Biomedical subjects

C Médigue

Publications and source records attributed to C Médigue.

At least 19 recordsLinked to original sources

PubMed2001

Relationship between pulse interval and respiratory sinus arrhythmia: a time- and frequency-domain analysis of the effects of atropine.

Respiratory sinus arrhythmia (RSA) estimation is commonly used as a non-invasive index of cardiac vagal tone. To test this relationship, vagal tone was augmented or blocked using atropine. The study was carried out using 14 healthy volunteers, following beta-adrenoceptor blockade (10 mg bisoprolol per os) and during controlled respiration (0.25 Hz) in order to limit the confounding effects of cardiac sympathetic tone and respiration pattern changes. Atropine was slowly infused intravenously over a 30-min period up to a vagolytic cumulative dose of 0.04 mg/kg. The instant vagal tone was compared to the instant RSA value obtained from a time-/frequency-domain analysis of pulse interval (PI). RSA and PI varied in the same direction with an initial increase corresponding to the early vagomimetic effect of atropine followed by a decrease during the vagolytic phase. The comparative percentage fluctuations of RSA and PI over this large vagal tone range indicate that RSA is more sensitive (about twofold) than PI in reflecting fluctuations around the set point. This dissociated behaviour of PI and heart rate variability could be important to our understanding of the circulatory changes that result from fluctuations in vagal inputs to the sinus node.

Adrenergic beta-Antagonists↗

PubMed2001

Altered baroreflex gain during voluntary breathing in chronic heart failure.

BACKGROUND: We assessed the behavior of the baroreflex (BR) gain in chronic heart failure (CHF) patients using the spectral analysis method during application of a forcing stimulus, i.e. respiration. METHODS: Simultaneous RR interval and arterial pressure fluctuation recordings were obtained during two random-order periods of voluntary paced-breathing (0.15 Hz and 0.25 Hz) in seven patients with moderate CHF (NYHA class II/III; EF, 30+/-9%; peak VO(2), 18+/-5 ml kg(-1) min(-1)) and six age-matched controls. BR gain was assessed in the time (sequential method) and frequency (cross-spectral gain in the low and high frequency) domains. RESULTS: Slower breathing was associated with a BR gain decrease in CHF patients whereas a BR gain increase was evidenced in controls (BR gain: 6+/-5 ms mmHg(-1) at 0.25 Hz vs. 4+/-3 ms mmHg(-1) at 0.15 Hz, P<0.05 in CHF; BR gain: 12+/-7 ms mmHg(-1) at 0.25 Hz vs. 15+/-7 ms mmHg(-1) at 0.15 Hz, P<0.05 in controls). CONCLUSIONS: Voluntary breathing, which involves cortical centers in the brain, had major effects on cardiovascular system controller gain in CHF patients, indicating an impairment of the central neural regulation of the autonomic outflow.

Adult↗

PubMed1999

Imagene: an integrated computer environment for sequence annotation and analysis.

MOTIVATION: To be fully and efficiently exploited, data coming from sequencing projects together with specific sequence analysis tools need to be integrated within reliable data management systems. Systems designed to manage genome data and analysis tend to give a greater importance either to the data storage or to the methodological aspect, but lack a complete integration of both components. RESULTS: This paper presents a co-operative computer environment (called Imagenetrade mark) dedicated to genomic sequence analysis and annotation. Imagene has been developed by using an object-based model. Thanks to this representation, the user can directly manipulate familiar data objects through icons or lists. Imagene also incorporates a solving engine in order to manage analysis tasks. A global task is solved by successive divisions into smaller sub-tasks. During program execution, these sub-tasks are graphically displayed to the user and may be further re-started at any point after task completion. In this sense, Imagene is more transparent to the user than a traditional menu-driven package. Imagene also provides a user interface to display, on the same screen, the results produced by several tasks, together with the capability to annotate these results easily. In its current form, Imagene has been designed particularly for use in microbial sequencing projects. AVAILABILITY: Imagene best runs on SGI (Irix 6.3 or higher) workstations. It is distributed free of charge on a CD-ROM, but requires some Ilog licensed software to run. Some modules also require separate license agreements. Please contact the authors for specific academic conditions and other Unix platforms. CONTACT: imagene home page: http://wwwabi.snv.jussieu.fr/imagene

Bacillus subtilis↗

PubMed1999

Detecting and analyzing DNA sequencing errors: toward a higher quality of the Bacillus subtilis genome sequence.

