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Biomedical subjects

A Ponton

Publications and source records attributed to A Ponton.

At least 19 recordsLinked to original sources

Rotational magnetic particles microrheology: the Maxwellian case.

An experimental method based on the rotational dynamics of a magnetic probe is reported to measure the local viscoelasticity of soft materials on microscopic scales. The technique is based on the alignment of dipolar chains of submicrometer magnetic particles in the direction of an applied magnetic field. On one hand, light scattering is used to detect the chains' oscillations over a 0.001-100 Hz frequency range when submitted to an oscillating magnetic field and leads to global microrheological measurements. On the other hand, the chains' rotation toward a permanent magnetic field is observed with a microscope, allowing a local determination of viscoelastic properties on the scale of the chains of particles. We demonstrate the accuracy of both assays with a micellar Maxwellian solution and validate theoretical predictions.

Journal Article↗

Flow birefringence, stress optical rule and rheology of four micellar solutions with the same low shear viscosity.

The flow birefringence and the rheological properties of four viscoelastic solutions having nearly the same zero shear viscosity and subjected to shear flows are investigated in the linear and non-linear domains. The surfactant used for the samples is the cetyltrimethylammonium chloride in water at the concentration of 100 mmol/l with an organic salt, the sodium salicylate. The low shear viscosity curve versus the salt concentration is non-monotonic and has two maxima separated by a minimum forming four domains in which the salt concentration is chosen. For the two solutions belonging to the inner branch, i.e. between the two maxima, a simple Maxwellian behaviour is observed and shear banding occurs as confirmed by the flow birefringence pictures. Contrary to the results of P. Fisher (1996) where the unstable flow regime is restricted to the first decreasing part of the low shear viscosity curve of a cetylpyridinium chloride solution, we show that shear banding exits in a wider domain of the salt concentration.

Birefringence↗

Dynamic viscoelastic properties of silica alkoxide during the sol-gel transition.

The viscoelastic properties of silica alkoxide gel during the sol-gel transition (SGT) are analysed using an extended shear relaxation modulus expression with a functional form based on a product of power law and Debye-Maxwell relaxation kernels. The dynamic properties are probed by small-amplitude oscillatory shear measurements in three viscoelastic domains (pre-SGT, SGT, post-SGT). Using analytical expressions for the storage G'(omega) and loss G''(omega) moduli in these three domains, it is shown that the divergence of the mean characteristic relaxation time in the pre-SGT domain can be successfully described by a percolation with bond fluctuation dynamics. It is also shown that the equilibrium shear modulus in the post-SGT domain can be successfully described by a percolation model based on an analogy with an electrical network. The amplitude and the critical exponent of the power law relaxation at the gelation time first introduced by Winter and Chambon are estimated in the pre- and post-SGT domains.

Journal Article↗

Local rheological probes for complex fluids: application to Laponite suspensions.

We present an experimental method allowing a direct measurement of the local rheological behavior of complex fluids. A magnetic probe is inserted into the bulk of the fluid and submitted to a controlled magnetic force or torque, which induces a mechanical perturbation of the fluid. The geometry of the perturbation can be varied using two kinds of probes: a magnetic bead submitted to a homogeneous magnetic force in one direction, and a magnetic needle that can turn inside the material under the effect of an applied magnetic torque. Two complex viscoelastic fluids are investigated. First, a surfactant solution, which has a linear mechanical behavior in the range of the applied stresses, is used to test and validate the experimental methodology. We then use the local probes to investigate a Laponite colloidal suspension, which exhibits nonlinear behavior such as thixotropy, shear thinning, and aging. In this latter fluid, we find an exponential growth of the rheological relaxation time versus the system age, a power-law dependence of the fluid viscosity on the applied stress, and a dynamical yield stress which saturates with the fluid aging time.

Journal Article↗

Rheological study of the sol-gel transition in silica alkoxides.

