Biomedical subjects

S Perrey

Publications and source records attributed to S Perrey.

25 records · Page 2Linked to original sources

PubMed1999

Embryonic lethality and defective neural tube closure in mice lacking squalene synthase.

Squalene synthase (SS) catalyzes the reductive head-to-head condensation of two molecules of farnesyl diphosphate to form squalene, the first specific intermediate in the cholesterol biosynthetic pathway. We used gene targeting to knock out the mouse SS gene. The mice heterozygous for the mutation (SS+/-) were apparently normal. SS+/- mice showed 60% reduction in the hepatic mRNA levels of SS compared with SS+/+ mice. Consistently, the SS enzymatic activities were reduced by 50% in the liver and testis. Nevertheless, the hepatic cholesterol synthesis was not different between SS+/- and SS+/+ mice, and plasma lipoprotein profiles were not different irrespective of the presence of the low density lipoprotein receptor, indicating that SS is not a rate-limiting enzyme in the cholesterol biosynthetic pathway. The mice homozygous for the disrupted SS gene (SS-/-) were embryonic lethal around midgestation. E9.5-10.5 SS-/- embryos exhibited severe growth retardation and defective neural tube closure. The lethal phenotype was not rescued by supplementing the dams either with dietary squalene or cholesterol. We speculate that cholesterol is required for the development, particularly of the nervous system, and that the chorioallantoic circulatory system is not mature enough to supply the rapidly growing embryos with maternal cholesterol at this developmental stage.

Animals↗

PubMed1999

Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice.

Lipoprotein lipase (LPL) is known to play a crucial role in lipoprotein metabolism by hydrolyzing triglycerides; however its role in atherogenesis has yet to be determined. We have previously shown that low density lipoprotein receptor knockout mice overexpressing LPL are resistant to diet-induced atherosclerosis due to the suppression of remnant lipoproteins. Plasma lipoproteins and atherosclerosis of apolipoprotein (apo) E knockout mice which overexpress the human LPL transgene (LPL/APOEKO) were compared with those of control apoE knockout mice (APOEKO). On a normal chow diet, LPL/APOEKO mice showed marked suppression of the plasma triglyceride levels compared with APOEKO mice (54 vs. 182 mg/dl), but no significant changes in plasma cholesterol and apoB levels. Non-high density lipoproteins (HDL) from LPL/APOEKO mice had lower triglyceride content, a smaller size, and a more positive charge compared with those from APOEKO mice. Cholesterol, apoA-I, and apoA-IV were increased in HDL. Although both groups developed hypercholesterolemia to a comparable degree in response to an atherogenic diet, the LPL/APOEKO mice developed 2-fold smaller fatty streak lesions in the aortic sinus compared to the APOEKO mice. In conclusion, overproduction of LPL is protective against atherosclerosis even in the absence of apoE.

Animals↗

PubMed1998

External loading does not change energy cost and mechanics of rollerski skating.

The purpose of this study was to examine the effects of external loading on the energy cost and mechanics of roller ski skating. A group of 13 highly skilled male cross-country skiers roller skied at 19.0 ( SD 0.1) km x h(-1) without additional load and with loads of 6% and 12% body mass (mb). Oxygen uptake (VO2), knee and ankle joint kinematics, roller-ski electromyogram (EMG) of the vastus lateralis and gastrocnemius lateralis muscles, and roller ski velocity were recorded during the last 40 s of each 4-min period of roller skiing. One-way repeated measures ANOVA revealed that the VO2 expressed relative to total mass (mtot), joint kinetics, eccentric-to-concentric ratio of the integrated EMG, velocity changes within a cycle, and cycle rate did not change significantly with load. The subsequent analysis of the effect of load on each resistance opposing motion suggested that the power to sustain changes in translational kinetic energy, potential energy, and overcoming rolling resistance increased proportionately with the load. The lack of a significant change in VO2/mtot with external loading was associated with a lack of marked change in external mechanical power relative to mtot. The existence of an EMG signal during the eccentric phase prior to the thrust (concentric phase), as well as the lack of significant delay between the two phases, showed that a stretch-shortening cycle (SSC) occurs in roller ski skating. Taken together, the present results would suggest that external loading up to 12% mb does not increase storage and release of elastic energy of lower limb muscles during SSC in roller ski skating.

Adult↗

PubMed1998

Stretch-shortening cycle in roller ski skating: effects of technique.

