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Biomedical subjects

P Marchal

Publications and source records attributed to P Marchal.

At least 19 recordsLinked to original sources

Head and neck squamous cell carcinoma transcriptome analysis by comprehensive validated differential display.

Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples. The resulting 820 nonredundant sequences were analysed by high throughput bioinformatics analysis. Human proteins were identified for 73% (596) of the DD sequences. A large proportion (>50%) of the remaining unassigned sequences match ESTs (expressed sequence tags) from human tumours. For the functionally annotated proteins, there is significant enrichment for relevant biological processes, including cell motility, protein biosynthesis, stress and immune responses, cell death, cell cycle, cell proliferation and/or maintenance and transport. Three of the novel proteins (TMEM16A, PHLDB2 and ARHGAP21) were analysed further to show that they have the potential to be developed as therapeutic targets.

Amino Acid Sequence↗

Phase behavior and rheological properties of enzymatically synthesized trehalose decanoate aqueous solutions.

Surface tension properties of an enzymatically synthesized equimolar mixture of trehalose mono- and didecanoate in aqueous solutions have been determined. At 20 degrees C a critical micellar concentration (CMC) of 50 micromol/l and a minimal surface tension of 28 mN/m have been obtained. Above the CMC, it has been shown that up to a concentration of 42 wt%, and in a 20-60 degrees C temperature range the sugar ester aqueous solutions do not form any crystalline structure, nor present any phase transition, and the trehalose decanoate molecules form an isotropic worm-like micellar phase. The rheological properties indicate however a more complicated picture in the same concentration and temperature ranges. In steady shear, the viscosity of the trehalose decanoate solutions do not exhibit any shear rate dependence from 1 to 100 s(-1) for concentrations up to 42 wt%. Below 0.8 wt%, the viscosity remains constant and close to that of water; then, between 0.8 and 23 wt%, the viscosity shows a quadratic increase with surfactant concentration. For higher concentrations, up to 42 wt%, no further significant increase in viscosity is observed. In oscillatory shear experiments, the solutions exhibit viscoelastic properties. The observed rheological behavior as a function of concentration and temperature may be due to a progressive evolution of the trehalose decanoate molecular associations: as the concentration increases, the system evolves towards an entangled and/or partially branched or cross-linked micellar network, and eventually a multiconnected network of cross-linked micelles.

Cross-Linking Reagents↗

Physical alginate hydrogels based on hydrophobic or dual hydrophobic/ionic interactions: bead formation, structure, and stability.

Hydrophobically associating alginate (AA) derivatives were prepared by covalent fixation of dodecyl or octadecyl chains onto the polysaccharide backbone (AA-C12/AA-C18). In semidilute solution, intermolecular hydrophobic interactions result in the formation of physical hydrogels, the physicochemical properties of which can be controlled through polymer concentration, hydrophobic chain content, and nonchaotropic salts such as sodium chloride. The mechanical properties of these hydrogels can then be reinforced by the addition of calcium chloride. The combination of both calcium bridges and intermolecular hydrophobic interactions leads to a decrease in the swelling ratio accompanied by an increase of elastic and viscous moduli. Beads made of hydrophobically modified alginate were obtained by dropping an aqueous solution of alginate derivative into a NaCl/CaCl2 solution. As compared to unmodified alginate beads, modified alginate particles proved to be stable in the presence of nongelling cations or calcium-sequestering agents. However, evidence is presented for a more heterogeneous structure than that of plain calcium alginate hydrogels with, in particular, an increase in the effective gel mesh size, as determined by partition and diffusion coefficient measurements.

Journal Article↗

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC).

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a large-scale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12-13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets.

Aged↗

Amphiphilic derivatives of sodium alginate and hyaluronate for cartilage repair: rheological properties.

Various amphiphilic derivatives of sodium alginate and hyaluronate were prepared by covalent fixation of long alkyl chains (dodecyl and octadecyl) with various ratios on the polysaccharide backbones via ester functions. In the semidilute regime, aqueous solutions of the resulting compounds exhibited the typical rheological properties of hydrophobically associating polymers: tremendous enhancement of zero shear rate Newtonian viscosity, steep shear-thinning behavior, and formation of physically cross-linked gel-like networks. The influence of the alkyl chain length, its content on the polysaccharide and of the polymer concentration in the solution was well identified. All obtained results are discussed with respect to the schedule of conditions related to materials, which could be used for cartilage repair, such as in synovial fluid viscosupplementation as well as in cartilage replacement. In particular, it is seen that HA-C(12)-5 (hyaluronate substituted with 5% of dodecyl chains) and HA-C(18)-1 (hyaluronate substituted with 1% of octadecyl chains) in a 0.15N NaCl solution at 8 g/L have rheological properties quite similar to those of healthy synovial fluid. On the other hand, the rheological parameters of solutions at 8 g/L in 0.15N NaCl of some of derivatives, such as, for example, AA-C(12)-8 (alginate substituted with 8% of dodecyl chains) or HA-C(18)-2, are well fitted for a use in cartilage repair.

Alginates↗

1H nuclear magnetic resonance relaxometric characterization of fat and water states in soft and hard cheese.

