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Biomedical subjects

J Dupont

Publications and source records attributed to J Dupont.

At least 91 records · Page 5Linked to original sources
PubMed1991

[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↗
PubMed1990

Ditercalinium, a nucleic acid binder, inhibits the respiratory chain of isolated mammalian mitochondria.

Ditercalinium (a 7H-pyridocarbazole dimer) has been designed to bisintercalate into double-stranded DNA with high affinity. In this paper we provide evidence for inhibitory interactions of ditercalinium with electron transport in isolated rat liver mitochondria. It is shown that ditercalinium probably inhibits the electron transfer between membrane cytochrome c and oxygen (cytochrome c oxidase activity) and the electron transfer between the matrix side of inner membrane (Complexes II and III) and membrane cytochrome c. The level of inhibition of the last oxidation step of the respiratory chain appears to be highly dependent on the drug/membrane diphosphatidylglycerol ratio. It is suggested that the mechanism of cytochrome c oxidase inhibition by ditercalinium could be due to the complexation with the diphosphatidylglycerol environment essential for its activity rather than to a drug-enzyme direct interaction. This hypothesis is strengthened by experiments with pure cytochrome oxidase. Therefore, the interaction of ditercalinium with diphosphatidylglycerol may be envisaged as one factor, among others, responsible for its hepatotoxicity.

Animals↗
PubMed1990

Immunohistochemical evidence for GABAergic cell bodies in the medial nucleus of the trapezoid body and in the lateral vestibular nucleus in the guinea pig brainstem.

The presence of gamma-aminobutyric acid (GABA) in two brainstem nuclei is demonstrated by using a pre-embedding immunohistochemical procedure followed by staining intensification. Firstly, immunoreactivity was found in numerous cell bodies and profiles of the medial nucleus of the trapezoid body (MNTB). Secondly, numerous neurons including giant Deiters' cells, terminals and fibers were strongly labelled within the lateral vestibular nucleus (LVN). These observations suggest that the inhibitory part of the efferent innervation of outer hair cells in the cochlea can originate from the MNTB, and that GABAergic neurons in the LVN may contribute to information processing within this nucleus.

Animals↗
PubMed1990

GABA immunoreactivity of calyceal nerve endings in the vestibular system of the guinea pig.

Neurotransmitters involved in the vestibular system are largely uncharacterized. On the basis of results of earlier electrophysiological and immunohistochemical experiments, glutamate and gamma-amino-butyric acid (GABA) have been proposed in both mammalian and non-mammalian species as afferent transmitters between the sensory cell and the afferent dendrite. GABA is also suspected to act as an efferent neurotransmitter in the cochlea. We describe in this study the immunocytochemical localization of GABA within the vestibular end organs in the guinea pig. GABA immunoreactivity was found in the calyceal nerve endings surrounding type I hair cells of the vestibular epithelia. The most significant labelings were obtained in the crista ampullaris. Labeling was more difficult to observe in the utricular and saccular macula. These results contribute to the recent proposal that the calyx has a secretory function, and suggest that GABA may have a modulatory influence upon the type I hair cells.

Animals↗
PubMed1990

Eicosanoid synthesis in children with cholestatic disease.

The possibility of malabsorption of triglycerides contained in the diets of children with cholestasis suggests a deficiency of essential fatty acids and, therefore, probable effects on eicosanoid metabolism. Children with either biliary atresia (BA) or syndromatic paucity of interlobular bile ducts (PILBD) were evaluated as to plasma and platelet total lipid fatty acid composition and synthesis of prostaglandins (PG) E1, PGE2, PGI2, PGF2, and thromboxane (TXB2) by whole blood incubated at 37 degrees C for 10 min. In both diseases linoleate deficiency was present as shown by low 18:2 fatty acids in plasma lipids. The children with BA had lower plasma arachidonate than controls but normal eicosanoid synthesis except for excess PGI2. Those with PILBD had low platelet arachidonate and were severely deficient in TXB2 synthesis (less than 10% of controls). Three children with PILBD were fed a supplement of structured triglyceride (Captex 810) intended to provide as much as 10% of energy as linoleate for 2-3 months. Results for these three cases suggested that insufficient linoleate was absorbed to increase plasma linoleate and differences in eicosanoids could not be attributed to linoleate supplementation.

