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Biomedical subjects

M Lefevre

Publications and source records attributed to M Lefevre.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential response to low-fat diet between low and normal HDL-cholesterol subjects.

Heart attacks frequently occur in normolipidemic subjects with low concentration of high density lipoproteins (</=35 mg/dL). A low-fat diet is generally recommended to patients with coronary heart disease. A low-fat diet decreases both low density (LDL) and high density lipoproteins (HDL). We have shown that on an Average American Diet, subjects with different HDL-cholesterol (HDL-C) levels have different HDL subpopulation profiles. In low HDL-C subjects (</=35 mg/dL), the apoA-I-only subpopulation alpha(1) is significantly decreased compared to individuals with normal HDL-C levels (>35 mg/dL). We hypothesized that as subjects with low HDL-C already have low HDL concentrations, the major decrease of HDL-C will occur in subjects with normal HDL-C when a low-fat diet is consumed. Normolipidemic male subjects consumed three diets differing in total fat and saturated fat composition (AAD: 37%, Step-1: 28%, Step-2: 24% total fat) for 6 weeks in a three-period double-blind randomized crossover design. Plasma lipids and apolipoproteins were determined and changes in distribution of HDL subpopulations were evaluated. As a result of a low-fat diet, low HDL-C individuals slightly decreased their HDL-C, but substantially decreased their LDL-C resulting in a significant improvement in the LDL-C/HDL-C ratio. However, subjects with normal HDL-C levels decreased both their LDL-C and HDL-C resulting in an unchanged LDL-C/HDL-C ratio. We also observed significant differences in response to low-fat diets in HDL-C and alpha(1) concentrations between low and normal HDL-C subjects. In the normal HDL-C group, consumption of a low-fat diet also resulted in redistribution of apoA-I-containing HDL subpopulations, indicated by a decrease in the large apoA-I-only alpha(1) subpopulation. These data demonstrate that male subjects with low HDL-C respond to a low-fat diet differently than individuals with normal HDL-C.

Adult↗
PubMed2000

[Osler endocarditis of a ventricular septal defect in a 21-month old child].

The authors report a case of streptococcus mitis endocarditis of a ventricular septal defect in a 21 months old girl admitted for necrotic purpura of the lower limbs and a history of general ill health and pyrexia for two months. The severity of this case of endocarditis was illustrated by the importance of the vasculitis, the biological signs of infection (disseminated intravascular coagulation), and the size of the vegetation. The vegetation extended from the tricuspid valve as far as the pulmonary orifice which was partially obstructed, causing signs of right ventricular failure. The portal of entry was not found. Surgical ablation of the vegetation with tricuspid valvuloplasty was necessary after 48 hours of antibiotherapy. The outcome after one year's follow-up is good. The diagnosis of bacterial endocarditis must be considered even in very young children, especially those with congenital heart disease, and, in particular, ventricular septal defect.

Echocardiography↗
PubMed1999

HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects.

BACKGROUND: Little information is available about HDL subpopulations during dietary changes. OBJECTIVE: The objective was to investigate the effect of reductions in total and saturated fat intakes on HDL subpopulations. DESIGN: Multiracial, young and elderly men and women (n = 103) participating in the double-blind, randomized DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activities) Study consumed 3 different diets, each for 8 wk: an average American diet (AAD: 34.3% total fat,15.0% saturated fat), the American Heart Association Step I diet (28.6% total fat, 9.0% saturated fat), and a diet low in saturated fat (25.3% total fat, 6.1% saturated fat). RESULTS: HDL(2)-cholesterol concentrations, by differential precipitation, decreased (P < 0.001) in a stepwise fashion after the reduction of total and saturated fat: 0.58 +/- 0.21, 0.53 +/- 0.19, and 0.48 +/- 0.18 mmol/L with the AAD, Step I, and low-fat diets, respectively. HDL(3) cholesterol decreased (P < 0.01) less: 0.76 +/- 0.13, 0.73 +/- 0.12, and 0.72 +/- 0.11 mmol/L with the AAD, Step I, and low-fat diets, respectively. As measured by nondenaturing gradient gel electrophoresis, the larger-size HDL(2b) subpopulation decreased with the reduction in dietary fat, and a corresponding relative increase was seen for the smaller-sized HDL(3a, 3b), and (3c) subpopulations (P < 0.01). HDL(2)-cholesterol concentrations correlated negatively with serum triacylglycerol concentrations on all 3 diets: r = -0.46, -0.37, and -0.45 with the AAD, Step I, and low-fat diets, respectively (P < 0.0001). A similar negative correlation was seen for HDL(2b), whereas HDL(3a, 3b), and (3c) correlated positively with triacylglycerol concentrations. Diet-induced changes in serum triacylglycerol were negatively correlated with changes in HDL(2) and HDL(2b) cholesterol. CONCLUSIONS: A reduction in dietary total and saturated fat decreased both large (HDL(2) and HDL(2b)) and small, dense HDL subpopulations, although decreases in HDL(2) and HDL(2b) were most pronounced.

