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Biomedical subjects

P Moulin

Publications and source records attributed to P Moulin.

At least 73 records · Page 4Linked to original sources
PubMed1994

Gender effects on the distribution of the cholesteryl ester transfer protein in apolipoprotein A-I-defined lipoprotein subpopulations.

Two subpopulations of apolipoprotein A-I-containing lipoproteins, those containing only apoA-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I/A-II), were isolated by immunoaffinity chromatography of plasma from 44 subjects, comprising four groups (male or female, with or without hyperlipidemia). ApoA-I-defined particles (LpAs) were assessed for their content of cholesteryl ester transfer protein (CETP) and for their ability to act as substrates for CETP. Although plasma CETP concentration was similar in all groups, the plasma concentration of LpA-I-associated CETP was significantly higher in females than in males (1.56 +/- 0.11 versus 0.93 +/- 0.13 mg/l, P < 0.05). In females, the major fraction of CETP was found in LpA-I, whereas in normolipidemic males CETP was evenly distributed between LpA-I and LpA-I/A-II, and in hyperlipidemic males the majority of CETP was found in LpA-I/A-II. In all groups, the percentage of CETP in LpA-I was correlated with the concentration of apoA-I in LpA-I (r = 0.64, P < 0.001). Native gradient gel electrophoresis of isolated LpAs showed that CETP was broadly distributed within different sized particles. LpA-I and LpA-I/A-II showed similar efficiency of CETP-mediated cholesteryl ester exchange with LDL. In conclusion, even though LpA-I has a much higher apparent affinity for CETP than LpA-I/A-II, both LpAs can bind CETP and act as equivalent CETP substrates in vitro. Thus, in subjects with low levels of LpA-I (notably hyperlipidemic males), most of the plasma neutral lipid exchange will involve LpA-I/A-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Effects of pravastatin on apolipoprotein-specific high density lipoprotein subpopulations and low density lipoprotein subclass phenotypes in patients with primary hypercholesterolemia.

UNLABELLED: The HMG-CoA reductase inhibitor class of cholesterol-lowering agents reduces very low density lipoproteins (VLDL) and low density lipoproteins (LDL) and slightly increases high density lipoproteins (HDL). However, the effects of these agents on subclasses within the LDL and HDL fractions are not well understood. We have employed an HMG-CoA reductase inhibitor, pravastatin, to determine if LDL subclass phenotypes, as determined by gradient gel electrophoresis, and HDL particles containing both apolipoprotein (apo) A-I and A-II, Lp(AI w AII), and those containing apo A-I but not A-II, Lp(AI w/o AII) are affected by pravastatin (10 mg daily). Twenty-four subjects with LDL-cholesterol (LDL-C) > 160 mg/dl, triglyceride (TG) < 350 mg/dl and no recent myocardial infarction or secondary causes of hypercholesterolemia were enrolled. Compared with an age- and sex-matched normolipidemic reference group (controls), the hypercholesterolemic subjects had reduced levels of Lp(AI w/o AII) and increased levels of Lp(AI w AII) at baseline. In addition, both of their HDL subpopulations had significantly more small (7.0-8.2 nm) particles (P < 0.02 and 0.0001) but significantly fewer large (9.2-11.2 nm) particles (P < 0.002 and 0.0001). Pravastatin induced statistically significant (P < 0.001) reductions in plasma total C (15%), LDL-C (18%), and apo B (16%). While apo A-I and A-II levels increased 5% (P < 0.001) and 6% (P < 0.05), respectively, concentration, composition, and size abnormalities in Lp(AI w AII) and Lp(AI w/o AII) persisted. Lp(a), apo E and cholesteryl ester transfer protein (CETP) levels also did not change. Although changes in LDL subclass phenotypes were observed, all changes involved the intermediate phenotype, and no significant changes in LDL peak particle diameter were seen in either group. Interrelationships between CETP, LDL subclass phenotypes and HDL subpopulations were also seen. CONCLUSIONS: Although pravastatin decreased plasma apo B and LDL lipid concentrations, no major changes were seen in LDL subclass phenotypes or HDL subpopulations even in the presence of abnormalities associated with arteriosclerosis. Similarly, CETP, which is believed to play a role in HDL and LDL particle size distribution, did not change with pravastatin treatment. Further research is needed to determine the pathophysiological basis of abnormal HDL and LDL subclasses in hypercholesterolemia and explore methods of rectifying the abnormalities.

