Biomedical subjects

Olivier Michel

Publications and source records attributed to Olivier Michel.

18 recordsLinked to original sources

PubMed2006

Evaluation of oral corticosteroids and phosphodiesterase-4 inhibitor on the acute inflammation induced by inhaled lipopolysaccharide in human.

BACKGROUND: Endotoxins are pro-inflammatory substances present in the environment. In man, inhalation of its purified derivative lipopolysaccharide (LPS) induces inflammation related to macrophages and neutrophils. Corticosteroids and phosphodiesterase (PDE)-4 inhibitors have inhibiting effects on macrophages and neutrophils, respectively. This study investigated the effect of prednisolone and of the PDE-4 inhibitor cilomilast on the LPS-induced acute inflammation. METHODS: The study was a placebo-controlled, double-blind crossover design. On three occasions, at 2 weeks interval, 16 healthy subjects inhaled 50 microg LPS after a 6-day treatment with cilomilast (15 mg bd), prednisolone (10 mg bd) or placebo. For the assessment of the inflammatory response, induced sputum was obtained before inclusion and 6h post-LPS while blood samples were collected before, 6 and 24 h post-LPS. RESULTS: Inhaled LPS induced an increase in sputum neutrophils (p<0.0001), logMMP-9 (p<0.05), logMMP-9/TIMP-1 (p<0.01) and logTNF-alpha (p<0.02). At the blood level there were significant rise in neutrophilia (p<0.001), E-selectin (p<0.02), C-reactive protein (CRP) (p<0.001) and LPS-binding protein (p<0.001). There was both a slight, but not significant, increase in body temperature and decrease in forced expiratory volume in 1 s (FEV(1)). Neither prednisolone nor cilomilast had protective effect on the LPS-induced airways' inflammation. The LPS-induced CRP acute-phase protein of inflammation (0.58+/-0.13 and 3.52+/-0.41 mg/dL, before and after LPS, respectively) was significantly inhibited by a pre-treatment with prednisolone (1.39+/-0.32 mg/dL, p<0.01) and attenuated (2.65+/-0.30 mg/dL, p=0.09) with cilomilast. CONCLUSION: In healthy subjects, while the LPS-induced airways' inflammation was not modified either by oral prednisolone or by PDE-4 inhibitor cilomilast (at actual dosage), the LPS-induced acute phase of blood inflammation was reduced by prednisolone.

Acute Disease↗

PubMed2006

Declarative modeling of a neurulation-like process.

MGS is an experimental programming language dedicated to the modeling and the simulation of a special kind of discrete dy- namical systems. Dynamical systems with a dynamical structure (or (DS)(2)) arise when the state space is not fixed a priori but is jointly computed with the current state during the simulation. In this case the evolution function is often given through local rules that drive the interaction between some system components. MGS offers a new kind of data structure, topological collections, to describe the state of a dynamical system, and a new kind of control structure, transformations, to express local and discrete evolution laws. These two notions permit an easy specification of (DS)(2). We propose in this paper a presentation of the MGS language and its main contributions. We show that various topological collections can be unified using concepts developed in combinatorial algebraic topology: cellular complexes and topological chains. Then we apply the notions brought by MGS to model and simulate the first step towards the simulation of the neurulation process in developmental biology where a sheet of cells evolves to a neural tube. It is a direct description of the modification of the topology of an arbitrary structure expressed in terms of local discrete evolution laws.

Computer Simulation↗

PubMed2006

History and results of the two inter-laboratory round robin endotoxin assay studies on cotton dust.

BACKGROUND: In the US cotton industry, airborne cotton dust levels are regulated, and other countries are moving to specify safety limits for airborne endotoxins. There is concern about potential respiratory health hazards associated with agricultural and other organic dusts. In laboratories, ranking which samples have high and low levels of endotoxin is usually in good agreement between laboratories. When different laboratories assay identical samples, the levels differ. The objective of this research was to evaluate the intra- and inter-laboratory variability for 13 laboratories measuring endotoxin in cotton dust. METHOD: Two inter-laboratory round robin endotoxin assay studies were conducted using cotton dust. In the first round robin, each laboratory used their normal in-house assay method and then used a common extraction protocol. In the second round robin, a common extraction protocol and endotoxin assay kit was used. RESULTS: The intra-laboratory results had small variations but inter-laboratory results had very high variations. The inter-laboratory results using a common extraction protocol showed reduced differences. Using the same extraction protocol and endotoxin assay kit, the intra-laboratory variation was small and inter-laboratory variation was reduced but not enough for inter-laboratory agreement. Most of the laboratories were able to discern between the high and low endotoxin concentration dusts. CONCLUSIONS: Standardization has reduced the differences in results between laboratories and possibly further standardization may bring closer inter-laboratory agreement.

