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Biomedical subjects

M J Leroy

Publications and source records attributed to M J Leroy.

At least 37 records · Page 2Linked to original sources

Electrogenic malate uptake and improved growth energetics of the malolactic bacterium Leuconostoc oenos grown on glucose-malate mixtures.

Growth of the malolactic bacterium Leuconostoc oenos was improved with respect to both the specific growth rate and the biomass yield during the fermentation of glucose-malate mixtures as compared with those in media lacking malate. Such a finding indicates that the malolactic reaction contributed to the energy budget of the bacterium, suggesting that growth is energy limited in the absence of malate. An energetic yield (YATP) of 9.5 g of biomass.mol ATP-1 was found during growth on glucose with an ATP production by substrate-level phosphorylation of 1.2 mol of ATP.mol of glucose-1. During the period of mixed-substrate catabolism, an apparent YATP of 17.7 was observed, indicating a mixotrophy-associated ATP production of 2.2 mol of ATP.mol of glucose-1, or more correctly an energy gain of 0.28 mol of ATP.mol of malate-1, representing proton translocation flux from the cytoplasm to the exterior of 0.56 or 0.84 H+.mol of malate-1(depending on the H+/ATP stoichiometry). The growth-stimulating effect of malate was attributed to chemiosmotic transport mechanisms rather than proton consumption by the malolactic enzyme. Lactate efflux was by electroneutral lactate -/H+ symport having a constant stoichiometry, while malate uptake was predominantly by a malate -/H+ symport, though a low-affinity malate- uniport was also implicated. The measured electrical component (delta psi) of the proton motive force was altered, passing from -30 to -60 mV because of this translocation of dissociated organic acids when malolactic fermentation occurred.

Adenosine Triphosphate↗

The effect of vasoactive intestinal peptide (VIP) on the contractile activity of human uterine smooth muscle.

1. In the present study we examined the in vitro effect of vasoactive intestinal peptide (VIP) on spontaneous contractions in both inner and outer layers of non-pregnant human myometrium. A dose-dependent relaxation was observed, but with a marked difference in sensitivity to VIP between the two layers, with an IC50 value of 1 x 10(-8) and 1 x 10(-5) mol L in the outer and inner layers, respectively. 2. We also established that VIP did not directly stimulate the adenylate cyclase activity. The only slight stimulations were observed in non-initial rate conditions. The maximal response of this indirect effect was obtained for VIP concentrations between 1 x 10(-9) and 1 x 10(-8) mol/L and this occurred to the same extent (an approximately 1.4-fold increase) in both layers. However this response is specific, since structurally related peptides such as glucagon, gastric inhibitory polypeptide (GIP), secretin, or human growth hormone-releasing factor (hGRF) had no effect in our preparations. 3. Autoradiographic studies revealed that specific VIP binding sites were located on the vascularization of the intermediate vascular layer and on arterioles and venules distributed in the inner and outer myometrial layers. They were also present in the endometrium, but not on smooth muscle cells of either layer. 4. Such observations could provide evidence for another signal transduction pathway to mediate the biological effect of VIP. An additional intermediate step on the vascularization distributed in all of the muscle cannot be excluded.

Adenylyl Cyclases↗

Sensitivity of the human myometrial adenylate cyclase to calcium and calmodulin.

The calcium-calmodulin-dependent regulation of adenylate cyclase was studied in membranes from pregnant human myometrium. In the absence or presence of exogenous calmodulin, free calcium concentrations greater than 50 nmol/l inhibited the adenylate cyclase activity. Activation of the enzyme by calmodulin (0.1-1 mumol/l) was calcium-dependent and maximal at 10 nmol/l free calcium. The myometrial adenylate cyclase activity was stimulated by the guanyl nucleotide, Gpp(NH)p. In the presence of the guanyl nucleotide, the activatory effect of the calcium-calmodulin complex disappeared. The activatory effect of exogenous calmodulin was dependent on endogenous calmodulin present in the myometrial membranes. Trifluoroperazine and calmidazolium were able to inhibit the adenylate cyclase activity.

Adenylyl Cyclases↗

Comparison of lead levels in human permanent teeth from Strasbourg, Mexico City, and rural zones of Alsace.

