PubMed Health⌕ Search

Biomedical subjects

C Pasquier

Publications and source records attributed to C Pasquier.

At least 19 recordsLinked to original sources
PubMed2005

Suppression of MR gradient artefacts on electrophysiological signals based on an adaptive real-time filter with LMS coefficient updates.

Electrocardiogram (ECG) acquisition is still a challenge as gradient artefacts superimposed on the electrophysiological signal can only be partially removed. The signal shape of theses artefacts can be similar to the QRS-complex, causing possible misinterpretation during patient monitoring and false triggering/gating of the MRI. For their real-time suppression, an adaptive filter is proposed. The adaptive filter is based on the noise-canceller configuration with LMS coefficient updates. The references of the noise canceller are the three gradient signals that are acquired simultaneously with the noisy ECG. Tests were done on patients, on volunteers and using an MR-safe ECG simulator. The noise canceller's performance was measured offline, simulating real-time processing by point-by-point operations. To create worst-case scenarios, clinical sequences with strong- and fast-switching gradients have been chosen. The noise-cancelling filter reduces the gradient artefacts' peak amplitudes by 80-99% after adaptation, without changing the desired ECG signal shape. The estimated reduction of total average power of the MR gradient artefacts is 62-98%. The proposed filter is capable of reducing artefacts due to strong- and fast-switching gradients in real-time applications and worst-case situations. The quality of the ECG is sufficiently high that a standard one-lead QRS-detector can be used for gating/triggering the MRI. For permanent patient monitoring, further improvements are needed.

Algorithms↗
PubMed2004

THEA: ontology-driven analysis of microarray data.

MOTIVATION: Microarray technology makes it possible to measure thousands of variables and to compare their values under hundreds of conditions. Once microarray data are quantified, normalized and classified, the analysis phase is essentially a manual and subjective task based on visual inspection of classes in the light of the vast amount of information available. Currently, data interpretation clearly constitutes the bottleneck of such analyses and there is an obvious need for tools able to fill the gap between data processed with mathematical methods and existing biological knowledge. RESULTS: THEA (Tools for High-throughput Experiments Analysis) is an integrated information processing system allowing convenient handling of data. It allows to automatically annotate data issued from classification systems with selected biological information coming from a knowledge base and to either manually search and browse through these annotations or automatically generate meaningful generalizations according to statistical criteria (data mining). AVAILABILITY: The software is available on the website http://thea.unice.fr/

Abstracting and Indexing↗
PubMed2004

[Impact of reverse transcriptase inhibitors on sperm mitochondrial and genomic DNA in assisted reproduction techniques].

For the last ten years, antiretroviral therapy (ARV) has improved the prognosis in HIV-1 infection and showed a better control of the viral excretion by reducing viral shedding in semen. However, nucleoside analogues reverse transcriptase inhibitors (NRTI) therapy reported important adverse effects. Most of these side effects observed seem to be linked with a common mechanism: mitochondrial activity alteration. Since the introduction of protocols for HIV-1 serodiscordant couples, with male infected partners under NRTI therapy, many results in the literature such as: semen characteristics and pregnancies, drew the attention of research teams. Many studies have suggested that NRTI has an affect on semen parameters, but proposed mechanisms of these effects have rarely been discussed. NRTI have a great affinity for the reverse transcriptase of HIV-1. Because many NRTI are not only inhibitors of reverse transcriptase but also inhibitors of the DNA polymerase beta and gamma, several toxic effects can be considered. Nevertheless, this specificity is not absolute and "accidental" incorporations of NRTI can occur on genomic sperm DNA. Only one study on genomic sperm DNA with patients under NRTI therapy was published without concluding results. Recently, studies have suggested that NRTI exposure could induce an alteration on mitochondrial energy-generating ability of spermatozoa. NRTI are known to induce an increase in the generation of reactive oxygen species, which results in the degradation of mitochondrial transmembrane potential (Deltapsim). This loss of Deltapsim can tend to release some specific apoptosis factors, such as cytochrome c, that initiates programmed cell death. Sperm DNA fragmentation, associated to apoptosis, was reported as a possible cause of recurrent pregnancy loss. If the incorporation of NRTI was reported in genomic DNA of somatic cells, the absence of data on the genomic sperm DNA justifies further studies concerning the effects of paternal exposure to NRTI on the genomic material of the male gamete, in particular because of its implication in the zygote development after fertilization.

Anti-HIV Agents↗
PubMed2004

Virological exploration of individuals with discordant HIV screening tests.

