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Biomedical subjects

J Dupont

Publications and source records attributed to J Dupont.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1979

The relationship of dietary fats to prostaglandin biosynthesis.

The direct and indirect evidence that the fatty acid composition of dietary fat is involved in the regulation of prostaglandin biosynthesis was reviewed. Direct evidence included effects of essential fatty acid deficiencies and excesses on endogenous tissue levels and production rates of prostaglandins by several tissues. Indirect evidence included lipolytic, platelet aggregatory, hypertensive, inflammatory and immune responses. In general, composition of dietary fat did not affect prostaglandin biosynthesis unless a biochemical essential fatty acid deficiency was induced or the linoleate to saturated fatty acids ratio of the dietary fat was greater than 5. Most results were interpreted in light of changing fatty acid composition; however, very few direct measurements have been made.

Adipose Tissue↗
PubMed1979

Increased prostaglandin synthesis in childhood diabetes mellitus.

Prostaglandins are synthesized from the fatty acids, linoleic and arachidonic acids, and are associated with increased platelet aggregation as has been found in blood from patients with diabetes mellitus. In the present study blood was obtained from 40 children with diabetes and from 20 control children for measurements of fatty acid and PGE1, PGE2, and PGF2alpha levels. The production of PGE2 and PGF2alpha was significantly elevated in blood from the children with diabetes at all times measured. The mean quantitative plasma linoleic acid levels were also higher in the patients. The increased PG synthesis may be related to the vascular problems that occur in patients with diabetes.

Adolescent↗
PubMed1978

Abnormal levels of prostaglandins and fatty acids in blood of children with cystic fibrosis.

12 children with cystic fibrosis (C.F.) had lower levels of the essential fatty acid, linoleic acid, in plasma and in red blood cells, than did control children, and production of prostaglandin F2alpha (P.G.F2alpha) was higher than in controls. After 10 months of oral linoleic-acid supplementation in 6 of the children with C.F., the linoleic-acid levels in plasma, red cells, and platelets were higher and P.G.F2alpha production was lower than in the 6 children with C.F. who received a placebo lipid. Prostaglandin F2alpha is associated with bronchoconstriction and its increased production in children with C.F. might be causally related to their chronic pulmonary disease.

Child↗
PubMed1978

Thyroid function and blood pressure in two new strains of spontaneously hypertensive and normotensive rats.

1. The influence of thryoid function on the development of hypertension was studied in strains of spontaneously hypertensive (SH) and normotensive rats. 2. Surgical thyroidectomy decreased systolic blood pressure more markedly in SH rats than in normotensive rats. The effects of oral administration of 5 and 100 micrograms of thyroxine 24 h-1 100 g-1 were studied in the thyroidectomized animals. In the two strains the blood pressure returned to control levels only after administration of the larger dose. 3. The evolution of body weight, total plasma tri-iodothyronine (T3) and tetraiodothyronine (T4) concentrations were followed as a function of age in SH rats and normotensive rats from 5 to 21 weeks. At each age, SH rats showed significantly larger body weight and decreased T4 concentrations. Plasma T3 in SH rats was lower than in normotensive rats until 15 weeks of age, after which the difference was not significant. At 11 weeks, plasms free T3 and T4 concentrations were slightly lower in SH rats than in normotensive rats. 4. The more marked hypotensive effects of surgical thyroidectomy in SH rats cannot be related to increased thyroid function.

Aging↗
PubMed1976

Fatty acid and prostaglandin composition of left ventricular myocardium from dexamethasone-treated dogs with severe low output syndrome (LOS).

The effects of dexamethasone (DEX) administration on the left ventricular myocardial content of fatty acids and prostaglandins E1, E2 and F2alpha were studied. Following a complete right and left cardiac catheterization, either DEX (8 mg/kg) or an equivalent volume of its vehicle was given intravenously 30 minutes prior to low output syndrome (LOS induction, and supplemental doses of DEX (4 mg/kg) or vehicle administered at 15 and 75 minutes post-LOS induction. Low output syndrome was induced by intravenous administration of a myocardial depressor protein (MDP) which has been isolated from the venom of the Western diamondback rattlesnake, Crotalus atrox. Neither DEX nor its vehicle had a significant effect during the entire experiment, that is, in the normal or low cardiac output state in most of the hemodynamic parameters investigated. The three hour mortality rate for the DEX-treated animals was 22% (n=10) while that of the control group was 41% (n=26) indicating that the beneficial effects of this corticosteroid are not really apparent from hemodynamic evaluation alone. Since DEX only had a significant post-LOS induction effect in maintaining a lower left ventricular end-diastolic and pulmonary capillary wedge pressures, a higher arterio-venous oxygen saturation difference, and a more efficient contractile state of myocardial fibers (Vmax), an indirect correlation to coronary arterial blood flow at the subcellular level was sought. To this effect, prostaglandins and specific lipid classes of left ventricular myocardium (LVM) from control and LOS animals receiving either vehicle or DEX were analyzed. Low output state induction alone raised myocardial PG levels above those of sham-catheterized animals; on the other hand, dexamethasone induced a significant decrease in the three prostaglandins studied when administered to control (no LOS) animals. In the presence of LOS, however, dexamethasone overrode in part the increase in PGE1 and PGE2 brought about by LOS while in the case of PGF2alpha the LOS effect was totally prevented and its concentration was not significantly higher than in control animals receiving dexamathasone. LOS induction led to an increase in myristic and arachidonic acids and a decrease in palmitic and linolenic acids. Dexamethasone administration to control animals increased the concentration of stearic acid above all the other groups but decreased the concentration of linolenic acid when compared to DEX-treated animals with LOS or sham-catheterized animals. There were no significant differences in the total myocardial lipid among the four groups of animals studied. It is suggested that the potentially beneficial effects of corticosteroid administration to animals with low output syndrome are related to their effects on fatty acid and prostaglandin content of myocardium.

Animals↗