During the determination of a DNA sequence, the introduction of artifactual frameshifts and/or in-frame stop codons in putative genes can lead to misprediction of gene products. Detection of such errors with a method based on protein similarity matching is only possible when related sequences are available in databases. Here, we present a method to detect frameshift errors in DNA sequences that is based on the intrinsic properties of the coding sequences. It combines the results of two analyses, the search for translational initiation/termination sites and the prediction of coding regions. This method was used to screen the complete Bacillus subtilis genome sequence and the regions flanking putative errors were resequenced for verification. This procedure allowed us to correct the sequence and to analyze in detail the nature of the errors. Interestingly, in several cases in-frame termination codons or frameshifts were not sequencing errors but confirmed to be present in the chromosome, indicating that the genes are either nonfunctional (pseudogenes) or subject to regulatory processes such as programmed translational frameshifts. The method can be used for checking the quality of the sequences produced by any prokaryotic genome sequencing project.

Bacillus subtilis↗

PubMed1997

The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Bacillus subtilis↗

PubMed1997

Instant power spectrum analysis of heart rate variability during orthostatic tilt using a time-/frequency-domain method.

BACKGROUND: Spectral analysis of heart rate (HR) variability (HRV) requires, as a rule, some level of stationarity and, as a result, is inadequate to quantify biological transients. A time-/frequency-domain method (TF) was developed to obtain an instant spectral power (SP) of HRV during tilt. METHODS AND RESULTS: HR was recorded by Holter monitoring in volunteers and analyzed with a TF, the smoothed pseudo-Wigner-Ville transformation (SPWVT), with the table inclination randomly set or continuously increased while the table rotated in head-up position. (1) The SPWVT assesses, beat by beat, the instant center frequency (ICF) of the SP. ICF correlates better with instant HR than the ratio of low- (LF) to high-frequency (HF) oscillations. The transient effect of tilt is better characterized as a shift of SP toward lower frequencies than by changes in amplitudes. (2) The method evidences variations of HR from one second to another. During the passage to head-up position, the vagal withdrawal and the sympathetic activation occur nearly simultaneously, as indicated by the instant changes in both LF and HF amplitudes and ICF. (3) The averaged results of the SPWVT give results similar to those previously obtained with autoregressive algorithms. CONCLUSIONS: The SPWVT is a new tool to explore HR transitions such as periods before episodes of arrhythmias on a time scale of one beat and allows quantification of an instant frequency index (ICF) that closely reflects the instantaneous relationship between sympathetic and vagal modulations.

Adult↗

PubMed1997

Heart rate and heart rate variability, a pharmacological target.

Heart rate varies with respiration, blood pressure, emotion, etc., and heart rate variability (HRV) is presently one of the best indices to predict fatal issues in cardiac failure and after myocardial infarction. HRV depends on various reflexes. In addition, parallel studies of HRV and the myocardial adrenergic and muscarinic transduction system in experimental models of cardiac hypertrophy (CH) have suggested that the myocardial phenotype at the sinus-node level may also play a role. A transgenic strain of mice with atrial overexpression of the beta 1-adrenergic receptors was generated with attenuated HRV, which demonstrates that the phenotype itself is a determinant of HRV. HRV is explored by noninvasive techniques, including simple determination of the standard error of the mean, time-domain analysis, and Fourier transformation. We recently developed a time and frequency domain method of analysis, the smoothed pseudo-Wigner-Ville transformation, which allows better exploration of nonstationarity. Nonlinear methods have also been applied due to the extreme complexity of the biological determinants, and have provided evidence of a chaotic attractor in certain conditions. It is proposed that in steady state a very simple process, which is not completely deterministic, could better explain intermit interval regulations than chaotic behavior. In contrast, under extreme circumstances the regulation proceeds using chaotic behavior. Arrhythmias and HRV can be quantitated in 16-month-old unanesthetized spontaneously hypertensive rats (SHR). Ventricular premature beats are more frequent in SHR than in age-matched controls; they disappear after converting enzyme inhibition (CEI) relative to the reduction of both cardiac hypertrophy and ventricular fibrosis. HRV is attenuated in SHR, as it is in compensatory CH in humans. When CH is prevented, HRV returns to normal. CEI is therefore antiarrhythmic. Another pharmacological application of this concept concerns the bradycardic agents that may improve HRV.