Adult↗
PubMed1998

ELISA detection of restriction site polymorphisms in the pig ryanodine receptor locus.

We compare two strategies for ELISA detection of restriction site polymorphisms (EDRSP) that are suitable for high-throughput genotyping of the pig ryanodine receptor point mutation (RYR1(hal)). In both procedures, target DNA is amplified by PCR with one primer that is 5' biotinylated and a second primer that is 5' fluoresceinylated. PCR products are captured in duplicate wells on a streptavidin-coated, 96-well plate. The duplicates may be treated in two ways. In a single restriction enzyme assay, one duplicate is exposed to a restriction enzyme that cuts one allele specifically, and the second duplicate is exposed to no restriction enzyme. In a dual restriction enzyme assay, the second replicate is exposed to a second restriction enzyme that cuts the alternate allele specifically. Thereafter, the two procedures are similar; anti-fluorescein antibodies conjugated to peroxidase are allowed to bind to the fluoresceinylated ends, the plate is washed, and a substrate is converted to a colored end product. The ratio of the absorbances in the two wells is used to classify subjects by genotype. When the dual restriction enzyme assay is run, three genotype groups are easily distinguishable. When the single restriction enzyme assay is run, heterozygotes generate values that may overlap with those of the homozygotes that are not cut by the restriction enzyme. Dual restriction enzyme assays are more accurate than single restriction enzyme assays; however, single restriction enzyme assays are sufficient for identifying pigs that carry RYR1(hal).

Animals↗
PubMed1998

Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1.

Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All meals and snacks, except Saturday dinner, were prepared and served by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximately 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant in most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced. In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population.

Adult↗
PubMed1997

Normolipidemic subjects with low HDL cholesterol levels have altered HDL subpopulations.

Epidemiological studies have established that plasma concentration of HDL is inversely correlated with the risk of coronary heart disease, even in the absence of increased LDL cholesterol levels. We postulate that specific HDL subpopulations may be responsible for antiatherogenic properties of HDL. HDL subpopulations were quantitated by two-dimensional gel electrophoresis in 79 normolipidemic healthy male subjects. To eliminate the influence of diet, volunteers consumed an average American diet for 6 weeks. After the diet period, subjects were stratified according to their HDL cholesterol (HDL-C) levels to low HDL-C < 0.91 mmol/L (< 35 mg/dL), medium > 0.91 < 1.30 mmol/L (> 35 < 50 mg/dL), and high > or = 1.30 mmol/L (> or = 50 mg/dL) groups. Plasma triglycerides and insulin levels were in the normal range, but subjects with low HDL-C levels had higher concentrations of plasma triglycerides and insulin than subjects with medium or high HDL-C concentrations. The absolute concentration (mg/dL) of apoA-I in the largest alpha-migrating HDL subpopulation (alpha 1) was (P < .01) lower in the low HDL-C subjects compared with the medium and high HDL-C groups. The relative concentration (percent distribution) of apoA-I was decreased (P < .01) in alpha 1 and increased (P < .01) in alpha 3 subpopulations. A positive correlation between HDL-C and alpha 1 (P < .001) and a negative correlation between HDL-C and alpha 3 were observed. The inverse correlation of apoA-I distribution (relative concentration) between alpha 1 and alpha 3 suggests an interconversion of alpha 1 and alpha 3 subpopulations, possibly by cholesteryl ester transfer protein. Pre-beta subpopulations showed an inverse trend with HDL-C, while the pre-alpha subpopulation behaved similarly to the alpha-migrating subpopulation. Colocalization of apoA-I and apoA-II particles in the different HDL subpopulations demonstrated that alpha 1, pre-beta 1, and pre-beta 2 subpopulations are apoA-I-only particles rather than apoA-I:A-II particles.

