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Biomedical subjects

M Petitjean

Publications and source records attributed to M Petitjean.

At least 19 recordsLinked to original sources
PubMed2006

MolDIA: XML based system of molecular diversity analysis towards virtual screening and QSPR.

In this paper a new chemoinformatics tool for Molecular Diversity Analysis (MolDIA) is introduced. The objective of this system is the analysis of molecular similarity and diversity through the treatment of structural and physicochemical information. Current needs for chemical databases include the analysis, the management and the retrieval of chemical information. The implementation of eXtended Markup Languages (XML) is proposed as a basis for representing and structuring the chemical information contained in data structures and databases. The adequate descriptor vector and related physicochemical properties have been defined and constructed. The benefits of XML in chemoinformatics are discussed, as well as, the applications of this system in a virtual screening environment.

Computational Biology↗
PubMed2006

Elucidation of chiral recognition processes of macrocyclic antibiotic vancomycin.

A theoretical investigation was carried out on the retention and separation of enantiomeric molecules including nonsteroidal anti-inflammatory drugs, anti-neoplastic compounds and N-derivatized amino acids by capillary electrophoresis using macrocyclic antibiotics, a new class of chiral selectors, as stationary phase. Firstly docking methods were used to study the enantiorecognition in chiral electrophoresis. The molecular dynamics simulations of the two diastereoisomer complexes were then performed in order to understand how these antibiotics recognize the enantiomers. Another approach was applied in this study to establish a quantitative structure-enantioselectivity relationship (QSER) model, able to describe the resolution of a series of chiral compounds in capillary electrophoresis using vancomycin as the resolving agent.

Anti-Bacterial Agents↗
PubMed2006

Testing of pulmonary function in a professional cycling team.

AIM: Asthma affecting elite athletes has been studied mainly in subjects practicing winter sports. The aim of our study was to test the pulmonary function in order to evaluate bronchial hyper-responsiveness prevalence in a team of 25 male professional cyclists (27.9+/-3.9 years old with a VO(2max) equal to 69.9+/-6.6 mL.min(-1) x kg(-1)). METHODS: Using a questionnaire that queried the presence or absence of asthma history or common symptoms of exercise induced bronchospasm, 72% of the subjects had upper airway or bronchial symptoms. Using a pneumotachograph, we recorded a forced flow-volume curve at rest, after a maximal exercise test with ambient air, and after beta2-agonist inhalation, then during a methacholine challenge. RESULTS: In our study, 52% of the subjects showed clinical symptoms associated with bronchial responsiveness during methacholine test, a proportion which is much higher than the average population (3-20%). However, ERS-ATS pulmonary function testing criteria at rest (reduced FEV1, FEV1/FVC, FEF25-75%) were not fulfilled by any of them. In the asthmatic group, O2max was significantly higher (70.5+/-6 vs 68.6+/-8.2 mL.min-1.kg-1, P<0.05). This remained true for submaximal loads suggesting that ventilation energy cost related to bronchial hyper-responsiveness was also higher. CONCLUSIONS: We have reported in this study that professional cyclists have a far higher prevalence of bronchial hyper-responsiveness than the average population, which can be regarded as a real health issue.

Adrenergic beta-2 Receptor Agonists↗
PubMed2005

Optimization of a model of red blood cells for the study of anti-oxidant drugs, in terms of concentration of oxidant and phosphate buffer.

The aggression of erythrocytes by an oxidative stress induces hemolysis. This paper aims to valid a model of erythrocytes in terms of composition of the phosphate buffer solution and of concentration of a well-known oxidant, AAPH. Three compositions of phosphate buffer solution are mixed with three concentrations of oxidant. The influence of these two parameters on hemolysis is independently studied by a variance analysis and a Kruskal-Wallis test when ANOVA is not available. The hemolysis rate increases with time at fixed oxidant concentration, but is not influenced by the composition of the buffer solution. The highest hemolysis rate, 90%, was only measured within 2 h with the highest oxidant concentration. If we retain this concentration of oxidant, the lower concentration of the buffer can by eliminated by a significant less hemolysis and the highest concentration of the buffer can by chosen in regard of the better precision for a similar hemolysis compared to the mean buffer. We hope to study the effect of anti-oxidant agent with such a model of erythrocytes.

Antioxidants↗
PubMed1999

Acoustic myography during voluntary isometric contraction reveals non-propagative lateral vibration.