Animals↗

PubMed1996

Molecular basis of the regression of cardiac hypertrophy.

Cardiac failure is a disease which involves three different mechanisms: (1) the limits and imperfections of the general process of myocardial adaptation to mechanical stress, which includes various changes in genetic expression, including an increased collagen mass, but an unchanged collagen concentration; (2) the limits and imperfections of the adaptational process at the peripheral level which allows the entire organism to adapt to the low cardiac output; (3) fibrosis, an augmented collagen concentration, which is not a direct consequence of mechanical overload, but depends on aging, myocardial ischemia or hormonal changes. Middle-aged spontaneously hypertensive rats (SHRs) represent a good model of the common clinical situation. Three-month treatment with a CEI reduces, in parallel, arterial hypertension, left ventricular hypertrophy and ventricular fibrosis. Holter monitoring was also performed in these animals. Untreated SHRs when compared to age-matched Wistar rats have an increased number of ventricular premature beats which are suppressed by the treatment. In addition, heart rate variability has been quantified by using the pseudo Wigner-Villé transformation, a time and frequency domain method. The low frequency oscillations are hampered in SHRs. CEI normalizes this parameter.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Decreased heart rate variability in transgenic mice overexpressing atrial beta 1-adrenoceptors.

Heart rate variability (HRV) depends on various reflexes, including the baroreflex or respiratory reflex. Experimental studies have suggested that the sinoatrial node density in G protein-linked receptors may be involved. Transgenic mice, with a specific eightfold atrial overexpression of human beta 1-adrenoceptor (beta 1-AR), have been generated to evaluate the role of the atrial beta 1-AR density on HRV. The heart rate was monitored using telemetry, and the signal was analyzed using a quantitative time-frequency domain analysis, the smoothed pseudo-Wigner-Ville method, and phase portrait maps. 1) Heart rate was unchanged, but the two normal components of HRV were decreased in transgenic mice. Transgenic mice have an unshortened life span and no arrhythmias. 2) Challenge of the animals by propranolol showed no modulation of the HRV in transgenic mice compared with controls. 3) In isolated atrial strips from transgenic mice, basal contractility was increased and there was no isoproterenol-induced inotropic effect. 4) The basal level of adenosine 3',5'-cyclic monophosphate production was lowered in transgenic mice, suggesting a shift in adenylate cyclase isoforms.

Adenylyl Cyclases↗

PubMed1996

Linear and non-linear analyses of heart rate variability: a minireview.

To complete traditional time- and frequency-domain analyses, new methods derived from non-linear systems analysis have recently been developed for time series studies. A panel of the most widely used methods of heart rate analysis is given with computations on mouse data, before and after a single atropine injection.

Animals↗

PubMed1995

Analysis of a Bacillus subtilis genome fragment using a co-operative computer system prototype.

Analysis of the huge volume of data generated by large scale sequencing projects requires the construction of new, sophisticated computer systems. These systems should be able to manage the biological data as well as the results of their analysis. They should also help the user to choose the most appropriate methods, and to string them together in order to solve a global analysis task. In this paper we present the prototype of a software system providing an environment for the analysis of large-scale sequence data. As a first step toward this end, this environment has been put to the test within the Bacillus subtilis genome sequencing project. This system integrates both the descriptive knowledge of the entities involved (genes, regulatory signals and the like) and the methodological knowledge comprising an extensible set of analytical methods. A knowledge representation based on two existing object-oriented models is used to implement this integrated system. In addition, the present prototype provides a suitable user interface both for displaying simultaneously the results generated by several methods and for interacting with the objects. We present in this paper the analysis of a B. subtilis genome fragment, present in data libraries but not annotated. Annotation of the genes present in the fragment allowed us to combine the results of several methods used for predicting coding sequences, and to characterize it as comprising a cryptic phage, the skin element. Comparison between the annotation of the skin element and a standard region of the chromosome indicated that local features of the nucleotide sequence could discriminate between phage and non-phage DNA sequence.

Bacillus subtilis↗

PubMed1995

Detection of new genes in a bacterial genome using Markov models for three gene classes.

