Search PubMedSearch

Biomedical subjects

J Dupont

Publications and source records attributed to J Dupont.

At least 19 recordsLinked to original sources

Future directions for nutrient requirements--lipids.

Recent advances in instrumentation and methodologies are redefining the study of lipid nutrition by allowing probing for subtle responses to marginal variations in nutrients. Stable isotope labeling studies allow demonstration of chain elongation, desaturation, chain shortening and resynthesis in humans. Essential fatty acid deficiency affects membrane physicochemical properties and membrane-bound protein activity. Understanding of the molecular functions of dietary fat has progressed to conceptualization of complex competing and complementary interactions and signals. The physical properties of lipids--insolubility in water and amphipathic qualities--underlie their physiological function. These findings will lead to new biomarkers of health status.

Dietary Fats

Analytical procedure for use of conductance measurement to estimate Escherichia coli in shellfish.

Assays were performed with a Malthus AT Microbiological Analyzer to define an analytical procedure to estimate Escherichia coli counts in live bivalve shellfish by conductance measurement. The growth conditions used (Malthus Coliform Broth at 44 degrees C) were selective for E. coli, and interference was noted only when Klebsiella pneumoniae were at least 100 times as numerous as E. coli. Different sample preparation procedures and seeding conditions were tested to obtain good quality conductance curves. The best results were observed when: (a) meat and shell liquor were diluted 1:3 with tryptone salt water and homogenized in a Waring blender for 1 min at 15,000 rev min-1; and (b) the inoculum was taken from the liquid phase of the homogenate 20 min after blending and mixed immediately with the culture medium. Detection parameter threshold values were adjusted (first difference 1.5 microS for the baseline and 3.5 microS for detection, second difference 0.2 microS) to improve detection time reliability. The repeatability of conductance measurements was very good (S.D. as % response mean ranged from 1.9 to 3.3) with the protocol used.

Animals

Freud's analysis of Ferenczi as revealed by their correspondence.

The relationship between Freud and Ferenczi was a very intimate one. Nevertheless--or consequently--when Ferenczi decided to undergo his own analysis, he couldn't imagine anyone other then Freud as his analyst. This remained true in spite of Freud's clearly expressed reluctance to analyse Ferenczi. The analysis stimulated very intense and passionate transference feelings in Ferenczi. In response, Freud desperately tried to cool down the situation, apparently by trying to keep things on an intellectual level. This analysis, carried out in three brief sections, was interrupted the first time by the beginning of World War I, the second time because the time planned for the analysis was over, and the final time because Freud obviously felt that it could not go further and considered it 'finished', even if not 'terminated'. It left unresolved a great part of the father-son relationship in both the transference and in the countertransference (Nemes, 1988). According to Ferenczi, Freud failed to analyse his negative transference. I would add the supposition that Freud also ignored his negative countertransference. This analytic experience certainly added to the complexity of their subsequent relationship, in spite of the warm feelings between them and the permanence of their friendship. Indications of that complexity can be found in the writings of both men.

Correspondence as Topic

MPTP induced hemiparkinsonism in monkeys: behavioral, mechanographic, electromyographic and immunohistochemical studies.