Air Microbiology↗

PubMed2006

Chlorinated pool attendance, atopy, and the risk of asthma during childhood.

The pool chlorine hypothesis postulates that the rise in childhood asthma in the developed world could result at least partly from the increasing exposure of children to toxic gases and aerosols contaminating the air of indoor chlorinated pools. To further assess this hypothesis, we explored the relationships between childhood asthma, atopy, and cumulated pool attendance (CPA). We studied 341 schoolchildren 10-13 years of age who attended at a variable rate the same public pool in Brussels (trichloramine in air, 0.3-0.5 mg/m3). Examination of the children included a questionnaire, an exercise-induced bronchoconstriction (EIB) test, and the measurement of exhaled nitric oxide (eNO) and total and aeroallergen-specific serum IgE. CPA by children (range, 0-1,818 hr) emerged among the most consistent predictors of asthma (doctor diagnosed or screened with the EIB test) and of elevated eNO, ranking immediately after atopy and family history of asthma or hay fever. Although the risk of elevated eNO increased with CPA [odds ratio (OR) = 1.30; 95% confidence interval (CI), 1.10-1.43] independently of total or specific serum IgE, the probability of developing asthma increased with CPA only in children with serum IgE > 100 kIU/L (OR for each 100-hr increase in CPA = 1.79; 95% CI, 1.07-2.72). All these effects were dose related and most strongly linked to pool attendance before 6-7 years of age. Use of indoor chlorinated pools especially by young children interacts with atopic status to promote the development of childhood asthma. These findings further support the hypothesis implicating pool chlorine in the rise of childhood asthma in industrialized countries.

Asthma↗

PubMed2005

Organic dust induced inflammation--role of atopy and TLR-4 and CD14 gene polymorphisms.

BACKGROUND: Polymorphisms in the genes controlling for CD14 and TLR-4 may influence the outcome of endotoxin-induced effects. MATERIALS AND METHODS: A study was performed on 146 workers in industries with exposure to organic dust containing endotoxin and 53 controls. Endotoxin exposure was measured at representative work sites. Inflammagenic markers, cytokines, and CD14 and TLR-4 polymorphisms were determined in blood. RESULTS: Among workers, serum levels of esinophilic cationic protein (ECP) were lower compared to controls and the proportion of atopics was lower. Atopic persons had lower levels of IL-6 and IL-8, both among controls and exposed. IL-6 and ECP values were lower among those with TLR-4 /+896 AG and GG polymorphisms as compared to AA. Among atopic workers with CD-14(-550) polymorphism CC, IL-8 was lower. COMMENTS: The results suggest that CD14 and TLR-4 polymorphisms influence regulators of the inflammation induced by endotoxin in organic dusts. Atopic persons have a lower secretion of certain inflammatory cytokines.

Case-Control Studies↗

PubMed2005

Exercise-induced respiratory symptoms are poor predictors of bronchoconstriction.

Exercise-induced asthma (EIA) is a possible cause of poor physical performance in children. No data are available on the value of respiratory symptoms to discriminate children with bad physical fitness from children with EIA. We evaluated respiratory symptoms in school-age children during and after exercise in relation to EIA. The population of 149 primary schools (849 classes with 15,241 children) was enrolled in the study. EIB was assessed using the 6-min free-running-test (6MFRT) in 15,241 children. At the end or at premature arrest of the 6MFRT, signs reported by the children and clinical symptoms observed by supervising physicians were recorded. Peak flow measurements were obtained before and 5 and 10 min after the 6MFRT, a decrease of 15% or more being defined as significant. The 6MFRT was positive in 7.4% of primary schoolchildren. Girls were more likely to have a positive test than boys (8.5% vs. 6.4%, P < 0.001), and children living in urban areas more than those living in rural areas (8.9% vs. 7.0%, P < 0.01). Premature arrest was seen in 3.5% (i.e., n = 353) of the children. The main reasons for premature arrest were dyspnea and chest pain. Among them, only 21% had a positive 6MFRT, while 89% with a positive 6MFRT could terminate the test. Premature arrest, breathlessness, chest tightness, wheezing, and cough had a positive predictive value to detect a EIA of 21.9%, 20.8%, 36.4%, 41.2%, and 28.3%, respectively, and a sensitivity of 10.8%, 29.5%, 14.9%, 4.8%, and 13.0%, respectively. In conclusion, EIA was detected in 7.4% of schoolchildren. A slightly higher incidence was observed in girls and children from an urban area. Neither premature arrest nor clinical signs and symptoms were good predictors of EIA in primary schoolchildren.