Screening for HIV infection can use many algorithms. When two different HIV antibody assays are used, discordant results may occur. To discriminate between HIV seroconversion, HIV variant infection and false positive reactivity, 30 consecutive subjects with two discordant HIV antibody-screening assays were extensively investigated for HIV infection. No subject had HIV seroconversion or reached HIV seropositivity criteria after a follow-up of 3 months. By contrast 36% became HIV negative by the use of both HIV screening assays. p24 Antigen, HIV-1 RNA, HIV-1 DNA, HIV-2 DNA assays and HIV isolation by sensitive culture were unable to identify HIV infection in the 30 subjects with discordant HIV screening assays. The data suggest that the use of two HIV screening assays increase false-positive HIV results without increasing clinical sensitivity. To compliment follow-up of HIV screening, early testing for HIV RNA could be useful to identify or eliminate a recent infection.

Adolescent↗
PubMed2004

[Human T lymphotropic virus: from molecular epidemiology to disease].

Human T lymphotropic virus (HTLV) is a retrovirus presenting several novel features. Although the dominant modes of transmission are conventional, i.e., blood-borne, sexual and mother-to-child, HTLV), the distribution of HTLV infection is highly variable within human populations. Unlike HIV, the genome of HTLV shows low variability but, like HIV, HTLV originates from old world monkeys and apes. Although the virus can induce severe diseases, this course is observed in only a small number of infected people. Determinant factors for development of adult T cell leukemia (ATL) and tropical spastic paraparesis (TSP) are complex and treatment outcomes have been disappointing.

Deltaretrovirus↗
PubMed2003

Mott transition and transport crossovers in the organic compound kappa-(BEDT-TTF)2Cu[N(CN)2]Cl.

We have performed in-plane transport measurements on the two-dimensional organic salt kappa-(BEDT-TTF)(2)Cu[N(CN)(2)]Cl. A variable (gas) pressure technique allows for a detailed study of the changes in conductivity through the insulator-to-metal transition. We identify four different transport regimes as a function of pressure and temperature (corresponding to insulating, semiconducting, "bad metal," and strongly correlated Fermi-liquid behaviors). Marked hysteresis is found in the transition region, which displays complex physics that we attribute to strong spatial inhomogeneities. Away from the critical region, good agreement is found with a dynamical mean-field calculation of transport properties using the numerical renormalization group technique.

Journal Article↗
PubMed2003

Determining hepatitis C genotype by analyzing the sequence of the NS5b region.

Assays to determine the hepatitis C virus (HCV) genotype have recently become useful for clinical decision making and may be suitable for epidemiological investigations, such as identifying HCV outbreaks in a given population. Molecular assays are the most common diagnostic tools for HCV genotyping. This study compares two genome typing assays, one, the Trugene 5'NC genotyping kit, uses the sequence of the 5' non-coding (5'NC) region and the other, a non-commercial assay, uses the non-structural 5b (NS5b) region. Serum samples from 203 chronically HCV-infected patients were tested. The 5'NC and the NS5b assays were both very effective in identifying the genotype (99 and 98.5%) and the results with the two methods were always concordant for the genotype. The NS5b analysis permitted the identification of the subtype in all samples, whereas the 5'NC region assay did not in 33% of samples. The NS5b analysis showed that one patient had a mixed infection with HCV subtypes 1a and 2c, while the 5'NC assay did not. It is concluded that phylogenetic analysis using both the 5'NC and the NS5b regions are reliable and convenient methods for HCV typing in clinical practice. But analysis of the NS5b region may be more useful for tracing the source of an HCV infection.

5' Untranslated Regions↗
PubMed2003

Automated extraction and quantification of human cytomegalovirus DNA in whole blood by real-time PCR assay.

The measurement of human cytomegalovirus (HCMV) DNA in blood is becoming the standard method for monitoring HCMV infection in immune-suppressed and unsuppressed patients. As various blood compartments can be used, we have compared the HCMV DNA measured in whole blood (WB), peripheral blood leukocytes (PBL), and plasma by real-time PCR. We tested 286 samples: HCMV DNA was extracted automatically from WB and PBL with the MagNA Pure instrument (Roche Molecular Biochemicals) and manually from plasma samples. The HCMV DNA from WB, PBL, and plasma was measured by real-time Light Cycler PCR. Primers and probe were located in the UL 83 region. HCMV DNA was detected more frequently in WB (88.5%) than in the PBL (65.7%) (P < 0.0001) or the plasma (55.2%) (P < 0.0001). There was a good correlation between the positive results in WB and in PBL (r = 0.68; P < 0.0001), and 3.15 log(10) genome copies in 200000 PBL, equivalent to the threshold value of 50 pp65-positive polymorphonuclear cells per 200000 leukocytes, was equivalent to 3.4 log(10) genome copies in 200 microl of WB. WB was shown to be suitable for automated extraction and the quantitation of HCMV DNA by real-time Light Cycler PCR by analysis of serial samples from representative patients of various populations. This system may be very useful for monitoring of immune-suppressed and unsuppressed patients.

