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A Porta

Publications and source records attributed to A Porta.

At least 19 recordsLinked to original sources
PubMed1999

An homologue of the human 100-kDa protein (p100) is differentially expressed by Histoplasma capsulatum during infection of murine macrophages.

Using differential display reverse transcription-PCR (DDRT-PCR) we have identified several sequences that are specifically expressed by Histoplasma capsulatum during infection of murine macrophages (MPhi). Here, we report the characterization of a clone, pHc12, identified as a differentially expressed gene 1 hour after infection of MPhi. Screening of a cDNA library of H. capsulatum allowed us to isolate a clone, pHc12-E, that contains the complete coding sequence. We show that after infection the level of transcription of this gene increases about 5 fold. Analysis of its sequence revealed the presence of an open reading frame of 890 aa (ORF890) that shares respectively 30 and 33% identity with human and Caenorhabditis elegans p100 kD and rat p105 kD co-activator proteins. Using the two-dimensional Hydrophobic Cluster Analysis (HCA) method, we showed that H. capsulatum ORF890 and p100 kD co-activator proteins are clearly related. The H. capsulatum protein consists of a four-fold repeated module (domains I to IV) like the p100 kD co-activator proteins, whose three-dimensional (3D) structure is related to staphylococcal thermonuclease, followed by a modified fifth "hybrid" domain which partially resembles the structure of the tudor domain found in multiple copies in the Drosophila melanogaster tudor protein. These data strongly suggest that ORF890 is homologous to human p100 kD and that this protein, named Hcp100, may play an essential role during infection by co-activating the expression of specific genes.

Amino Acid Sequence↗
PubMed1998

Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control.

BACKGROUND: Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). METHODS AND RESULTS: In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75 degrees tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index alpha, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LFSAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced alpha similarly in both groups. CONCLUSIONS: COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

Adult↗
PubMed1998

Central vagotonic effects of atropine modulate spectral oscillations of sympathetic nerve activity.

BACKGROUND: Low-dose atropine causes bradycardia either by acting on the sinoatrial node or by its effects on central muscarinic receptors increasing vagal activity. Any central muscarinic effects of high-dose atropine on RR interval are masked by peripheral muscarinic blockade at the sinoatrial node, which causes tachycardia. Effects of central parasympathetic activation on sympathetic activity are not known. METHODS AND RESULTS: Using power spectral analysis of RR interval, intra-arterial blood pressure, respiration, and muscle sympathetic nerve activity (MSNA), we examined the effects of both low (2 microgram/kg IV) and high (15 microgram/kg IV) doses of atropine. After low-dose atropine, RR increased by 9+/-1% (P<0.0001), the low-frequency (LF) component (in normalized units, NU) of RR variability decreased by -32+/-8%, and the high-frequency (HF)NU component increased (+74+/-19%); hence, LF/HF of RR variability fell by 52+/-10% (all P<0.01). Although overall MSNA did not change, LFNU of MSNA decreased (-15+/-5%), HFNU of MSNA increased (+31+/-3%), and LF/HF of MSNA fell (-41+/-8%) (all P<0.01). After high-dose atropine, LFNU of MSNA decreased (-17+/-12%), HFNU of MSNA increased (+22+/-3%), and LF/HF of MSNA fell (-51+/-21%) (all P<0.02). CONCLUSIONS: Increasing central parasympathetic activity with low-dose atropine is associated with an increase in the HF and a decrease in the LF oscillations of both RR interval and MSNA variability. High-dose atropine similarly induces an increase in the HF and a decrease in the LF components of MSNA variability. Thus, central parasympathetic activation is able to modulate the oscillatory characteristics of sympathetic nerve traffic to peripheral blood vessels.

Adult↗
PubMed1998

Identification and isolation by DDRT-PCR of genes differentially expressed by Histoplasma capsulatum during macrophages infection.