When isolated muscle synchronous contraction is evoked during in vitro twitches, mechanical vibrations at the surface of the muscle reflect resonant behavior. In contrast, voluntary contraction corresponds to the asynchronous contraction of recruited motor units, therefore, this kind of excitation could lead to different muscle vibrational behavior. We have studied human biceps brachii muscle during voluntary contraction in 10 healthy subjects. Low and high levels of voluntary contraction were explored with simultaneous recording of surface vibration by two sensors located longitudinally or perpendicular to the muscle's main axis. Cross-correlation and coherence functions were computed. Coherence functions revealed a common vibration frequency band between 17 and 28 Hz. Cross correlation functions revealed in-phase vibration for longitudinal sensors and opposite phase vibration for perpendicular sensors thus confirming a lateral bending movement. This behavior suggests that the acoustic myogram is the response of the muscle as a global resonant structure to the local fluctuations of pressure.

Acoustics↗
PubMed1999

Conformational variation of the central CG site in d(ATGACGTCAT)2 and d(GAAAACGTTTTC)2. An NMR, molecular modelling and 3D-homology investigation.

The determination of the solution structure of two self-complementary oligomers d(ATGACGTCAT)2 (CG10) and d(GAAAACGTTTTC)2 (CG12), both containing the 5'-pur-ACGT-pyr-3' sequence, is reported. The impact of the base context on the conformation of the central CpG site has been examined by a combined approach of: (a) 2D 1H-NMR and 31P-NMR; (b) molecular mechanics under experimental constraints; (c) back-calculations of NOESY spectra and iterative refinements of distances; and (d) 3D-homology search of the central tetrad ACGT within the complete oligonucleotides. A full NMR study of each fragment is achieved by means of standard 2D experiments: NOESY, 2D homonuclear Hartmann-Hahn spectroscopy, double-quantum-filtered COSY and heteronuclear 1H-31P correlation. Sugar phase angle, epsilon-zeta difference angle and NOE-derived distances are input as experimental constraints to generate molecular models by energy minimization with the help of jumna. The morass program is used to iteratively refine the structures obtained. The similarity of the two ACGTs within the whole oligonucleotides is investigated. Both the decamer and the dodecamer adopt a B-like DNA conformation. However, the helical parameters within this conformational type are significantly different in CG12 and CG10. The central CpG step conformation is not locked by its nearest environment (5'A and 3'T) as seen from the structural analysis of ACGT in the two molecules. In CG12, despite the presence of runs of A-T pairs, CpG presents a high twist of 43 degrees and a sugar phase at the guanine of about 180 degrees, previously observed in other ACGT-containing-oligomers. Conversely, ACGT in CG10 exhibits strong inclinations, positive rolls, a flat profile of sugar phase, twist and glycosidic angles, as a result of the nucleotide sequence extending beyond the tetrad. The structural specificity of CG10 and its flexibility (as reflected by its energy) are tentatively related to the process of recognition of the cyclic AMP response element by its cognate protein.

Base Sequence↗
PubMed1998

Transferrins--a mechanism for iron uptake by lactoferrin.

Iron uptake by bovine lactoferrin from nitrilotriacetatoFe(III) [FeN(Ac)3] in the presence of bicarbonate has been investigated at pH 7.1-8.7. Deprotonated apolactoferrin interacting with bicarbonate or carbonate extracts iron from nitrilotriacetatoFe(III); the direct second-order rate constant k1 = (4.90 +/- 0.20)x10(4) M(-1) s(-1), a reverse second-order rate constant k(-1) = (1.80+/-0.05)x10(5) M(-1) s(-1), and the iron-exchange equilibrium constant K1 = 0.25+/-0.05. The newly formed iron-protein complex loses a single proton with proton dissociation constant K3a = (17+/-0.5) nM, then undergoes a modification in its conformation followed by the loss of two or three protons; the first-order rate constant k2 = (1.0+/-0.10) s(-1). This induces a new modification in the conformation; the first-order rate constant k3 = (8.75+/-0.40)x10(-3) s(-1). This second modification in conformation controls the rate of iron uptake by the N site of the protein and is followed by a single proton loss; K5a = 8.0 nM. Finally, the holoprotein or the monoferric lactoferrin in their final equilibrated states are produced by a third modification in the conformation occurring in about 9000 s. The mechanism of iron uptake by lactoferrin is very similar to that of serum transferrin with a cooperativity between the C and N sites upon iron uptake but with lower rates, higher affinities and at least one more proton loss involved. These differences may be the result of slight discrepancies in the intimate structures of binding sites for serum transferrin and lactoferrin. In order to analyse the cooperativity between these iron-binding sites, the three-dimensional position of the chain of amino acid residues separating the N and C lobes of human apo-, holo- and dicopper-lactoferrin have been compared by the recognition of the three-dimensional shape dissimilarity program. The interlobe peptides of human hololactoferrin and apolactoferrin showed only 75.5 % tridimensional similarity, indicating that iron uptake affects the three-dimensional structure of the interlobe chain.

