Images in cardiovascular medicine. A quadricuspid aortic valve with severe aortic regurgitation.
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Aortic Valve↗
Biomedical subjects
Philippe Cluzel
Publications and source records attributed to Philippe Cluzel.
Hidden stochastic nature of a single bacterial motor.
The rotary flagellar motor of Escherichia coli bacterium switches stochastically between the clockwise (CW) and counterclockwise (CCW) direction. We found that the CW and CCW intervals could be described by a gamma distribution, suggesting the existence of hidden Markov steps preceding each motor switch. Power spectra of time series of switching events exhibited a peaking frequency instead of the Lorentzian profile expected from standard kinetic two-state models. Our analysis indicates that the number of hidden steps may be a key dynamical parameter underlying the switching process in a single bacterial motor as well as in large cooperative molecular systems.
Bacterial Proteins↗
Dynamical determinants of drug-inducible gene expression in a single bacterium.
A primitive example of adaptation in gene expression is the balance between the rate of synthesis and degradation of cellular RNA, which allows rapid responses to environmental signals. Here, we investigate how multidrug efflux pump systems mediate the dynamics of a simple drug-inducible system in response to a steady level of inducer. Using fluorescence correlation spectroscopy, we measured in real time within a single bacterium the transcription activity at the RNA level of the acrAB-TolC multidrug efflux pump system. When cells are exposed to constant level of anhydrotetracycline inducer and are adsorbed onto a poly-L-lysine-coated surface, we found that the acrAB-TolC promoter is steadily active. We also monitored the activity of the tet promoter to characterize the effect of this efflux system on the dynamics of drug-inducible transcription. We found that the transcriptional response of the tet promoter to a steady level of aTc rises and then falls back to its preinduction level. The rate of RNA degradation was constant throughout the transcriptional pulse, indicating that the modulation of intracellular inducer concentration alone can produce this pulsating response. Single-cell experiments together with numerical simulations suggest that such pulsating response in drug-inducible genetic systems is a property emerging from the dependence of drug-inducible transcription on multidrug efflux systems.
Anti-Bacterial Agents↗
Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by patient and site of involvement: results in eight patients.
OBJECTIVE: Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown origin, characterized by infiltration of tissues by spumous histiocytes. ECD features heterogeneous systemic manifestations, and the general prognosis remains poor despite various treatment options. METHODS: We treated 8 patients with multisystemic ECD with subcutaneous interferon-alpha (IFNalpha) at a dosage of 3-9 x 10(6) units 3 times weekly, for a median duration of 23 months (range 1-46 months). RESULTS: Treatment was generally well tolerated, and side effects remained limited to fever following injections. Treatment was discontinued in 1 patient, because of severe depression. During treatment, some manifestations of ECD disappeared (i.e., xanthelasma, exophthalmos, papilledema, and intracranial hypertension). The efficacy of IFNalpha on cardiovascular ECD was variable, however. Treatment resulted in partial regression of "coated aorta" in some cases and clear failure in others; 2 patients died. The level of C-reactive protein diminished sharply in 5 patients. CONCLUSION: IFNalpha might be a valuable first-line therapy for prolonged treatment of ECD. However, the efficacy of IFNalpha varies among patients and according to the sites of disease involvement, and symptoms may fail to respond to treatment, especially in patients with severe multisystemic forms of ECD with central nervous system and cardiovascular involvement.
Adolescent↗
Protein expression enhancement in efflux-deleted mutant bacteria.
We applied a single-cell assay to characterize how transcription dynamics affects protein expression levels of a tetracycline-inducible gene expression system. Transcriptional activity of the tetracycline promoter in response to a steady level of inducer is steady in DeltaacrAB efflux mutant but pulsating in wildtype Escherichia coli cells. We found that the expression level of the green fluorescent protein is several folds higher in DeltaacrAB efflux mutant than in wildtype cells.
Escherichia coli↗
Multimodality imaging of percutaneous closure of the left atrial appendage.
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Aged, 80 and over↗
Real-time RNA profiling within a single bacterium.