Establishment of infection and disease implies modifications in the genetic programmes of the cell systems that are involved and the differential expression of genes in both parasite and host. In order to identify and isolate relevant genes of the fungus, Histoplasma capsulatum, in which expression is specifically induced during its interaction with murine macrophages (Mphi), we performed a comparative analysis of the pattern of gene expression of the fungus before and after exposure to, and internalization into Mphi by using differential display reverse transcriptase-PCR (DDRT-PCR). Using a limited set of primer combinations, six cDNA fragments of H. capsulatum were identified and isolated; five representing fungal genes in which expressions were enhanced during Mphi infection, whereas one mRNA fragment was down-regulated. Slot blots followed by Northern blot analyses confirmed that the transcripts detected with cDNA clones were over expressed after 1 h of Mphi infection, whereas no transcripts were detected with mRNA purified from H. capsulatum before infection. Sequence analyses and database searches revealed no significant homology to any known sequence for five of these clones. One of the clones showed homology to the rat p105 kD protein, and to the p100 kD co-activator proteins of human and Caenorhabditis elegans. To our knowledge, this is the first experimental evidence that specific genes are differentially expressed by a fungal pathogen when it is exposed to, and phagocytosed by Mphi. Furthermore, these results show that the DDRT-PCR procedure has adequate sensitivity to detect fungal genes induced during parasite-host interaction to identify potential new targets that can be used to develop new antifungal drugs.

Amino Acid Sequence↗
PubMed1998

Quantifying electrocardiogram RT-RR variability interactions.

A dynamic linear parametric model is designed to quantify the dependence of ventricular repolarisation duration variability on heart period changes and other immeasurable factors. The model analyses the beat-to-beat series of the RR duration and of the interval between R- and T-wave apexes (RT period). Directly from these two signals, a parametric identification procedure and spectral decomposition techniques allow RT variability to be divided into RR-related and RR-unrelated parts and allow the RT-RR transfer function to be calculated. RT variability is driven by RR changes at low frequency (LF, around 0.1 Hz) and high frequency (HF, at the respiratory rate), whereas, at very low frequencies, the RR-unrelated contribution to the total RT variability is remarkable. During tilt at LF the RR-related RT percentage power increases (p < 0.02), the RR-unrelated RT percentage power remains unchanged, the gain of the RT-RR relationship largely increases (p < 0.001), and the phase is not significantly modified. Both the RR-related and the RR-unrelated RT percentage powers at LF are not affected by controlled respiration, and an increase in the RT-RR gain at HF is observed (p < 0.02). The proposed analysis may help to describe the regulation of the ventricular repolarisation process and to extract indexes quantifying the coupling between heart period and ventricular repolarisation interval changes.

Electrocardiography↗
PubMed1998

Performance assessment of standard algorithms for dynamic R-T interval measurement: comparison between R-Tapex and R-T(end) approach.

Three automatic approaches to ventricular repolarisation duration measurement (R-Tapex, R-T(end threshold) and R-T(end fitting) methods) are compared on computer-generated and real ECG signals, in relation to their reliability in the presence of the most common electrocardiographic artefacts (i.e. additive broadband noise and additive and multiplicative periodical disturbances). Simulations permit the evaluation of the amount of R-T beat-to-beat variability induced by the artefacts. The R-T(end threshold) method performs better than the R-T(end fitting) one, and, hence, the latter should be used with caution when R-T(end) variability is addressed. Whereas the R-Tapex method is more robust with regard to broadband noise than the R-T(end threshold) one, the reverse situation is observed in the presence of periodical amplitude modulations. A high level of broadband noise dose not prevent the detection of the central frequency of underlying R-T periodical changes. Comparison between the power spectra of the beat-to-beat R-T variability series obtained from three orthogonal ECG leads (X,Y,Z) is used to assess the amount of real and artefactual variability in 13 normal subjects at rest. The R-Tapex series displays rhythms at high frequency (HF) with a percentage power on the Z lead (57.1 +/- 4.9) greater than that on the X and Y leads (41.9 +/- 4.6 and 46.1 +/- 4.9, respectively), probably because of respiratory-related artefacts affecting the Z lead more remarkably. More uniform HF power distributions over X,Y,Z leads are observed in the R-T(end threshold) series (31.8 +/- 3.8, 39.2 +/- 4.1 and 35.1 +/- 4.2, respectively), thus suggesting minor sensitivity of the R-T(end threshold) measure to respiratory-related artefacts.

Algorithms↗
PubMed1998

Measuring regularity by means of a corrected conditional entropy in sympathetic outflow.

A new method for measuring the regularity of a process over short data sequences is reported. This method is based on the definition of a new function (the corrected conditional entropy) and on the extraction of its minimum. This value is taken as an index in the information domain quantifying the regularity of the process. The corrected conditional entropy is designed to decrease in relation to the regularity of the process (like other estimates of the entropy rate), but it is able to increase when no robust statistic can be performed as a result of a limited amount of available samples. As a consequence of the minimisation procedure, the proposed index is obtained without an a-priori definition of the pattern length (i.e. of the embedding dimension of the reconstructed phase space). The method is validated on simulations and applied to beat-to-beat sequences of the sympathetic discharge obtained from decerebrate artificially ventilated cats. At control, regular, both quasiperiodic and periodic (locked to ventilation) dynamics are observed. During the sympathetic activation induced by inferior vena cava occlusion, the presence of phase-locked patterns and the increase in regularity of the sympathetic discharge evidence an augmented coupling between the sympathetic discharge and ventilation. The reduction of complexity of the neural control obtained by spinalization decreases the regularity in the sympathetic outflow, thus pointing to a weaker coupling between the sympathetic discharge and ventilation.