Arachidonic Acid↗
PubMed1990

Food uses and health effects of corn oil.

This review of corn oil provides a scientific assessment of the current knowledge of its contribution to the American diet. Refined corn oil is composed of 99% triacylglycerols with polyunsaturated fatty acid (PUFA) 59%, monounsaturated fatty acid 24%, and saturated fatty acid (SFA) 13%. The PUFA is linoleic acid (C18:2n-6) primarily, with a small amount of linolenic acid (C18:3n-3) giving a n-6/n-3 ratio of 83. Corn oil contains a significant amount of ubiquinone and high amounts of alpha- and gamma-tocopherols (vitamin E) that protect it from oxidative rancidity. It has good sensory qualities for use as a salad and cooking oil. Corn oil is highly digestible and provides energy and essential fatty acids (EFA). Linoleic acid is a dietary essential that is necessary for integrity of the skin, cell membranes, the immune system, and for synthesis of icosanoids. Icosanoids are necessary for reproductive, cardiovascular, renal, and gastrointestinal functions and resistance to disease. Corn oil is a highly effective food oil for lowering serum cholesterol. Because of its low content of SFAs which raises cholesterol and its high content of PUFAs which lowers cholesterol, consumption of corn oil can replace SFAs with PUFAs, and the combination is more effective in lowering cholesterol than simple reduction of SFA. PUFA primarily lowers low-density-lipoprotein cholesterol (LDL-C) which is atherogenic. Research shows that PUFA has little effect on high-density-lipoprotein cholesterol (HDL-C) which is protective against atherosclerosis. PUFA generally improves the ratio of LDL-C to HDL-C. Studies in animals show that PUFA is required for the growth of cancers; the amount required is considered to be greater than that which satisfies the EFA requirement of the host. At this time there is no indication from epidemiological studies that PUFA intake is associated with increased risk of breast or colon cancer, which have been suggested to be promoted by high-fat diets in humans. Recommendations for minimum PUFA intake to prevent gross EFA deficiency are about 3% of energy (en%). Recommendations for prevention of heart disease are 8-10 en%. Consumption of PUFA in the United States is 5-7 en%. The use of corn oil to contribute to a PUFA intake of 10 en% in the diet would be beneficial to heart health. No single source of salad or cooking oil provides an optimum fatty acid (FA) composition. Many questions remain to be answered about the relation of FA composition of the diet to various physiological functions and disease processes.

Animals↗
PubMed1989

Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta).

Steroid 11 beta-hydroxylase (P-450(11) beta) is a mitochondrial cytochrome P-450 enzyme necessary for cortisol biosynthesis. Deficiency of 11 beta-hydroxylase causes a hypertensive form of congenital adrenal hyperplasia. A partial cDNA clone encoding this enzyme has been previously isolated and the corresponding gene, CYP11B1, mapped to human chromosome 8q. This gene has now been isolated along with a second linked homologous gene, CYP11B2. Each gene contains nine exons. The eight introns are identical in location to the introns of the CYP11A gene encoding another mitochondrial P-450 enzyme, cholesterol desmolase, confirming that 11 beta-hydroxylase and cholesterol desmolase are in the same gene family within the P-450 superfamily. The nucleotide sequences of CYP11B1 and B2 are 95% identical in coding regions and about 90% identical in introns. The putative proteins encoded by CYP11B1 and B2 each contain 503 amino acids including a 24-residue signal peptide and have sequences that are 93% identical to each other and 75% identical to the predicted sequence of bovine P-450(11) beta. There are no obviously deleterious mutations in coding sequences of CYP11B2. However, the 5'-flanking regions of CYP11B1 and B2 have diverged considerably, and B2 transcripts were not detected in human adrenal mRNA or among cDNA clones.

Adrenal Glands↗
PubMed1989

Cholesterol and prostaglandin synthesis by cultured human skin fibroblasts in the Alagille syndrome involving paucity of interlobular bile ducts.