The sol-gel transition of the system tetramethylorthosilicate-water-methanol under basic conditions has been studied by rheological measurements. The gelation time t(g) has been determined from the measurements of the elastic G' and viscous G'' moduli as a function of time at different frequencies according to Winter's criterion. At gelation time the frequency dependence of both moduli follows a power law with an exponent related to the fractal dimension of the network structure. Different initial monomer concentrations, hydrolysis molar ratios, and temperatures are studied. The decrease of the gelation time with an increase of initial monomer concentration or hydrolysis molar ratio is well-described by a power law. An apparent activation energy is deduced from the temperature dependence of gelation time.

Journal Article↗

Activity and mRNA abundance of Delta-5 and Delta-6 fatty acid desaturases in two human cell lines.

We analyzed fatty acid biosynthesis in Chang and ZR-75-1 cells. Both cell lines could desaturate and further elongate substrates for Delta-5 desaturase. ZR-75-1 but not Chang cells showed Delta-6 desaturation of 18:2n-6, 18:3n-3, 24:4n-6 and 24:5n-3. In both cell lines, the mRNA abundance can be related to Delta-5 or Delta-6 fatty acid desaturase activities. These results suggest that desaturase genes could have, at least in part, independent control mechanisms and that Delta-6 desaturase impairment is not specific to any particular step of the fatty acid metabolic pathways, which may diminish the rationale for the existence of at least two distinct enzymes.

Breast Neoplasms↗

Feasibility and reliability of ankle/arm blood pressure index in preventive medicine.

Despite its potential usefulness for assessing preclinical atherosclerosis and cardiovascular risk, the ankle/arm blood pressure index (AAI) has not yet been the matter of study evaluating its feasibility and reliability by nonspecialist doctors in a general population. This study was planned for two steps. In step 1, the measurement of AAI, (ratio between Doppler systolic pressure at the ankle for each lower limb and the highest value of Doppler systolic pressure of the two upper limbs), should be performed by 50 general practitioners (GPs), 50 social security center physicians, and 50 occupational health physicians in 3,000 male smokers, 40 to 59 years, without clinical cardiovascular disease. In step 2, AAI measurement, coupled with echography-Doppler of iliofemoral arteries, should be repeated by a specialist in all subjects with decreased AAI (<0.90) and the first two subjects with normal AAI recruited in step 1 by each nonspecialist. The number of physicians and subjects participating in step 1 was lower than planned (80 physicians and 962 subjects) with the greatest defect for GPs (six physicians and 35 subjects) and the prevalence of decreased AAI was low (28 subjects). AAI measurement was repeated in step 2 in only 12 subjects with decreased AAI in step 1 and in 124 subjects with normal AAI in step 1. Five of the six subjects with decreased AAI in step 2 also had decreased AAI in step 1 and 123 of the 130 subjects with normal AAI in step 2 also had normal AAI in step 1. As regards echographic stenosis, decreased AAI had a sensitivity of 44% and a specificity of 98%. AAI seems more feasible for occupational health physicians and social security center physicians and AAI is also reliable for nonspecialists previously trained, but its predictive value as regards echographic stenosis is poor in asymptomatic subjects, which may limit its usefulness for detecting preclinical atherosclerosis.

Adult↗

Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu.

Hydrogen peroxide (H2O2) is considered to be a mediator of apoptotic cell death but the mechanism by which it induces apoptosis is unclear. Here, we show that cells undergoing apoptosis from exposure to H2O2 display a significant decrease in intracellular concentration of superoxide (O2-) which is associated with a reduction of the intracellular milieu, as measured by an increase in the GSH/GSSG ratio and a decrease in intracellular pH. The notion that a decrease in intracellular O2- concentration triggers apoptosis is supported by the observation that H2O2-mediated apoptosis could be retarded in cells in which the intracellular O2- concentration is maintained at or above the cellular baseline level by inhibition of the major O2- scavenger superoxide dismutase (Cu/Zn SOD). Taken together, our observations indicate that a decrease in the intracellular O2- concentration, reduction and acidification of the intracellular milieu constitute a signal for H2O2-mediated apoptosis, thereby inducing a reductive as opposed to an oxidative stress.

Apoptosis↗

Repression of the 5-lipoxygenase gene by c-myb overexpression in differentiated HL-60 cells.