A comparative study of the mean lead concentrations in enamel and dentin of human premolars and permanent molars was conducted by means of a systematic sampling procedure with energy-dispersive x-ray fluorescence analysis. In a first series of analyses, no significant statistical differences in mean lead concentrations at various levels of enamel and dentin were noted between young patients of Strasbourg and those of small villages of Alsace, nor between elderly patients living in these two locations, despite the fact that motor traffic was significantly lower in the rural zones. However, in both locations, a significantly higher concentration of lead was observed in enamel and dentin in relation to age. In a second series of analyses, the mean lead concentrations of both dental hard tissues of premolars and permanent molars of young individuals from Strasbourg, rural Alsace, and Mexico City were compared. Significantly higher mean lead concentrations were found in enamel and dentin samples from Mexico City. This was most evident for inner coronal dentin (5.7 and 6.1 times greater than in teeth of Strasbourg and rural zones of Alsace, respectively) and for pulpal root dentin (6.9 and 8.9 times greater than in teeth of Strasbourg and rural zones of Alsace). It is proposed that the higher lead concentrations are related to the higher lead content of motor gasoline and to more intense traffic conditions. The dental hard tissues appear to be of value for the study of environmental lead pollution.

Adolescent↗

Functional coupling of the alpha 2-adrenergic receptor-adenylate cyclase complex in the pregnant human myometrium.

We previously reported that in the pregnant human myometrium the binding sites labeled with [3H]idazoxan have the pharmacological characteristics of alpha 2-adrenergic receptors. Competitive experiments have also revealed that the stable guanine nucleotide analog guanyl-5'-imidodiphosphate decreases the apparent affinity of norepinephrine and clonidine for myometrial [3H]idazoxan-binding sites. In the present study, the alpha 2-adrenergic mechanism in this tissue was further approached by measuring adenylate cyclase responses and examining the different pertussis toxin-sensitive G-proteins. The two alpha 2-adrenergic agonists norepinephrine and clonidine inhibited adenylate cyclase activity in both the outer and inner layers of the pregnant human myometrium. The inhibitory effect of these agonists is completely reversed by alpha 2-adrenergic antagonists such as yohimbine and idazoxan. Pretreatment with pertussis toxin completely suppresses the inhibition of adenylate cyclase mediated by alpha 2-adrenergic receptors, suggesting that an inhibitory protein of the Gi type is involved. Pertussis toxin, known to catalyze the ADP ribosylation of the alpha-subunit of several G-proteins, labels three substrates at 39, 40, and 41 kDa. The more intense labeling occurring on the 40- to 41-kDa components are assigned to alpha-subunits of Gi-like proteins, whereas that at 39 kDa might correspond to a Go alpha-like substrate. These results indicate the presence of alpha 2-adrenergic receptors in the human myometrium at the end of pregnancy that are functionally linked to inhibition of adenylate cyclase activity via the Gi protein.

Adenosine Diphosphate Ribose↗

Cisplatin-induced anemia: a potential interference with iron metabolism at erythroid progenitors level.

To elucidate the potential mechanisms of anemia induced by cisplatin (CDDP) we have evaluated hemolysis, dyserythropoiesis, ferrokinetics and cytotoxicity on erythroid progenitors in 12 patients treated by a CDDP-containing combination chemotherapy and in 6 patients treated by a similar combination but without CDDP. Eight patients, from the CDDP treated group, experienced a pronounced anemia. None had signs of hemolysis. Ferrokinetic study showed a very deep and protracted decrease of 59Fe incorporation during the chemotherapy cycle and the following 2 weeks. These results, along with a normal medullary erythroblastic cellularity, suggest that CDDP induces a deep but transient erythropoiesis alteration leading to anemia in some cases.

Adult↗

[Oligo-elements of the amniotic fluid from normal, hypotrophic and trisomy 21 fetuses].

Oligo-elements concentrations were measured between 16-18 weeks of normal pregnancy in the amniotic fluid of 84 women who delivered children with a normal weight, 16 women who had term delivery of hypotrophic children, and 7 women who delivered trisomic children (5 trisomy 21, one trisomy 18 and one trisomy 10p). Copper, zinc, bromine, lead, rubidium assays were carried out using fluorescence X spectrophotometry with dispersion of energy. The oligo-elements levels are not different in the three groups of amniotic fluid: hypotrophic, trisomic or normal fetuses. These results are compared with those previously reported.

Adult↗

Correlation between selective inhibition of the cyclic nucleotide phosphodiesterases and the contractile activity in human pregnant myometrium near term.

