Biomedical subjects

F Moreau

Publications and source records attributed to F Moreau.

At least 19 recordsLinked to original sources

PubMed2006

[Diffuse uptake of brown fat on computed-tomography coupled positron emission tomoscintigraphy (PET-CT) for the exploration of extra-adrenal pheochromocytoma].

We report an observation of strong bilateral uptake on a PET-CT scan compatible with activation of brown adipose tissue in a patient with extra-adrenal pheochromocytoma. A 42-year-old man was hospitalized for hypersudation together with weight loss and palpitations. Heart rate was 120 bpm and fasting blood glucose 1.36 g/l. Endocrine explorations revealed elevated serum chromogranine which reached 517 ng/ml (19-38). The norepinephrine level reached 49.7 nmol/l (<4.00) and urinary norepinephrine and normetanephrine levels reached 13977 nmol/24h (<414) and 32 micromol/24h (0.4-2.5) respectively. The thoraco-abdominal and pelvic scan showed a 6 cm diameter paraaortic hypervascularized mass with an infiltrative lesion of both perirenal area and mediastinal tissue without adenopathies. The abdominal MRI revealed the mass with a low intensity signal in T1 and a slight high intensity signal in T2. MIBG and octreoscan scintigraphies were negative. 18F-DG PET showed intensed uptake in the tumor mass together with intense, diffuse and bilateral uptake above and below the diaphragm. The mass was resected. Histological examination of the surgical specimen confirmed the diagnosis of extra-adrenal pheochromocytoma with an index of 13% cellular proliferation without cell atypia. There was a hypervascularization with small islets of brown adipose tissue in the perirenal fat. Both plasmatic and urinary catecholamines decreased to the normal range after the operation and PET-scan normalized. Bilateral spread of the radiotracer uptake was probably due to brown adipose tissue activation by excessive sympathetic stimulation induced by catecholamines released by the tumor.

Abdominal Neoplasms↗

PubMed2004

BiaCore analysis of leptin-leptin receptor interaction: evidence for 1:1 stoichiometry.

Leptin is a hormonal protein involved in energy homeostatis that acts to inhibit food intake, to stimulate energy expenditure, and to influence insulin secretion, lipolysis, and sugar transport. Its action is mediated by a specific receptor whose activation is highly controversial. As a member of the cytokine receptor superfamily, it has been predicted to be activated by ligand-induced dimerization. However, recent evidence has indicated that this receptor exists as a dimer in both ligand-free and ligand-bound states. Here, the BiaCore has been used to measure the kinetics and stoichiometry of the interaction between the leptin and its receptor. Human or mouse receptor chimeras comprising two receptor extracellular domains fused to the Fc region of IgG(1) were captured on to the sensor via protein G. Kinetic data fitted to the simplest 1/1 model. The observed stoichiometry at ligand saturation was 1:1. Analyzing the binding mode and the reaction stoichiometry allowed us to conclude that the leptin receptor dimerization is not induced by ligand binding. This contradicts the common paradigm of cytokine receptor activation. Furthermore, data demonstrated a high-affinity interaction. The KD was 0.23+/-0.08 nM, with ka = (1.9 +/- 0.4) x 10(6) M(-1)s(-1) and kd = (4.4 +/- 0.6) x 10(-4) s(-1) for human leptin with its cognate receptor. Similar results were observed for the affinity of different species of leptin binding to mouse leptin receptor.

Amino Acid Sequence↗

PubMed2004

[Sleep apnea syndrome in the elderly].

INTRODUCTION: Sleep apnoea/hypopnoea syndrome (SAHS) is distinct in the elderly as age-related co-morbidity may be aggravated by sleep-related breathing disorders or may mask typical clinical symptoms. STATE OF ART: The SAHS prevalence in the elderly varies from one study to another, with an average rate of 25% that might increase according to the importance of associated pathologies. Clinical symptoms tend to be the neurological manifestations of excessive daytime sleepiness and cognitive deterioration. PERSPECTIVES: Treatment of SAHS should include weight reduction strategies if obesity is present. There is no role for surgery in this age group. On the other hand, adjustable oral appliances can be used depending on the severity of the SAHS, but nasal continuous positive airway pressure (CPAP) remains the most effective therapy available. Acceptance of and compliance with CPAP treatment is as good in this age group as in younger patients, with remarkable effectiveness in terms of improvement in daytime sleepiness and cognitive function. However, the effectiveness of treatment for SAHS is related to the level of symptoms present and this should be taken into account when making a therapeutic decision. CONCLUSIONS: These results fully justify treatment of SAHS in the elderly, but the decision to treat should be governed by the level of clinical symptoms from SAHS.

