Biomedical subjects

M Benhamou

Publications and source records attributed to M Benhamou.

At least 19 recordsLinked to original sources

PubMed2005

Colloidal aggregation in polymer blends.

We consider here a low-density assembly of colloidal particles immersed in a critical polymer mixture of two chemically incompatible polymers. We assume that, close to the critical point of the free mixture, the colloids prefer to be surrounded by one polymer (critical adsorption). As result, one is assisted to a reversible colloidal aggregation in the nonpreferred phase, due the existence of a long-range attractive Casimir force between particles. This aggregation is a phase transition driving the colloidal system from dilute to dense phases, as the usual gas-liquid transition. We are interested in a quantitative investigation of the phase diagram of the immersed colloids. We suppose that the positions of particles are disordered, and the disorder is quenched and follows a Gaussian distribution. To apprehend the problem, use is made of the standard phi(4) theory, where the field phi represents the composition fluctuation (order parameter), combined with the standard cumulant method. First, we derive the expression of the effective free energy of colloids and show that this is of Flory-Huggins type. Second, we find that the interaction parameter u between colloids is simply a linear combination of the isotherm compressibility and specific heat of the free mixture. Third, with the help of the derived effective free energy, we determine the complete shape of the phase diagram (binodal and spinodal) in the (Psi,u) plane, with Psi as the volume fraction of immersed colloids. The continuous "gas-liquid" transition occurs at some critical point K of coordinates (Psi(c) = 0.5,u(c) = 2). Finally, we emphasize that the present work is a natural extension of that, relative to simple liquid mixtures incorporating colloids.

Journal Article↗

PubMed2005

[Increase in right-to-left intracardiac shunt with non-invasive ventilation].

INTRODUCTION: Hypoxia caused by an increase in right-to-left shunt has been reported in patients with patent foramen ovale treated with levels of positive end-expiratory pressures (PEEP) greater than 10 cmH2O. This phenomenon has not previously been described with non-invasive ventilation (NIV). CASE REPORT: A 23 year-old man with tetralogy of Fallot and a severe kyphoscoliosis was admitted at the hospital for chronic dyspnoea. Arterial blood gases on room air: pH 7.43, PaCO2 39 mmHg, PaO2 67 mmHg, HCO3- 25 mmol/l, SaO2 95%. Nocturnal oxymetry showed severe hypoxaemia resistant to oxygen. NIV with PEEP of 3 cm H2O was commenced. With ventilation, his oxygenation worsened. An echocardiogram performed during NIV showed an increase in the right-to-left interventricular gradient from 22 to 37 cmH2O, and of the right ventriculo-auricular gradient from 76 to 142 mmHg. Furthermore, his oxygen saturation decreased progressively from 95 to 85%. Following removal of NIV, the patient recovered in 15 minutes. DISCUSSION: We report an increased right-to-left intracardiac shunt in a patient with tetralogy of Fallot. Compression of pulmonary vessels and cardiac cavities induced by NIV may have been enhanced by a reduction in thoracic compliance related to kyphoscoliosis. Right-to-left shunt in patients with kyphoscoliosis may be a contra-indication to NIV.

Adult↗

PubMed2005

Kinetics of microphase separation in interpenetrated polymer networks in solution.

We present here a theoretical study of the early kinetics of the microphase separation in crosslinked polymer blends, made of two incompatible polymers A and B, dissolved in a common good solvent. Use is made of an extended blob model used previously for the investigation of the static properties of such a transition. We are interested in the variation of the relaxation rate, tau(q), versus the wave number q, in the vicinity of the spinodal temperature. We first show that kinetics is entirely dominated by local motions, which are of Rouse type. Slow motions are absent, because of the permanent presence of crosslinks. Second, we find that the characteristic frequency, omega (q) = tau(q)(-1), increases with increasing wave number q according to a sixth power law, that is omega (q) approximately q6 phi(-9/4), where phi is the overall monomer volume fraction. Therefore, the swelling of strands due to the excluded-volume forces leads to a renormalization of the characteristic frequency by a multiplicative factor scaling as phi(-9/4). The main conclusion is that the presence of a good solvent necessitates relaxation rates less important than those relative to crosslinked mixtures in the molten state.