Asthma, Exercise-Induced↗

PubMed2005

Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings.

BACKGROUND: Animal models of lung inflammation have validated the plasma 16-kd Clara cell protein (CC16) as a peripheral marker of the permeability of the alveolocapillary barrier. OBJECTIVE: We investigated in human beings whether inhaled LPS induced a rise in airways permeability measured by the plasma changes in CC16. METHODS: The CC16 was measured in plasma from 15 subjects exposed to LPS by inhalation, during which the kinetics and the dose-response relationship of LPS-induced CC16 were evaluated. Because LPS-induced response involves macrophages activation, the protective effect of oral methylprednisolone was also evaluated. RESULTS: An inhalation of 50 microg LPS induced a significant ( P < .001) rise in CC16 after 6 hours (from 7.24 [+/-0.68] microg/L to 10.69 [+/-0.99] microg/L) that normalized at 24 hours (6.65 [+/-0.33] microg/L). The CC16 response was dose-related, with the no-response threshold 0.5 microg LPS. A 6-day treatment with 20 mg/d methylprednisolone inhibited significantly ( P < .001) the CC16 response to 50 microg LPS. CONCLUSION: Exposure to LPS by inhalation in healthy subjects induces an intravascular leakage of CC16 that can be blocked by corticosteroids. These observations further validate plasma CC16 as a noninvasive test of the alveolocapillary barrier permeability.

Administration, Oral↗

PubMed2005

[Pharmacological treatment in severe dementia].

Medical treatment of severe dementia is now available. Decrease of psychobehavioral disturbances, autonomy loss or care-giver burden appear as the main objective rather than reduction of cognitive deficits. Acetylcholinesterase inhibitors (AChE-I) should be maintained in patients with severe dementia when initiated in mild or moderate dementia. Memantine is the specific treatment for patients with severe dementia, even if they received AChE-I. To treat the psychobehavioral disturbancies, serotoninergic agents and thymoregulators are the first line drugs. Medical treatment should only be co-prescribed with a global care of all co-morbidities, autonomy loss and patient's and care-giver's burden, and associated with psychological and organisational support.

Activities of Daily Living↗

PubMed2005

Bacterial contamination of indoor air, surfaces, and settled dust, and related dust endotoxin concentrations in healthy office buildings.

Endotoxin, a characteristic external fraction of the outer membrane from Gram-negative bacteria, continuously shed into the environment, is considered as an important risk factor for human health. Our purpose was to study the bacterial species contaminating healthy working environments. Airborne, working surfaces and carpet dust samples were collected from 25 offices. Bacterial species were identified with biochemical ApiSystem strips. Endotoxin concentrations in settled dust were measured with the kinetic chromogenic Limulus assay. The airborne bacterial level varied from 44-2,511, with a median of 277 cfu/m(3). Bacterial contamination on surfaces ranged from 1-1000, with 33 cfu/25 cm(2) as median value. On carpets, bacterial concentration ranged from 0.73-185 x 10(5) cfu/g, with 7.28 x 10(5) cfu/g as median value. Endotoxin concentration varied from 4.6-116.2 EU/mg, with a median of 20.3 EU/mg. Altogether, 501 bacterial strains were isolated. The species variability was greater in Gram-negative bacteria than in Gram-positive cocci with 41 versus 34 various species. In conclusion, people working in healthy offices can be exposed to large concentrations of airborne and dust bacteria and related endotoxin concentrations, giving a risk of work-related diseases.

Air Microbiology↗

PubMed2003

Systemic responsiveness to lipopolysaccharide and polymorphisms in the toll-like receptor 4 gene in human beings.