Adult↗
PubMed2001

Mother-to-child transmission of HIV infection and CTL escape through HLA-A2-SLYNTVATL epitope sequence variation.

Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV infection. Evasion of the immune response by CTL escape is associated with progression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful control of viraemia. In order to test this hypothesis, escape through the dominant HLA-A2-restricted CTL epitope SLYNTVATL (p17 Gag residues 77-85 SL9) in the setting of mother-to-child-transmission (MTCT) was investigated. Initial data from two families in which the HIV-infected mother expressed HLA-A*0201 and had transmitted the virus to other family members were consistent with this hypothesis. In addition, analysis of the gag sequence phylogeny in one family demonstrated that CTL escape variants can be successfully transmitted both horizontally and vertically. To test the hypothesis further, a larger cohort of transmitting mothers (n=8) and non-transmitters (n=14) were studied. Variation within the SL9 epitope was associated with expression of HLA-A2 (P=0.04) but overall no clear link between variation from the SL9 consensus sequence and MTCT was established. However, the high level of background diversity within p17 Gag served to obscure any possible association between escape and MTCT. In conclusion, these studies highlighted the obstacles to demonstrating CTL escape arising at this particular epitope. Alternative strategies likely to be more definitive are discussed.

Amino Acid Sequence↗
PubMed2001

First molecular characterization of HIV-1 Tunisian strains.

In order to identify HIV-1 subtypes circulating in Tunisia, blood specimens from 25 HIV-1 infected Tunisian patients were collected. Proviral HIV-1 DNA was genotyped by sequence analysis of the C2-V3 env region. HIV-1 subtypes were determined in 21 DNA sequences: 20 were of subtype B and one was a circulating recombinant form (CRF02 AG). Subtype B largely dominates the epidemiology of HIV-1 infection in Tunisia, suggesting the probable imported origin of HIV-1 infection, but further studies are needed to investigate the potential diversification of HIV-1 isolates in Tunisia.

DNA, Viral↗
PubMed2001

PRED-CLASS: cascading neural networks for generalized protein classification and genome-wide applications.

A cascading system of hierarchical, artificial neural networks (named PRED-CLASS) is presented for the generalized classification of proteins into four distinct classes-transmembrane, fibrous, globular, and mixed-from information solely encoded in their amino acid sequences. The architecture of the individual component networks is kept very simple, reducing the number of free parameters (network synaptic weights) for faster training, improved generalization, and the avoidance of data overfitting. Capturing information from as few as 50 protein sequences spread among the four target classes (6 transmembrane, 10 fibrous, 13 globular, and 17 mixed), PRED-CLASS was able to obtain 371 correct predictions out of a set of 387 proteins (success rate approximately 96%) unambiguously assigned into one of the target classes. The application of PRED-CLASS to several test sets and complete proteomes of several organisms demonstrates that such a method could serve as a valuable tool in the annotation of genomic open reading frames with no functional assignment or as a preliminary step in fold recognition and ab initio structure prediction methods. Detailed results obtained for various data sets and completed genomes, along with a web sever running the PRED-CLASS algorithm, can be accessed over the World Wide Web at http://o2.biol.uoa.gr/PRED-CLASS.

Computational Biology↗
PubMed2001

Macrothrombocytopenia with abnormal demarcation membranes in megakaryocytes and neutropenia with a complete lack of sialyl-Lewis-X antigen in leukocytes--a new syndrome?

A new megathrombocytopenic syndrome with giant platelets in peripheral blood and severe thrombocytopenia was diagnosed in a 4-month-old boy. His clinical course included repeated hemorrhagic incidents leading to death at age 37 months. Bone marrow ultrastructural analysis revealed numerous dystrophic megakaryocytes with giant membrane complexes. Although these features were similar to those described for megakaryocytes in mice lacking the gene for transcription factor p45-NF-E2, no abnormalities in the p45-NF-E2 gene could be documented. Platelet membrane analysis showed a reduction in glycoprotein (GP) Ib, but normal content of GPIIb and GPIIIa. Analysis of genes encoding for GPIb alpha and beta, GPV, and GPIX ruled out the possibility that the observed platelet abnormality is a variant of Bernard-Soulier syndrome. A moderate neutropenia was associated with a complete lack of expression of sialyl-Lewis-X on the surface of polymorphonuclear neutrophils. A common defect in posttranslational modification of glycoproteins could account for the diverse cellular abnormalities.

