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Biomedical subjects

D Brun

Publications and source records attributed to D Brun.

At least 19 recordsLinked to original sources

Two types of MGDG synthase genes, found widely in both 16:3 and 18:3 plants, differentially mediate galactolipid syntheses in photosynthetic and nonphotosynthetic tissues in Arabidopsis thaliana.

In Arabidopsis, monogalactosyldiacylglycerol (MGDG) is synthesized by a multigenic family of MGDG synthases consisting of two types of enzymes differing in their N-terminal portion: type A (atMGD1) and type B (atMGD2 and atMGD3). The present paper compares type B isoforms with the enzymes of type A that are known to sit in the inner membrane of plastid envelope. The occurrence of types A and B in 16:3 and 18:3 plants shows that both types are not specialized isoforms for the prokaryotic and eukaryotic glycerolipid biosynthetic pathways. Type A atMGD1 gene is abundantly expressed in green tissues and along plant development and encodes the most active enzyme. Its mature polypeptide is immunodetected in the envelope of chloroplasts from Arabidopsis leaves after cleavage of its transit peptide. atMGD1 is therefore likely devoted to the massive production of MGDG required to expand the inner envelope membrane and build up the thylakoids network. Transient expression of green fluorescent protein fusions in Arabidopsis leaves and in vitro import experiments show that type B precursors are targeted to plastids, owing to a different mechanism. Noncanonical addressing peptides, whose processing could not be assessed, are involved in the targeting of type B precursors, possibly to the outer envelope membrane where they might contribute to membrane expansion. Expression of type B enzymes was higher in nongreen tissues, i.e., in inflorescence (atMGD2) and roots (atMGD3), where they conceivably influence the eukaryotic structure prominence in MGDG. In addition, their expression of type B enzymes is enhanced under phosphate deprivation.

Amino Acid Sequence↗

The multigenic family of monogalactosyl diacylglycerol synthases.

Because the synthesis of monogalactosyldiacylglycerol (MGDG) is unique to plants, identified as an important marker of the plastid envelope, involved in a key step of plastid biogenesis and is the most abundant lipid on earth, MGDG synthase activity was extensively analysed at the biochemical and physiological levels. In the present paper, we present our current knowledge on the MGDG synthase's function, structure and topology in envelope membranes, and discuss possible roles in plant cell glycerolipid metabolism. The recent discovery of a multigenic family of MGDG synthases raised the possibility that multiple isoenzymes might carry out MGDG synthesis in various tissues and developmental stages.

Amino Acid Sequence↗

[How do physicians evaluate their medical school training. Retrospective survey of 4 groups of medical students 8-11 years after graduation].

A survey was conducted among 250 graduates of the Bobigny School of Medicine (University Paris-Nord) who had completed medical school from 1986 to 1989 in order to ascertain their opinion concerning the training received. Ninety former students (36%) responded. The mean age of the sample was 34 years; 46 women and 44 men. Most (88.9%) were practicing medicine, principally as general practitioners (61.8%). 81.6% felt they had been well prepared to practice medicine. The rate of satisfaction was higher in the area of fundamental science than in clinical science. The responders generally felt that teaching and validation methods should emphasize real situations. The main criticism concerning the curriculum was an insufficient degree of professionalism, particularly in fields currently of particular importance: epide miology, health economics, education, prevention, office management. Training was also considered to be insufficient in medical techniques, communication, priority decision making, team work, emergency care, organization of time and handling stress. The responders suggested that the future curriculum should focus more on information search, research methodology and computer science. The results of this survey collaborate findings of recent retrospective long-term analyses conducted in other European countries.

Education, Medical, Continuing↗

A French dental school programme appraisal by alumni of 5-9 years standing.

The objective of this study was to analyse the perception of the practical value of their training experience for 4 groups of alumni graduated between 1986 and 1989 at the Faculty of Odontology, University Paris 5. The 240 participants (45% response rate) perceived their training to have been adequate with respect to procedural activities. On the other hand, the graduates expressed a desire for more emphasis in emergencies, interpersonal relationship, office management and such clinical topics as fixed prosthodontics, surgery and periodontics. Surveys aimed at alumni may be useful for the evaluation of programme results and to determine which items should be added or deleted according to either health criteria or the conditions of dental practice.

Attitude of Health Personnel↗

Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia.