Characterizing the dynamics of specific RNA levels requires real-time RNA profiling in a single cell. We show that the combination of a synthetic modular genetic system with fluorescence correlation spectroscopy allows us to directly measure in real time the activity of any specific promoter in prokaryotes. Using a simple inducible gene expression system, we found that induced RNA levels within a single bacterium of Escherichia coli exhibited a pulsating profile in response to a steady input of inducer. The genetic deletion of an efflux pump system, a key determinant of antibiotic resistance, altered the pulsating transcriptional dynamics and caused overexpression of induced RNA. In contrast with population measurements, real-time RNA profiling permits identifying relationships between genotypes and transcriptional dynamics that are accessible only at the level of the single cell.
Bacterial Proteins↗
AgentCell: a digital single-cell assay for bacterial chemotaxis.
MOTIVATION: In recent years, single-cell biology has focused on the relationship between the stochastic nature of molecular interactions and variability of cellular behavior. To describe this relationship, it is necessary to develop new computational approaches at the single-cell level. RESULTS: We have developed AgentCell, a model using agent-based technology to study the relationship between stochastic intracellular processes and behavior of individual cells. As a test-bed for our approach we use bacterial chemotaxis, one of the best characterized biological systems. In this model, each bacterium is an agent equipped with its own chemotaxis network, motors and flagella. Swimming cells are free to move in a 3D environment. Digital chemotaxis assays reproduce experimental data obtained from both single cells and bacterial populations.
Algorithms↗
Traumatic pseudoaneurysm of the descending thoracic aorta inflicted by a spinal osteophyte.
This report describes a case involving a traumatic pseudoaneurysm of the descending thoracic aorta resulting from direct contusion inflicted by the tip of a spinal osteophyte at the level of T11-T12. Endovascular repair with placement of a custom-made endograft by the femoral route was performed after routine arteriography to locate the origin of the Adamkiewicz artery.
Aneurysm, False↗
Static mechanical properties of custom-made aortic endografts.
Several cases of delayed aortic rupture after endovascular aneurysm repair have been attributed to in vivo endograft fatigue. Such complications could involve damage to structural components during introduction. The purpose of this study was to compare forces applied during introduction to forces needed to damage the endograft. Testing was carried out on the custom-made endograft (CMEG) that has been in almost exclusive use at our center since 1996. Findings showed that the force applied during introduction was less than the force necessary to damage the endograft. No alteration in the mechanical properties of the CMEG was observed immediately after implantation.
Aorta↗
A non-rigid registration approach for quantifying myocardial contraction in tagged MRI using generalized information measures.
We address the problem of quantitatively assessing myocardial function from tagged MRI sequences. We develop a two-step method comprising (i) a motion estimation step using a novel variational non-rigid registration technique based on generalized information measures, and (ii) a measurement step, yielding local and segmental deformation parameters over the whole myocardium. Experiments on healthy and pathological data demonstrate that this method delivers, within a reasonable computation time and in a fully unsupervised way, reliable measurements for normal subjects and quantitative pathology-specific information. Beyond cardiac MRI, this work redefines the foundations of variational non-rigid registration for information-theoretic similarity criteria with potential interest in multimodal medical imaging.
Adult↗
Assessment of myocardial function: a review of quantification methods and results using tagged MRI.
Tagged MRI provides a noninvasive way to assess the regional function of the heart. Clinical use of myocardial strain measurements from tagged MRI requires identifying new normative values. As for cardiac motion estimation, a variety of methods for quantifying myocardial deformations have been proposed in the image analysis and medical literature, based on heart geometry and continuum mechanics. This article comparatively reviews existing quantification techniques, and synthesizes their results to establish confidence intervals for the standard deformation parameters.
Heart↗
Central venous stenosis as a complication of ipsilateral haemodialysis fistula and pacemaker.
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Aged↗
French women from multiplex abdominal aortic aneurysm families should be screened.