Aged↗

PubMed2003

[Sleep apnea syndrome in the elderly].

Aged↗

PubMed2000

Consequences of omega -6-oleate desaturase deficiency on lipid dynamics and functional properties of mitochondrial membranes of Arabidopsis thaliana.

We probed the role of the polyunsaturated fatty acids on the dynamic and functional properties of mitochondrial membranes using the fad2 mutant of Arabidopsis thaliana, deficient in omega-6-oleate desaturase. In mitochondria of this mutant, the oleic acid content exceeded 70% of the total fatty acids, and the lipid/protein ratio was greatly enhanced. As a consequence, local microviscosity, probed by anthroyloxy fatty acid derivatives, was increased by 30%, whereas the lipid lateral diffusion, assayed using 1-pyrenedodecanoic acid, was approximately 4 times increased. Functional parameters such as oxygen consumption rate under phosphorylating and nonphosphorylating conditions and proton permeability of the inner mitochondrial membrane were significantly reduced in fad2 mitochondrial membranes, while the thermal dependence of the respiration was enhanced. Moreover, metabolic control analysis of the respiration clearly showed an enhancement of the control exerted by the membrane proton leaks. Our data suggest that the loss of omega-6-oleate desaturase activity in Arabidopsis cells induced an enhancement of both microviscosity and lipid/protein ratio of mitochondrial membranes, which in turn were responsible for the change in lateral mobility of lipids and for bioenergetic parameter modifications.

Arabidopsis↗

PubMed1999

Mutational analysis of the promoter region of the porA gene of Neisseria meningitidis.

The porA gene encodes the class 1 outer membrane protein (OMP1) in Neisseria meningitidis and is under transcriptional control. Promoter regions of porA from different clinical isolates were sequenced and were found to differ in the number of guanosine residues in a poly(G) track located upstream of the -10 region. Isolates that did not express OMP1 had up to nine G residues in the poly(G) track or an adenosine residue within this poly(G) track. Using beta-galactosidase as a reporter gene, the transcriptional activities of the promoter regions of the porA gene from three strains, two of which do not express OMP1, were assayed in both Escherichia coli and N. meningitidis. Mutations in the poly(G) track were created by site-directed mutagenesis and promoter fusions were further analyzed in E. coli and N. meningitidis. The number of nucleotides in the poly(G) track influenced promoter activity: reduction of a poly(G) track of 12nt by one and by two guanosine residues reduced promoter activity. Within the poly(G) track, replacement of an adenosine residue by a guanosine residue increased the promoter activity; replacement of a guanosine residue by an adenosine residue decreased the activity. The similar transcriptional activities for the mutated promoters in E. coli and N. meningitidis are compatible with similar control mechanisms for transcriptional control in both organisms.

Base Sequence↗

PubMed1998

Stress Induction of Mitochondrial Formate Dehydrogenase in Potato Leaves

In higher plants formate dehydrogenase (FDH, EC 1.2.1.2.) is a mitochondrial, NAD-dependent enzyme. We previously reported that in potato (Solanum tuberosum L.) FDH expression is high in tubers but low in green leaves. Here we show that in isolated tuber mitochondria FDH is involved in formate-dependent O2 uptake coupled to ATP synthesis. The effects of various environmental and chemical factors on FDH expression in leaves were tested using the mitochondrial serine hydroxymethyltransferase as a control. The abundance of FDH transcripts is strongly increased under various stresses, whereas serine hydroxymethyltransferase transcripts decline. The application of formate to leaves strongly enhances FDH expression, suggesting that it might be the signal for FDH induction. Our experiments using glycolytic products suggest that glycolysis may play an important role in formate synthesis in leaves in the dark and during hypoxia, and in tubers. Of particular interest is the dramatic accumulation of FDH transcripts after spraying methanol on leaves, as this compound is known to increase the yields of C3 plants. In addition, although the steady-state levels of FDH transcript increase very quickly in response to stress, protein accumulation is much slower, but can eventually reach the same levels in leaves as in tubers.