Animals↗
PubMed1998

Summation of elementary phonomyograms during isometric twitches in humans.

To study its summation principle, the phonomyogram (PMG) from the first interosseus dorsalis muscle was recorded in five subjects during single twitches evoked by electrical stimulation over the motor point. By increasing the current pulse from threshold to maximal intensity, PMG amplitude increased linearly with motor unit recruitment. The twitch amplitude-intensity relationship was also linear. The PMG amplitude was therefore linearly related to the external force. For all these relationships highly significant correlation coefficients were found. These relationships were interpreted as being a consequence of an orderly recruitment, although, contrary to what happens during voluntary contraction, the largest and strongest motor units were recruited before the smallest and weakest ones during axon electrical stimulation. The PMG onset always preceded twitch onsets as indicated by latency measurements [mean 3.2 (SD 1.3) ms versus 11.5 (SD 3.9) ms, respectively]. Moreover, PMG and twitch latencies may have been significantly reduced by recruitment, suggesting that orderly recruitment influenced both PMG amplitude and occurrence. These results were interpreted as being the result of the summation of elementary PMG from every contracting motor unit and the stiffness change of the muscle medium occurring with recruitment.

Acoustics↗
PubMed1997

Time-frequency analysis of the muscle sound of the human diaphragm.

The time-frequency characteristics of muscular sounds (phonomyogram) produced by the contraction of the human diaphragm under various contractile states is evaluated with the cone-kernel distribution. The results show that the instantaneous frequency of the phonomyogram of the diaphragm has a high cross-correlation (an average of 0.91 +/- 0.06) with the transdiaphragmatic pressure, with a delay varying between 25 and 35 ms. The instantaneous frequency response of the phonomyogram of the diaphragm shows a behaviour similar to that of the frog muscle; it rapidly rises and then fades out. However, the maximum of the instantaneous frequency of the phonomyogram of the diaphragm is not proportional to the maximum of the transdiaphragmatic pressure. This analysis also demonstrates the usefulness of the cone-kernel distribution for studying frequency-modulated signals like the muscular sound signals.

Diaphragm↗
PubMed1997

Diaphragmatic fatigue investigated by phonomyography.

Diaphragmatic phonomyogram (PMG) evoked by maximal bilateral phrenic nerve stimulation has previously been described as a good index of contractility of fresh and fatigued diaphragm. In the present study we hypothesized that diaphragmatic contractility changes could be even more simply evaluated by recording the relationship between the PMG and the compound motor action potential (CMAP) amplitudes during graded submaximal unilateral phrenic nerve stimulation at various intensities. Relationships between CMAPs and PMGs from left and right hemidiaphragms were recorded by means of surface electrodes and miniature microphones placed over the lower rib cage (eighth intercostal space) in five healthy subjects before and after a diaphragmatic fatigue task. These relationships in each subject were linear. The slope of these relationships decreased by 61.1 +/- 20.7% and by 70.4 +/- 14.6% on the right and left side respectively, but the intercepts did not change significantly. By comparison, transdiaphragmatic twitch pressure during maximal bilateral stimulation (PdiT) declined by 49.4 +/- 15%. We conclude that PMG during submaximal unilateral phrenic nerve stimulation is a reliable index of diaphragm contractility changes caused by fatigue. Using this method we have shown that all diaphragmatic motor units can be affected by fatigue.

Action Potentials↗
PubMed1996

Insertional action of the abdominal muscles in rabbits and dogs.