Adult↗
PubMed1993

Exercise training decreases plasma cholesteryl ester transfer protein.

To assess the effect of exercise on the plasma concentration of cholesterol ester transfer protein (CETP) and its possible influence in mediating the exercise-associated redistribution of cholesterol among plasma lipoproteins, we measured plasma CETP in 57 healthy normolipidemic men and women before and after 9 to 12 months of exercise training. The training protocol resulted in significant changes in VO2max (mean +/- SD, +5.3 +/- 3.5 mL.kg-1 x min-1), body weight (-2.5 +/- 3.5 kg), plasma triglycerides (-25.7 +/- 36.3 mg/dL), high-density lipoprotein cholesterol (HDL-C) (+2.6 +/- 6.2 mg/dL), and ratios of total cholesterol to HDL-C (-0.30 +/- 0.52) and low-density lipoprotein cholesterol (LDL-C) to HDL-C (-0.18 +/- 0.45) (all P < or = .05) but no change in lipoprotein(a). CETP concentration (in milligrams per liter) fell significantly in response to training in both men (n = 28, 2.47 +/- 0.66 to 2.12 +/- 0.43; % delta = 14.2%; P < .005) and women (n = 29, 2.72 +/- 1.01 to 2.36 +/- 0.76; % delta = 13.2%; P < .047). The CETP change was observed both in subjects who lost weight (n = 28, delta mean weight = -5.0 kg; delta CETP = -0.42 +/- 0.79; % delta = 15.4%; P < .009) and in those who were weight stable (n = 29, delta mean weight = -0.12 kg; delta CETP = -0.29 +/- 0.78; % delta = 10.4%; P < .055).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Alternative splicing of the mRNA encoding the human cholesteryl ester transfer protein.

The plasma cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of lipids between plasma lipoproteins. The human CETP gene is a complex locus encompassing 16 exons. The CETP mRNA is found in liver and small intestine as well as in a variety of peripheral tissues. While the CETP cDNA from human adipose tissue was being cloned, a variant CETP cDNA was discovered which excluded the complete sequence encoded by exon 9, but which was otherwise identical to the full-length CETP cDNA, suggesting modification of the CETP gene transcript by an alternative RNA splicing mechanism. RNase protection analysis of tissue RNA confirmed the presence of exon 9 deleted transcripts and showed that they represented a variable proportion of the total CETP mRNA in various human tissues including adipose tissue (25%), liver (33%), and spleen (46%). Transient expression of the exon 9 deleted cDNA in COS cells or stable expression in CHO cells showed that the protein encoded by the alternatively spliced transcript was inactive in neutral lipid transfer, smaller, and poorly secreted compared to the protein derived from the full-length cDNA. Endo H digestion suggested that the inactive, cell-associated protein was present within the endoplasmic reticulum. The experiments show that the expression of the human CETP gene is modified by alternative splicing of the ninth exon, in a tissue-specific fashion. The function of alternative splicing is unknown but could serve to produce a protein with a function other than plasma neutral lipid transfer, or as an on-off switch to regulate the local concentration of biologically active protein.

Adipose Tissue↗
PubMed1992

An interaction between the human cholesteryl ester transfer protein (CETP) and apolipoprotein A-I genes in transgenic mice results in a profound CETP-mediated depression of high density lipoprotein cholesterol levels.