Journal Article↗

PubMed1998

Sequencing of porA from clinical isolates of Neisseria meningitidis defines a subtyping scheme and its genetic regulation.

Subtyping Neisseria meningitidis by methods that rely on monoclonal antibody (mAb) reactivity results in an unusually high number of strains that are not subtypeable. To subtype 48 strains isolated (1993-1994) in the province of Quebec that were not subtypeable by mAb-based techniques, we used DNA sequencing of the variable regions of porA, a gene that encodes the class 1 outer membrane protein. We assigned subtypes to all the previously nonserosubtypeable isolates and identified some novel subtypes. Because our sequencing strategy included the promoter region of porA, different isolates were compared in their sequences of the porA promoter region. A poly(G) stretch lies between the -10 and -35 regions of the promoter; replacement of a G residue by an A residue in this region resulted in loss of expression of porA. No correlation was found between the number of G residues in the poly(G) stretch and the level of expression; a minimum of 10 G residues is required in this stretch for expression of porA. One isolate expressed no class 1 outer membrane protein because of the insertion sequence IS1301 in the coding region of porA. Another isolate did not express the protein owing to a frame-shift mutation within the coding region of porA. Sequencing of porA allowed assignments of subtypes to previously uncharacterized isolates and provided insights about the regulation of expression of this gene in N. meningitidis.

Amino Acid Sequence↗

PubMed1998

[Impact of hospital infection on medical expenditures in a continuing care and rehabilitation service at a geriatric hospital].

The costs of medical expenditures such as drugs, medical devices (MD), biological assays and nurses workload, were measured, before and after the onset of nosocomial infection (NI), in rehabilitation care departments of a 1000-beds geriatric teaching hospital. Data were collected retrospectively in medical records and nursing records. Nurse's workload was measured by the French indicator "Soins Infirmiers Personnalisé à la Personne Soignée" (SIIPS). A week before and a week after the diagnosis of hospital-acquired infection, medical consumptions were compared. During the study 38 of the 206 patients admitted in rehabilitation care wards presented hospital-acquired infection. Data were collected for 31 of these 38 patients. Nosocomial infections are associated with an increased pharmaceutical dispensing: medication (mainly antibiotics) and medical device's cost; and an increased nurse's workload. This study suggests that infection surveillance may be helpful to a better understanding of pharmaceutical dispensing variation in geriatric rehabilitation care departments.

Aged↗

PubMed1997

Outer membrane proteins and serosubtyping with outer membrane vesicles from clinical isolates of Neisseria meningitidis.

The currently practiced protocol for routine serosubtyping of Neisseria meningitidis relies on reactivity of whole cells to monoclonal antibodies against the class 1 outer membrane protein (OMP) in ELISAs or dot-blots. This procedure, however, failed to yield serosubtyping information in 28% (48/174) of clinical isolates (1993-1994) in the province of Québec, Canada. These 48 strains were characterized by OMP profiles and ELISAs with outer membrane vesicles (OMVs). Forty out of the 48 strains expressed class 1 OMP, indicating that the inability to assign a serosubtype was not owing to the absence of the class 1 OMP. Of these, 15 (38%) were serosubtypable in ELISAs with outer membrane vesicles. Thus, 81% (141/174) of all meningococcal strains were serosubtypable with ELISAs using whole-cells or OMVs. Because the routinely used procedure for serosubtyping of meningococci is limited in providing serosubtype information, alternate procedures are proposed to obtain comprehensive information for epidemiological identification of this bacterium.

Bacterial Outer Membrane Proteins↗

PubMed1997

Subtyping of Neisseria meningitidis strains isolated in Quebec, Canada: correlation between deduced amino acid sequences and serosubtyping techniques.