Adult↗
PubMed1997

ApoE genotype does not predict lipid response to changes in dietary saturated fatty acids in a heterogeneous normolipidemic population. The DELTA Research Group. Dietary Effects on Lipoproteins and Thrombogenic Activity.

Recent studies have suggested that variations in apoE genotypes may influence the magnitude of plasma lipid changes in response to dietary interventions. We examined the ability of apoE genotype to predict plasma lipid response to reductions in percent of calories from total fat (TF) and saturated fat (SF) in a normolipidemic study population (n = 103) heterogeneous with respect to age, gender, race, and menopausal status. Three diets, an average American diet (34.3% TF, 15.0% SF), an AHA Step 1 diet (28.6% TF, 9.0% SF), and a low saturated fat (Low-Sat) diet (25.3% TF, 6.1% SF) were each fed for a period of 8 weeks in a three-way crossover design. Cholesterol was kept constant at 275 mg/d; monounsaturated and polyunsaturated fat were kept constant at approximately 13% and 6.5% of calories, respectively. Fasting lipid levels were measured during each of the final 4 weeks of each diet period. Participants were grouped by apoE genotype: E2 (E2/2, E2/3, E2/4); E3 (E3/3); E4 (E3/4, E4/4). Relative to the average American diet, both the Step 1 and Low-Sat diets significantly reduced total cholesterol, LDL cholesterol, and HDL cholesterol in all three apoE genotype groups. No evidence of a significant diet by genotype interaction, however, could be identified for any of the measured lipid and lipoprotein end points. Additional analysis of the data within individual population subgroup (men and women, blacks and whites) likewise provided no evidence of a significant diet by genotype interaction. Thus, in a heterogeneous, normolipidemic study population, apoE genotype does not predict the magnitude of lipid response to reductions in dietary saturated fat.

Adult↗
PubMed1997

[Juvenile GM2 gangliosidosis with progressive spinal muscular atrophy onset].

GM2 gangliosidosis are caused by a beta-hexosaminidase A enzyme deficiency. Mutations in the gene leaving residual enzyme activity give rise to juvenile and adult forms of the disease which have a great clinical heterogeneity. We report three cases which have been considered for some time as Kugelberg-Welander disease. beta-hexosaminidase A was determined with the sulfated synthetic substrate, 4-méthylumbelliferyl-N-acetylglucosamine 6-sulfate (4-MUGS), which allowed the diagnosis. Two of these cases from one family had normal values of hexosaminidase A in serum as found in the B1 variant. Compound mutations were detected. The B1 variants had a classical B1 mutation (G533-->A) and a new mutation located on exon 11. The patient of the second family had the classical mutation of adult GM2 gangliosidosis (Gly269-->Ser) and a new mutation on exon 1, at the initiation codon.

Adult↗
PubMed1995

A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype.

We describe two adult siblings who had had mild GM2 gangliosidosis since childhood. They presented with spinal muscular atrophy and dysarthria, and one sibling also had mental disturbances. Laboratory studies established the diagnosis of the B1 variant of GM2 gangliosidosis, because the hexosaminidase (Hex) A deficiency was not present upon testing with the unsulfated synthetic substrate 4-methylumbelliferyl N-acetylglucosaminide. HEXA gene analysis proved that the patients are compound heterozygotes for the previously identified G533-->A mutation and for a new mutation, G1171-->A, at exon 11. This new mutation affects a conserved amino acid and results in a Val-->Met substitution at position 391 of the HEXA gene. Full sequence of the alpha-subunit cDNA of Hex A revealed no other mutation. Assays for Hex A activities in patients suspected of having GM2 gangliosidosis should be performed with the sulfated substrate 4-methylumbelliferyl N-acetylglucosamine 6-sulfate.