Journal Article↗

PubMed2005

Kinetics of phase separation in ramified polymer blends of arbitrary topology.

We present here a theoretical study of kinetics of phase separation within a mixture made of two chemically incompatible ramified polymers. For simplicity, we assume that they have the same topology. We are interested in the variation of the relaxation rate, tau(q), versus the wave number q, in the vicinity of the spinodal temperature. The kinetics is governed by local (Rouse) and reptation motions (faster and slower modes). For qRG >> 1 (RG being the gyration radius), kinetics is entirely controlled by local motions where each chain moves inside its own tube, and we show that the corresponding characteristic frequency, tau(q)(-1), scales as tau(q)(-1) approximately kappaGq6, where kappaG is a known topological factor. For qR(G) << 1, however, kinetics is rather dominated by long-wavelength (reptation) motions where unlike ramified polymers creep inside a long tube. For this case, we find that tau(q)(-1) approximately delta (0) q2 (chi(c) - chi), where delta (0) is another known topological factor that represents the total mobility of free monomers belonging to connected chains and reticulation points, and chi(c) accounts for the critical value of the segregation parameter. Finally, the derived relaxation rate must be compared to that relative to a linear polymer mixture.

Journal Article↗

PubMed2004

Statistical mechanics of a colloidal suspension in contact with a fluctuating membrane.

Surface effects are generally prevailing in confined colloidal systems. Here we report on dispersed nanoparticles close to a fluid membrane. Exact results regarding the static organization are derived for a dilute solution of nonadhesive colloids. It is shown that thermal fluctuations of the membrane broaden the density profile, but on average colloids are neither accumulated nor depleted near the surface. The radial correlation function is also evaluated, from which we obtain the effective pair potential between colloids. This entropically driven interaction shares many similarities with the familiar depletion interaction. It is shown to be always attractive with range controlled by the membrane correlation length. The depth of the potential well is comparable to the thermal energy, but depends only indirectly upon membrane rigidity. Consequences for the stability of the suspension are also discussed.

Colloids↗

PubMed2004

Force between unlike star-polymers versus the solvent quality.

We re-examine here the computation of the effective force between two star-polymers A and B of different chemical nature, which are immersed in a common solvent. This force originates from the excluded-volume interactions and chemical segregation. We assume that the solvent quality may be different for the two unlike star-polymers, that is the solvent can be 1) a good solvent for A and B, 2) a good solvent for A and a Theta-solvent for B, or 3) a Theta-solvent for the two polymers. The purpose is a quantitative study of the effect of the solvent quality on the effective force, which is a function of the center-to-center distance. Calculations are achieved using the renormalization theory applied to the Edwards continuous model. We first show that, when the mutual interactions are present, the effective force decays as the inverse of distance, but with a universal amplitude depending on the solvent quality. Second, we demonstrate the existence of three kinds of forces related to situations 1), 2) and 3) described above, and give the third-order epsilon-expansions (epsilon = 4 - d, 4 is the critical dimension) of the corresponding amplitudes. These series can be resummed using the Borel-Leroy techniques to obtain the best three-dimensional values for the expected force amplitudes. Finally, this work must be regarded as a natural extension of a published one which dealt with the same problem, but where the solvent was assumed to be good for the two unlike star-polymers.

Journal Article↗

PubMed2004

Exact effective force between star-polymers in a Theta-solvent.

We re-examine here the computation of the effective force between two star-polymers of respective numbers of branches f(1) and f(2), immersed in a common Theta-solvent. Such a force originates essentially from the repulsive three-body interactions. To achieve this, we take advantage of some established results using renormalization theory for three-dimensional star-polymers, or conformal invariance for two-dimensional ones. We first show that, in dimension d = 3, the force, F(r), decreases with the center-to-center distance r as F(r)/kappa BT congruent with Af1f2 x [r ln (R2/r2]-1 (r<R), with the exact universal amplitude Af1f2 = f1f2(f1 + f2 - 2)/22. Second, in dimension d = 2, we find that the force decays more slowly as F(r)/kappa BT congruent with Bf1f2 x r-1 (r<R), with the exact universal amplitude Bf1f2. For high distances compared to the gyration radius, R approximately a square root of N, of a single polymer chain at the Theta-point, an exponential decay of the force is expected.