Routine serosubtyping of Neisseria meningitidis relies upon reactivity of whole cells to monoclonal antibodies (mAbs). This procedure is limited in providing maximum serosubtype information because some epitopes in whole cells are masked and because mAbs are currently unavailable for some epitopes. To address masking of epitopes in whole cells, we isolated outer membrane vesicles (OMVs) from nine representative meningococcal strains that were isolated (1991-1993) in the province of Quebec, Canada; the OMVs were used in enzyme-linked immunosorbent assay for reactivity to mAbs, and improved serosubtyping information was obtained. A recent proposal assigns subtypes based on deduced amino acid sequences in the variable regions of the class 1 outer membrane protein. This scheme maintains the subtyping nomenclature that is based on reactivity to mAbs by defining the sequences in the epitopes recognized by the mAbs. We used this technique to assign subtypes to the meningococcal strains isolated in Quebec. For the strains tested, serosubtyping using mAbs and subtyping based on deduced amino acid sequences were in complete agreement. Subtyping using deduced amino acid sequences is superior because it does not depend on the availability of mAbs.

Amino Acid Sequence↗

PubMed1997

Cardiotoxic effects of salmeterol in comparison with salbutamol on the isolated perfused Langendorff-heart of the rat.

beta 2-Adrenoceptor agonists used in the relief of bronchospasm have long been known to produce circulatory side-effects. Salmeterol (CAS 89365-50-4) is a novel long acting highly selective beta 2-agonist. We used the Langendorff-heart rat model (constant perfusion pressure) to compare the direct effects of salbutamol (CAS 18559-94-9, SAL) and salmeterol (SMT) on the cardiac performances and their toxic cardiac effects (induced by 3 mmol/l perfusate calcium). At the first step the concentration-effect curve was established for the maximal concentration (Cmax) of salbutamol leading to the maximal chronotropic effect on the heart for 20 min after a 20 min stabilization period (basal values). All hearts were consequently submitted to a 20 min Krebs-Henseleit perfusion in order to study the reversibility of the myocardial performances. The types of the myocardial and coronary beta-adrenoceptors involved in SAL (Cmax) effects were identified using a selective beta 1 (atenolol) and a beta 2 (butoxamine) antagonist. SAL induced an increase in the heart rate via a selective stimulation of the beta 1-adrenoceptors (beta 1-AR). SMT appeared to be more potent than SAL on the heart rate. Direct toxic drug effects on the heart appeared gradually with SAL whereas they appeared sharply at the highest concentration of SMT. The enzyme leakage observed during the recovery period was more pronounced with SMT than SAL. Perhaps, this phenomenon might be due to the lipophilicity of SMT. However, these direct cardiac effects of SMT have to be considered in association with its airway smooth muscle relaxant effect (therapeutic effect) which has been proven much more potent than those of SAL. Therefore SMT was less cardiotoxic than SAL at similar therapeutic concentrations.

Adrenergic beta-Agonists↗

PubMed1996

Protonophoric activity of eutypine, a toxin from Eutypa lata, in plant mitochondria.

Eutypine is a toxin produced by Eutypa lata, the causal agent of the dying-arm disease of grapevine. We have previously shown that this toxin behaves as a lipophylic weak acid (pK = 6.2) and induces drastic changes in both the respiration and energy balance of grapevine cells. In the present study, the molecular mode of action of eutypine at the mitochondrial level, using methyl-eutypine, the unprotonable derivative of the toxin, has been investigated. The effects of these molecules on mitochondrial respiration and membrane potential were compared using isolated mitochondria from grapevine cells in suspension cultures or potato tuber mitochondria. Eutypine induces marked stimulation of oxygen consumption and a depolarizing effect, while methyl-eutypine exhibits a very small effect on both the rate of oxygen uptake and membrane potential. For high eutypine concentrations, a mixed effect corresponding to a direct inhibition of electron transport and uncoupling can be observed. In addition, below 200 microM, eutypine displays a linear relationship between oxidation rate and membrane potential similar to that of the classical protonophore carbonyl cyanide-m-chlorophenylhydrazone (CCCP). However, unlike CCCP, eutypine induces a potential-dependent proton conductance that can be due to the potential-dependent migration of the dissociated form of the toxin across the membrane. It is concluded that eutypine uncouples mitochondrial oxidative phosphorylation and decreases the ADP/O ratio in grapevine cells by increasing the proton leaks via a cyclic protonophore mechanism. The physiological aspects of these results are discussed.

Alkynes↗

PubMed1996

Liver preservation below 0 degrees C with UW solution and 2,3-butanediol.