Adult↗
PubMed1993

Comparison of the lipid and apolipoprotein composition of skeletal muscle and peripheral lymph in control dogs and in dogs fed a high fat, high cholesterol, hypothyroid-inducing diet.

Most studies of peripheral interstitial fluid lipoprotein composition have been made on interstitial fluid-derived from skin and connective tissue. We developed techniques which allowed simultaneous comparison of lymph (a model of interstitial fluid) from skeletal muscle and skin in control (C) and cholesterol-fed (CF) dogs. Lipoprotein fractions were separated by ultracentrifugation. Skeletal muscle interstitial fluid HDL concentrations were approximately twice those of skin. However, the concentration of VLDL-LDL particles was similar in both interstitial spaces. HDL particles from both microvascular beds showed evidence of extensive remodelling when compared to plasma HDL from the same animal. Relative to apo A-I, skeletal muscle HDL was enriched in free cholesterol and apo E (C and CF dogs) and apo A-IV (CF dogs). Skin-derived HDL was consistently enriched in free cholesterol, apo E and A-IV in both C and CF dogs. These studies indicate that similar remodeling of plasma HDL occurs in widely different tissues which together constitute approximately 70% of the total interstitial space. The relatively high concentration of plasma-derived and remodeled HDL within the interstitial space of skeletal muscle is consistent with that tissue's importance in reverse cholesterol transport.

Animals↗
PubMed1993

Chronic peripheral lymphatic cannulation in the dog.

Peripheral lymph collected acutely has been commonly sampled as representative of non-visceral interstitial fluid. By developing a prenodal lymphatic-lymphatic (L-L) shunt, we were able to collect peripheral lymph for 3-5 days in unanesthetized dogs. The L-L shunt was constructed entirely of medical grade silicone rubber tubing designed with a slip of coupling which allowed the shunt to be disconnected for lymph collection and reconnected at night. Average peripheral lymph flow (4.9 ml/hr leg) in unanesthetized dogs was almost twice the flow rate previously observed in anesthetized dogs. The average lymph/plasma total protein concentration ratio (0.16), however, was similar to that previously found in anesthetized dogs. Lymph protein concentration fell with the collection during the day and became more concentrated at night. Lymph flow did not change greatly during daytime collection. Average peripheral lymph collection volume was greater than 200 ml/dog. The L-L shunt allows collection of prenodal-lymph in experiments where unanesthetized dogs are required (e.g., feeding studies). They also are useful when multiple protocols are conducted on the same dog or when large volumes of peripheral lymph are required.

Animals↗
PubMed1991

Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats.

We investigated the relative effects of different dietary saturated fats on the size distribution, apolipoprotein (apo) and chemical composition of HDL in fasted rats. Male Sprague-Dawley rats (174 +/- 2 g) were fed diets containing 0.035% cholesterol and 16% fat (wt/wt) from corn oil (CO diet) or from 2% CO plus 14% butterfat (BF diet), beef tallow (BT diet), palm oil (PO diet) or coconut oil (CN diet) for 6 wk. Apparent lipid digestibility was significantly lower with the PO and BT diets vs. the CO, BF and CN diets. Plasma total cholesterol levels were significantly higher in rats fed the PO and BT diets than in rats fed the BF and CN diets but were not different among the PO-, BT- and CO-fed groups. Nondenaturing gradient gel electrophoresis immunoblot analysis indicated that HDL apo A-I and E resided on particles with significantly smaller modal diameters in rats fed all saturated fats compared with those fed the CO diet. Chemical analyses indicated that HDL generally contained proportionately less protein and more triglyceride, free cholesterol and apo E with saturated fat feeding than with CO diet feeding. Significantly higher plasma and VLDL triglyceride levels were noted with ingestion of the BT, PO or CN diet than with the CO diet. Butterfat feeding resulted in lower plasma triglycerides and HDL-esterified cholesterol than did feeding the other saturated fats. Very low density lipoprotein triglyceride concentrations were inversely correlated with HDL modal diameter of apo E containing lipoproteins (P less than 0.005). These data provide further evidence of the interrelationship of triglyceride and HDL metabolism and suggest that mechanisms independent of cholesterol ester transfer protein may mediate this response in rats.