Animals↗
PubMed1998

Lipoprotein(a) levels and apolipoprotein(a) polymorphism in type 1 diabetes mellitus: relationships to microvascular and neurological complications.

To investigate plasma concentrations of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] polymorphism in relation to the presence of microvascular and neurological complications in type 1 diabetes mellitus, 118 young diabetic patients and 127 age-matched controls were recruited. Lp(a) levels were higher in patients than in controls, but the apo(a) isoforms distribution did not differ between the two groups [higher prevalence of isoforms of high relative molecular mass (RMM) in both groups]. Microalbuminuric patients had Lp(a) levels significantly greater than normoalbuminuric patients, and normoalbuminuric patients showed higher Lp(a) levels than controls. Patients with retinopathy or neuropathy showed similar Lp(a) levels to those without retinopathy or neuropathy. No differences in apo(a) isoforms frequencies were observed between subgroups with and without complications (higher prevalence of isoforms of high RMM in every subgroup). However, among patients with retinopathy, those with proliferative retinopathy had higher Lp(a) levels and a different apo(a) isoforms distribution (higher prevalence of isoforms of low RMM) than those with non-proliferative and background retinopathy (higher prevalence of isoforms of high RMM). Our data suggest that young type 1 diabetic patients without microalbuminuria have Lp(a) levels higher than healthy subjects of the same age. Lp(a) levels are further increased in microalbuminuric patients. High Lp(a) levels and apo(a) isoforms of low RMM seem to be associated with the presence of proliferative retinopathy, but have no relation to neuropathy.

Adult↗
PubMed1998

Assessment of the coupling between RTapex and RR interval as an index of temporal dispersion of ventricular repolarization.

To evaluate the dynamic characteristics of the relationship between the RT and RR intervals we analyzed the RR/RTapex variability interaction with a dynamic parametric model whose parameters can be directly estimated from the beat-to-beat series RR and RTapex intervals. The model is designed to separate the fraction of RTapex variability driven by RR changes from that independent of RR variations and to quantify the gain and phase of the relationship between RR and RTapex intervals. The percentage of RTapex variability driven by RR variability was significantly greater in young normal subjects in comparison with postmyocardial infarction patients as well as with age-matched control subjects. This new approach based on the quantification of the RTapex variability dependent and independent of beat-to-beat RR interval changes could be used to quantify the degree of uncoupling between the two signals thus providing a new and noninvasive index of temporal dispersion of ventricular repolarization.

Adult↗
PubMed1997

Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans.

BACKGROUND: Spectral analysis of RR interval and systolic arterial pressure variabilities may provide indirect markers of the balance between sympathetic and vagal cardiovascular control. METHODS AND RESULTS: We examined the relationship between power spectral measurements of variabilities in RR interval, systolic arterial pressure, and muscle sympathetic nerve activity (MSNA) obtained by microneurography over a range of blood pressures. In eight healthy human volunteers, MSNA, RR interval, intra-arterial pressure, and respiration were measured during blood pressure reductions induced by nitroprusside and during blood pressure increases induced by phenylephrine. Both low-frequency (LF; 0.10 +/- 0.01 Hz) and high-frequency (HF; 0.23 +/- 0.01 Hz) components were detected in MSNA variability. Increasing levels of MSNA were associated with a shift of the spectral power toward its LF component. Decreasing levels of MSNA were associated with a shift of MSNA spectral power toward the HF component. Over the range of pressure changes, the LF component of MSNA variability was positively and tightly correlated with LF components of RR interval (in normalized units; P < 10(-6)) and of systolic arterial pressure variability (both in millimeters of mercury squared and normalized units; P < 5 x 10(-5) and P < 5 x 10(-6), respectively). The HF component of MSNA variability was positively and tightly correlated with the HF component (in normalized units) of RR-interval variability (P < 3 x 10(-4)) and of systolic arterial pressure variability (P < .01). CONCLUSIONS: During sympathetic activation in normal humans, there is a predominance in the LF oscillation of blood pressure, RR interval, and sympathetic nerve activity. During sympathetic inhibition, the HF component of cardiovascular variability predominates. This relationship is best seen when power spectral components are normalized for total power. Synchronous changes in the LF and HF rhythms of both RR interval and MSNA during different levels of sympathetic drive are suggestive of common central mechanisms governing both parasympathetic and sympathetic cardiovascular modulation.