Blood Platelets↗
PubMed2001

Differential upregulation of cellular adhesion molecules at the sites of oxidative stress in experimental acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (AP)(2) is associated with exaggerated leukocyte adherence and activation. Endothelial cellular adhesion molecules (CAMs) can be induced by cytokines, but also directly by oxygen free radicals (OFRs), mediated by nuclear factor kappa-B (NF-kappa B). We investigated the behavior of inducible CAMs in relation to pancreatic oxidative stress. Our novel modification of cerium capture histochemistry (reaction of OFRs with cerium produces laser reflective Ce perhydroxide precipitates) combined with reflectance confocal laser scanning microscopy (CLSM) allows the histological codemonstration of in vivo OFR production and immunolabeled CAMs, or NF-kappa B. METHODS: Taurocholate AP was induced in rats; sham operated and normal animals served as controls. To achieve in situ, in vivo reaction of cerium with OFRs, animals were perfused with CeCl(3) solution at different time points (1, 2, 8, 24 h) and then sacrificed. E-selectin, P-selectin, ICAM-1, VCAM, and NF-kappa B p65 were labeled by immunofluorescence (IF) on frozen sections of cerium perfused pancreata. IF and Ce perhydroxide reflectance were simultaneously detected by CLSM. Pancreatic gene expression of the same CAMs was quantified by competitive RT-PCR (MIMIC internal control). RESULTS: Control pancreata showed negligible reflectance and minimal CAM expression. Early (1, 2 h) AP samples were characterized by intense, heterogeneous acinar OFR production, strong P-selectin, and increasing ICAM expression, with nuclear translocation of p65, histologically all colocalizing with the areas of acinar oxidative stress. Adherent polymorphonuclear leukocytes (PMNs) displayed weak OFR formation. Later (8, 24 h), a slowly declining P-selectin, but persisting ICAM-1 expression, was paralleled by widespread adherence of PMNs producing surprisingly large amounts of OFRs. VCAM and E-selectin showed a mild increase at 24 h. CAM gene activation was in good correlation with the protein expression. CONCLUSIONS: The early acinar oxidative stress is colocalized with NF-kappa B activation, preferential P-selectin, and ICAM upregulation in this AP model. Subsequently, adherent, activated PMNs become the major source of OFRs, thereby contributing to tissue damage.

Animals↗
PubMed2001

Determination of HCV genotype using two antibody assays and genome typing.

Two serotyping assays for hepatitis C virus (Serotyping 1-6 assay; Murex, UK and RIBA Serotyping SI; Chiron, USA) were compared to a standardized genotyping assay (Inno-LiPA HCV II; Innogenetics, Belgium) using serum samples collected from 126 patients chronically infected with hepatitis C virus. Serotyping was positive in 87% and 80% of the samples tested with Murex and Chiron, respectively, and concordant with genotyping in 93% and 88%, respectively. Sequence analysis of the NS5b region of 15 samples with discrepant typing results confirmed the Inno-LiPA finding in all instances. The Murex enzyme immunoassay serotyping method was less sensitive for identifying genotype 2 (P<0.05). The concordance with genotyping of the RIBA serotyping method was lower for genotype 2 than for the other genotypes (P<0.05).

Antibodies, Viral↗
PubMed2001

HIV-1 subtyping using phylogenetic analysis of pol gene sequences.

HIV-1 pol gene sequencing is now used routinely in France to identify mutations associated with resistance to reverse transcriptase (RT) or protease (PR) inhibitors. These sequences may also provide other information, such as the HIV-1 subtype. HIV-1 subtyping was compared using the RT and PR gene sequences to heteroduplex mobility assay (HMA) of the envelope gene. The RT and PR genes of 51 samples that had been subtyped earlier by HMA were sequenced. Sequences were aligned and subtypes were determined by phylogenetic analysis with reference HIV sequences. HMA gave the following subtypes: A (20), B (19), C (1), D (3), F (1), G (3) and CRF01-AE (4). Phylogenetic analysis of the RT gene gave: A (5), B (19), C (2), D (3), F (1), G (6), J (2), CRF01_AE (4), CFR02_AG (7) and undetermined (2). PR gene analysis did not infer subtypes with sufficient confidence. HMA and RT subtyping was not in agreement in nine cases. RT subtyping can identify CFR02_AG and CRF01_AE variants from A subtype RT. It was shown that phylogenetic analysis of the RT gene could provide a useful method for HIV-1 subtyping. The length of the amplicon and the relative performance of each primer pair used in this study favoured RT sequences as a subtyping tool. One potential advantage over env subtyping HMA is the ability to identify some circulating recombinant forms (CRFs).

Base Sequence↗
PubMed2001

A novel tool for the prediction of transmembrane protein topology based on a statistical analysis of the SwissProt database: the OrienTM algorithm.

OrienTM is a computer software that utilizes an initial definition of transmembrane segments to predict the topology of transmembrane proteins from their sequence. It uses position-specific statistical information for amino acid residues which belong to putative non-transmembrane segments derived from statistical analysis of non-transmembrane regions of membrane proteins stored in the SwissProt database. Its accuracy compares well with that of other popular existing methods. A web-based version of OrienTM is publicly available at the address http://biophysics.biol.uoa.gr/OrienTM.

Algorithms↗