Variation in plasma-cholesterol concentration and the expression of coronary heart disease in patients with homozygous familial hypercholesterolaemia (FH) is well documented, but the underlying reasons for variation are not clearly defined. Because FH is caused by mutations at the low-density-lipoprotein-gene locus, we compared plasma-cholesterol concentrations in 21 FH homozygotes with either the greater than 10 kb deletion (promoter region and exon 1) (11 subjects) or the exon 3 missense (trp66-->gly) mutation (10 subjects) of the low-density-lipoprotein gene. Subjects with the greater than 10 kb deletion had a higher mean plasma-cholesterol concentration than those with the exon 3 mutations (26.7 vs 16.1 mmol/L; p = 0.000006), and there was no overlap in individual plasma-cholesterol concentrations between subjects in the two groups. Although the frequency of coronary heart disease was similar in the two groups, age-of-onset was earlier in subjects with the greater than 10 kb deletion (p = 0.059). Also, coronary deaths were more frequent (p = 0.044) and occurred at an earlier age (p = 0.009) in subjects with the greater than 10 kb deletion. Our results provide evidence that there is less variation in plasma-cholesterol concentrations among FH homozygotes when they are subdivided into groups according to low-density-lipoprotein-receptor-gene defect. Furthermore, differences in plasma-cholesterol concentrations are reflected in the severity of coronary heart disease expression.

Adolescent↗

[Primary lipoprotein lipase deficiency. Study in Quebec].

Primary lipoprotein lipase deficiency is a rare autosomal recessive disease that causes hyperchylomicronaemia complicated by pancreatitis. Recent advances in molecular biology have facilitated its diagnosis and enabled heterozygous subjects to be identified. Numerous mutations are responsible for lipoprotein lipase deficiency. In some eastern regions of Quebec province homozygotes have been found in very high concentrations: up to 200 times the frequency observed in all other parts of the world. Heterozygocity may represent 1 in 40 subjects. Two mutations account for 95 percent of the Quebec cases, and each of them has its own characteristic geographical distribution. These peculiarities have been ascribed to a founder effect suggested by the analysis of the first colons' migrations and by the study of homozygotes' genealogy. Most of the ancestors of the Quebec carriers came from northwestern France in the 17th century, and heterozygotes alleged to be healthy carriers of the trait may have a predisposition to premature development of a cardiovascular disease. Their blood lipid levels and the composition of their lipoproteins (particularly those with low density) are suggestive of an atherogenic potential similar to that of hyperapobetalipoproteinaemia or familial combined hyperlipidaemia. Molecular biology would be a useful tool to confirm or infirm this hypothesis and to identify subjects at risk of developing a cardiovascular disease.

Cardiovascular Diseases↗

Influence of diets containing cow's milk or soy protein beverage on plasma lipids in children with familial hypercholesterolemia.

The present article summarizes the effects of diets containing either cow's milk or soy protein beverage on plasma lipids and lipoproteins in children with familial hypercholesterolemia. After a stabilization period of 6 weeks without any hypolipemic medication, 10 subjects aged 6-12 years were randomly assigned to either cow's milk or soy protein beverage with subsequent crossover after a washout period, each of 4 weeks duration. During the experimental periods, subjects were fed diets containing 20% of energy as protein, of which 35% was from cow's milk protein or soy protein isolate, 28% of energy as fat with a polyunsaturated:monounsaturated:saturated fat ratio of 1:3:3, and less than 200 mg/day of cholesterol. The soy protein beverage, compared to cow's milk, induced significant reductions in plasma triglycerides and very-low-density lipoprotein cholesterol, as well as a significant increase in high-density lipoprotein cholesterol, indicating that consumption of soy protein beverage may be beneficial for the prevention of coronary heart disease in children with familial hypercholesterolemia.

Adult↗

Prevalence, geographical distribution and genealogical investigations of mutation 188 of lipoprotein lipase gene in the French Canadian population of Québec.

Familial lipoprotein lipase deficiency (FLD) is of particular interest to the French Canadian population of Québec since the largest concentration of homozygotes and carriers of this genetic disease in the world resides in this area. We have previously described a missense mutation (M-188) in the lipoprotein lipase (LPL) gene which was present in FLD patients belonging to different ancestries, including a number of French Canadians (Monsalve MV et al. J Clin Invest 1990: 86: 728-734). In the present report, we show that this mutation, although found in largest absolute numbers among French Canadians as compared to other groups in the world, accounts for only a small proportion (24%) of all the LPL mutant alleles in this population. The M-188 occurs either in the homozygote state or as a compound heterozygote with another LPL mutation. Analysis of geographic distribution indicates that the M-188 is more prevalent in western Québec, with the highest carrier rate in the Mauricie region. Genealogical reconstruction leads to the recognition of four founders for M-188, all emigrants from France to Québec in the 17th century.

Base Sequence↗

[Double-blind clinical and echocardiographic study of oral enoximone versus placebo in severe cardiac insufficiency].