This paper reports on the involvement of c-MYB in the regulation of 5-lipoxygenase gene expression during differentiation of human HL-60 cells. We demonstrate that c-MYB binds the 5-lipoxygenase promoter in undifferentiated cells but not in DMSO-differentiated cells. Also, we show that overexpression of c-myb cDNA in differentiated HL-60 cells represses the 5-lipoxygenase gene expression.

Arachidonate 5-Lipoxygenase↗

The CD95 (APO-1/Fas) receptor activates NF-kappaB independently of its cytotoxic function.

Engagement of the CD95 (APO-1/Fas) receptor induces apoptosis in a variety of cell types. However, the nature of the cytotoxic signal and the intermediate messenger molecules remain to be elucidated. In an effort to understand CD95-mediated signaling, we assessed possible changes in the DNA binding activity of NF-kappaB as a result of CD95 engagement in various tumor cells. By performing electrophoresis mobility shift assays, we show that CD95 can stimulate the DNA binding activity of NF-kappaB in a variety of cells, irrespective of their sensitivity or resistance to CD95-mediated cytotoxicity. Moreover, deletion of 37 carboxyl-terminal residues from the cytoplasmic domain of CD95, which abrogates CD95-mediated apoptosis, only marginally affects NF-kappaB activation. Taken together, these observations indicate that CD95 has a function that involves activation of NF-kappaB and that appears to be unrelated to its role as an inducer of apoptotic cell death.

Apoptosis↗

Changes in chromatin conformation regulate the 5-lipoxygenase gene expression during differentiation of HL60 cells.

The HL60 cell line does not express the 5-lipoxygenase gene prior to differentiation with various agents. In this paper we have shown by DNase I sensitivity that the chromatin conformation of the 5-lipoxygenase gene changes following differentiation of HL60 cells with dimethyl sulfoxide (DMSO). Moreover, run-on analysis suggests that transcription of the 5-lipoxygenase gene is enhanced after differentiation. We proposed that the chromatin conformation represses the expression of the 5-lipoxygenase gene in HL60 cell line and that differentiation of these cells with DMSO changes the chromatin conformation, which allows the expression of the 5-lipoxygenase gene. The HeLa cells which, like the HL60 cells, do not express the 5-lipoxygenase, were insensitive to DNase I treatment. These results suggest that chromatin structure might represent a form of regulation for the 5-lipoxygenase gene.

Arachidonate 5-Lipoxygenase↗

Highly purified guinea pig type II pneumocytes have the leukotriene A4 hydrolase but do not express 5-lipoxygenase activity.

Guinea pig lung cells have been obtained by enzymatic digestion of lung tissue and type II pneumocytes have been purified by centrifugal elutriation and adherence on Petri dishes coated with guinea pig IgG. The cells have been characterized by histochemical staining of alkaline phosphatase and by electron microscopy. Arachidonic acid metabolism was studied by incubating purified type II pneumocytes with exogenous arachidonic acid in the presence or absence of calcium ionophore A23187 or with leukotriene A4. The reverse phase high performance liquid chromatography profiles of cells stimulated with calcium ionophore and/or arachidonic acid did not show peaks co-eluting with authentic leukotrienes, which suggested that these cells do not express 5-lipoxygenase activity. On the other hand, type II pneumocytes converted exogenous leukotriene A4 into leukotriene B4; a small amount of peptido-leukotrienes, accounting for less than 5% of total leukotrienes produced, was also detected. It is suggested that transcellular metabolism of leukotriene A4 between type II pneumocytes and other lung cells containing the 5-lipoxygenase may contribute to the previously reported LTB4 production by guinea pig lungs. The type II pneumocyte purification technique described represents a useful alternative to cell culture for studying arachidonic acid metabolism and other cell functions.

Animals↗

[Intestinal parasitic diseases and environment in Sahelo-Sudanese towns: the case of Pikine (Senegal)].