A single infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) into the right internal carotid artery of Macaca mulatta monkeys resulted in akinesia and rigidity of the contralateral limb. The immunohistochemical study revealed a dramatic reduction in the number of TH-immunoreactive cells in the substantia nigra of the infused side (70-81%). After unilateral MPTP-treatment movement parameters and EMG activity were altered; the agonist muscle developed increased EMG activity associated with a shift of antagonist muscle activity. These results confirm that hemiparkinsonian monkeys are a valuable model of parkinsonism which can be useful in studies of movement disorder physiology and therapy of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Genotyping for 10 mutations in the CYP21 gene was performed in 88 families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Southern blot analysis was used to detect CYP21 deletions or large gene conversions, and allele-specific hybridizations were performed with DNA amplified by the polymerase chain reaction to detect smaller mutations. Mutations were detected on 95% of chromosomes examined. The most common mutations were an A----G change in the second intron affecting pre-mRNA splicing (26%), large deletions (21%), Ile-172----Asn (16%), and Val-281----Leu (11%). Patients were classified into three mutation groups based on degree of predicted enzymatic compromise. Mutation groups were correlated with clinical diagnosis and specific measures of in vivo 21-hydroxylase activity, such as 17-hydroxyprogesterone, aldosterone, and sodium balance. Mutation group A (no enzymatic activity) consisted principally of salt-wasting (severely affected) patients, group B (2% activity) of simple virilizing patients, and group C (10-20% activity) of nonclassic (mildly affected) patients, but each group contained patients with phenotypes either more or less severe than predicted. These data suggest that most but not all of the phenotypic variability in 21-hydroxylase deficiency results from allelic variation in CYP21. Accurate prenatal diagnosis should be possible in most cases using the described strategy.

Adrenal Hyperplasia, Congenital

[Tinnitus: peripheral and central aspects].

Tinnitus is often related to a peripheral impairment which seems to trigger an abnormal autonomous functioning of the central auditory system. Moreover peripheral stimulations may diminish, and even suppress their perception, either through masking or through inhibition of an aberrant neuronal activity. Here we present an experimental model of peripheral deafferentation in which a decrease of neurochemical activity is observed in the brainstem auditory nuclei, followed by a progressive recovery after the peripheral destruction. This activity could represent a central morphofunctional correlate of tinnitus. Development of experimental models of tinnitus must be continued. Such models should allow the study of the basic physiological mechanisms behind tinnitus and suggest some therapeutic approaches which could be objectively evaluated.

Animals

Effects of dietary fat on cholesterol movement between tissues in CBA/J and C57BR/cdJ mice.

Differences in dietary fats cause differences in cholesterol metabolism in mice. CBA/J mice are resistant to diet-induced hypercholesterolemia and atherosclerosis; they adjust hepatic hydroxymethyl-glutaryl-CoA reductase activity (HMGR) to maintain homeostasis; C57BR/cdJ mice are susceptible, but young animals are thought to maintain homeostasis by changing fecal excretion of sterols. Compartmental modelling of movement of [4-14C]cholesterol was used to analyze movement of cholesterol between serum and liver, heart, and carcass in mice fed 40 en% fat, polyunsaturated to saturated fatty acid ratio (P/S) = 0.24 (US74) or 30 en% fat, P/S = 1 (MOD). Dietary effects were quite pronounced, while strain effects were more subdued. The C57/cdJ animals appear to regulate the overall cholesterol balance by reducing synthesis, as do the CBA/J animals, even though synthesis is not reduced to the same degree as in the CBA/J animals. Both diet and strain influence the whole-animal turnover rate, with slower turnover occurring for C57BR/cdJ animals and animals fed the US74 diet.

Animals

Mitochondrial uptake of bridged bis-methylpyridinium aldoximes and induction of the "petite" phenotype in yeast.

The 3,3'-[omega,omega'-alkanediylbis(oxy)]bis[2- (hydroxyimino)methyl]-1-methylpyridinium derivatives bearing a linking chain of 4, 5 and 6 methylene groups are accumulated in mitochondria with increasing efficiency under the effect of the electrical potential. Accumulation does not take place with derivatives carrying a 2 and 3 methylene-long linking chain. The uptake process is saturable. The efficiency of the various derivatives to induce the "petite" phenotype in yeast reflects the uptake rate observed with purified mitochondria.

DNA Damage

The relationship between thromboxane and cytosolic calcium modifiers in rat platelets.