We further investigated the statistical features of the three classes of Escherichia coli genes that have been previously delineated by factorial correspondence analysis and dynamic clustering methods. A phased Markov model for a nucleotide sequence of each gene class was developed and employed for gene prediction using the GeneMark program. The protein-coding region prediction accuracy was determined for class-specific Markov models of different orders when the programs implementing these models were applied to gene sequences from the same or other classes. It is shown that at least two training sets and two program versions derived for different classes of E. coli genes are necessary in order to achieve a high accuracy of coding region prediction for uncharacterized sequences. Some annotated E. coli genes from Class I and Class III are shown to be spurious, whereas many open reading frames (ORFs) that have not been annotated in GenBank as genes are predicted to encode proteins. The amino acid sequences of the putative products of these ORFs initially did not show similarity to already known proteins. However, conserved regions have been identified in several of them by screening the latest entries in protein sequence databases and applying methods for motif search, while some other of these new genes have been identified in independent experiments.

Algorithms↗

PubMed1995

Cooperative computer system for genome sequence analysis.

Analysis of the huge volumes of data generated by large scale sequencing projects clearly requires the construction of new sophisticated computer systems. These systems should be able to handle the biological data as well as the results of the analysis of this data. They should also help the user to choose the most appropriate method for a simple task and to string together the methods needed to solve a global analysis task. In this paper we present the prototype of a software system that provides an environment for the analysis of large-scale sequence data. In a first approach this environment has been put to the test within the B. subtilis sequencing project. This system integrates both a descriptive knowledge of the entities involved (genes, regulatory signals etc.) and the methodological knowledge concerning an extendable set of analytical methods (i.e. how to solve a sequence analysis problem through task decomposition and method selection). A knowledge representation based on two existing object-oriented models, named Shirka and SCARP, is used to implement this integrated system. In addition, the present prototype provides a suitable user interface for both displaying the results generated by several methods and interacting with the objects. We present in this paper an overview of the knowledge-based models used to build this integrated system, and a description of the way in which biological entities and sequence analysis tasks are represented. We give illustrations of the co-operation between user and system during the problem solving process. Such a system constitutes a computer workbench for molecular biologists studying the genetic programs of living organisms.

Bacillus subtilis↗

PubMed1994

Heart rate and heart rate variability during sleep in small-for-gestational age newborns.

To assess the influence of intrauterine growth retardation on heart rate (HR) and HR variability during sleep, we performed polygraphic recordings in 10 small-for-gestational age (SGA) and 16 appropriate-for-gestational age (AGA) newborns. Both groups were clinically and neurologically normal and were at 37 to 41 wk conceptional age. RR intervals were analyzed using the short-time Fourier transform in three frequency bands: 1) high frequency, with a period 3-8 heartbeat; 2) mid frequency, with a period 10-25 heartbeat; and 3) low frequency, with a period 30-100 heartbeat. In both active and quiet sleep, SGA newborns significantly differed from AGA newborns by having a shorter RR interval (p < 0.01) and lower amplitude of HR variability in all bands (p < 0.05) except low frequency in quiet sleep. Quiet sleep differed from active sleep by having a longer RR interval (p < 0.05), higher high-frequency variability (p < 0.02) in both SGA and AGA newborns, and lower low-frequency variability (p < 0.005 for AGA newborns). Our data give evidence of clear modifications of both sympathetic and parasympathetic HR control in the at-risk SGA population. Similarity of between-state characteristics suggests maintained CNS control of HR in SGA as well as in AGA newborns. We speculate that between-group HR and HR variability differences may be related to augmented metabolic rate in SGA compared with AGA newborns.

Basal Metabolism↗

PubMed1993

Heart-rate variability in low-risk prematurely born infants reaching normal term: a comparison with full-term newborns.

To investigate the influence of prematurity and postnatal age on the maturation of the autonomic nervous system function, we analysed heart-rate and heart-rate variability in twelve prematurely born infants (< 37 weeks gestational age) reaching the conceptional age of 37-41 weeks. These neonates were compared with sixteen 37-41 week conceptional age newborns (< 10 days postnatal age). Heart-rate variability was analysed by spectral analysis of interbeat intervals using Short-Time Fourier Transform. We found that during both active and quiet sleep, the durations of RR-intervals were shorter and the amplitude of heart-rate variability in different frequency bands was lower in prematures reaching term than in newborns of the same conceptional age (P < 0.001). Between-state comparison showed differences in both groups. In both groups, low-frequency heart-rate variability was higher in active sleep than in quiet sleep. Between-state differences of RR-intervals and high-frequency heart-rate variability were present only in newborns (P < 0.01). Discrimination between newborns and prematures reaching term, based on RR-intervals and heart-rate variability, was correct in both sleep states with errors between 7 to 16%. However, in both newborns and prematures reaching term, between-state discrimination showed less reliable results, especially for quiet sleep discrimination with 24% (in PRT) and 20% (in NB) of errors. Our results, especially information given by factor analysis, suggest that the differences between newborns and prematures reaching term, concerning RR-interval and heart-rate variability, may be related to a changed balance between the sympathetic and parasympathetic nervous systems with a diminished parasympathetic component of heart rate control in prematures reaching term, as compared to newborns.