The insertional action of the abdominal muscles was studied in supine anesthetized, apneic rabbits and dogs by comparing the changes in esophageal pressure (Pes), upper and lower rib cage circumference (Cru,u and Crc,I) and lung volume (VL) in response to electrical stimulation of all abdominal muscles before and after evisceration. In eviscerated animals, abdominal muscle contraction increased Pes and decreased both VL and Cre,I, but had no effect on Crc,u. Maximal responses were obtained at submaximal intensities of stimulation, and became larger with increasing lung volume. Relative to the vital capacity in intact animals, maximal delta VL for stimulation performed at FRC and TLC were 7.2 +/- 2.9(SD) and 39.5 +/- 7% in rabbits, and 6.3 +/- 0.8 and 18.3 +/- 5.9% in dogs, respectively. Relative to the changes in lung volume occurring with maximal contraction of the abdominal muscles in intact animals, the values of delta VL observed in the eviscerated animals amounted to approximately 35 and approximately 45% for stimulation performed at FRC and TLC, respectively. Hence, abdominal muscles exert substantial insertional action on the lower rib cage that can result in appreciable lung deflationary effects, particularly at elevated lung volumes.

Abdominal Muscles↗
PubMed1996

Effects of lung volume and fatigue on evoked diaphragmatic phonomyogram in normal subjects.

BACKGROUND: A diaphragmatic phonomyogram (PMG) evoked by maximal phrenic nerve stimulation at end expiratory lung volume (FRC) has been previously described as a good index of changes in diaphragmatic contractility with fatigue. A study was undertaken to assess whether this conclusion could be extended to different lung volumes. METHODS: Diaphragmatic compound motor action potentials (CMAPs) were recorded on each side of the chest by the means of surface electrodes placed over the eight intercostal spaces in five healthy subjects. Diaphragmatic PMGs from both sides were recorded with condenser microphones fixed to the skin close to the CMAP recording electrodes. Oesophageal and gastric balloon tipped catheters were employed to measure transdiaphragmatic pressure twitches (TwPDI) which served as the standard measure of changes in diaphragmatic contractility. PMG and TwPDI responses were compared at different lung volumes over inspiratory capacity both before and after fatiguing inspiratory resistive loading. RESULTS: No consistent relationship was found in different subjects or on different days in the same subject between PMG and lung volume or between PMG and TwPDI. However, the PMG:CMAP ratio from both sides at any given lung volume decreased after fatigue in roughly the same proportion as the TwPDI. CONCLUSIONS: These results show that, although PMG can detect changes in diaphragmatic contractility caused by fatigue in normal subjects, lung volume changes need to be controlled and each subject should serve as his or her own control.

Action Potentials↗
PubMed1995

Phonomyogram from single motor units during voluntary isometric contraction.

The purpose of this study was to determine the characteristics of the specific phonomyogram (PMG) of active motor units activated during voluntary isometric contractions. The electromyogram (EMG) and PMG were recorded from 87 anconeus motor units in 14 subjects. The elementary PMG from single motor units was analysed with a spike-triggered averaging technique. The electro-acoustical delay was 3.5 (SD 1.1) ms, which is within the range of values reported in the literature for PMG evoked by motor nerve stimulation. All motor units demonstrated a pattern of impulsive sounds with a duration of 87.2 (SD 10.7) ms. These results would imply that PMG is linked to the contractile activity of the motor units. These results also would suggest that PMG recorded from a contracting muscle in situ reflects the summation of elementary PMG during voluntary contraction more than the overall mechanical properties of the muscle.

Acoustics↗
PubMed1994

Phonomyogram of the diaphragm during unilateral and bilateral phrenic nerve stimulation and changes with fatigue.

As previously demonstrated in humans, contracting skeletal muscles vibrate laterally and generate sound. The amplitude of this acoustic signal, called the phonomyogram (PMG), is related to muscle force production. As in limb muscles, the diaphragm might produce mechanical tissue vibrations and a PMG. We recorded diaphragm twitches during phrenic nerve stimulation in normal subjects at FRC. Diaphragmatic compound motor action potentials (CMAP) were recorded on each side of the chest by surface electrodes over the eighth intercostal space. Condenser microphones were fixed to the skin close to the electrodes, and esophageal and gastric balloons employed to measure transdiaphragmatic pressure (Pdi). For unilateral and bilateral supramaximal single shocks (0.1 ms), PMG onset latencies from either side (12.4 +/- 0.6 ms) were intermediate between those of CMAP (7.3 +/- 0.7 ms) and of Pdi (20.3 +/- 2.8 ms). By varying stimulation intensity, significant linear relationships were obtained between CMAP and PMG amplitudes on each side. A significant linear relationship was also found between PMG for each side and Pdi peak values. PMG and Pdi both decreased with fatigue of the diaphragm. We conclude that PMG in response to single phrenic nerve shocks is a noninvasive index of electromechanical coupling, recruitment, and transdiaphragmatic pressure generation by the diaphragm.