Platelet activity is controlled, in part, by cytosolic free ionized calcium concentration ([Ca++]i). Regulation of platelet thromboxane (TXB2) synthesis may be by regulation of [Ca++]i. Dietary linoleate is a regulator of TXB2 synthesis, therefore, it may act by influencing [Ca++]i. Aspirin is a regulator of TXB2 synthesis by inhibition of cyclooxygenase; ouabain and nifedipine are regulators of [Ca++]i. This study was conducted to determine whether these affectors of TXB2 synthesis and [Ca++]i cause associated responses. Male nonobese Zucker rats were fed diets supplying 30% of energy (en%) as fat. Dietary fat was a mixture of corn oil and beef tallow to provide 3.0, 4.5, 6.0, or 7.5 en% linoleic acid, with cholesterol added to provide equal cholesterol in all diets. Rats were fed for 30 days with 6 rats/diet. Isolated rat platelets were assayed for FA composition; the percentage of linoleic acid in platelet FA rose linearly with increasing dietary linoleate (r = 0.76, P less than 0.0001). Resting and thrombin-stimulated platelet [Ca++]i and TXB2 synthesis were measured in the presence or absence of extracellular calcium and aspirin, ouabain, or nifedipine. Aspirin caused reductions in both parameters; nifedipine blocked [Ca++]i, but did not affect TXB2; ouabain increased both. Changes induced by those modifiers of TXB2 and platelet [Ca++]i caused changes that were in the same direction for both. CaCl2 caused an increase in both and the [Ca++]i was correlated with the square root of the TXB2; without CaCl2 the two were negatively correlated; aspirin, ouabain, and nifedipine treatments resulted in no significant correlations. The results suggest that there is a common modifier of [Ca++]i and TXB2 synthesis.

Animals

Studies of women eating diets with different fatty acid composition. I. Plasma lipoproteins and steroid excretion.

Moderate changes in dietary fat composition have been recommended to improve plasma cholesterol status. Such changes have not been studied extensively in women. This research evaluates plasma lipoprotein and steroid excretion changes in young women who consumed a diet similar to US average consumption in 1974 [40 en% fat, polyunsaturated (P) to saturated fatty acid (S) ratio, P/S = 0.3, US74] or a diet modified to contain 30 en% fat, P/S = 1.0 (MOD). Following a preexperimental period of self-selected diets, young women were fed the diets for 28-day periods in a crossover design with 10 women at the University of Nebraska, Lincoln, and 10 at Iowa State University, Ames. Plasma lipoproteins and steroid excretion were quantitated and the compositions determined. Data were analyzed for race (five Chinese, 14 Caucasians) and for diet carryover effects, as well as for primary diet effects. In the Chinese women, the US74 diet raised total and very-low-density lipoprotein (VLDL) cholesterol compared to prior self-selected or modified diets; in the Caucasian women the MOD diet lowered total, low-density lipoprotein (LDL), and VLDL cholesterol. The diet carryover was evident in total high-density lipoprotein (HDL) and HDL3 cholesterol. Total HDL and HDL3 cholesterol in response to the US74 diet were unchanged from the MOD diet when the US74 diet followed the MOD diet, but were lower than modified when the US74 diet followed self-selected diets. The US74 diet resulted in greater neutral sterol excretion than the MOD diet; this response was more marked in the self-selected, US74, MOD sequence than in the self-selected, MOD, US74 sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Studies of women eating diets with different fatty acid composition. II. Urinary eicosanoids and sodium, and blood pressure.

Dietary fatty acid composition is known to affect various aspects of eicosanoid metabolism. This research was conducted to evaluate effects of a diet similar to the US average consumption in 1974 (40 en% fat, polyunsaturated to saturated fatty acid ratio, P/S = 0.3) or a diet modified to contain 30 en% fat, P/S = 1.0, on eicosanoid metabolism in young women. Following a period on self-selected diets, women in Nebraska and Iowa were fed the diets for 28-day periods in a crossover design. Urinary eicosanoids, sodium (Na) excretion, and blood pressure were determined. Diet effects were confounded by carryover effects. For urinary eicosanoids the sequence of higher saturated fat (SFA) followed by lower SFA resulted in significantly greater excretion, whereas the reverse order of diets did not cause significant changes. Diastolic blood pressure was not affected by diet, but systolic pressure was lower with the modified diet in the lower to higher-SFA sequence. The change from self-selected to experimental diets does not seem to account for the carryover effects. The interpretation is that linoleate is depleted from tissues more slowly than it is repleted. Effects upon Na excretion were related to SFA more than to linoleate in the diet.