Animals↗
PubMed1991

Adult forms of metachromatic leukodystrophy: clinical and biochemical approach.

The clinical and biochemical characteristics of metachromatic leukodystrophy (MLD), true adult forms and late juvenile forms which are still living at adulthood, are reviewed as they both are observed in adult Neurology and Psychiatry departments. Mental deterioration is often the first symptom, evolving progressively; and dementia finally occurs. The latency before the appearance of neurological objective symptoms may be long and extend for several years. In many cases, the behavioral abnormalities are the first symptoms. Some of these forms have been diagnosed as schizophrenia. Very seldom, neurological symptoms, especially ataxia, occur without cognitive or psychiatric disturbances. Most of these cases have pyramidal and cerebellar symptoms, at diverse degrees. Seizures can also occur which is some cases can be early symptoms associated to mental deterioration. The association of central and peripheral neurological symptoms is very characteristic of MLD. The peripheral neuropathy is not generally clinically evidenced, but is rarely missing electrophysiologically. Arylsulfatase A determination should be performed for diagnosis as a first step, and confirmed by the accumulation of sulfatide, either by quantitative determinations in urine or by the sulfatide loading test. It is as yet not clear why certain forms have a rather rapid evolution in 5 years, and others have a very protracted course during decades.

Adolescent↗
PubMed1990

Molecular typing of nosocomial isolates of Legionella pneumophila serogroup 3.

In Paris, France, an outbreak of pneumonia due to Legionella pneumophila serogroup 3 was observed in Necker (four cases) and Pitié (six cases) hospitals. Neither the 10 clinical isolates nor 5 tap water isolates from Necker Hospital harbored plasmids. Clinical and environmental serogroup 3 isolates and serogroup 3 reference strain Bloomington 2 were analyzed by chromosomal probe fingerprinting. rRNA, 16S and 23S from Escherichia coli and a randomly cloned 15-kilobase-pair nucleotide sequence from L. pneumophila serogroup 3 were used as probes. All strains tested showed a single pattern after HindIII digestion of DNA and hybridization with the 32P-end-labeled rRNA probe, whereas three patterns were obtained after hybridization with the 32P-labeled 15-kilobase-pair DNA probe. One pattern was given by all clinical and tap water isolates from Necker Hospital, another one was given by all clinical isolates from Pitié Hospital, and a last one was given by reference strain Bloomington 2. Thus, molecular analysis showed that the two hospital outbreaks of legionellosis were unrelated and could link the outbreak in Necker Hospital to contaminated tap water.

Bacterial Typing Techniques↗
PubMed1989

Preferential redistribution of lipoprotein-unassociated apoA-IV to an HDL subpopulation with a high degree of LCAT modification.

The relationship between LCAT mediated HDL modification and the redistribution of lipoprotein-unassociated apoA-IV to HDL was investigated in vitro. Immunoaffinity-isolated rat lipoprotein-unassociated apoA-IV was added to apoB-, apoE-, apoA-IV depleted, [3H]cholesterol labelled rat plasma and incubated at 37 degrees C. The addition of lipoprotein-unassociated apoA-IV resulted in a modest (10%) but significant reduction in the rate of cholesterol esterification. Incubations conducted in the presence of active LCAT led to a time-dependent increase in the amount of the 3H label retained by an anti-apoA-IV immunoaffinity column. Lipoproteins retained by the anti-apoA-IV immunoaffinity column had experienced a greater conversion of [3H]cholesterol to [3H]cholesteryl esters (48% esterification at 30 min) than the unretained lipoproteins (19% esterification at 30 min). These data suggest that during the course of LCAT-induced cholesterol esterification, lipoprotein-unassociated apoA-IV transfers to a subpopulation of HDL which has been modified by LCAT to a greater extent than the remaining HDL. Further analysis of the data demonstrates that 48% cholesterol esterification is sufficient to allow apoA-IV to be accommodated on the surface of an HDL particle.

Animals↗