Biomedical subjects
Publications and source records attributed to N Garnier.
UNLABELLED: MAGOS is a web server allowing automated protein modelling coupled to the creation of a hierarchical and annotated multiple alignment of complete sequences. MAGOS is designed for an interactive approach of structural information within the framework of the evolutionary relevance of mined and predicted sequence information. AVAILABILITY: The web server is freely available at http://pig-pbil.ibcp.fr/magos.
JUSTIFICATION: According to French regulations concerning the risk of Creutzfeldt-Jakob disease transmission, traceability procedures of all sterile medical devices which need to be reused are mandatory. Despite sterilization processes, the reusable laryngeal mask airway (LMA) prion disease transmission remains possible. As a result, the disposable LMA has been introduced. OBJECTIVE: Assuming clinical equivalence was achieved, the cost of disposable vs reusable LMA was studied in a university hospital. STUDY DESIGN: A Cost-minimization analysis of disposable vs reusable laryngeal mask airway was realised. METHODS: Disposable LMA cost was calculated as the sum of product cost and elimination cost. Reusable LMA were autoclaved after hospital purchasing in two separate sterilizing processing units of the same hospital. Reusable LMA cost was determined combining materiel and labor costs. RESULTS: The reusable LMA cost depended on the sterilizing processing unit concerned and varied between 9.59 Euros and 9.69 vs 8.38 Euros for the single-use LMA. CONCLUSION: With the cost savings made possible by use of disposable LMA in both labor and consumables, this practice should be considered.
In small systems where relevant energies are comparable to thermal agitation, fluctuations are of the order of average values. In systems in thermodynamical equilibrium, the variance of these fluctuations can be related to the dissipation constant in the system, exploiting the fluctuation-dissipation theorem. In nonequilibrium steady systems, fluctuations theorems (FT) additionally describe symmetry properties of the probability density functions (PDFs) of the fluctuations of injected and dissipated energies. We experimentally probe a model system: an electrical dipole driven out of equilibrium by a small constant current I, and show that FT are experimentally accessible and valid. Furthermore, we stress that FT can be used to measure the dissipated power P = R I2 in the system by just studying the PDFs' symmetries.
Using hydrothermal waves in a long narrow channel as an ideal supercritical nonlinear wave system, we study the critical behavior at onset for a finite cell with poorly reflecting boundaries. We observe a spatially nonuniform global eigenmode localized near the end of the cell and associated with a wave front invading the cell. The onset of this mode-corresponding to the absolute instability transition-is shifted above the value corresponding to convective instability, measured in an annular channel with periodic boundary conditions. Experimental critical exponents are discussed in the framework of existing theoretical descriptions and quantitative comparison with the complex Ginzburg-Landau model is attempted.
INTRODUCTION: Kaposi's disease is an angiogenic multifocal cancer process that has several forms, namely Mediterranean, African, HIV-associated, and secondary to a preexisting immunodepressive state (hematological disorder, corticosteroid therapy, immunodepressive treatment). Whatever its form, Kaposi's sarcoma is probably associated with a chronic viral human herpes type 8 infection (HHV8). EXEGESIS: This virus has been implicated in the pathogenesis of multiple myeloma (17 cases recorded to date). In the present study, a further case of Kaposi's sarcoma associated with multiple myeloma has been reported. However, Epstein-Barr virus, cytomegalovirus, hepatitis B and C, HIV and HHV8 serologies were negative. Radiotherapy on the lower limbs was initiated. CONCLUSION: It is concluded that HHV8 does not appear to play a pathogenic role in cases of multiple myeloma, given the rarity of the association between Kaposi's sarcoma/multiple myeloma/HHV8.
Two 500-ps molecular dynamics simulations performed on the single transmembrane domain of the ErbB-2 tyrosine kinase receptor immersed in a fully solvated dilauroylphosphatidyl-ethanolamine bilayer (DLPE) are compared to vacuum simulations. One membrane simulation shows that the initial alpha helix undergoes a local pi helix conversion in the peptide part embedded in the membrane core similar to that found in simulation vacuum. Lipid/water/peptide interaction analysis shows that in the helix core, the intramolecular peptide interactions are largely dominant compared to the interactions with water and lipids whereas the helix extremities are much more sensitive to these interactions at the membrane interfaces. Our results suggest that simulations in a lipid environment are required to understand the dynamics of transmembrane helices, but can be reasonably supplemented by in vacuo simulations to explore rapidly its conformational space and to describe the internal deformation of the hydrophobic core.
The aim of this study was to determine and identify the factors associated with shortening or lengthening time interval from stroke onset to performance of computed tomography (CT) scan in stroke patients admitted to three French emergency departments. All suspected stroke patients were eligible (n = 317). The time intervals between stroke onset and presentation to the emergency department and between CT scan request and CT scan performance were determined. Twelve variables likely to influence time interval before presentation to the emergency department, and five variables likely to influence time interval before CT scan performance were evaluated using stepwise regression analysis. Of the 317 patients included in the study, the mean time interval from stroke onset to CT scan performance for 180 patients was 7 hours 46 minutes (466 minutes). The mean time interval between stroke onset and presentation to the emergency department was 4 hours 36 minutes (276 minutes), varying according to the study site, level of initial severity, medical contact before admission, witnesses at stroke onset, and mode of transportation. The mean time interval between request and CT scan performance was 2 hours 14 minutes (134 minutes), varying upon the site, hour of CT scan request, type of stroke and level of severity at admission. It is concluded that current delays in stroke management are often incompatible with early treatment. The public needs to be informed and admission procedures reorganized. Improved response to the urgency of ischaemic stroke is required as well as direct access to the scanner during periods of scheduled use.