BACKGROUND: The response to lipopolysaccharide exposure is highly variable and might be a result of genetic diversity between individuals. The toll-like receptor 4 (TLR-4) is the principal receptor for lipopolysacharide. OBJECTIVES: We investigated the association between single-nucleotide polymorphisms in the TLR4 locus and levels of systemic inflammatory markers in response to lipopolysaccharide. METHODS: Healthy subjects (n = 116) were genotyped for the most frequent polymorphisms found in the promoter and coding region of the TLR4 gene (-2026A/T, -1607T/C, +896A/G, and +1196C/T relative to the translation start site). Subjects were challenged with 20 microg lipopolysaccharide by inhalation. RESULTS: Polymorphisms at +896 and +1196 were in complete linkage disequilibrium, and no homozygotes for the less common allele, G and T respectively, were found. After lipopolysaccharide inhalation, subjects heterozygous for either TLR-4/+896 or TLR4/+1196 had significantly lower numbers of white blood cell counts and lower levels of C-reactive protein and lipopolysaccharide-binding protein compared with homozygotes with the common allele. None of the heterozygous subjects (n = 18) except 1 were high responders to lipopolysaccharide (defined as a rise in C-reactive protein > 10 mg/L), whereas 36 of 98 homozygous subjects were high responders (P <.02). No association was observed between the TLR-4/-2026 and TLR-4/-1607 polymorphisms and lipopolysaccharide responsiveness. CONCLUSION: The single-nucleotide polymorphisms at position +896 or +1196 in the TLR-4 gene is associated with systemic inflammatory hyporesponsiveness to inhaled lipopolysaccharide.

Acute-Phase Proteins↗

PubMed2003

Modeling the topological organization of cellular processes.

The cell as a dynamical system presents the characteristics of having a dynamical structure. That is, the exact phase space of the system cannot be fixed before the evolution and integrative cell models must state the evolution of the structure jointly with the evolution of the cell state. This kind of dynamical systems is very challenging to model and simulate. New programming concepts must be developed to ease their modeling and simulation. In this context, the goal of the MGS project is to develop an experimental programming language dedicated to the simulation of this kind of systems. MGS proposes a unified view on several computational mechanisms (CHAM, Lindenmayer systems, Paun systems, cellular automata) enabling the specification of spatially localized computations on heterogeneous entities. The evolution of a dynamical structure is handled through the concept of transformation which relies on the topological organization of the system components. An example based on the modeling of spatially distributed biochemical networks is used to illustrate how these notions can be used to model the spatial and temporal organization of intracellular processes.

Algorithms↗

PubMed2003

Circulating regulatory anti-T cell receptor antibodies in patients with myasthenia gravis.

Serum anti-T cell receptor (TCR) Ab's are involved in immune regulation directed against pathogenic T cells in experimental models of autoimmune diseases. Our identification of a dominant T cell population expressing the Vbeta5.1 TCR gene (TCRBV5-1), which is responsible for the production of pathogenic anti-acetylcholine receptor (AChR) autoantibodies in HLA-DR3 patients with early-onset myasthenia gravis (EOMG), prompted us to explore the occurrence, reactivity, and regulatory role of anti-TCR Ab's in EOMG patients and disease controls with clearly defined other autoantibodies. In the absence of prior vaccination against the TCR, EOMG patients had elevated anti-Vbeta5.1 Ab's of the IgG class. This increase was restricted largely to EOMG cases with HLA-DR3 and with less severe disease, and it predicted clinical improvement in follow-up studies. EOMG patient sera containing anti-TCR Ab's bound specifically the native TCR on intact Vbeta5.1-expressing cells and specifically inhibited the proliferation and IFN-gamma production of purified Vbeta5.1-expressing cells to alloantigens in mixed lymphocyte reaction and the proliferation of a Vbeta5.1-expressing T cell clone to an AChR peptide, indicating a regulatory function for these Ab's. This evidence of spontaneously active anti-Vbeta5.1 Ab's in EOMG patients suggests dynamic protective immune regulation directed against the excess of pathogenic Vbeta5.1-expressing T cells. Though not sufficient to prevent a chronic, exacerbated autoimmune process, it might be boosted using a TCR peptide as vaccine.

Adolescent↗

PubMed2003

Role of lipopolysaccharide (LPS) in asthma and other pulmonary conditions.

Endotoxin significantly contaminates house dust and is an enhancing factor for asthma severity. Natural exposure to endotoxin in early life could influence immune development and protect from the risk of developing atopy. This article will focus on published data showing that home environmental contamination by endotoxin can participate in chronic airways diseases, in particular asthma.

Adjuvants, Immunologic↗

PubMed2002

Hyperstructures, genome analysis and I-cells.

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.

Algorithms↗

PubMed2002

Time-resolved tracking of a sound scatterer in a complex flow: nonstationary signal analysis and applications.