BACKGROUND: Multiplex abdominal aortic aneurysm families (MAAAFs) (> or =1 subject plus the proband) represent 1% to 34% of abdominal aortic aneurysm (AAA), but the percentage in France is unknown. METHOD: The MAAAF rate was retrospectively defined by analysis of 3 groups: 72 of 104 consecutive individuals undergoing AAA surgery during 1994, 24 of 53 women and 35 of 76 men with giant (> or =9 cm) AAA operated on during 1986 to 1994. MAAAF characteristics were determined based on 10 families issued from these 3 groups and 34 others identified nationwide. Data were obtained from a standardized questionnaire for probands and relatives, detailed pedigrees of each family, and computed tomography (CT) scans without contrast medium of the aorta and lower limb arteries for first-degree relatives > or =40-year-of age. RESULTS: The MAAAF rate was 4.2% for the consecutive-surgery patients (proband M/F ratio, 17:1; mean age at surgery, 68.5 +/- 8.5 years). CT detected no additional AAA among them (screened individuals M/F ratio, 0.63; mean age, 54.0 +/- 11.2 years). MAAAF rates were 8.3% and 14.3% for the women's and giant-AAA groups with CT screening, respectively. Characteristics were investigated in 104 affected subjects from 44 MAAAFs: female relatives were more often affected than probands (P < 0.025). Compared with men, affected female relatives were significantly older at diagnosis and surgery (P < 0.05 and P < 0.02, respectively), as were affected women (P < 0.02 and P < 0.01, respectively). CT scan screening identified significantly more AAA and abdominal aortic dilatations among the 44 MAAAFs than the consecutive-surgery group (5 and 4, respectively; P < 0.001). CONCLUSION: Although the MAAAF rate seems low in France, women from MAAAF were affected more often and later, suggesting that they should be screened.
Adult↗
From molecular noise to behavioural variability in a single bacterium.
The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals. In studying intracellular networks, most experiments and mathematical models have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.
Adaptation, Physiological↗
Quantification of myocardial function using tagged MR and cine MR images.
Magnetic Resonance Imaging (MRI) is recognized as a relevant modality for dynamically imaging the heart anatomy and function, and achieving satisfying qualitative diagnosis. Reliable methods for quantitatively analyzing cardiac motion from MR images remain, however, to be elaborated. This paper presents a novel approach for measuring myocardial deformations from tagged MRI sequences. Based on efficient pixel-based statistical non-rigid registration, it allows for automatically extracting local/global deformation parameters at the pixel and myocardial segment scales. Its performances for assessing the myocardial function are illustrated both for the normal heart and for pathologies of the ischemic and dilated cardiomyopathic type.
Adult↗
An endovascular stent relieves celiac and mesenteric ischemia in acute aortic dissection.
We report the case of a 63-year-old patient with bowel ischemia related to an acute type B dissection. The patient was successfully treated with a covered stent graft inserted at the level of the descending thoracic aorta.
Acute Disease↗
Comparative diagnostic performances of auscultation, chest radiography, and lung ultrasonography in acute respiratory distress syndrome.
BACKGROUND: Lung auscultation and bedside chest radiography are routinely used to assess the respiratory condition of ventilated patients with acute respiratory distress syndrome (ARDS). Clinical experience suggests that the diagnostic accuracy of these procedures is poor. METHODS: This prospective study of 32 patients with ARDS and 10 healthy volunteers was performed to compare the diagnostic accuracy of auscultation, bedside chest radiography, and lung ultrasonography with that of thoracic computed tomography. Three pathologic entities were evaluated in 384 lung regions (12 per patient): pleural effusion, alveolar consolidation, and alveolar-interstitial syndrome. RESULTS: Auscultation had a diagnostic accuracy of 61% for pleural effusion, 36% for alveolar consolidation, and 55% for alveolar-interstitial syndrome. Bedside chest radiography had a diagnostic accuracy of 47% for pleural effusion, 75% for alveolar consolidation, and 72% for alveolar-interstitial syndrome. Lung ultrasonography had a diagnostic accuracy of 93% for pleural effusion, 97% for alveolar consolidation, and 95% for alveolar-interstitial syndrome. Lung ultrasonography, in contrast to auscultation and chest radiography, could quantify the extent of lung injury. Interobserver agreement for the ultrasound findings as assessed by the kappa statistic was satisfactory: 0.74, 0.77, and 0.73 for detection of alveolar-interstitial syndrome, alveolar consolidation, and pleural effusion, respectively. CONCLUSIONS: At the bedside, lung ultrasonography is highly sensitive, specific, and reproducible for diagnosing the main lung pathologic entities in patients with ARDS and can be considered an attractive alternative to bedside chest radiography and thoracic computed tomography.
Aged↗