Children with Alagille syndrome show high serum cholesterol (15-20 mmol/L). To establish correlation of this unusual level of cholesterol with the regulation of cholesterol metabolism, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) activity and synthesis of cholesterol, fatty acids and acidic steroids from [14C]acetate were determined in cultured skin fibroblasts from 2-3 year old children. Prostaglandin E2 (PGE2) synthesis and nucleic acid synthesis were determined in cells when they were growing in medium containing normal, Alagille or fetal bovine serum. These values were similar to values of controls. HMGR activity was found to be similar in cells of control and children with the syndrome, whether the cells were incubated in lipoprotein-deficient or normal medium. Incorporation of acetate into cholesterol was inhibited to a greater extent by lipoprotein-containing medium in control than in children with the syndrome. Fatty acid synthesis was similar in all conditions. 1-7% of the recovered lipid radioactivity in cells and medium separated as acidic steroids. Serum from a donor patient, when included in the medium, did not affect PGE2 or nucleic acid synthesis compared with normal human or fetal bovine serum. The data suggest that cells of children with Alagille syndrome may have a membrane defect of transfer of cholesterol (LDL receptor defect) leading to excessive cholesterol synthesis. Also, synthesis of acidic steroids (bile acid-like material) and their secretion into the medium occurs in normal fibroblasts and those from children with the syndrome.

Acetates↗
PubMed1989

Food safety and health effects of canola oil.

Canola oil is a newly marketed vegetable oil for use in salads and for cooking that contains 55% of the monounsaturated fatty acid; oleic acid, 25% linoleic acid and 10% alpha-linolenate [polyunsaturated fatty acid (PUFA)], and only 4% of the saturated fatty acids (SFAs) that have been implicated as factors in hypercholesterolemia. It is expressed from a cultivar of rapeseed that was selectively bred from old varieties in Canada to be very low in erucic acid--a fatty acid suspected to have pathogenic potential in diets high in the original rapeseed oil in experimental animals. Canola oil is free of those problems. It is the most widely consumed food oil in Canada, and has been approved for Generally Recognized as Safe (GRAS) status by the Food and Drug Administration (FDA) of the United States Department of Health and Human Services. The fatty acid composition of canola oil is consistent with its use as a substitute for SFAs, in meeting the dietary goals recommended by many health associations: an average diet containing about 30% of calories as fat made up of less than 10% SFAs, 8-10% PUFAs in a ratio of linoleic to linolenic acids between 4:1 and 10:1, the remainder being monounsaturated fatty acids. No single oil meets these current recommendations for ratios of PUFA/monounsaturated/polyunsaturated fatty acid ratios as the sole source of cooking and salad oil.

Consumer Product Safety↗
PubMed1989

Relationship of dietary fat to plasma fatty acids, blood pressure, and urinary eicosanoids in adult men.

This experiment was conducted to determine the relationships between modest changes in dietary linoleate, blood pressure (BP) response, and levels of eicosanoid synthesis in humans. Products of eicosanoids which appear in blood were measured in urine: PGI2, 6-keto-PGF1 alpha (KPGI2); TXA2, (TXB2); PGF2 alpha, 13,14-dihydro-15-keto-PGF2 alpha, (MPGF2 alpha). Twenty-three adult men were fed controlled diets having 25 energy percent fat, and having P/S ratios of either 0.3 (low-PUFA) or 1.0 (high-PUFA), for a total of 12 weeks, with a switchover between P/S ratios at 6 weeks. The results showed that, under the conditions of this study, BP was significantly reduced by reducing dietary fat intake from about 37 to 25 energy percent. However, no further effects on BP were produced by increasing the P/S ratio from 0.3 to 1.0. KPGI2 excretion was significantly lowered on both controlled diets as compared to the self-selected (SS) diet. However, MPGF2 alpha was lowered only on the low-PUFA diet as compared to the self-selected diet. No significant decrease in TXB2 excretion was observed. Both MPGF2 alpha and KPGI2 excretion were positively correlated with urine volume and sodium excretion. On the SS diet, but not on the controlled diets, MPGF2 alpha excretion was negatively correlated with plasma linoleate and positively correlated with stearate. On the low-PUFA diet, MPGF2 alpha excretion increased with the intake of linoleate, while, on the high-PUFA diet, it decreased. This may have been due to the limited amounts of linoleate available in the low-PUFA diet (3.2-3.4 energy percent) as compared to that in the high-PUFA diet. Both KPGI2 and MPGF2 alpha excretion were positively correlated with systolic and diastolic BP. These results suggest that the amount of dietary linoleate is an important factor in the regulation of prostaglandin synthesis in humans.