Discriminant Analysis↗

PubMed1993

Colibri: a functional data base for the Escherichia coli genome.

Several data libraries have been created to organize all the data obtained worldwide about the Escherichia coli genome. Because the known data now amount to more than 40% of the whole genome sequence, it has become necessary to organize the data in such a way that appropriate procedures can associate knowledge produced by experiments about each gene to its position on the chromosome and its relation to other relevant genes, for example. In addition, global properties of genes, affected by the introduction of new entries, should be present as appropriate description fields. A data base, implemented on Macintosh by using the data base management system 4th Dimension, is described. It is constructed around a core constituted by known contigs of E. coli sequences and links data collected in general libraries (unmodified) to data associated with evolving knowledge (with modifiable fields). Biologically significant results obtained through the coupling of appropriate procedures (learning or statistical data analysis) are presented. The data base is available through a 4th Dimension runtime and through FTP on Internet. It has been regularly updated and will be systematically linked to other E. coli data bases (M. Kroger, R. Wahl, G. Schachtel, and P. Rice, Nucleic Acids Res. 20(Suppl.):2119-2144, 1992; K. E. Rudd, W. Miller, C. Werner, J. Ostell, C. Tolstoshev, and S. G. Satterfield, Nucleic Acids Res. 19:637-647, 1991) in the near future.

Bacterial Proteins↗

PubMed1993

Building large knowledge bases in molecular biology.

Large scale genome sequencing projects are now producing hugh amounts of data which can be readily stored and managed within data base management systems, and analyzed using dedicated software packages. The results of these analyzes should also be stored with the input DNA sequences. The increasing complexity and size of the objects to be described and managed have led biologists to rely on advanced data models such as the object-oriented model. As a joint effort between our computer science and molecular biology research projects, the knowledge bases we have developed in molecular genetics have shown however that the basic object-oriented model is not fully adapted to the complexity of some biological situations encountered. Advanced descriptive capabilities, provided only by knowledge models originated from the AI field, are required. Composite or evolving objects, multiple viewpoints, constraints, tasks and methods, textual annotations are some examples of such capabilities. They are illustrated by biological situations for which they appeared to be necessary. Supporting powerful reasoning mechanisms (e.g. object classification, constraint propagation or qualitative simulators), they allow the development of large knowledge bases in molecular biology. These knowledge bases are expected to become the adequate support for co-operative distributed research efforts.

Artificial Intelligence↗

PubMed1992

Heart rate variability in normal sleeping full-term and preterm neonates.

To assess maturation of the Autonomic Nervous System (ANS) and sleep states, Heart Rate Variability (HRV) was studied in 24 healthy sleeping newborns, aged from 31 to 41 weeks, conceptional age (CA). Spectral analysis of the interbeat interval (RR) signal, was performed by Short-Time Fourier Transform, in three frequency bands: high (HF), of purely vagal origin, mid (MF), and low (LF), vagal and sympathetic, thus allowing evaluation of both branches of the ANS, observed in Active Sleep (AS = REM Sleep) and in Quiet Sleep (QS = nREM Sleep). Principal Component Analysis, Discriminant Analysis, and hypothesis tests were used to investigate the evolution of spectral variables and their relation with sleep states. HF, MF, LF, and mean RR all increased with age; the differences from the premature to the full-term group, were more marked, as a whole, in AS than in QS. HF showed the highest increase from the premature (31-36 weeks CA) to the intermediate (37-38) group, whereas LF showed equal differences from the premature to the intermediate, and from the intermediate to the full-term (39-41) groups. These results suggest a steep increase in vagal tone at 37-38 weeks CA, with stability afterwards, and a more regular increase in sympathetic tone from 31 to 41 weeks CA.

Analysis of Variance↗