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Biomedical subjects

S Lévesque

Publications and source records attributed to S Lévesque.

11 recordsLinked to original sources
PubMed2002

Premutation and intermediate-size FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles.

We previously reported a 1:259 prevalence of female carriers of FMR1 premutation-size alleles (greater than 54 triplet repeats) in the general population. We now have screened 10 572 independent males from the same population for similar alleles using high-throughput Southern blotting. We identified 13 male carriers of an allele with more than 54 repeats. This corresponds to a prevalence of 1:813 males (95% confidence interval 1:527 to 1:1781). Haplotype analysis of four markers flanking the triplet array revealed that the prevalence of the major fragile X mutation-associated haplotype was increased among FMR1 alleles of 40-54 repeats. Although sequencing of highly unstable premutation alleles from fragile X families revealed only pure CGG tracts, this was not the case for alleles of similar size that were identified in males from the general population. Forty-eight out of forty-nine alleles of 40 or more triplets had one or two AGG interruptions. This observation, combined with the observation of the enrichment of major fragile X syndrome haplotypes in all alleles of this size, is evidence that the loss of an AGG interruption in the triplet repeat array is not necessary for expansion of normal alleles of 29-30 triplets to intermediate size. The loss of AGG interruptions thus appears to be a late event that leads to greatly increased instability and may be related to the haplotype background of specific FMR1 alleles.

Fragile X Messenger Ribonucleoprotein 1↗
PubMed2001

Novel bicyclic lactam inhibitors of thrombin: potency and selectivity optimization through P1 residues.

Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl interaction have been prepared. The binding energy lost after the removal of the activated carbonyl was recaptured through a series of modifications of the P1 residues of the bicyclic lactam inhibitors. Selected substituted compounds displayed useful pharmacological profiles both in vitro and in vivo.

Animals↗
PubMed2000

Sequencing of peach latent mosaic viroid variants from nine North American peach cultivars shows that this RNA folds into a complex secondary structure.

We sequenced 34 new peach latent mosaic viroid (PLMVd) variants isolated from nine different peach cultivars. This study provides the widest view of PLMVd diversity reported to date and includes the original characterization of North American variants, which cannot be differentiated from European sequences. PLMVd appears as a species in which each isolate is a complex mixture of RNAs. Analysis of base-pair covariations supports the hypothesis that PLMVd folds into a complex branched structure with the potential of including three new pseudoknots. The resulting "globular-like" structure is in contrast to the rod-like one adopted by most other viroids.

Base Sequence↗
PubMed1999

Lipid uptake across the wall of an expanded polytetrafluoroethylene vascular graft.

Previous studies have shown that vascular grafts were prone to inducing an atherosclerosis-like phenomenon, thus possibly jeopardizing their performance. Furthermore, lipid retention, observed in most synthetic arterial prostheses explanted from humans, appears to have an important role in the progression of this atherosclerotic process, therefore hindering the healing process and neo-intima formation of these synthetic conduits. The current study examined lipid concentration profiles across prosthesis membranes exposed to lipid dispersion under various transmural pressures, flow rates, and durations of exposure. It was demonstrated that the lipids rapidly permeated the prosthesis membrane, as lipid advection increased to a maximum, then steadily decreased until the membrane became completely impermeable to the fluid. The concentration of lipids within the grafts was monitored using FT-IR microspectroscopy, then correlated as a function of time in order to evaluate the mass transfer coefficients and lipid saturation concentration. Lipid sorption, as a function of time, was described by a mechanism taking into account two first-order kinetic models. The lipids were first rapidly adsorbed onto the Teflon(R), potentially influenced by the strong affinity of these lipids for the highly hydrophobic polytetrafluoroethylene polymer. This affinity then enhanced the germination of the lipid deposits that filled in the prosthesis wall. For lipid retention as a function of the transmural pressure and flow rate, no clear tendency was established.

Bioprosthesis↗
PubMed1998

Potent bicyclic lactam inhibitors of thrombin: Part I: P3 modifications.

Peptidomimetic inhibitors of general structure 1 have been prepared. Optimization of the binding affinities of these compounds through variation of the P3 hydrophobic residue is described. Selected substituted bicylic lactams displayed interesting pharmacological profiles both in vitro and in vivo.

Animals↗
PubMed1996

Effects of dietary gamma-linolenic acid and prenatal ethanol on mouse brain and behavior.

Pregnant B6D2F mice were treated with ethanol (25% Kcal) from days 5-17 of gestation. The diet was supplemented with either 18 : 2n-6 [linoleic acid (LA)] or 18 : 3n-6 [gamma-linolenic acid (GLA)] throughout the study. Ethanol reduced 20 and 22 carbon n-6 and n-3 fatty acids in the brains of adult offspring. Feeding of GLA, compared with LA, increased levels of 20 : 3n-6 and 22 : 4n-6, but reduced 22 : 6n-3, particularly in the offspring of dams administered ethanol during gestation; adult brain weight was also lower in this group. Ethanol reduced the number of viable litters and adult body weight, and GLA reduced birth weight. Neither prenatal ethanol nor GLA affected open-field activity in adult males, nor did either treatment have an effect on the duration of immobility in the forced swimming test. However, GLA did affect circadian activity by increasing running wheel activity during the dark cycle, and decreasing it slightly during the light cycle. These results do not support a beneficial effect of GLA in preventing the developmental effects of ethanol; we suggest caution in the administration of high doses of GLA with ethanol during pregnancy.

