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P Andre

Publications and source records attributed to P Andre.

101 records · Page 6Linked to original sources

Analysis of the topological changes induced on cells exposed to adhesive or mechanical stimuli.

Fluorescent probes are widely used to study cell structure and function. However, few reports were devoted to a quantitative analysis of the intracellular distribution of fluorescent markers. In the present work, we describe the topographical changes of surface and cytoskeletal markers on individual cells subjected to adhesive or mechanical interaction. Conjugates were prepared with a cytotoxic T-lymphocyte clone and target cells. Specific antigens, membrane phospholipids, surface glycoconjugates, and polymerized actin were labeled with fluorescent antibodies or biochemical probes. The analysis of fluorescence distributions in conjugates demonstrated a selective reorganization of the plasma membrane with a gathering of some molecular species in the intercellular adhesion area. Furthermore, individual phagocytic cells were sucked into glass micropipets, then stained with fluorescent phallacidin to analyze the effect of mechanical efforts on the cytoskeleton organization. The concentration of polymerized actin was found to be similar in mechanically-induced protrusions and whole cells. It is concluded that adhesive interactions may result in marked cell polarization and formation of membrane zones with a particular biochemical composition. The submembranar cytoskeleton might play a role in this process.

Actins↗

Interferon and ursodeoxycholic acid combined therapy in chronic viral C hepatitis: controlled randomized trial in 203 patients.

AIMS: This prospective randomized trial was carried out in order to determine whether the long-term administration of ursodeoxycholic acid after discontinuation of interferon had any beneficial effect on the clinical course of hepatitis C virus infection. METHODS: Enrolled in the study were 203 patients with chronic active hepatitis C. They were all given: interferon alpha-2a (3 MU subcutaneously thrice a week) and ursodeoxycholic acid (10 mg/kg/day) for 9 months. At month 9, biochemical responders only were randomized into ursodeoxycholic acid treatment or placebo for 12 additional months (double blind study). RESULTS: At the end of interferon therapy, 71 patients (37%) were virological responders and 107 (56%) patients were biochemical responders and were randomized: 54 into the ursodeoxycholic acid group and 53 into the placebo group. Sustained response was evaluated 12 months after withdrawal of interferon. Sustained biochemical and virological responses were, respectively, 30% and 22% in the ursodeoxycholic acid group and 46% and 32% in the placebo group, which did not significantly differ. Histological evolution of fibrosis and necrotic inflammatory activity were similar in the two groups. CONCLUSION: Continuation of ursodeoxycholic acid therapy after withdrawal of interferon in patients with end-of-treatment response did not result in any significant improvement either in the maintenance of response to interferon or in liver histology.

Adolescent↗

Effect of botulinum D toxin on human neutrophilic leukocytes and localization of its substrates.

Botulinum D toxin has been shown to ADP-ribosylate 22-kD proteins in neutrophilic leukocytes, but the function of these GTP-binding proteins remains unknown. In analogy to small GTP-binding proteins like SEC4 to YPT1, it has been suggested that botulinum D toxin substrates might be involved in secretory process of myeloid cells. Three main findings lead to the opposite conclusion. First of all, in human neutrophils, botulinum D toxin does not modify the release of azurophilic and specific granules induced by a chemoattractant (a formylpeptide) or a phorbol ester. Second, botulinum D toxin ADP-ribosylates 24 to 26-kD proteins that are only present in plasma membranes of human neutrophils. The membrane location of these substrates differs largely from that of the GTP-binding proteins involved in exocytosis and located in granules. Finally, since the same quantity of the toxin substrates is present in neutrophils as in their precursors, HL60 cells (which are devoid of specific granules and characterized by immature azurophilic granules and NADPH oxidase), it is unlikely that endogenous botulinum D toxin substrates are directly involved in the secretory responses of neutrophils.

Botulinum Toxins↗

[Paraneoplasic acrokeratosis of Bazex (author's transl)].

Acrokeratosis of Bazex is a true paraneoplasic syndrome of evocative by its acromegalic and symetric topography of erythemato-keratosic lesions. It always reveals an aerodigestive epithelioma. Its diagnosis is very useful for early treatment of the epithelioma. Its diagnosis is very useful for early treatment of the epithelioma. Its evolution is parallel with primitive cancer and is the best criteria of watching.

Acromegaly↗

Depression of the vestibulospinal reflex by intravermal microinjection of GABAA and GABAB agonists in the decerebrate cat.