Journal Article↗

PubMed2004

[Cardiotoxicity associated with trastuzumab (herceptin). An undesired effect leads towards a model of cardiac insufficiency].

Anticancer chemotherapy continues to advance. One of the new therapeutic orientations is the targeting of receptors which regulate the tumoral activity of the malignant cells. Trastuzumab is the prototype of these new chemotherapeutic agents. It is a monoclonal antibody directed against a tyrosine kinase receptor related to the EGF (Epidermal Growth Factor): the HER receptor. This receptor is also present in myocardial cells. Blockade of this myocardial receptor could cause severe cardiotoxicity about which some information is available but which continues to pose many problems. This data should be known as cardiologists will be consulted before the prescription of Trastuzumab and could also be confronted by these cardiotoxic effects. Precise physiopathological explanations have already been published from experimental studies which show the deleterious effects of the suppression of certain HER receptors on the heart. These studies not only explain all the clinical signs of Trastuzumab's cardiotoxicity but also suggest ways of preventing and treating some of these cases of cardiac failure.

Antibodies, Monoclonal↗

PubMed2003

[Impact of biochemisty on the duration of treatment for pulmonary embolus].

Can the biochemical evidence for "new thrombophilic factors" influence the duration of AVK treatment following the occurrence of a first pulmonary embolus? Certainly for the classic but very rare antithrombin defects as well as for the existence of circulating anticoagulant. Possibly for protein C and S defects. On the other hand, the existence of a heterozygotic "Leiden" mutation of factor V, or factor II, and an increase of factors VIII, IX, or XI, do not at present warrant a change in AVK prescription. In effect, in the case where the existence of a thrombogenic state implies a prolongation of AVK treatment with its significant potential complications, it is indispensable that the risk/benefit ratio is well founded, which is not the case for these "new" thrombophilic states. The coexistence of several of these new biochemical anomalies (for example the association of a factor V and factor II mutation) probably represents an excess risk of thrombosis, but in this situation the reasoning remains the same. On the other hand, faced with a confirmed recurrence, the studies in the literature tell us that very long term treatment should be debated independently from the biochemical results. It is conceivable that there are biochemical anomalies (sometimes quite frequent which should be viewed as "normal variants") which, although they have great significance for improving the understanding of venous thrombo-embolic disease, do not at present warrant a change in our therapeutic protocols. Another facet of the problem concerns the use of D-dimers following the first months of AVK treatment in order to possibly distinguish patients at low risk of recurrence. The first results of this approach are interesting, but require confirmation before they can be used in practice.

4-Hydroxycoumarins↗

PubMed2001

IgE receptor type I-dependent tyrosine phosphorylation of phospholipid scramblase.

To identify new effectors of IgE receptor (FcepsilonRI) signaling, we purified proteins from FcepsilonRI-stimulated RBL-2H3 rat mast cells on anti-phosphotyrosine beads and generated mouse monoclonal antibodies (mAb) against these proteins. Two mAbs bound to a protein that was identified as a new isoform of phospholipid scramblase (PLSCR) after screening an RBL-2H3 cDNA expression library. This isoform differed from PLSCR1 by the absence of an exon 3-encoded sequence and by an insert coding six QGPY(P/A)GP repeats. The PLSCR family of proteins is responsible for a redistribution of phospholipids across the plasma membrane. Although rat PLSCR is a 37-kDa protein, anti-phosphotyrosine immunoblots revealed the presence of 37-49 kDa phosphoproteins in the material immunoprecipitated with either anti-PLSCR mAb but not with unrelated monoclonal or polyclonal antibodies. Depletion of PLSCR resulted in the absence of these phosphoproteins. Additional experiments led to the identification of these phosphoproteins as phospho-PLSCR itself. Stimulation of RBL-2H3 cells upon FcepsilonRI engagement resulted in a dramatic increase in PLSCR tyrosine phosphorylation. A comparison of the relative amounts of phospho-PLSCR and nonphosphorylated PLSCR demonstrated that only a tiny fraction was thus modified, indicating a finely targeted involvement of PLSCR in FcepsilonRI signaling. Thus, this study reports the cloning of a new isoform of PLSCR, as well as the first observation that a member of the PLSCR family is a target for tyrosine kinases and is involved in signaling by an immune receptor. These findings open new perspectives on the role of phospholipid scramblases and to the mechanisms involved in their regulation.

