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C Langlet

Publications and source records attributed to C Langlet.

At least 19 recordsLinked to original sources
PubMed2005

Mid-lumbar segments are needed for the expression of locomotion in chronic spinal cats.

In acute experiments performed in decerebrated and spinalized (T13) cats, an intraspinal injection of clonidine, a noradrenergic agonist, restricted to mid-lumbar segments L3-L4, can induce hindlimb locomotion, whereas yohimbine, a noradrenergic antagonist, can block spinal locomotion, and a second spinal lesion at L4 can abolish all locomotor activity. In the present study, we investigated whether the abolition of locomotion after this second spinal lesion was due to an acute spinal shock or to the functional disconnection of the rostral and caudal lumbar segments. In seven cats, first spinalized at T13 and having recovered treadmill locomotion, a second transection was performed at lower lumbar levels. Video and electromyographic recordings were used to evaluate locomotor performance. Results show that after a second transection at L2 or rostral L3 levels, spinal locomotion was maintained; when the second lesion was performed at caudal L3 or L4, all locomotor activity was abolished even after several weeks of attempted locomotor training; vigorous fast paw shakes (FPS) were observed in all cases; and after an intraperitoneal injection of clonidine in cats with a second transection below L4, perineal stimulation induced hyperextension of the hindlimbs but no locomotion. Considering that the main motoneuron pools of the hindlimbs are caudal to L4 and are still functional after the second spinal transection, as evidenced by the presence of FPS, we conclude that the mid-lumbar spinal segments are essential for the specific expression of spinal locomotion but not necessarily for other rhythmic motor patterns.

Adrenergic alpha-Agonists↗
PubMed2004

[Secondary surfactant deficiencies in extremely low birth weight premature infants].

Primary deficiency of surfactant is responsible for the respiratory distress syndrome and concerns premature neonates born before 33 weeks of gestation. However, newborns may develop respiratory disorders related to a secondary deficiency or dysfunction of surfactant. We report the course of three extremely low birth weight premature infants who experienced clinical respiratory decompensation at two weeks and showed a marked improvement after exogenous natural surfactant administration.

Humans↗
PubMed2002

Recovery of locomotion in the cat following spinal cord lesions.

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Animals↗
PubMed2001

Time course of recovery of the somatosensory map following hindpaw sensory deprivation in the rat.

Hindlimb sensory deprivation is known to induce a decrease in the cortical representation of hindpaw, and an increase in the size of the cutaneous receptive fields. The aim of the present study was to determine (i) the time-course of recovery when the rat retrieves a normal use of its limbs after a 14-day period of sensory disruption and (ii) whether a 1-day period of sensory deprivation is sufficient to induce a plasticity. Our results indicate that the remodelling of the cortical map was not observed after 1 day of sensory deprivation. On the other hand, the recovery was achieved after 6 h. These findings suggest that a procedure reducing sensory function resulted in reversible changes in the somatosensory cortex. The recovery was more rapid than the induction of plasticity.

Animals↗
PubMed2001

Hypodynamia--hypokinesia induced variations in expression of fos protein in structures related to somatosensory system in the rat.

There have been many reports describing modifications of the sensory and motor cortex following various types of disuse. Hypodynamia--hypokinesia is characterized by the absence of weight-bearing and by a decrease in motor activity. We have shown a reorganization of the cortical cartography after hypodynamia--hypokinesia. In order to give an anatomical account for this cortical plasticity, we set out to determine whether cerebral and spinal structures exhibited variations of their neuronal activation. For this purpose, immunocytochemical detection of Fos protein was performed in the rat brain and spinal cord. Following stimulation of the sciatic nerve, Fos protein was detected in the primary and secondary somatosensory cortex in control rats and in rats submitted to an episode of 14 days of hypodynamia--hypokinesia. Results showed that the stimulation of the sciatic nerve induced an increase in the number of Fos-immunoreactive neurons in all these structures. Moreover, after hypodynamia--hypokinesia, the number of Fos-immunoreactive neurons was increased in the primary and secondary somatosensory cortex and in the spinal cord. These results provide evidence for a higher activation of cortical cells after hypodynamia--hypokinesia in comparison to controls. These data support the hypothesis that hypodynamia--hypokinesia contributes to the development of functional plasticity.

Animals↗
PubMed2000

Membrane rafts and signaling by the multichain immune recognition receptors.

The recent recognition of the presence of rafts in the plasma membrane and of their involvement in cell signaling has strongly stimulated the search for their function in receptor-mediated signal transduction in lymphocytes. Recent progress suggests that a general feature of membrane rafts is to serve as platforms wherein the signaling cascades triggered through different multichain immune recognition receptors (e.g. the TCR, BCR and FcepsilonRI) are initiated and organized.

Cell Membrane↗
PubMed2000

Effect of microgravity on the electromyographic activity of two upperlimb muscles during a goal-directed movement and during locomotion.