Blood Pressure↗
PubMed1997

[Commonplace use of "H"].

OBJECTIVES: Describe characteristic use of cannabis and tobacco. CASE REPORT: A young couple were nicotine-dependent smokers who also regularly used cannabis. After treatment for nicotine withdrawal they no longer had a craving for cigarettes but use of hashish increased. DISCUSSION: Although illegal in France, consumption of cannabis has become commonplace. Short-term risk may be low but the liposolubility of hallucinogenic tetrahydrocannabinol retards elimination leading to the risk of neuropsychiatric disorders after chronic, or even episodic use.

Adult↗
PubMed1997

Non-invasive assessment of the changes in static and oscillatory components of peripheral pressure/flow relationships produced by moderate exercise in humans.

OBJECTIVE: The generalized sympathetic activation induced by exercise is accompanied by an increase in heart rate, blood pressure and vascular resistance in non-exercising vascular beds. The aim of the present study was to test the feasibility of assessing, non-invasively, the static and oscillatory pressure/flow relationships of peripheral arteries and their continuous changes during dynamic exercise. DESIGN: We studied 44 healthy humans at rest, during moderate exercise (recumbent bicycle exercise) and recovery using a totally non-invasive approach. METHODS: Arterial pressure was measured using a plethysmographic device, and ipsilateral brachial artery flow and palmar skin microcirculation flow were assessed with continuous wave Doppler and laser Doppler, respectively. Continuous, long data segments (> 90 s) were acquired with a personal computer and used to determine the changes of pressure/flow relationships of peripheral arteries during dynamic exercise. A new simplified method utilizing a transfer function analysis extracted automatically unequivocal indexes of static and oscillatory properties of vascular system. RESULTS: Moderate exercise induced significant increases of the static (Zo) and oscillatory (Zc) components of peripheral pressure/flow relationships in both brachial artery and skin microcirculation beds. Both indexes returned to control values during early recovery. CONCLUSIONS: This simple, non-invasive approach was capable of assessing the changes of static and oscillatory vascular properties induced by dynamic exercise. This method could be applied for a better understanding of the vascular modifications that occur in other physiological or pathophysiological conditions also characterized by increases in sympathetic drive.

Adult↗
PubMed1997

Spectral decomposition in multichannel recordings based on multivariate parametric identification.

A method of spectral decomposition in multichannel recordings is proposed, which represents the results of multivariate (MV) parametric identification in terms of classification and quantification of different oscillating mechanisms. For this purpose, a class of MV dynamic adjustment (MDA) models in which a MV autoregressive (MAR) network of causal interactions is fed by uncorrelated autoregressive (AR) processes is defined. Poles relevant to the MAR network closed-loop interactions (cl-poles) and poles relevant to each AR input are disentangled and accordingly classified. The autospectrum of each channel can be divided into partial spectra each relevant to an input. Each partial spectrum is affected by the cl-poles and by the poles of the corresponding input; consequently, it is decomposed into the relevant components by means of the residual method. Therefore, different oscillating mechanisms, even at similar frequencies, are classified by different poles and quantified by the corresponding components. The structure of MDA models is quite flexible and can be adapted to various sets of available signals and a priori hypotheses about the existing interactions; a graphical layout is proposed that emphasizes the oscillation sources and the corresponding closed-loop interactions. Application examples relevant to cardiovascular variability are briefly illustrated.

Algorithms↗
PubMed1996

Presence of vasomotor and respiratory rhythms in the discharge of single medullary neurons involved in the regulation of cardiovascular system.