The effect of enoximone was assessed by a randomised double blind trial versus placebo. The clinical status of the patients was evaluated by the NYHA classification and quality of life score. Inotropic state was estimated from the maximum acceleration of aortic and pulmonary blood flow recorded by Doppler echocardiography. Thirty patients with severe cardiac failure, aged 66.4 +/- 14 years, symptomatic despite maximal therapy associating diuretics, digitalis, nitrate derivatives and angiotensin converting enzyme inhibitors, were included. Fifteen patients were given enoximone 100 mg three times a day orally (Group E) and the other 15 were given a placebo (Group P). The NYHA class and quality of life scores were assessed at D0, D4 and D31. Doppler echocardiography and Holter recordings were performed on D0 and D31. The two groups were comparable at D0. Ten patients abandoned the trial, 3 from Group E (including 1 death) and 7 from Group P (including 3 deaths). At D4, 13 patients from Group E and 8 from Group P were clinically improved (p < 0.05). At D31, the clinical state was stable or improved in 10 of the 12 patients in Group E and 6 of the 8 patients in Group P (NS). No secondary effects were severe enough to warrant the withdrawal of treatment: the frequency of ventricular extrasystoles was comparable in the two groups at D0 and D31. At D31 the maximal aortic acceleration had increased by 20% compared with D0 (p < 0.05) and the maximal pulmonary acceleration by 31% (p < 0.05) in Group E. The same parameters showed no significant change in Group P (-6% and +5% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of a soy-protein beverage on plasma lipoproteins in children with familial hypercholesterolemia.

The effects of soy protein (35% of protein energy) given as a beverage and those of cow-milk proteins were investigated on plasma lipoprotein concentrations in children with familial hypercholesterolemia (FH). Subjects were randomly assigned to either the soy-protein or cow-milk-protein experimental period, with subsequent crossover after a washout period, each period lasting 4 wk. Diets were planned to provide 20% energy as protein, 28% as fat (polyunsaturated:monounsaturated:saturated fatty acids, 1:3:3) and less than 200 mg cholesterol/d. No changes were observed in either plasma cholesterol, low-density-lipoprotein cholesterol, or apolipoprotein concentrations. However, the soy beverage significantly reduced the concentrations of triglyceride and very-low-density-lipoprotein cholesterol (P less than 0.05) and significantly increased the concentrations of high-density-lipoprotein cholesterol (HDL-C) and HDL3-C (P less than 0.04 and P less than 0.03, respectively). These results indicate that the administration of soy protein may induce clinically beneficial effects in children with FH.

Apolipoproteins↗

Beneficial effects of the calcium antagonist isradipine on apolipoproteins in hypertensive patients.

The objective of the study was to assess the effects of the calcium antagonist isradipine on plasma lipids, lipoproteins, and apolipoproteins in patients with essential hypertension. After a four-week placebo wash-out period, 73 patients (41 men, 32 women) were studied in a double-blind, randomized, crossover study comparing sustained-release isradipine (isradipine SR) with the standard isradipine formulation. Nineteen patients received 5 mg/day and 54 patients 10 mg/day. Lipids were evaluated at the end of the placebo period and after 12 weeks of treatment with isradipine. In both treatment groups, lipid and lipoproteins were not modified. However, apolipoprotein A-I levels increased significantly (P less than .001) and the ratio of apolipoprotein B to apolipoprotein A-I concentration decreased significantly (P less than .01) irrespective of gender. These data show that the levels of plasma apolipoprotein A-I, a strong predictor of coronary heart disease, are favorably affected by isradipine of either formulation. The mechanisms of this effect remain to be elucidated.

Adult↗

Founder effect in familial hyperchylomicronemia among French Canadians of Quebec.

Familial hyperchylomicronemia has reached a high prevalence in the French Canadian population of eastern Quebec. The birth places of 58 carriers identified through the birth of one affected child clustered in three regions. The genealogies of these 58 individuals showed that no founder was common to all of them. Three sets of founders were found, one for each region, with little overlapping between two regions. These results strongly suggest that more than one mutation, introduced by the French migrants in the 17th century, are segregating in the French Canadian population. Perche, a region situated between Paris and Normandy, appeared to be the most likely putative center of diffusion of at least one mutation in the lipoprotein lipase gene segregating in the modern-day French Canadian population of Quebec.

France↗

[Ostial stenosis of the left main coronary artery after mediastinal radiotherapy. Apropos of a case].

Coronary artery disease (CAD) is a well-known complication of mediastinal irradiation. We report a case of subocclusive ostial stenosis of the left main coronary artery, in a 27 years old man, who had been irradiated 14 years before for a stage 4 Hodgkin's disease. Among the 68 reported cases of CAD attributed to radiotherapy, 11 involved an ostial stenosis of either right coronary artery, or left main coronary artery or both. Thus mediastinal irradiation seems to be a definite cause of ostial coronary artery stenosis; several types of myocardial revascularization have been suggested for this kind of CAD.

Adult↗