We have previously described two transgenic mouse lines, one heterozygous for the human apo A-I gene and the other heterozygous for a human cholesteryl ester transfer protein (CETP) minigene driven by the mouse metallothionein-I gene promoter. In the current study, these two lines were crossed producing control, HuCETPTg, HuAITg, and HuAICETPTg mice to study the influence of CETP on HDL cholesterol levels, particle size distribution, and metabolism in animals with mouse and human-like HDL. In the HuCETPTg and HuAICETPTg animals, zinc induction approximately doubled plasma CETP activity, with no activity in plasma from the control and HuAITg animals. The only significant effect of CETP on lipoprotein subfraction cholesterol concentrations was for HDL-C. Compared to control animals, HuCETPTg animals had lower HDL-C, 20% before and 35% after Zn induction, and compared to HuAITg animals, HuAICETPTg animals had lower HDL-C, 35% before and 66% after Zn induction. Control and HuCETPTg HDL consist primarily of a single size population with a mean diameter of 10.00 +/- 0.10 nm and 9.71 +/- 0.05 nm, respectively. HuAITg HDL consists primarily of three distinct HDL size subpopulations with peak diameters of 10.35 +/- 0.08 nm, 8.80 +/- 0.06 nm, 7.40 +/- 0.10 nm, and HuAICETPTg HDL also consists primarily of three distinct HDL size subpopulations with peak diameters of 9.87 +/- 0.05 nm, 8.60 +/- 0.10 nm, 7.30 +/- 0.15 nm before, and 9.71 +/- 0.08 nm, 8.50 +/- 0.11 nm, 7.27 +/- 0.15 nm after zinc induction, respectively. Western blotting analysis of nondenaturing gradient gels of plasma with a monoclonal antibody to CETP indicated that in HuCETPTg and HuAICETPTg mice, 22 and 100%, respectively, of the CETP was HDL associated. Turnover studies with HDL doubly labeled with 125I apo A-I and 3H cholesteryl linoleate indicated that the CETP-induced fall in HDL-C was associated with increased HDL-cholesterol ester fractional catabolic rate in both the absence and presence of human apo A-I, suggesting CETP-mediated transfer of HDL-cholesterol ester to apo B-containing lipoproteins. In summary, these studies suggest that CETP has a much more profound effect on HDL cholesterol levels in transgenic animals expressing human apo A-I. This may be due to an enhanced interaction of CETP with human compared to mouse apo A-I or to the HDL particles they produce.

Animals↗
PubMed1992

Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia.

Hyperlipidemia is a prominent feature of the nephrotic syndrome. Lipoprotein abnormalities include increased very low and low density lipoprotein (VLDL and LDL) cholesterol and variable reductions in high density lipoprotein (HDL) cholesterol. We hypothesized that plasma cholesteryl ester transfer protein (CETP), which influences the distribution of cholesteryl esters among the lipoproteins, might contribute to lipoprotein abnormalities in nephrotic syndrome. Plasma CETP, apolipoprotein and lipoprotein concentrations were measured in 14 consecutive untreated and 7 treated nephrotic patients, 5 patients with primary hypertriglyceridemia, and 18 normolipidemic controls. Patients with nephrotic syndrome displayed increased plasma concentrations of apoB, VLDL, and LDL cholesterol. The VLDL was enriched with cholesteryl ester (CE), shown by a CE/triglyceride (TG) ratio approximately twice that in normolipidemic or hypertriglyceridemic controls (P < 0.001). Plasma CETP concentration was increased in patients with untreated nephrotic syndrome compared to controls (3.6 vs. 2.3 mg/l, P < 0.001), and was positively correlated with the CE concentration in VLDL (r = 0.69, P = 0.004) and with plasma apoB concentration (r = 0.68, P = 0.007). Treatment with corticosteroids resulted in normalization of plasma CETP and of the CE/TG ratio in VLDL. An inverse correlation between plasma CETP and HDL cholesterol was observed in hypertriglyceridemic nephrotic syndrome patients (r = -0.67, P = 0.03). The dyslipidemia of nephrotic syndrome includes increased levels of apoB-lipoproteins and VLDL that are unusually enriched in CE and likely to be atherogenic. Increased plasma CETP probably plays a significant role in the enrichment of VLDL with CE, and may also contribute to increased concentrations of apoB-lipoproteins and decreased HDL cholesterol in some patients.

Adult↗
PubMed1991

Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice.

The human cholesteryl ester transfer protein (CETP) facilitates the exchange of neutral lipids among lipoproteins. In order to evaluate the effects of increased plasma CETP on lipoprotein levels, a human CETP minigene was placed under the control of the mouse metallothionein-I promoter and used to develop transgenic mice. Integration of the human CETP transgene into the mouse genome resulted in the production of active plasma CETP. Zinc induction of CETP transgene expression caused depression of serum cholesterol due to a significant reduction of high density lipoprotein cholesterol. There was no change in total cholesterol content in very low and low density lipoproteins. However, there was a decrease in the free cholesterol/cholesteryl ester ratio in plasma and in all lipoprotein fractions of transgenic mouse plasma, suggesting stimulation of plasma cholesterol esterification. The results suggest that high levels of plasma CETP activity may be a cause of reduced high density lipoproteins in humans.

Animals↗
PubMed1991

Mammalian adipose tissue and muscle are major sources of lipid transfer protein mRNA.