It is known that ultrasound techniques yield nonintrusive measurements of hydrodynamic flows. For example, the study of the echoes produced by a large number of particles insonified by pulsed wavetrains has led to a now-standard velocimetry device. In this paper, a new technique for the measurement of the velocity of individual solid particles moving in fluid flows is proposed. It relies on the ability to resolve in time the Doppler shift of the sound scattered by the continuously insonified particle. For this signal-processing problem two classes of approaches can be used: time-frequency analysis and parametric high-resolution methods. In the first class the spectrogram and reassigned spectrogram is considered, and applied to detect the motion of a small bead settling in a fluid at rest. In nonstationary flows, methods in the second class are more robust. An approximated maximum likelihood (AML) technique has been adapted, coupled with a generalized Kalman filter. This method allows for the estimation of rapidly varying frequencies; the parametric nature of the algorithm also provides an estimate of the variance of the identified frequency parameters.

Journal Article↗

PubMed2002

Second inter-laboratory study comparing endotoxin assay results from cotton dust.

Previously, a large two-part inter-laboratory round robin endotoxin assay study was completed. This first study showed that when cotton dust samples, which are practically identical, are assayed for endotoxin that the intra- laboratory results had a very small variation while intra-laboratory results of the sample had a very high variation. In the first part of the study, each laboratory followed its own in-house assay protocol; but in the second part of the study, when the extraction protocol was standardized, the inter-laboratory results showed a lower variation, which suggested that with further standardization, further reduction of differences between laboratories might be achieved in order that results between laboratories would become more comparable. The results stimulated interest in extending the study to include cotton dust with two levels of endotoxin, standardization of the extraction protocol, and using the same assay kit from the same production lot. The results of this second round robin endotoxin assay study indicate that differences between laboratories are still high, but most of the laboratories could discern the cotton dusts with the different levels of endotoxin.

Chemistry Techniques, Analytical↗

PubMedDate not supplied

Declarative simulation of dynamicals systems: the 812 programming language and its application to the simulation of genetic networks.

A major part of biological processes can be modeled as dynamical systems (DS), that is, as a time-varying state. In this article, we advocate a declarative approach for prototyping the simulation of DS. We introduce the concepts of collection, stream and fabric. A fabric is a multi-dimensional object that represents the successive values of a structured set of variables. A declarative programming language, called 8 1/2 has been developed to support the concept of fabrics. Several examples of working 8 1/2 programs are given to illustrate the relevance of the fabric data structure for simulation applications and to show how recursive fabric definitions can be easily used to model various biological phenomena in a natural way (a resolution of PDE, a simulation in artificial life, the Turing diffusion-reaction process and various examples of genetic networks). In the conclusion, we recapitulate several lessons we have learned from the 8 1/2 project.

Programming Languages↗

PubMedDate not supplied

Changes in serum pneumoproteins caused by short-term exposures to nitrogen trichloride in indoor chlorinated swimming pools.

Nitrogen trichloride (NCl(3)) is an irritant gas released in the air of indoor pools sanitized with chlorine-based disinfectants. In the present study we investigated the effects of NCl(3) on the pulmonary epithelium of pool attendees by measuring the leakage into serum of three lung-specific proteins (pneumoproteins): the alveolar surfactant-associated proteins A and B (SP-A and SP-B) and the bronchiolar 16 kDa Clara cell protein (CC16). These pneumoproteins were measured in the serum of 29 recreational swimmers (16 children and 13 adults) before and after attending a chlorinated pool with a mean NCl(3) concentration of 490 microg m(-3). Pneumoprotein changes in serum were also studied in 14 trained swimmers performing an intensive 45 min standardized swimming session in a chlorinated pool (mean NCl(3) concentration of 355 microg m(-3)) and for the purposes of comparison in a non-chlorinated pool sanitized by the copper/silver method. Serum CC16 was not increased in recreational swimmers, but in trained swimmers serum levels of this protein peaked immediately after strenuous exercise, both in the copper/silver pool and in the chlorinated pool. This acute increase in airway permeability is probably the consequence of the mechanical stress on the epithelial barrier caused by overinflation and/or hyperventilation during intense exercise. Serum levels of SP-A and SP-B were unaffected by strenuous exercise in the copper/silver pool. The two proteins were, however, significantly increased in a time-dependent manner in recreational and trained swimmers attending the chlorinated pool. The intravascular leakage of SP-A and SP-B was already statistically significant after only 1 h of exposure to pool air without exercising and remained elevated for 12 h after. These changes were not associated with decrements in lung function. The ability of NCl(3) to acutely disrupt the lung epithelium barrier was confirmed in mice using serum CC16 and plasma proteins in bronchoalveolar lavage fluid as permeability markers. The significance of these permeability changes induced by NCl(3) in the deep lung is presently unknown. In view of the increasing and widespread human exposure to this gas not only in indoor pools but also in a variety of other situations, these findings warrant further study.

Adolescent↗