Experiments performed in decerebrate cats have shown that unilateral microinjection into the cerebellar anterior vermis of a GABAA (muscimol) or a GABAB agonist (baclofen) decreased the gain of the vestibulospinal reflex involving the ipsilateral triceps brachii (iVSR). On the contrary, the phase angle of the reflex was not significantly modified. These effects started 5 to 10 min after the injection and persisted for at least 1 to 2 h before disappearing. Just the opposite changes in gain of the VSR were obtained after local microinjection of the GABAA (bicuculline) or the GABAB antagonist (saclofen). The area on which the GABAergic agents were effective was located within the third and/or the fourth folium rostral to the fissura prima (culmen), at the laterality of 1.0 to 1.4 mm with respect to the midline. This vermal region corresponded to the zone B of the cerebellar cortex, which receives a labyrinth input and projects to the ipsilateral lateral vestibular nucleus, where it exerts a prominent inhibitory influence. It is suggested that GABA agonists inhibit the Purkinje (P)-cells' activity, thus reducing the labyrinthine-induced modulation of the firing rate of these neurons by mossy and climbing fiber afferents. Since the vermal P-cells discharge outphase with respect to the excitatory VS neurons, we may explain why a reduced output of these P-cells results in a reduced gain of the VSR. These experiments provide evidence that the cerebellar anterior vermis exerts a positive influence on the basic VSR gain.

Animals↗

Changes in gain and spatiotemporal properties of the vestibulospinal reflex after injection of a GABA-A agonist in the cerebellar anterior vermis.

Experiments were performed to study the influence of the cerebellar anterior vermis on both amplitude and directional properties of the vestibulospinal (VS) reflexes. In decerebrate cats, the multiunit EMG activity of the medial head of the forelimb extensor triceps brachii was recorded during wobble of the whole animal at 0.15 Hz. With this procedure the animals were submitted to a tilt characterized by a fixed amplitude (10 degrees) and by a direction moving at constant velocity over the horizontal plane, in both a clockwise (CW) and a counterclockwise (CCW) direction. These dynamic stimuli permitted characterization of the triceps muscle response to animal tilt as a single vector in the horizontal plane. The gain of this vector was taken as the mean value obtained for the CW and CCW responses, while its orientation corresponded to the direction of head displacement, lying midway between the maximal response directions to CW and CCW rotations. The temporal phase was evaluated as the half difference between the directions of the CW and CCW responses. In all the experiments the response vector of the triceps brachii was closely aligned with the transverse axis and pointed to the side-down direction. Unilateral inactivation of the cerebellar anterior vermis after microinjection, in one or two folia of lobule V, of the GABA-A agonist muscimol (0.5 microL at 8 micrograms/microL saline), consistently and reversibly reduced in 20 to 40 min the amplitude of the EMG modulation of the ipsilateral triceps brachii to 46% to 80% of the control value, while only a small shift (up to 30 degrees) of the response vector occurred either nosewards or tailwards. Small shifts in temporal phase were also observed. These findings suggest that the Purkinje (P)-cells, which usually fire out of phase with respect to the VS neurons, contribute positively to the amplitude of the VS reflexes. It was previously shown that P-cells with response vectors covering all the directions of animal displacement are present in small regions of the cerebellar anterior vermis; it is likely that these neurons represent functional units facilitating the VS reflexes elicited by animal tilt in the direction of their response vectors. By suppressing the activity of these cells, muscimol injections would lead to a general depression of the triceps responses to animal displacement, not associated with prominent changes in directional specificity.

Animals↗

Neck influences on the spatial properties of vestibulospinal reflexes in decerebrate cats: role of the cerebellar anterior vermis.

The vestibulospinal (VS) reflexes elicited by animal rotation modify the activity of limb musculature, thus preserving balance and postural stability. We investigated whether the orientation of these postural responses is strictly dependent upon the direction of head displacement or else can be modified by extralabyrinthine inputs to the goal of stabilizing body position. The experiments were performed in decerebrate cats, in which the effects of static body-to-head displacements were tested on the multiunit EMG responses of the medial head of the triceps brachii to wobble of the whole animal at 0.15 Hz, 10 degrees, both in the clockwise (CW) and counterclockwise (CCW) direction. These stimuli allowed us to determine the muscle response vector, whose orientation component corresponds to the direction of head displacement giving rise to the maximal EMG response. When the animal body was kept straight with respect to the head, the triceps response vector was always oriented close to the transverse axis, pointing to the side-down direction. Following 30 degrees of body-to-head displacement around a vertical axis passing through the first-second cervical joints, the response vectors of both the left and the right muscles shifted in the same direction of body rotation, thus remaining approximately perpendicular to the body axis. The change in muscle vector orientation corresponded on the average to the angle of body-to-head displacement. Only slight changes in amplitude of the muscle responses were observed. These findings imply that the maximal activation of the triceps brachii always occurred for the same direction of body displacement, irrespective of the pattern of discharge of vestibular afferents, which is determined by the direction of head displacement. The rotation of the triceps response vector induced by body-to-head displacement was reduced or suppressed by inactivation of the ipsilateral cerebellar anterior vermis, following local microinjection of the GABA(A) agonist muscimol. These findings indicate that 1) the sensory input which results from changing the body position with respect to the head, probably originating from neck receptors, is able to modify the pattern of the VS reflexes, which appear to be organized in a body-centered reference frame, and 2) the cerebellar vermis is required for the proper execution of this sensorimotor transformation.

Animals↗