Amino Acid Sequence↗

PubMed2001

[Duration of antivitamin K therapy in venous thromboembolic disease. Certainties and uncertainties].

The necessity of anticoagulant treatment after a pulmonary embolus or a deep venous thrombosis has been demonstrated. The modalities of this treatment have been well established, especially the usefulness of initial heparin therapy followed by a period of antivitamin K treatment with an "ideal target INR" between 2 and 3. One of the last questions in this therapeutic protocol is the duration of antivitamin K treatment. The choice of duration of treatment must be made on numerous criteria. It is necessary to distinguish the circumstances of the occurrence of the DVT or the PE and the context. It is thus possible for less than 3 months treatment in secondary venous thrombo-embolic disease, which occurs in precise, recognised circumstances for which the cause will have been controlled. Otherwise, in so-called idiopathic venous thrombo-embolic disease, which is distinguished by a higher prevalence of recurrences, it is known that long-term antivitamin K treatment is effective for the thrombo-embolic recurrences but at the price of a risk of haemorrhage. Finally thrombo-embolic recurrences also benefit from a long treatment. These circumstances of occurrence are thus important in order to decide the choice of treatment duration. But, in our opinion, the compliance to antivitamin K treatment remains the primary criterion to consider. The dilemma facing the prescriber is to evaluate the risk-benefit ratio of each patient, asking especially if the antivitamin K treatment surveillance of a particular patient will be done as well as in the randomised studies. For the future, long-term antivitamin K does not perhaps represent the only therapeutic option. The results of studies evaluating the durations of long-term treatment with less intense levels of anticoagulation (INR < 2) as well as therapeutic alternatives to antivitamin K (antiaggregants or other antithrombins) are awaited.

4-Hydroxycoumarins↗

PubMed2001

[Venous thromboembolism and cancer].

Malignant disease predisposes to deep venous thrombosis (DVT) or pulmonary embolism (PE) in several ways. One classical situation is that of DVT or PE with no apparent cause which may be the first sign of an occult cancer. In this domain, although the epidemiological data is well known, it is important to recognise the limitations of "blind" investigations. Another situation is more common. The patients have a diagnosed malignancy and thromboembolic disease is the main extra-cancer complication. The approach to this problem is changing, both in primary prevention where many trials have already reported encouraging results, and in the treatment after the event where classical therapeutic protocols are not always well adapted. Ancestral fears of the prescription of anticoagulants in cancer patients must cede to a more objective benefit/risk analysis which seems to be very favourable in some situations. Moreover, some publications have demonstrated a chance finding of a possible anticancer effect of antithrombotic agents.

Anticoagulants↗

PubMed2000

Determination of the interaction force between two adsorptive surfaces delimiting a critical binary polymer blend

We consider a mixture of two incompatible polymers A and B, confined between two parallel surfaces of the same chemical nature, separated by a distance L. It is assumed that both surfaces strongly adsorb one of the species (A) at high temperature. It is also assumed that a demixing transition occurs at a critical temperature T(c) below the adsorption temperature T(a). The strong adsorption implies that the composition of species A on surfaces is quenched even when the temperature is lowered. The presence of strong density fluctuations near the critical point induces an interaction between the surfaces. We reexamine this attractive force and determine its dependence with the thickness L, when the latter is smaller than the thermal correlation length. We find that, in the vicinity of the critical point, this force decreases with distance as L-4. We show that the corresponding amplitude is a universal number, independent of the value of the composition on surfaces, and we give its exact expression. Finally, we note that the present system may be considered as a typical model enabling one to understand qualitatively and quantitatively the flocculation of colloids embedded in critical binary polymer blends.