The aim of this work was to study the spin spin (T2) relaxation components of one hard cheese and three soft cheeses to characterize fat and water states. NMR signals were measured at 6 degrees C with a 0.47 T NMR device. The transverse relaxation decay was fitted using the Marquardt method. The T2 relaxometric behaviour of the cheeses under consideration was characterized by four relaxation components. To understand the chemical composition of each NMR component, we studied anhydrous milk fat extracted from each cheese analysed. At 6 degrees C, the fat was 60% crystalline. In cheese, the solid fat was found mainly in the shorter relaxation component with a T2 of 17 micros. The intensity of the NMR relaxation with a T2 > 1 ms was explained by the amount of water, liquid fat and proteins, and the associated relaxation time varied as a function of the process used. The composition of each relaxation component was confirmed by the temperature effect and the influence of the fat content on the NMR cheese signal. NMR relaxometry was able to provide information on water behaviour (i.e. the quantity and level of interactions with proteins) and on the solid:liquid ratio of anhydrous milk fat in the cheese.

Cheese↗

Fatal Mycobacterium tuberculosis brain abscess in an immunocompetent patient.

A non-HIV-infected 63-y-old woman presented seizures and coma during the course of Mycobacterium tuberculosis infection. Computerized tomography scan led to the diagnosis of a large compressive brain abscess. The patient died with multiorgan failure. Systematic central nervous system investigations should be done in cases of disseminated tuberculosis.

Brain Abscess↗

Streptococcus salivarius acute meningitis with latent petromastoiditis.

A 48-y-old woman, with a previous history of neurosurgical intervention for a trigeminal neurinoma, presented with acute meningitis due to Streptococcus salivarius. There were significant changes in the petrous region, as revealed by MRI, leading to the diagnosis of associated latent subacute mastoiditis.

Acute Disease↗

Embryonic electronics.

Within the general domain of bio-inspired computing, a particular trend over the past few years has been that of constructing actual hardware devices that are inspired by nature. This paper describes one such project-Embryonics (embryonic electronics)-inspired in particular by the process of embryogenesis. Our ultimate objective is the construction of large-scale integrated circuits, exhibiting the properties of self-repair (healing) and self-replication, found until now only in living beings. We present the silicon-based artificial cell, followed by a description of mechanisms operating at the cellular level: cellular differentiation, cellular division, regeneration, and replication. We then present the cell's composition as an ensemble of lower-level elements, known as 'molecules'. As electronic chips grow evermore complex, the need for self-repair capabilities will become increasingly crucial. The Embryonics approach represents one possible way of confronting this pivotal problem.

Cell Differentiation↗

John von Neumann: the founding father of artificial life.

Aside from being known for his contributions to mathematics and physics, John von Neumann is considered one of the founding fathers of computer science and engineering. Not only did he do pioneering work on sequential computing systems, but he also carried out a major investigation of parallel architectures, leading to his work on cellular automata. His exceptional vision and daring, borrowing from biology the concept of genomic information even before the discovery of DNA's double helix, led him to propose the concept of self-reproducing automata.

Artificial Intelligence↗

Eye fixations near corners: evidence for a centre of gravity calculation based on contrast, rather than luminance or curvature.

Subjects scanned line drawings of polygons in order to count the number of corners. The positions their eyes fixated were studied as a function of the size of the angle and whether the apex of the angle was present or absent. The results showed that the eyes tended to land at a position near the centre of gravity of the corner configurations. The observed landing positions were coherent with the hypothesis that the centre of gravity was calculated within an attentional spotlight centered on the apex of the corners, and that the calculation was based not on the total luminance distribution, nor on the distribution of energy in a neurophysiologically motivated curvature detector, but simply on the basis of a contrast detector.

Adult↗

Irreversible inhibition of rat S-adenosylmethionine decarboxylase by 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine.

5'-([(Z)-4-Amino-2-butenyl]methylamino)-5'-deoxyadenosine [Z)-AbeAdo) was tested in vitro and in vivo as a potential inhibitor of S-adenosyl-L-methionine decarboxylase (AdoMetDC), a pyruvoyl-containing enzyme, purified from rat liver. In vitro (Z)-AbeAdo produces a time- and dose-dependent irreversible inhibition of the enzyme. Saturation kinetics are observed when the enzyme is preincubated with (Z)-AbeAdo in the presence of 50 microM putrescine, a known activator of AdoMetDC. Under these conditions kinetic constants were measured (Ki = 0.56 +/- 0.04 microM; tau 1/2 = 0.51 +/- 0.03 min). The inhibition is not relieved by prolonged dialysis of the inactivated enzyme. The turnover number for (Z)-AbeAdo, i.e. the number of inactivator molecules required to inactivate one enzyme molecule, is approximately 1.5. The selectivity of (Z)-AbeAdo was explored: the compound is not a substrate of adenosine deaminase, mitochondrial monoamine oxidase and diamine oxidase, but is slowly oxidized by benzylamine oxidase from rat aorta. The (E)-isomer of AbeAdo, is at least 100-fold less active than (Z)-AbeAdo as a time-dependent inhibitor of rat liver AdoMetDC. In rats, intraperitoneal administration of (Z)-AbeAdo produces a rapid, long-lasting and dose-dependent decrease of AdoMetDC activity in ventral prostate, testis and brain.

Adenosylmethionine Decarboxylase↗

Selective inactivation of MAO-B by benzyl-dimethyl-silyl-methanamines in vitro.

The alpha-silyl amines benzyl-dimethyl-silyl-methanamine and the p-fluoro and p-chloro derivatives are potent time-dependent inhibitors of rat brain MAO-B. The inhibition exhibits saturation kinetics, takes place in the enzyme active-site and is irreversible. The most potent inhibitor in the series is 4-fluorobenzyl-dimethyl-silyl-methanamine (KI = 11 microM, tau 1/2 = 2.3 min). Its selectivity for the B-form relative to the A-form of rat brain MAO is higher than 10(4). Benzyl-dimethyl-silyl-methanamines may represent a new family of anti-Parkinsonian agents.

Animals↗