'. These observations support the conclusion that the in vitro acquisition of suppressor activity is a consequence of the maturation of suppressor cell precursors of the monocytic lineage induced by a receptor-ligand type interaction with a non-adherent cell subset that is clearly distinct from mature T. B and natural killer (NK) cells. [ABSTRACT FROM AUTHOR]

Handheld XRF (HHXRF) is an analytical tool often used for chemical characterization, environmental analysis or mineral exploration. However, few studies deal with its potential use as a quality control instrument within an industrial context, such as mineral processing or transformation. Quartz is an ideal test material; it is a simple matrix allowing for better isolation of different parameters including detection limits, precision and accuracy, instrumental drift, surface representativeness and sample preparation. In this study, we determined that the specific limit of detection was lower than 70 μg/g for TiO 2 , Fe 2 O 3 and CaO. The HHXRF analyzed pressed pellets of matrix-matched reference materials. Estimates for TiO 2 , Fe 2 O 3 and CaO were similar to certified values, while estimates for low concentration light elements (Al 2 O 3 and MgO) were less accurate. For faster and higher throughput, as often required in an industrial context, HHXRF can be used directly on mineral sample without sample preparation. Five in-situ determinations on a 10-cm-sided block of quartz, produced an accuracy acceptable for industrial needs. However, in-situ determinations are limited by the flatness of the analytical surface, and minute accessory phases can induce some erratic results. Our tests suggest, however, that HHXRF is generally suitable for the control quality of quartz in an industrial context. [ABSTRACT FROM AUTHOR]

Abstract Background The identification of differentially expressed genes (DEGs) from Affymetrix GeneChips arrays is currently done by first computing expression levels from the low-level probe intensities, then deriving significance by comparing these expression levels between conditions. The proposed PL-LM (Probe-Level Linear Model) method implements a linear model applied on the probe-level data to directly estimate the treatment effect. A finite mixture of Gaussian components is then used to identify DEGs using the coefficients estimated by the linear model. This approach can readily be applied to experimental design with or without replication. Results On a wholly defined dataset, the PL-LM method was able to identify 75% of the differentially expressed genes within 10% of false positives. This accuracy was achieved both using the three replicates per conditions available in the dataset and using only one replicate per condition. Conclusion The method achieves, on this dataset, a higher accuracy than the best set of tools identified by the authors of the dataset, and does so using only one replicate per condition.

Abstract Objective To evaluate the validity (study 1) and the reproducibility (study 2) of an interviewer-administered food frequency questionnaire (FFQ). Method The FFQ was designed at Laval University and contains 91 items and 33 subquestions. Study 1: The FFQ was compared against a 3-day food record (2 week-days and 1 weekend-day), at week 0, 6 and 12 of a nutritional intervention. Study 2: In order to evaluate the reproducibility of the FFQ, 2 registered dietitians administered the FFQ 4-weeks apart among subjects who were not part of the nutritional intervention. Results Study 1: Mean values for intake of most nutrients assessed by the FFQ and by the 3-day food record were not statistically different. Energy-adjusted correlation coefficients for major macronutrients ranged from 0.36 for proteins to 0.60 for carbohydrates (p ≤ 0.01). Agreement analysis revealed that on average, 35% of the subjects were classified in the same quartile when nutrients were assessed by either the 3-day food record or the FFQ. Study 2: Significant associations were observed between dietary measurements derived from the two FFQs administered 4 weeks apart. Correlation coefficients for the reproducibility of macronutrients ranged from 0.66 for carbohydrates to 0.83 for lipids after energy adjustment. On average, 46% of the subjects were classified in the same quartile when nutrient intakes were assessed by either FFQ. Conclusion These data indicated that the FFQ developed has a good validity and is reproducible.

"The aim of the present study was to assess the impact of a ""Health-at-every-size"" (HAES) intervention on psychological variables and body weight the weight-preoccupied overweight/obese women. Those women were randomized into three groups (1) HAES, (2) social support (SS), (3) waiting-list (WL), and were tested at baseline, post-treatment and six-month and one-year follow-ups. All participants presented significant psychological improvement no matter if they received the HAES intervention or not. However, even if during the intervention, the three groups showed improvements, during the follow up, the HAES group continued to improve while the other groups did not, even sometimes experiencing some deterioration. Furthermore, in the HAES group only, participant's weight maintenance 12 months after the intervention was related to their psychological improvement (quality of life, body dissatisfaction, and binge eating) during the intervention. Thus, even if, in the short-term, our study did not show distinctive effects of the HAES intervention compared to SS and WL on all variables, in the long-term, HAES group seemed to present a different trajectory as psychological variables and body weight are maintained or continue to improve, which was not the case in other groups. These differential long-term effects still need to be documented and further empirically demonstrated." [ABSTRACT FROM AUTHOR]