The present study was carried out to determine the ability of various pharmacological agents to selectively inhibit each cytosolic form of phosphodiesterase isolated from the longitudinal layer of human myometria near term. Among the drugs tested, zaprinast specifically inhibits the first form of PDE which hydrolyses both substrates (cAMP and cGMP) and is stimulated by the Ca2+-calmodulin complex. A second form of PDE specific for cAMP hydrolysis and Ca2+-calmodulin insensitive is only present during pregnancy. Rolipram is the most potent and selective inhibitor of this second form. It is also the most efficient compound to inhibit in vitro the spontaneous contractions of near term myometria. The double effect of rolipram suggests an important role of the second form of PDE in the mechanisms of contractility during the pregnancy. In addition rolipram or other derivatives might be of a therapeutic interest in the prevention of prematurity in so far as they are devoid of undesirable maternal and fetal side effects.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Zinc and strontium analyses by energy dispersive X-ray fluorescence in human permanent teeth.

The zinc and strontium content of enamel and dentine from humans aged 9-64 yr was analysed, after systematic sampling, by X-ray fluorescence. Relatively high levels of zinc were found in both hard tissues but there was no significant increase with age. Zinc content decreased significantly from outer to inner enamel and increased significantly again from peripheral to pulpal coronal and root dentine. The strontium content was significantly higher in enamel than in dentine; there was a significant increase with age in enamel but not in dentine. However, outer and inner enamel showed no significant difference in strontium content. Almost similar amounts of strontium were found in coronal and root dentine.

Adolescent↗

[Multiple elemental organic components of the broncho-alveolar lavage fluid in normal subjects and in various lung pathologies (excluding silica and asbestos fibers)].

Owing to a technical analysis enabling the detection of mineral elements present in trace amounts in small volumes, an analysis of the liquid obtained in 148 broncho-alveolar lavages could be studied. The elements consistently recovered were as follows: iron, copper, zinc, nickel, lead and titanium. Normal values were established. In the absence of exposure, there was no significant difference distinguishing the different pulmonary diseases studied. In occupational disease, the presence of iron in large quantities, tungsten, nickel and rare earths could be shown objectively, as well as the persistence of gold or iodine after medical absorption. However, this preliminary work does not allow one to establish a formal correlation between the alveolar concentrations obtained and the pulmonary disease observed.

Adolescent↗

[Disorders of plasma trace elements in diabetes. Relation to blood glucose equilibrium].

The influence of glycaemic control and diabetes characteristics on plasma concentrations of magnesium, zinc, copper, selenium, rubidium and bromine has been evaluated in 44 diabetics (30 insulin-dependent, 14 non insulin-dependent), and the results obtained were compared to those of 309 control subjects of the same mean age. Diabetics had reduced plasma magnesium concentrations (P less than 0.01) but normal erythrocyte magnesium levels. Plasma zinc and selenium concentrations were reduced, whereas those of copper were increased and those of bromine and rubidium were normal. Correlation between glycaemic control, evaluated by measurement of glycosylated haemoglobin levels, and each of the parameters studied was only demonstrated with magnesium in insulin-dependent diabetics (r = -0.561; P less than 0.02). No correlation was found with the other clinical or anthropometric characteristics of the diabetic patients studied. Diabetes seems to be associated with numerous abnormalities of plasma trace elements and magnesium, but the mechanism of these abnormalities has not yet been elucidated. A decrease in zinc and selenium concentrations and an increase in copper concentrations might be additional factors of atherogenicity.

Adult↗

Different alpha 2-adrenoceptor densities in the circular and longitudinal layers of human near-term myometrium as revealed by [3H]-idazoxan binding studies.

[3H]-idazoxan, a specific alpha 2-adrenoceptor antagonist radioligand, has been used to characterize alpha 2-adrenoceptors in both circular and longitudinal layers of human near-term myometrium. [3H]-idazoxan binding is reversible, saturable and stereospecific. It labels with high affinity a single population of sites. Competition curves with different alpha 2-adrenoceptor agonists and antagonists show that the binding sites labelled with [3H]-idazoxan have the pharmacological characteristics of alpha 2-adrenoceptors. Though the KD value is similar in both layers (approximately 7 nM), the density of alpha 2-adrenoceptors in the circular layer (324 +/- 21 fmol/mg of protein) is significantly higher than in the longitudinal one (183 +/- 48 fmol/mg of protein).

Adrenergic alpha-Agonists↗

Age-related lead increase in human permanent teeth demonstrated by energy dispersive X-ray fluorescence.