Adult↗
PubMed1989

Dietary fat and cholesterol effects on cholesterol metabolism in CBA/J and C57BR/cdJ mice.

The aim of this study was to determine how small differences in dietary fats affect cholesterol metabolism in mice hypo- (CBA/J) and hyperresponsive (C57BR/cdJ) to diet-induced hypercholesterolemia. Six-wk-old male mice were fed either a diet corresponding to the U.S. average gross composition (US74, 40% of total energy as fat, 347 mg cholesterol/1000 Kcal, P/S = 0.24) or a modified-fat diet (30% of total energy as fat, 46 mg cholesterol/1000 Kcal, P/S = 0.91). After 8 wk of feeding, neither strain had developed hypercholesterolemia. CBA/J mice had higher concentrations of serum total and high-density lipoprotein (HDL) cholesterol and a higher esterified-to-free cholesterol ratio than did C57BR/cdJ mice. CBA/J mice maintained a constant serum cholesterol concentration mainly by adjusting the hepatic hydroxymethylglutaryl coenzyme A reductase (HMGR) activity, whereas C57BR/cdJ mice did so by changing the fecal excretion of cholesterol. Compared to the modified-fat diet, the US74 diet caused an increase in the ratio of total to HDL serum cholesterol, liver microsomal free cholesterol, fecal cholesterol and hepatic microsomal cholesterol 7 alpha-hydroxylase activity and a decrease in hepatic microsomal HMGR activity. We conclude that the metabolic responses to small differences in dietary fat are different in CBA/J and C57BR/cdJ mice.

Animals↗
PubMed1989

[The Freud-Ferenczi relationship studied in the light of their correspondence].

The Freud-Ferenczi relationship was a more complex one than it is commonly thought to have been in psychoanalytic circles. It started in a less idyllic manner than it is said to have done, and it did not end in the breaking off of their relationship as many believe it did. Nonetheless, the two men were possessed of very dissimilar temperaments: the nature of the demands they made on each other were complementary, but impossible to satisfy. This situation led to a number of cases of friction which appeared in association with several major events, but evidence of these conflicts is also to be found in a number of small signs that can be detected throughout the correspondence between the two men. Despite the great complexity of emotions at play in their relationship, it resulted in a strong and loyal friendship that withstood the most directly expressed differences in opinion.

History, 20th Century↗
PubMed1989

Farnesylacetone, a sesquiterpenic hormone of Crustacea, inhibits electron transport in isolated rat liver mitochondria.

Farnesylacetone (C18 H30 0) is a male hormone extracted from the androgenic gland of crab, Carcinus maenas. Appropriate enzymatic assays, as well as spectrophotometric studies, indicate that micromolar concentrations of farnesylacetone interact with the electron transport pathway of rat liver mitochondria. By the use of artificial electron donors and electron acceptors, it is shown that farnesylacetone immediately inhibits the electron transfer within complex I (NADH ubiquinone reductase activity) and complex II (succinate ubiquinone reductase activity). It is proposed that farneylacetone could interact with these two complexes of the respiratory chain at the level of the iron-sulfur centers implicated in the dehydrogenase activities. These observations are compared with the results obtained with terpenic molecules which interact with mitochondrial respiration.

Animals↗
PubMed1988

Effects of low fat diets differing in degree of fat unsaturation on plasma lipids, lipoproteins, and apolipoproteins in adult men.