Adrenergic Uptake Inhibitors↗
PubMed1994

The effects of dietary fatty acid composition combined with environmental enrichment on brain and behavior in mice.

In this study we investigated the effects of dietary fatty acid (FA) composition combined with postweaning environmental enrichment on brain fatty acid composition and behavior in mice. There were three dietary conditions: a saturated fat group deficient in essential fatty acids, a group deficient in n-3 fatty acids only, and a control group containing both n-3 and n-6 fatty acids in a ratio of 0.27. Animals were fed these diets during pregnancy and lactation and after weaning. Brain fatty acid composition was determined on days 1, 9, 17 and 25 after birth and in adult animals at 3 months. At weaning two females from each litter were assigned randomly to either an enriched or standard environmental condition. After six weeks in these environments they were tested in the Morris water maze and open field. Adult percentages of 22:6n-3 were present in the brain within the first week after birth. These values were reduced by 50% in the n-3 deficient diet and by 80% in the saturated fat diet; adult animals on the saturated fat diet were also severely retarded in growth. Animals fed the saturated fat diet were initially slightly slower in locating the hidden platform in the Morris maze relative to the control group, but this was not apparent in the reversal learning phase; a cued learning task using a visible platform indicated that these effects did not appear to be related to differences in motor or motivational capacities. The n-3 deficient group did not differ from either the saturated fat group or the controls. All dietary groups showed beneficial effects of environmental enrichment in decreasing their latency to locate the hidden platform, and these effects appeared to be partially independent of the increased swimming speed of the enriched animals. Enriched animals in all groups showed less rearing activity in the open field and spent more time stationary; the animals fed saturated fat reared less and travelled shorter distances more slowly. In all cases the effects of diet and environment were additive, thereby providing little support for the hypothesis that dietary fatty acid composition would affect the animals' capacity to benefit from the functional effects of environmental enrichment.

Animals↗
PubMed1994

Brain and behavioral effects of dietary n-3 deficiency in mice: a three generational study.

Feeding mice a diet deficient in n-3 fatty acids for three generations resulted in a 53% decrease in docosahexaenoic acid (DHA, 22:6n-3) in the brain. Maternal pup retrieval and social learning of a food preference are both tasks based on olfactory function. All dams made contact more readily with pups of their own dietary group, and animals of both dietary groups demonstrated the ability to learn a food preference through exposure to a conspecific that had previously eaten the food. Both groups showed similar ability to learn the location of the hidden platform in the Morris water maze, while the n-3 deficient animals were marginally faster in locating the platform on the cued trial. They were also more active when tested in the open field. While they did not differ in their duration of immobility in a forced swimming test, the deficient animals did have longer paw-lick latencies on a hot plate. Thus, in this study a significant reduction in brain n-3 fatty acid composition, while associated with some indications of change in emotional reactivity, did not impair olfactory function or learning of either a latent or spatial nature.

Animals↗
PubMed1994

Effects of different weight loss treatments on weight cycling and metabolic measures in male mice.

The effects of different weight loss treatments on subsequent weight regain, food efficiency, body composition, metabolic rate, and corticosterone concentrations were investigated in obese male B6D2F1 mice. Treatment groups were: restricted (RES, food restricted); exercised (EX, treadmill exercised); sham control (SHAM, treadmill exposure, not exercised); lab chow control (LC). Weight loss, regardless of treatment, resulted in increased rate of weight regain and food efficiency. There were significant alterations in body composition after a cycle of weight gain/loss. These results demonstrate that a cycle of weight gain/loss causes increased food efficiency and concomitant alterations in body composition in male mice.

Animals↗
PubMedDate not supplied

Effects of environmental enrichment on cortical depth and Morris-maze performance in B6D2F2 mice exposed prenatally to ethanol.

Pregnant mice were fed a liquid diet with 25% of the calories as ethanol from day 5 to 17 of gestation; controls received equivalent amounts of diet with maltose-dextrin substituted isocalorically for the ethanol. Two male weanlings from each litter were assigned randomly to an enriched or isolated environmental condition. After 6 weeks in these environments measures of brain growth were obtained, including thickness of frontal, parietal, and occipital cortex (study 1), or their behavioral capabilities were assessed in a Morris water maze (study 2). Ethanol decreased birth weight (both studies), postweaning body weight (study 2), and brain weight (study 1), while the enriched animals in both studies were heavier. Ethanol decreased the thickness of the occipital cortex only. All groups demonstrated learning by showing a decrease in latency to locate the hidden platform over the 5 days of testing; this was supported by their spending most time in the target quadrant during the probe trial. The latencies of the enriched animals were shorter than the isolated; covariance analysis indicated that this was not due solely to their faster swimming speed.

Animals↗