A survey carried out in Pikine (Senegal) on a sample of 5 groups of children drawn from ecologically representative sections of the town confirms the high prevalence in urban areas of Africa of intestinal infection, especially A. lumbricoides (35.6%), T. trichiura (35.4%), and Giardia (43.7%). The prevalence of A. lumbricoides (35.6%), T. trichiura (35.4%), and Giardia (43.7%). The prevalence of A. lumbricoides and T. trichiura are appreciably higher in the oldest sectors of the town or in those with a better sanitary standard: up to 47.7% for Ascaris and 46% for Trichuris. The use of X2 tests and log-linear analysis demonstrates a significant association between Ascaris and Trichuris. The highest prevalence for Giardia (56.8%) were to be found on the outskirts of the town, where the lowest prevalence of Ascaris (21.7%) and Trichuris (22.9%) were noted; moreover, age-based prevalence for the three parasites vary from one ecological area to another. The relationship between the urbanization process, the variation in environmental factors and intestinal parasitic infection, and the operational implications arising from this geographically-based approach are discussed.

Animals↗

Basal expression of the gene (TIMP) encoding the murine tissue inhibitor of metalloproteinases is mediated through AP1- and CCAAT-binding factors.

In cultured murine fibroblasts, the TIMP gene (encoding tissue inhibitor of metalloproteinases) is transcribed constitutively, although at low levels. We have used a cell-free system in which nuclear extracts prepared from murine L cells support transcription from TIMP DNA templates in vitro. This system was used to study the role of cis-acting DNA sequences in the constitutive expression of TIMP. Sequences important for expression are located both 5' and 3' (in intron 1) to the major transcription start point and are required to obtain detectable levels of transcription. These regions are specifically recognized by murine nuclear factors and contain DNA motifs whose sequences closely resemble binding sites for known transcriptional activators. In particular, the data strongly suggest a role for CCAAT-binding factor(s) and AP1-binding factors in the basal transcription of TIMP.

Animals↗

Structure and function of murine TIMP gene.

Specific inhibitors of metalloproteinases, such as TIMP, are potential regulators of tissue integrity. In order to understand their exact role in both normal and pathological processes we have initiated molecular studies on the TIMP gene and its product(s). We have used cDNA and genomic clones corresponding to the murine TIMP gene to define the intron-exon structure of the gene and to map multiple clustered sites where transcription is initiated; we have also partially characterized the cis-acting DNA sequences required for transcriptional activity. The murine TIMP cDNA has also been used in transcription/translation experiments to produce polypeptides which can be processed by endoplasmic reticulum membranes and which are biochemically active in inhibition of fibroblast interstitial collagenase. As a result of our analysis of the expression of the TIMP gene in different cell types and under varied conditions, we have observed an important increase of TIMP mRNA levels in mouse fibroblasts in response to physiological modulators (whole serum and double-stranded RNA) as well as a pathogen (NewCastle Disease Virus). In addition, an analysis of TIMP mRNA in several variants of a cell line derived from a spontaneous mammary adenocarcinoma, which possess different levels of metastatic potential indicated that the serum dependence of TIMP mRNA accumulation is different in metastatic as compared to nonmetastatic cells. The significance of these results in view of the role of TIMP in matrix maintenance is discussed.

Adenocarcinoma↗

Decreased expression of tissue inhibitor of metalloproteinases in metastatic tumor cells leading to increased levels of collagenase activity.

We have examined the expression of murine tissue inhibitor of metalloproteinases (TIMP) in nonmetastatic and metastatic cell lines derived from SP1 murine mammary adenocarcinoma cells. We observed decreased levels of TIMP mRNA and activity in metastatic cells as compared to their nonmetastatic equivalents in the absence of fetal bovine serum. Lower levels of TIMP mRNA correlated to decreased levels of transcription of the TIMP gene. Net collagenase activity was higher in metastatic cells, but metastatic and nonmetastatic cells secreted similar levels of total collagenase (mainly type IV). This suggests that decreased TIMP gene expression results in increased net collagenase activity in malignant cells.

Animals↗

Increased collagenase activity in metastatic cells as a result of decreased TIMP expression.

It has been postulated in a number of systems that increased metalloproteinase activity in different pathologies can be due to decreased levels of the specific inhibitor tissue inhibitor of metalloproteinases (TIMP). To date direct proof of such a mechanism has been lacking. We report that in metastatic variants which secrete increased levels of collagenase activity, this is due to decreased levels of TIMP activity and mRNA levels.

Adenocarcinoma↗