Long-term preservation of the liver is needed to transform liver transplantation from an emergency operation to an elective procedure and therefore to improve the results of liver transplantation. We explored the possibility of extending the cold ischemia time of the rat liver by using a preservation temperature below 0 degrees C together with the addition of a cryoprotective agent (2,3-butanediol) at a low concentration in the preservation solution. Rat livers were preserved for 72 h either with UW solution at +4 degrees C (group 1) or with a UW solution, to which 2,3-butanediol at 8% (at +4 degrees C (group 2) or at -4 degrees C (group 3, experimental group)) was added. Following the preservation process, the viability of the livers was assessed using the isolated perfused liver model. Enzymatic release, bile production, and portal venous flow were not significantly different between group 1 and group 3. In the two groups in which preservation included 2,3-butanediol, the enzymatic release was significantly greater when the preservation temperature was +4 degrees C. We conclude that, using this method, preservation of the rat liver below 0 degrees C seems feasible. However, despite its low concentration, some toxicity of 2, 3-butanediol was suspected. This would counterbalance the benefit resulting from the temperature-related decrease of the enzymatic activities involved in cold ischemia damage. The potential advantages of this method need to be confirmed by assessing liver viability using a liver transplantation model.

Adenosine↗

PubMed1996

Synthesis and biochemical properties of Z- and E-4,5-dehydrodethiobiotin.

Radical species are postulated intermediates in the formation of the carbon-sulfur bonds of biotin. It was of interest to examine the behaviour of unsaturated analogues which should give rise to allylic radicals. The two isomers of 4,5-dehydrodethiobiotin have been synthesized and labelled with 14C on their carboxylic acid group. When incubated with an in vitro system capable of transforming dethiobiotin into biotin, they covalently label biotin synthase.

Biotin↗

PubMed1995

Protonophoric activity of ellipticine and isomers across the energy-transducing membrane of mitochondria.

Ellipticine is an antitumor alkaloid capable of uncoupling mitochondrial oxidative phosphorylation. It behaves as a lipophilic weak base with pK = 7.40. We have investigated its molecular mode of action using several of its isomers with pK ranging between 5.8 and 7.7 and ellipticinium, which is a permanent cationic derivative. The effects of these molecules on mitochondrial oxygen uptake and transmembrane potential were compared at different pHs. Ellipticinium exhibited very low effects on both respiratory rate and membrane potential. By contrast, protonable derivatives showed maximal stimulation of oxygen uptake and depolarizing effects when the pH of the medium was close to the drug pK. These effects were lowered when the transmembrane delta pH was dissipated, which indicates that the neutral form of the drug is implicated in the uncoupling mechanism. In addition, protonable derivatives of ellipticine display a linear relationship between oxidation rate and transmembrane potential, which suggests that the uncoupling properties of these molecules result from a protonophoric mechanism. From these results, the following cyclic protonophoric mechanism is proposed for protonable ellipticines: (i) electrophoretical accumulation of the protonated form; (ii) deprotonation at the matrix interface; (iii) diffusion outwards; and (iv) reprotonation at the external interface.

Animals↗

PubMed1995

Successful -4 degrees C liver preservation in rats with University of Wisconsin solution and 2-3-butanediol.

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Adenosine↗

PubMed1993

Microspectrofluorometry of the protonation state of ellipticine, an antitumor alkaloid, in single cells.

The protonation state and intracellular distribution of ellipticine were investigated in single human mammary T47D cells by confocal laser microspectrofluorimetry. In the cell nucleus, only the protonated form of ellipticine was detected as a direct consequence of its apparent pK increase upon DNA binding. Both protonated and neutral forms were present in the aqueous cytoplasm, where the pH is close to the drug pK. When cells were incubated in high concentrations of K+, a condition that depolarizes the plasma membrane potential, ellipticine cellular accumulation was reduced. In the cytoplasm, ellipticine was mainly bound to mitochondria, and its protonation equilibrium was shifted toward the neutral form. The fluorescence spectrum of ellipticine bound to mitochondria was insensitive to valinomycin, whereas it was markedly shifted toward the protonated form after carbonyl cyanide p-trifluoromethoxy-phenylhydrazone or nigericin addition. Similar studies with ellipticine bound to isolated mitochondria suggest that it behaves as a fluorescent probe of mitochondrial pH in both isolated mitochondria and single living cells.

Biophysical Phenomena↗