Adult

Studies of women eating diets with different fatty acid composition. III. Fatty acids and prostaglandin synthesis by platelets and cultured human endothelial cells.

The aim of this study was to determine how plasma fatty acids (FA) of subjects eating either a diet designed to match the US diet consumed in 1974 in fat content and composition in accord with the HANES I survey (US74) or a diet modified to meet the US Dietary Goal Recommendations (MOD) are altered, and how the changes affect platelet thromboxane (TXB2) synthesis, and prostacyclin (PGI2) and prostaglandin E2 (PGE2) synthesis by cultured human endothelial cells. Following a period of recorded self-selected diets, 10 women ate the US74 diet for 4 weeks, changing to the MOD diet for the next 4 weeks (sequence 1), and 10 ate the MOD diet followed by the US74 diet (sequence 2). Plasma triglycerides, free FA, platelet FA composition, and red blood cell phospholipids responded to the change from self-selected to controlled diets, but differences in responses were not seen between US74 and MOD diets. Red blood cell total FA did not respond to dietary changes. Under collagen but not thrombin stimulation, platelet TXB2 synthesis was correlated with platelet arachidonate concentration but not serum cholesterol. Endothelial cells were isolated from umbilical cord veins and incubated for 72 hours with a 20% medium of the women's plasma. In sequence 1 (high saturated FA to high polyunsaturated fatty acids), but not in 2 (reverse order), plasma from subjects eating the MOD diet decreased (p less than 0.05) basal and thrombin-stimulated PGI2 and PGE2 synthesis by the cells. These cells had a higher content of linoleic acid than cells from subjects eating the US74 diet. Thus, our study suggests that an increase in the intake of linoleic acid from 4.8 to 7.6 en% decreases PGI2 and PGE2 synthesis by human endothelial cells, and supplementation of the diet with linoleic acid has a longer period of effectiveness than its decrease in the diet.

Adult

Saturated and hydrogenated fats in food in relation to health.

The report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults published in 1988 evoked great interest from the medical profession, the public, and food manufacturers. The merits of different dietary interventions to lower plasma cholesterol are debated in advertising, popular publications, and research publications. The present paper is a review of the contributions of saturated and trans fatty acids (FA) to the US diet, their metabolism, and effects upon plasma cholesterol. Saturated (SFA) and trans FA are metabolized to yield energy. They are not dietary essentials; SFA can be biosynthesized, and trans FA are not naturally occurring in plants, with only very small amounts in animals. Trans FA are produced in hydrogenation of liquid vegetable oils and are estimated to contribute 3-7% of the fat consumed. Most of the SFA in the US diet (35% of total fat consumed) is obtained from meat, poultry, fish, and dairy products (approximately 60%). The fats and oils consumed directly or as components of food products, mostly baked goods, contribute approximately 20% of the SFA. More than 30 years of research led the NCEP to conclude that SFA was the most potent dietary component in increasing plasma cholesterol, and that no more than 10% of the energy (en%) of the diet should be SFA. Trans FA are metabolized similarly to SFA, but no recommendation has been made about their consumption. Reduction of consumption of SFA should be practiced in a prudent manner, by reducing consumption of foods high in SFA, and not by eliminating classes of foods. Some changes in formulations of foods or preparation practices (type of frying fat) can be made. These modifications may decrease the palatability of the food, thereby presenting a challenge to the food industry. Substitution of fats hydrogenated to contain trans FA for fats high in SFA may not be beneficial to health. Labeling of foods would improve the ability of the consumer to make appropriate choices.