Journal Article↗

PubMed1996

Interleukin-10 inhibits cytokine generation from mast cells.

This report examines the effects of recombinant murine interleukin-10 (rmIL-10) on antigen-induced beta-hexosaminidase, leukotriene (LT)C4 and cytokine release from mouse bone marrow-derived mast cells (BMMC). BMMC sensitized to hapten-monoclonal IgE directed against dinitrophenol-bovine serum albumin (DNP-BSA) and challenged with 10 ng/ml DNP-BSA generated beta-hexosaminidase and LTC4-like material which was followed by tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA expression and protein release. Incubation of BMMC with 1-100 ng/ml rmIL-10 inhibited cytokine generation, without affecting beta-hexosaminidase and LTC4-like material release. TNF-alpha, but not GM-CSF mRNA expression, was also diminished in rmIL-10-treated BMMC, suggesting that down-regulation of cytokine production by rmIL-10 involves different mechanisms. These results identify a novel biological action of IL-10 as an inhibitor of cytokine production by stimulated mast cells.

Animals↗

PubMed1996

Protein tyrosine kinases in activation signal of human basophils through the immunoglobulin E receptor type l.

Human basophils activated through high-affinity immunoglobulin E (IgE) receptors (Fc epsilon RI) are involved in the late phase of the allergic reaction. To investigate the possible involvement of protein-tyrosine kinases in this activation we used human acute basophilic leukemia (ABL) cells in culture as well as a pure population of normal basophils in vitro-derived from human bone marrow precursor cells (HBMB). ABL cells were 50-80% basophils at various stages of maturation as assessed by staining, morphology, ultrastructure, and flow cytometry analysis, and only basophils in ABL cells expressed Fc epsilon RI. Aggregation of Fc epsilon RI by IgE and anti-IgE, IgE and antigen, or anti-Fc epsilon RI monoclonal antibodies on ABL cells or on HBMB, led to increased tyrosine phosphorylation of 120-, 100-, 80-, 72-, 50- to 65-, and 38-kDa substrates. Tyrosine phosphorylations in ABL cells were in basophils because 1) they were detected after a 5-s stimulation, 2) they were observed under conditions where mediator release is minimal, i.e., in the absence of extracellular calcium, 3) hapten addition during antigen stimulation resulted in almost total disappearance of tyrosine phosphorylations within 30 s. There was correlation between histamine release and tyrosine phosphorylation in anti-IgE dose-responses and in dose-responses of the tyrosine kinase inhibitor genistein. The tyrosine kinase p72syk was detected in the cells. Stimulation of ABL cells for 1 min resulted in extracellular calcium-independent tyrosine phosphorylation and activation of p72syk. Therefore, tyrosine kinases are involved in the early steps of human Fc epsilon RI signaling in basophils. Tyrosine kinases and their substrates could represent new potential therapeutic targets to prevent the development of the allergic reaction.

Aged↗

PubMed1994

Activation of protein tyrosine kinase p72syk by Fc epsilon RI aggregation in rat basophilic leukemia cells. p72syk is a minor component but the major protein tyrosine kinase of pp72.