The purposes of this study were 1) to examine the occurrence of the stretch-shortening cycle (SSC) in the three principal techniques of ski skating and 2) to test the hypothesis that differences in SSC behaviour may explain the choice of a technique when the grade is altered. Ten highly skilled male cross-country skiers roller skied at 5.3+/-0.1 m x s(-1) using the V1 skate (V1), V2-alternate (V2A), and V2 skate (V2) techniques. Knee and ankle joint kinematics, EMG of the vastus lateralis (VL) and gastrocnemius lateralis (GL) muscles, and roller ski velocity were recorded during the last 40 s of each bout of roller skiing. The existence of an EMG signal during the eccentric phase prior to the thrust, as well as the lack of significant delay between the two phases, showed that SSC occurs in the three techniques of roller ski skating with the exception of 50% of the subjects at the weak side knee with V1. The VL stretching velocity over the eccentric phase was higher (p < 0.005) with V2 and V2A than V1, indicating that less elastic energy was stored in the lower limbs extensor muscles with V1. This could partly explain why this technique is not used on flat terrains during races. However, no differences of average EMG activity or IEMG existed between techniques for either GL or VL during the concentric phase, suggesting that the theoretical advantage due to the SSC behaviour is minor in roller ski skating.

Adult↗

PubMed1996

Role of the low density lipoprotein (LDL) receptor pathway in the metabolism of chylomicron remnants. A quantitative study in knockout mice lacking the LDL receptor, apolipoprotein E, or both.

Two receptor pathways are thought to mediate the hepatic clearance of chylomicron remnants, (i) the low density lipoprotein receptor (LDLR) pathway and (ii) non-LDLR pathway. The current study was undertaken to quantitatively assess the contribution of each receptor pathway to hepatic catabolism of chylomicron remnants, by using mice that are deficient in apolipoprotein E (apoE) (apoE(-/-)), the LDLR (LDLR(-/-)), and both (apoE(-/-);LDLR(-/-)). Vitamin A fat tolerance tests showed that the area under the curves of the plasma excursions of retinyl ester in the LDLR(-/-), apoE(-/-), and apoE(-/-);LDLR(-/-) mice were 4, 12, and 12 times larger than those in wild-type mice. The retinyl ester accumulated in the plasma of the LDLR(-/-) mice was distributed in larger subfractions of triglyceride-rich lipoproteins, chylomicrons through very low density lipoprotein-C. These results indicate that the LDLR constitutes the major pathway for the clearance of retinyl ester. In support of this, agarose gel electrophoresis revealed that an oral fat load resulted in retention of chylomicrons in the LDLR(-/-) mice, which was not seen in wild-type mice. The observation that the apoE(-/-) mice showed larger retinyl ester excursion than LDLR(-/-) mice indicates that an apoE-dependent non-LDLR pathway is involved in the rest of the clearance of the retinyl ester. Together, we conclude that the LDLR pathway plays a significant role in the chylomicron remnant metabolism in mice fed a normal chow.

Animals↗

PubMed1995

Overexpression of human lipoprotein lipase protects diabetic transgenic mice from diabetic hypertriglyceridemia and hypercholesterolemia.

We investigated the role of the overexpression of lipoprotein lipase (LPL) in lipoprotein abnormalities in transgenic mice with streptozotocin-induced diabetes mellitus. Before the induction of diabetes, LPL activity was 4.6-fold in skeletal muscle and 2.0-fold higher in the heart in transgenic mice than in their nontransgenic littermates. LPL activity in skeletal muscles in diabetic nontransgenic mice and cardiac LPL activity in diabetic nontransgenic and transgenic mice were decreased. Body weights were similarly reduced, and no appreciable amount of adipose tissue was observed in diabetes in both groups. The plasma triglyceride level was lower in diabetic transgenic mice than in diabetic nontransgenic mice (33.2 +/- 22.5 versus 185.3 +/- 57.4 mg/dL). Induction of diabetes was associated with a significant increase in the plasma cholesterol level in nontransgenic mice (90.0 +/- 11.1 versus 163.9 +/- 39.3 mg/dL) but much less in transgenic mice. Our results indicate that overexpression of LPL in transgenic mice inhibited diabetes-associated hypertriglyceridemia and hypercholesterolemia but did not affect the loss of body weight induced by diabetes.

Animals↗

PubMed1995

A divide and conquer approach to multiple alignment.

We present a report on work in progress on a divide and conquer approach to multiple alignment. The algorithm makes use of the costs calculated from applying the standard dynamic programming scheme to all pairs of sequences. The resulting cost matrices for pairwise alignment give rise to secondary matrices containing the additional costs imposed by fixing the path through the dynamic programming graph at a particular vertex. Such a constraint corresponds to a division of the problem obtained by slicing both sequences between two particular positions, and aligning the two sequences on the left and the two sequences on the right, charging for gaps introduced at the slicing point. To obtain an estimate for the additional cost imposed by forcing the multiple alignment through a particular vertex in the whole hypercube, we will take a (weighted) sum of secondary costs over all pairwise projections of the division of the problem, as defined by this vertex, that is, by slicing all sequences at the points suggested by the vertex. We then use that partition of every single sequence under consideration into two 'halfs' which imposes a minimal (weighted) sum of pairwise additional costs, making sure that one of the sequences is divided somewhere close to its midpoint. Hence, each iteration can cut the problem size in half. As the enumeration of all possible partitions may restrict this approach to small-size problems, we eliminate futile partitions, and organize their enumeration in a way that starts with the most promising ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