The combined use of a systematic sampling procedure with energy dispersive X-ray fluorescence on non-erupted and erupted permanent premolars and molars in patients aged 9 to 64 years, who have lived all their lives in Strasbourg, showed a higher total lead content in dentine compared to enamel, with an approximate ratio of 2:1. In addition, a lead increase was observed in both tissues with age. The lead increase in dentine was more significant and the highest lead values were noted in the inner pulpal dentine layer of the oldest age group. When compared to similar lead studies made on permanent teeth in urban areas, it can be concluded that the lead content in the teeth of the inhabitants of Strasbourg can be considered as low.

Adolescent↗

A method of lead determination in human teeth by energy dispersive X-ray fluorescence (EDXRF).

A systematic sampling procedure was combined with a method of energy dispersive X-ray fluorescence (EDXRF) to study lead content and its variations in human teeth. On serial ground sections made on unembedded permanent teeth of inhabitants of Strasbourg with a special diamond rotating disk, 2 series of 500 microns large punch biopsies were made systematically in 5 directions from the tooth surface to the inner pulpal dentine with a micro-punching unit. In addition, pooled fragments of enamel and dentine were made for each tooth. On each punched fragment or pooled sample, lead content was determined after dissolution in ultrapure nitric acid, on a 4 microns thick polypropylene film, and irradiation with a Siemens EDXRF prototype with direct sample excitation by a high power X-ray tube with a molybdenum anode. Fluorescence was detected by a Si(Li) detector and calcium was used as an internal standard. This technique allowed a rapid, automatic, multielementary and non-destructive analysis of microsamples with good detection limits.

Biopsy↗

Adrenergic receptors in inner and outer layers of human myometrium near term: characterization of beta-adrenergic receptor sites by [125I]-iodocyanopindolol binding.

The beta-adrenergic receptors present in inner and outer layers of human myometrium near term were characterized using the radioiodinated antagonist iodocyanopindolol (ICYP). In both layers ICYP binding is saturable, rapidly reversible, stereoselective, and appears to occur in a single class of sites with a KD of 30 pmol/l. Adrenergic agonists compete for ICYP binding sites with an order of potency consistent with beta 2-adrenergic potencies: isoproterenol greater than epinephrine much greater than norepinephrine. Studies in which CGP 20712 A, a beta 1-adrenergic antagonist, competes for ICYP binding sites in human myometrium reveal that at least 65% of the beta-receptors present are beta 2-subtype, whatever the layer considered. At the 35th week of pregnancy, the density of beta-adrenergic receptors in the inner layer (15.2 fmol/mg of protein) is about 50% higher than in the outer layer. At term, the densities of beta-adrenergic receptors are reduced and exhibit the same values for both layers (5 fmol/mg of protein). These results indicate that the beta-adrenergic receptors in the two layers diminish during pregnancy and reach, at term, an equal and low level of density.

Binding Sites↗

Characterization by DEAE-cellulose chromatography of a single molecular form of cyclic nucleotide phosphodiesterase in the myometrium of nonpregnant women.

In the longitudinal layer of nonpregnant human myometrium, cyclic nucleotide phosphodiesterase (PDE) activity from the soluble fraction is resolved by DEAE-cellulose chromatography into a single peak which presents no substrate specificity and is calcium-calmodulin-sensitive. As in the homogenate and in the soluble fraction, this peak shows two affinities for cAMP and only one for cGMP. In the soluble fraction of preterm and nearterm myometria, a similar peak is identified, but it presents a biphasic kinetic pattern towards both substrates. During pregnancy, in contrast with the nonpregnant tissue, a second peak of PDE highly selective for cAMP hydrolysis has been isolated specifically in the myometrial soluble fraction. The physiological significance of these two enzymatic forms is still unknown, particularly the role of the cAMP-specific form in the control of uterine motility during pregnancy.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Simultaneous determination of Pt and essential trace elements in plasma by energy dispersive x-ray fluorescence (EDXRF).

Energy dispersive x-ray fluorescence allows the simultaneous determination of platinum and essential trace-elements in plasma and filtered plasma. Pharmacokinetics of platinum and the variations of trace-elements levels with respect to the normal mean values before and during the treatment are reported. Particularly during the treatment we observed that total iron concentration clearly increases in plasma, which suggests a hemolytic effect of the drug. However we can exclude this hypothesis by the simultaneous determination of potassium and rubidium levels, which do not increase as greatly as in hemolysed samples.

Antineoplastic Combined Chemotherapy Protocols↗