The effects of two low fat diets with differing ratios of polyunsaturated to saturated fatty acids (P/S) on blood lipids, lipoproteins (LP), and apolipoproteins (Apo) were studied in 23 adult men, 30-60 years old, using a crossover design. Both test diets had 25% fat calories with either a P/S of 0.3 (Diet 1) or a P/S of 1.0 (Diet 2) and equivalent amounts of cholesterol. The study consisted of four periods: a 5-week prestudy on self-selected diet (SS), two 6-week test diet periods followed by a second 5-week post-study period on the SS diet. When compared with the SS diet, Diet 2 lowered the mean plasma total cholesterol (TC) by about 20% (P less than 0.01). Low density lipoprotein (LDL) cholesterol was also decreased by about 18% by Diet 2 (P less than 0.01). The high P/S diet did not cause a change in total cholesterol in the high density lipoprotein (HDL) subclass2 (HDL2) when compared to the SS diet. Levels of triglycerides (TG) were slightly reduced in HDL2 but showed a greater reduction in HDL3 in both diets. Phospholipids (PL) were significantly reduced in HDL2 and in HDL3, but the reduction in HDL3 PL was not statistically significant. Apo A-I levels were not changed by either diet when compared with the SS diet, but Apo A-II levels of HDL2 and HDL3 were significantly decreased by the low fat diets, and there was no P/S effect. No other consistent changes in apoprotein levels occurred. Our data suggest that, in men with normal lipid levels, practical dietary changes involving a moderate increase in P/S from 0.3 to 1.0 in a low fat, low cholesterol diet do influence lipoprotein composition and apoprotein distribution in a short time. The reduction in cholesterol in total lipid composition and in LDL lipids which accompanied the reduction of dietary fat and cholesterol are considered to be beneficial.

Adult↗
PubMed1988

Hepatic hydroxymethylglutaryl coenzyme A reductase activity in inbred strains of mice.

Hydroxymethylglutaryl coenzyme A reductase (HMGR) activity is a major factor in the regulation of cholesterol homeostasis. Enzyme activity is known to vary with age, sex, diurnal cycle, and dietary properties in rats. Mice are available in numerous genetic strains and could be a useful inexpensive animal model for studying diet and genetic interactions in the regulation of cholesterol metabolism. Obese and non-obese C57BL/6J, CBA/J, and obese and non-obese DW dbPas mice were subjected to variations in light cycle, feeding schedule, and pectin and fat composition of their diets. They were then killed by decapitation, and hepatic microsomal HMGR analyzed. The mice responded in the same ways as rats to light cycle, feeding pattern, and sex difference. They exhibited marked differences in HMGR activity due to age, genotype, strain, and diet variations. We conclude that mice will, indeed, offer an excellent animal model for the study of cholesterol metabolism regulation.

Animals↗
PubMed1987

Intraplatelet levels of vWF:Ag and fibrinogen in myeloproliferative disorders.

Several platelet function abnormalities have been described in the myeloproliferative syndromes. We have measured the intraplatelet vWF:Ag and fibrinogen (FI) in the platelet lysates by Laurell technique in 11 patients with polycythemia vera (PV), 10 with essential thrombocythemia (ET), 14 with chronic myelocytic leukaemia (CML) and 3 with myelofibrosis (MF) and these results were correlated with platelet function abnormalities. Decreased intraplatelet levels of vWF:Ag and FI were found in all the patients with ET and MF, in 8 out of 11 PV and 3 out of 14 CML. A statistical significant correlation was observed between the intraplatelet levels of vWF:Ag and FI in the control group and in CML and PV, but no correlation was found in ET and MF. No correlation was observed between the plasmatic and the intraplatelet levels of vWF:Ag and FI in any group. Evidences of platelet activation (spontaneous platelet aggregation or circulating platelet aggregates) were observed in 40% of the cases with ET and PV, and all these cases had low intraplatelet levels of both antigens. None of the cases with MF had evidences of platelet activation and 2 out of 14 patients with CML had platelet activation. The deficiency of the dense bodies was less frequent than the depletion of the alpha granules (5 out of 11 PV, 4 out of 10 ET, 6 out of 14 CML and 2 out of 3 MF). The low intraplatelet contents of vWF: Ag and FI, more frequently observed in ET and PV, may be the result of platelet activation and in vivo release, but megakaryocyte dysfunction is more likely in myelofibrosis.

Antigens↗