The plasma cholesteryl ester transfer protein (CETP) catalyzes the transfer of cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich lipoproteins and plays a major role in the catabolism of HDL. Lipoprotein lipase (LPL) is the rate-limiting enzyme for hydrolysis of circulating triglyceride and is involved in HDL formation. We show that tissues containing LPL are major sources of CETP mRNA in several mammalian species, including some with low cholesteryl ester transfer activity in plasma. In hamsters, adipose tissue and heart were found to be the richest sources of both CETP and LPL mRNA; in situ hybridization studies showed that the same cell types (i.e. adipocytes or myocytes) contained CETP and LPL mRNA in these tissues. Isolated adipocytes synthesized active CETP. Dietary studies revealed a complex pattern of response of CETP mRNA levels in different tissues, which showed partial similarity to the changes in LPL mRNA abundance. However, high cholesterol diets resulted in increased CETP mRNA abundance in adipose tissue, heart, and skeletal muscle, without equivalent changes in LPL mRNA. Plasma HDL cholesteryl ester levels showed strong inverse correlations with CETP mRNA abundance in adipose tissue. The results suggest a conserved function of CETP in adipose tissue and heart, such as a co-ordinate action with LPL to enhance HDL turnover. Although there is considerable overlap in the tissue- and cell-specific pattern of CETP and LPL gene expression, dietary studies revealed only limited parallelism in response at the mRNA level. The increase in CETP mRNA in peripheral tissues in response to increased dietary cholesterol suggests that local induction of CETP synthesis may help to recycle cholesterol deposited in these tissues during lipolysis of dietary lipoproteins.

Adipose Tissue↗
PubMed1991

Serum lipoprotein lipid concentration and composition in homozygous and heterozygous patients with cholesteryl ester transfer protein deficiency.

Six homozygous, 10 heterozygous and 8 unaffected subjects in a CETP deficient family confirmed by CETP gene analysis were studied to characterize serum lipoproteins separated by ultracentrifugation, and to examine the relations between CETP levels and lipoprotein lipid concentration and composition. The serum CETP levels were measured by radioimmunoassay using 125I-labeled monoclonal antibodies (TP2). The serum CETP levels in the homozygotes were undetectable and those in the heterozygotes were significantly lower than those in the unaffected subjects (1.5 +/- 0.1 vs. 2.2 +/- 0.5 microgram/ml, P less than 0.01). In the HDL fraction, esterified cholesterol (EC) levels in the homozygotes were significantly increased (P less than 0.01), and those in the heterozygotes were slightly increased (n.s.), in comparison with those in the unaffected and the normolipidemic controls. The EC levels in the IDL fractions were lower in the homozygotes than in the normolipidemic controls. The EC/triglyceride (TG) molar ratios in IDL, the fraction obtained from the homo- and heterozygotes, were lower than those from the unaffected subjects (P less than 0.01 and less than 0.01, respectively), and the EC/TG ratios in the HDL fraction obtained from the homo- and heterozygotes were higher than those from the unaffected subjects (P less than 0.01 and n.s., respectively). Linear regression analysis showed that positive correlates of the serum CETP levels in all subjects were: IDL-EC (r = 0.463), HDL-TG (r = 0.603) and VLDL- and IDL-EC/TG ratio (r = 0.698 and 0.843).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Salter's innominate osteotomy. 20 years later...].

This is a retrospective review of nineteen innominate osteotomies with an average follow-up of 20, 6 years. These osteotomies were done mainly for treatment of late diagnosed congenital hip dislocation, or occasionally for persistent subluxation after orthopaedic treatment. The mean age at diagnosis was 2 years 2 months, at operation 3 years 5 months. We performed eight combined open reduction and pelvic osteotomies, eight associated pelvic and femoral varisation derotation osteotomies and only 3 isolated pelvic osteotomies. At follow-up the Charnley hip's score is 5.7 for pain; 5.4 for gait and performance, 5.6 for mobility. We found 15 hips without any significant pain and only 4 hips with mechanical pain. The Xray evaluation shows an average CE angle at 28.5 degrees, AC angle at 16 degrees and anterior coverage on "faux profil de Lequesne" at 40 degrees; 4 hips show arthritic changes, 4 others had important deformation of the head of the femur, but without diminution of the height of articular space. 6 hips (1/3) in 4 patients must be reoperated in adolescence because insufficiency of coverage of the head of the femur: 3 because technical errors and 3 because osteonecrosis with progressive cervicocephalic valgus. This historical serie with a very important follow-up, demonstrate that between 1/3 and 1/2 of cases have some kind of problems mainly radiological. The quality of results depends on the respect of the conditions and technique described by Salter, early diagnosis and absence of osteonecrosis eventually caused by prealable orthopaedic treatment.