Time resolved fluorescence of the phenylalanine residue (Phe) alone and included in the transmembrane domain (TMD) sequences of the epidermal growth factor receptor (EGFR) and ErbB-2 was studied using the synchrotron radiation source of light, and compared to molecular dynamics (MD) simulations. The fluorescence intensity decay is strongly sensitive to the environment. A mono-exponential decay was obtained for Phe amino acid alone in two different solvents and for Phe included in EGFR transmembrane sequence, with fluorescence lifetime values varying from 1.7 ns (EGFR) to 7.4 ns (Phe dissolved in water). In ErbB-2 transmembrane sequence three lifetimes were detected. The relative amplitude of the shortest one (0.14 ns) is smaller than 10%, whereas the others (0.6 and 2.2 ns) are almost equally represented. They have been attributed to different rotamers exchanging slowly. This interpretation is supported by MD simulations which evidence transitions in time series of the chi 1 dihedral angle of Phe observed in the case of ErbB-2. The anisotropy decays are similar for both peptides and indicate the presence of a correlation time in the nanosecond range (1-4 ns) and the probable existence of a very fast one (< 0.05 ns). Autocorrelation functions computed from MD simulations corroborate these results.
Dimerization models of c-erbB2 transmembrane domains (Leu651-Ile675) are studied by molecular mechanics and molecular dynamics simulations. Both wild and Glu mutated transmembrane helices exhibit the same relative orientation for favorable associations and dimerize preferentially in left-handed coiled-coil structures. The mutation point 659 belongs to the interfacing residues, and in the transforming domain, symmetric hydrogen bonds between Glu carboxylic groups stabilize the dimeric structure. The same helix packing found for the wild dimers, except side-chain-side-chain hydrogen bonds, suggests that the transmembrane domains dimerize according to similar process. Structural and energetical characterization of the models are presented.
The hypothesis of structural alteration in transmembrane helices for signal transduction process is viewed by molecular dynamics simulation techniques. For the c-erbB-2 transmembrane domain involved in oncogenicity, the occurrence of conformational changes has been previously described as transition from the alpha to pi helix. This dynamical feature is thoroughly analyzed for the wild phenotype and oncogenic sequences from a series of 18 simulations carried out on one nanosecond time scale. We show that these structural events do not depend upon the conditions of simulations like force field or starting helix coordinates. We demonstrate that the oncogenic mutations Val659 Glu, Gln and Asp do not prevent the transition. Furthermore, we show that beta branched residues, in conjunction with Gly residues in the c-erbB-2 sequence, act as destabilizers for the alpha helix structure, pi deformations are tightly related to other local structural motifs found in soluble and membrane proteins. These structural alterations are discussed in term of structure-activity relationships for the c-erbB-2 activating mechanism mediated by transmembrane domain dimerization.
A detailed study of the dynamical behavior of the 29-residue peptide including the transmembrane domain of p185c-erbB2 oncogene-encoded protein and of its V659E mutant is presented. In a first part of this work we analyse equal time correlation coefficients between the backbone dihedral angle fluctuations. Concerted motions are observed in the wild type transmembrane alpha-helix but not in the corresponding V659E intramembrane domain. The difference observed in the correlation pattern is attributed to the single amino acid replacement. In a second part, we investigate the propagation of the effect of a local conformational change along the transmembrane segment, one of the dominant hypotheses for signal transduction mechanisms of transmembrane receptors. The analysis of angular time correlation functions together with that of the response of the different residues to a local disturbance applied at the N-terminal side evidences a propagation phenomenon for the wild type peptide. This effect is much less clear for the mutated peptide. Furthermore we show that the first one is much more flexible than the second one.
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The c-erbB2 proto-oncogene encodes for a protein of 185kDa (p185) which becomes transforming upon the Val-->Glu transmembrane amino acid substitution. The transforming ability seems to be due to a substitution-resulting constitutive activation of the tyrosine kinase cytosolic domain of the protein. These observations prompted us to evaluate the structural and dynamical behavior of the transmembrane region of the wild and transforming p185 protein in order to understand the role of this region in the transduction mechanism. 160 ps molecular dynamics simulations in vacuo have been performed on two peptides corresponding to the sequence [651-679] of p185c-erbB2 protein and its transforming mutant Val659-->Glu659. These two sequences include the transmembrane domain and are initially postulated to be in an alpha-helix conformation. Noticeable differences in the flexibility of the two peptides are shown. The nontransforming sequence seems rather flexible and several conformational changes are detected at the junction of the mutation point [658-659] and at position Val665-Val666 during the 160 ps simulations. On the contrary, no transitions were observed for the mutated sequence which adopts a stable alpha-helix conformation. This difference in flexibility could be hypothesized as a factor involved in the regulation of the tyrosine kinase activity of p185c-erbB2.
Antioxidant status can be evaluated by blood selenium, vitamins A and E. The level of selenium was determined in whole blood, erythrocytes and plasma of 170 French people (70-95 years old) healthy and with intercurrent illness, by using PIXE (proton-induced X-ray emission analysis). These results are discussed with other values from the literature. Plasma levels of vitamins A and E have been measured by HPLC. All data were compared with those obtained for younger subjects. Healthy elderly people residing in a geriatric home received selenium supplements during 1 month. The influence of this supplementation brought to light a deficiency for this trace element. The correlation of aging and nutritional requirements with immune function, heart and cancer death rate is presented and discussed.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.