Action Potentials↗
PubMed1992

Evaluation of human dynamic contraction by phonomyography.

Phonomyogram (PMG, or acoustic myogram) is known to increase with force in isometric contractions. We investigated this relationship for dynamic contractions against different inertias. PMG and surface electromyogram (EMG) from biceps brachii and brachioradialis muscles were simultaneously recorded with the angular acceleration of elbow flexions. These were self-initiated movements (30 degrees) toward a fixed target and performed against two different inertias. PMG and EMG were integrated from the onset of the signal to the end of the acceleration phase. Phono- and electromechanical delays were also measured. For integrated EMG (iEMG), there was a linear relationship between integrated PMG (iPMG) and force, the slope of which did not depend on inertia. There was also a linear relationship between iPMG or iEMG and angular acceleration, with a higher slope for the highest inertia condition. There was also a family of linear relationships between iPMG or iEMG and angular acceleration, and their slopes depended on inertia. Measurements of the phono- and electromechanical delays showed that onset of PMG followed that of EMG but preceded onset of acceleration. It is suggested that PMG expresses tension of the underlying muscle contractile elements. Given the simplicity of the PMG method, we conclude that PMG allows convenient evaluation of muscle tension during human dynamic contraction.

Adult↗
PubMed1991

Cortical osteoclasts are less sensitive to etidronate than trabecular osteoclasts.

Acute osteoporosis after spinal cord injury is related to an early increase in osteoclastic resorption. Healthy subjects subjected to bed rest similarly increase their osteoclast number in trabecular bone. Bisphosphonates possess a highly antiosteoclastic activity. The effects of a 120 day bed rest period, with or without etidronate therapy on cortical bone were measured in 15 subjects. Cortical thickness and cortical porosity were measured on transiliac bone biopsies taken before and after the bed rest period. Osteoclasts were detected histochemically and were counted with a semiautomatic image analyzer. Cortical thickness, cortical porosity, and cortical osteoclast number were not significantly modified in subjects submitted to bed rest alone. In the etidronate-treated patients, cortical bone mass parameters were also found to be unaffected, but the most striking feature was that the osteoclast number was unchanged. Trabecular osteoclasts, on the contrary, were increased in the untreated subjects (+95.2%) but decreased in the treated subjects (-78%). Bone cells may have heterogeneous responses according to their trabecular or cortical location. Cortical osteoclasts seem to be unaffected by etidronate therapy.

Adult↗
PubMed1991

Alcoholic cirrhosis and osteoporosis in men: a light and scanning electron microscopy study.

Subjects with chronic alcoholism are associated with a higher prevalence of bone fractures, compared with age-matched controls. However, the pathogenesis of alcoholic osteopathy remains poorly understood. In this study, the bone cells activities and the bone matrix were studied using different techniques such as bone morphometry, scanning electron microscopy and computer reconstruction. Male patients (N = 20), aged 59.1 +/- 10.1 years, presenting a chronic decompensated alcoholic cirrhosis, were admitted into this study. A histomorphometric analysis of a transiliac bone biopsy was done after a double tetracycline labeling of the bone. A scanning electron microscopy (SEM) study was performed on eight out of the 20 patients on an additional biopsy. The bone mass was significantly decreased in cirrhotic patients. A marked defect in the osteoblastic function was observed with reduced osteoid parameters, lower mean wall thickness, and slower bone formation rate leading to a thinning of bone trabeculae. Conversely, trabecular resorption surfaces were markedly increased. SEM examination of bone biopsies was also consistent with delayed and impaired osteoblastic activity leading to extended and scalloped resorption surfaces covered by unusually thin layers of calcified collagen fibers. The reduced osteoblastic activity associated with normal osteoclastic function appears to play a major role in the pathogenesis of alcoholic osteoporosis leading to decreased bone mass with thinner trabeculae.

Aged↗