Activities of Daily Living↗
PubMed1988

[Long-term results of the Salter pelvic osteotomy].

We report the long-term results obtained with Salter's innominate osteotomy over an average follow-up time of 24 years. In 8 of 9 hips the innominate osteotomy was combined with an intertrochanteric femoral osteotomy. On average the acetabular angle was improved by 12 degrees. By 11 years post-operatively the acetabular angle had stabilized at a mean of 16 degrees, subsequently remaining the same through the follow-up period. The centre angle was improved by approximately 20 degrees. By 8 years post-operatively it was in the normal range around 27 degrees, remaining unchanged until the most recent follow-up examination. Among the 9 patients who were followed up there was only one mild deformity of the femoral head. We recommend Salter's innominate osteotomy for the treatment of dysplastic acetabulae with an acetabular angle of not much more than 40 degrees, for patients 2-4 years of age, and occasionally up to the age of 6.

Adolescent↗
PubMed1987

High density lipoprotein alterations induced by bezafibrate in healthy male volunteers.

The alterations of HDL structure and metabolism induced by bezafibrate administration were studied in healthy male volunteers. As usually observed in hyperlipaemic patients, bezafibrate induced a decrease of the plasma concentrations of apo B and LDL-cholesterol and an increase of that of HDL-cholesterol. Analysis of HDL by gradient polyacrylamide gel electrophoresis revealed that bezafibrate administration resulted in a change of the particle size distribution likely suggesting a drop of the HDL2/HDL3 ratio. This was accompanied by a 30% enhancement of the plasma concentration of apoprotein A-II, while that of apoprotein A-I remained unchanged. These data suggest an increase of the HDL concentration, preferentially in the HDL3 subfraction. In spite of these HDL alterations, there was no evidence of change in the three stages of the reverse pathway of cholesterol, since bezafibrate did not induce any significant alteration in the in vitro properties of plasma with respect to (a) cholesterol transport from cultured cells, (b) cholesterol esterification, and (c) transfer of cholesteryl esters from HDL to VLDL-LDL.

Adult↗
PubMed1986

[Long-term results in the treatment of clubfoot].

Long-term results in the treatment of congenital clubfoot are reported. The average follow-up time was 17.7 years (10-29.4 years). All 104 patients (148 clubfeet) were followed up personally. In addition to the clinical examination, a podogram was made and evaluated. Results were good to very good in 97% of patients with regard to complaints, in 83% concerning the level of functional ability, in 69% regarding clinical aspects of the foot, in 58% with regard to measurements of the podogram, and in 27% regarding movement. In clinical aspects and measurement of the podogram, significantly better results were obtained if the first operative correction took place within the first year of life. In patients in whom the anterior tibial tendon had been transferred, there was a higher percentage of falling medial arches. Patients in whom rotational osteotomy of the tibia had been carried out showed better foot position in relation to the femoral axis and worse foot position in relation to the malleolar axis than those in whom this operation had not been performed.

Achilles Tendon↗
PubMed1986

[New area of endemic goiter : the northeast Bénoué, (North Cameroon)].

Endemic goiter was thought to essentially spread in the southern part of Cameroun. In fact the North-East Benoué (NEB) area also appears to be concerned. We studied 1242 individuals from 5 representative villages. The overall goiter frequency was 28.4%. Study of emigrants showed a spreading of the endemic area towards the boundary part of Tchad. However increase of morbidity was related to the duration of settlement in NEB (18% after 1 year vs 34% after 5 years, p less than 0.01). Samples of urine from one single micturition were kept at 4 degrees C and assayed for iodide within 3 days. The results exhibited marked iodine deficiency (iodide : 9.6 +/- 1.5 micrograms/l; urinary ratio : iodide/creatinine : 17.9 micrograms/l). The way of preserving urine before iodine assay was critical. After 8 days of daylight exposure of the samples at 30 degrees C, the most part of assayable iodine had disappeared. The goitrogenic effect of manioc was weak : there was no relationship between the presence of goiter and the amount of ingested manioc. Concentration of thiocyanates in urine was correlated neither with manioc consumption nor with goiter volume. An automatic classification was obtained by computerization of several parameters. 88% of the patients distributed in 10 groups whose goiter frequencies were markedly different. Because of the well-defined characteristics of each group, it seems possible to perform valid biological or nutritional studies using a limited number of individuals.

Adolescent↗