Cholesterol

A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin.

Steroid 11 beta-hydroxylase (P450c11) deficiency (failure to convert 11-deoxycortisol to cortisol) causes less than 10% of cases of congenital adrenal hyperplasia in most populations, but it is relatively frequent in Jews of Moroccan origin. P450c11 is encoded by the CYP11B1 gene which is located on chromosome 8q22 along with a homologous gene of unknown function, CYP11B2. To identify mutations in CYP11B1 associated with 11 beta-hydroxylase deficiency in Moroccan Jews, oligonucleotides were used that selectively amplified portions of CYP11B1 in polymerase chain reactions without amplifying CYP11B2. Sequence analysis of amplified fragments from one patient revealed a single base substitution in exon 8, codon 448 from CGC (arginine) to CAC (histidine). This residue is within the "heme binding" peptide that contains a cysteine that is a ligand to the heme group. The equivalent of Arg-448 is found in every known eukaryotic P450, and therefore it seems likely that a mutation of this residue would adversely affect enzymatic activity. 11 of 12 affected alleles from six Moroccan Jewish families carried the mutation in codon 448. This mutation is not normally present in CYP11B2 and thus appears to have arisen in CYP11B1 as a true point mutation rather than a gene conversion.

Adrenal Hyperplasia, Congenital

Occurrence of faecal bacteria, Salmonella and antigens associated with hepatitis A virus in shellfish.

An investigation was carried out over a one year period to examine jointly the occurrence of faecal bacteria, salmonella and the presence of antigens associated with the hepatitis A virus (HAV) in oysters (Crassostrea gigas), mussels (Mytilus edulis, Mytilus galloprovincialis) and cockles (Cerastoderma edule), taken from 8 shellfish farming areas or natural beds along the French coast. For the faecal coliforms (FC) and faecal streptococci (FS), statistical analysis of the 176 samples examined shows a statistically significant difference between sampling stations (F = 44.39 and F = 26.69 respectively, p less than 0.001): 4 of the 8 stations are more highly contaminated. Salmonella and antigens associated with HAV were detected in 5% and 1.7% respectively of the samples analysed. Frequency of isolation of salmonella is higher for the group of sampling stations where the mean levels of contamination by FC and FS are highest. The presence of HAV associated antigens was detected for the group of stations showing the lowest mean contamination levels. Taking all sample stations together, the percentage of isolation of salmonella differs significantly (chi 2 = 7.28, p less than 0.01) for the two classes of FC established on the basis of the threshold value (300 FC). There is no difference between the two classes of FS. For the HAV-associated antigens, detection percentages are similar for the two classes of results for FC and FS. Within each sampling station, considered independently, no particular correlation was found between the various viral and bacterial markers investigated.

Animals

[Localization of pheochromocytomas by 131-I-meta-iodobenzylguanidine scintigraphy].

Scintigraphy using 131I-labeled meta-iodobenzylguanidine was performed in 89 patients. A diagnosis of pheochromocytoma was indicated by urinalysis in 28 cases and confirmed histologically in the 27 patients who underwent surgery. The tumor was located using scintigraphy and computed tomography. Fourteen isolated and 6 malignant metastatic pheochromocytomas were found as well as 8 pheochromocytomas associated with genetic disease. Scintigraphy located the tumors in 22 out of 28 cases; however, 3 adrenal pheochromocytomas and 3 malignant pheochromocytomas were not detected. Radioisotope perfusion scanning was more sensitive than computed tomography for the detection of bilateral adrenal pheochromocytoma. In the only case of a multifocal tumor, a combination of scintigraphy and computed tomography located all pheochromocytomas which were later resected. The high number of patients without elevated urine catecholamines and in whom scintigraphy did not alter the diagnosis shows that his technique should be applied only after demonstration of catecholamine hypersection.

3-Iodobenzylguanidine