We analyzed the discharges of 77 single neurons located in the rostral ventrolateral medulla (RVLM, n = 25), caudal ventrolateral medulla (CVLM, n = 18), lateral tegmental field (LTF, n = 19) and caudal raphe nuclei (n = 15). These recordings were made from 36 vagotomized and sinoaortic denervated cats that were either decerebrate (n = 27) or anesthetized with urethane (n = 9) and from 3 decerebrate cats with intact sinoartic and vagal nerves. These neurons were classified as sympathetic-related (n = 61) if spike triggered averaging showed that their naturally occurring discharges were correlated to either the cardiac related (2-6 Hz) or a faster (10 Hz) oscillation in inferior cardiac sympathetic nerve discharge. Neurons were classified as sympathetic-unrelated (n = 16) if they lacked these characteristics. We used autoregressive spectral techniques to detect additional slower oscillations hidden in the variability of neuronal discharge and possibly correlated to the oscillations of systolic arterial pressure (SAP). This analysis revealed the existence of a low frequency (LF) oscillation (0.12 +/- 0.02 Hz) in the discharges of 36 sympathetic-related and 9 sympathetic-unrelated neurons. In relation to 35 neurons in 21 animals there was also an LF component in SAP variability. In 29 instances the LF neuronal discharges and SAP variabilities were significantly correlated. In addition, there was a high frequency (HF) oscillation (0.34 +/- 0.06 Hz) in the discharges of 59 medullary neurons. In 56 cases the HF in neuronal discharge variability cohered to that in SAP variability. These data are the first to demonstrate the existence of an LF component in the discharges of individual medullary neurons, at least some of which were likely to be involved in the regulation of the cardiovascular system. Since these oscillations were evident in cats with section of sinoaortic and vagal nerves, they likely reflect central rhythmogenic properties.

Animals↗
PubMed1996

Classification of coupling patterns among spontaneous rhythms and ventilation in the sympathetic discharge of decerebrate cats.

The spontaneous low- and high-frequency rhythms in the sympathetic discharge of decerebrate artificially ventilated cats are affected by external ventilation. Two graphical methods (i.e. the space-time separation plot and the frequency tracking locus) are used to classify the non-linear interactions. The observed behaviours in the sympathetic discharge consist of phase-locked periodic dynamics (at various frequency ratios with ventilation), quasiperiodic and aperiodic patterns. They depend on the experimental condition. In control condition the sympathetic discharge appears more frequently locked to each ventilatory cycle (1:1 dynamics). However, some cases of quasiperiodic dynamics are found. A sympathetic activation stimulus, such as inferior vena cava occlusion, is able to synchronize slow rhythms in the sympathetic discharge to a subharmonic of ventilation. During a sympathetic inhibition stimulus, such as aortic constriction, 1:1 dynamics is detected but the amplitude of the sympathetic responses can be modulated by unlocked slow rhythms. Moreover some cases of aperiodic dynamics are observed. Vagotomy reduces the 1:1 coupling between sympathetic outflow and ventilation. Vagotomy plus spinalisation disrupts periodic dynamics in the sympathetic discharge so that irregular and complex patterns are found.

Animals↗
PubMed1996

Spectral analysis of short term R-Tapex interval variability during sinus rhythm and fixed atrial rate.

Analysis of heart rate variability has been proven useful in stratifying post myocardial patients at risk and in evaluating autonomic dysfunction. Recently augmented inter-lead variability of the QT interval has been associated with increased mortality as a result of arrhythmia and proposed as a marker of dispersion of ventricular repolarization. As the duration of the QT interval is largely dependent upon the length of the preceding cardiac cycle it is tempting to analyse whether neural mechanisms might also directly exert additional modulation. Using autoregressive algorithms we therefore analysed RR and R-Tapex interval variabilities in 15 normal subjects during sinus rhythm and in six patients with a fixed atrial rate. In controls mean R-Tapex interval and variance measured on the vector magnitude were, respectively, 245 +/- 6 ms and 5.1 +/- 0.7 ms2. Spectral analysis of R-Tapex indicated the presence of two spectral components which corresponded to the low and high frequency components of heart rate variability. In R-Tapex variability, high frequency (44 +/- 4 nu) was predominant over low frequency (29 +/- 4 nu). During controlled respiration, a manoeuvre associated with enhanced vagal modulation of sinus node, there was a further increase in high frequency (58 +/- 4 nu) whereas during tilt the low frequency component of R-Tapex variability became predominant (57 +/- 6 nu). In patients with a fixed atrial rate, variance was extremely low (3 +/- 0.9 ms2) and only a respiration-related high frequency component was recognizable in spectral analysis of RR and R-Tapex variabilities. This component was likely to depend upon mechanically induced changes in cardiac vector orientation. These data indicate that during sinus rhythm short-term R-Tapex interval variability is characterized by the same rhythmical components present in RR variability. However, the presence of a very low variance and of only a high frequency component in patients in whom the physiological variability of sinus node is abolished by atrial pacing. suggests that neural modulatory mechanisms do not exert a direct effect on the length of the R-Tapex interval.

Adult↗