Aggregation of the high affinity IgE receptors (Fc epsilon RI) on rat basophilic leukemia RBL-2H3 cells results in protein tyrosine phosphorylations. Previously we reported that there is prominent tyrosine phosphorylation of approximately 72-kDa proteins (pp72) and that the tyrosine kinase p72syk is one component of pp72. Here we studied further the relationship of p72syk to pp72. The aggregation of Fc epsilon RI induced the activation of p72syk which was parallel to its tyrosine phosphorylation. By in vitro kinase assay of immune complexes purified with anti-phosphotyrosine antibodies, p72syk was the major pp72 tyrosine kinase. However, by immunoblotting with anti-phosphotyrosine antibodies, p72syk was a minor component of pp72. The heterogeneous nature of pp72 was indicated by different studies. Under optimum conditions of one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, pp72 consisted of a heterogeneous group of 69-, 71-, and 72-kDa tyrosine-phosphorylated proteins. There were differences in the tyrosine phosphorylation of these proteins in cells activated in the absence of extracellular calcium or when stimulation was with the calcium ionophore A23187 or with phorbol myristate acetate. One of the proteins migrating at 69 kDa was p72syk. By two-dimensional gel electrophoresis pp72 was found to consist of multiple tyrosine-phosphorylated protens including 71-80-kDa proteins that associate with p53/56lyn. A 75-kDa tyrosine-phosphorylated protein, different from pp72, was identified as p75HS1 (SPY75). These results demonstrate the heterogeneous nature of the pp72 and that p72syk is activated after Fc epsilon RI aggregation.

Amino Acid Sequence↗

PubMed1994

The receptor with high affinity for IgE on rat mast cells is a functional receptor for rat IgG2a.

Rat mast cells express high-affinity receptors for IgE (Fc epsilon RI) and low-affinity receptors for IgG (Fc gamma R). In this study, the capacity of IgG to activate the rat basophilic leukemia (RBL-2H3) and rat peritoneal mast cells was investigated. Immune complexes formed with purified rat IgG and antigen as well as chemically cross-linked rat IgG induced histamine release from RBL-2H3 cells. This stimulation was inhibited by pre-incubation of the cells with saturating concentrations of monomeric IgE. With chemically cross-linked rat IgG of each subclass, only IgG2a stimulated histamine release from RBL-2H3 cells and this release was also inhibited by prior saturation of the Fc epsilon RI with monomeric IgE. Identical results were obtained with rat peritoneal mast cells. In binding experiments, IgE and cross-linked rat IgG2a bound to rat Fc epsilon RI transfected into CHO cells. Monomeric rat IgG2a, cross-linked rat IgG1, IgG2b, IgG2c and rabbit IgG did not bind to Fc epsilon RI. Stimulation of RBL-2H3 cells with aggregated IgG2a induced phosphorylation of tyrosines in the beta and gamma subunits of the Fc epsilon RI. Thus, although RBL-2H3 and rat peritoneal mast cells have Fc gamma R, the IgG-mediated stimulation of these cells for histamine release was by the Fc epsilon RI. Altogether, these data demonstrate that the rat Fc epsilon RI is a functional receptor with low affinity for rat IgG2a.

Animals↗

PubMed1993

Protein-tyrosine kinase p72syk in high affinity IgE receptor signaling. Identification as a component of pp72 and association with the receptor gamma chain after receptor aggregation.

Protein-tyrosine phosphorylation plays a critical role in the high-affinity IgE receptor (Fc epsilon RI) signaling. Here we investigated the involvement of the tyrosine kinase p72syk in Fc epsilon RI signaling in the rat mast cell line RBL-2H3. Specific antibodies were raised against peptides synthesized on the basis of the deduced peptide sequence of an essentially full-length rat syk cDNA. The expression of p72syk in RBL-2H3 cells was demonstrated with these antibodies. The aggregation of Fc epsilon RI led to the tyrosine phosphorylation of p72syk that was detected after 15 s of stimulation, reached a plateau by 5 min, and was not induced by calcium influx or protein kinase C activation. Association of p72syk with the tyrosine phosphorylated Fc epsilon RI gamma chain was detected only after receptor aggregation. We previously demonstrated that aggregation of the Fc epsilon RI on mast cells results in the tyrosine phosphorylation of a 72-kDa protein (pp72) involved in IgE signaling. The depletion of p72syk from RBL-2H3 cell lysates resulted in only a slight decrease in the amount of pp72. These results demonstrate that pp72 is composed of several phosphoproteins and identify p72syk as one component of pp72. These data, together with recent observations in T cells, indicate that the interaction between p72syk-related tyrosine kinases and zeta-related proteins could play an important role in signal transduction.

Amino Acid Sequence↗