It is well known that both neuromuscular and perceptual properties are affected during spaceflight. These modificaitons can therefore induce dramatic alterations in the mechanical basis of movements and locomotion disturbances. The main objectives of this study were: 1) to examine whether the nervous control of muscular activity in the upper limbs of the rhesus monkey (Macaca mulatta) was modified in a microgravity environment; and 2) to quantify the electromyographic (EMG) pattern of biceps (BI) and triceps (TRI) muscles pre-, in-, and postflight during performance of goal-directed movements and locomotion.

Adaptation, Physiological↗
PubMed1999

Short-term reorganization of the rat somatosensory cortex following hypodynamia-hypokinesia.

This study was performed to determine if hypodynamia-hypokinesia (HH) could induce a reorganization of the rat somatosensory cortex. The cortical hindpaw representation was determined by stimulating the limb and recording multi-unit cortical activity. The size of the cutaneous receptive fields was also measured. After 14 days of HH, the size of the cortical hindpaw representation was decreased. The proportion of small cutaneous receptive fields decreased while the large ones increased. After 7 days of HH, no change in the two studied parameters was noticed in five animals. In the other rats, a number of sites unresponsive to cutaneous stimulation or with high thresholds was observed. This study provides evidence of a plasticity of the somatosensory cortex induced by a situation that reduces both sensory and motor functions. The cortical reorganization occurs in two stages.

Analysis of Variance↗
PubMed1999

Short-term plasticity in primary somatosensory cortex of the rat after hindlimb suspension.

Since the last 25 years, the cortex is considered as a dynamic entity, susceptible of changes. Various types of modifications in stimuli may lead to the plasticity of the target neurons. These include immobilisation, denervation, amputation, deafferentation... In the somatosensory system, the most important changes are a substantial reorganisation of the cortical somatotopic representation, and an enlargement of the receptive fields (RF) of cortical neurons. Hindlimb suspension (HS) is characterized by the absence of weight-bearing and a reduced motor activity. In these conditions, the cutaneous receptors located on the foot sole are deactivated. Our hypothesis is that this condition of HS can produce a reorganisation of the somatosensory cortex (SmI) and a modification in the size of the cutaneous RF.

Animals↗
PubMed1998

Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains.

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.

Animals↗
PubMed1994

Tyrosine phosphorylation and activation of Vav GTP/GDP exchange activity in antigen receptor-triggered B cells.

Ag receptor triggering in B cells stimulates the activity of receptor-associated tyrosine protein kinases (TPK), leading to tyrosine phosphorylation of several cellular substrates, one of which is the Vav proto-oncogene product. We have recently determined that Vav is a TPK-regulated guanine nucleotide exchange factor for Ras in T cells. Here, we show that B cell extracts or Vav immunoprecipitates contain a Ras GDP/GTP exchange activity that is stimulated upon surface Ig (slg) triggering. The receptor-mediated stimulation of Vav exchange activity was blocked by the TPK antagonist, herbimycin A. Furthermore, immunodepletion of Vav from the B cell extracts removed approximately 80% of the Ras GDP/GTP exchange activity. These findings indicate, first, that B cell-derived Vav possesses GDP/GTP exchange activity for Ras; second, that the exchange activity of Vav is accelerated by a slg-triggered, herbimycin A-sensitive TPK and, third, that Vav accounts for most of the receptor-stimulated Ras GDP/GTP exchange activity. Thus, Vav may serve as a critical component in slg-mediated signal transduction pathways by coupling receptor-associated TPK to the activation of Ras proteins.

Animals↗
PubMed1994

The degree of CD8 dependence of cytolytic T cell precursors is determined by the nature of the T cell receptor (TCR) and influences negative selection in TCR-transgenic mice.

Although much has been learned about CD8 structure-function properties, it has so far not been tested whether the nature of the TCR is sufficient to transfer the property of CD8 dependence versus non-dependence to CD8+ cytotoxic T lymphocytes (CTL) and their precursors differentiating in T cell receptor (TCR)-transgenic (Tg) mice. In the present study, we compared the characteristics of dependence on CD8 for stimulation of CTL precursors and antigen-specific cytolysis by CD8+ T cells from two TCR-Tg mice expressing respectively the TCR (Tg) from a "CD8-dependent" and from a "CD8-independent" CTL clone, which were both reactive against the H-2Kb alloantigen and originated from H-2k mice. The results indicate that the property of the Tg+CD8+ cells from H-2k TCR-Tg mice corresponds to that of the CTL clone of origin, demonstrating that it is linked to the nature of the TCR. Consistent with this property, Tg+CD4+ cells could also differentiate into H-2Kb-specific CTL when originating from the "CD8-independent", but not from the "CD8-dependent" Tg-TCR. The influence of the property of "CD8 dependence" on negative selection occurring in TCR-Tg H-2k/b mice was apparent at two levels: (i) in the thymus, the extent of deletion was much more pronounced for the "CD8-independent" TCR-Tg mice; (ii) in the periphery, Tg+(hi) cells with low to negative CD8 expression were present for the "CD8-dependent" Tg-TCR, whereas only Tg+CD4-CD8- cells with low surface Tg-TCR and CD3 expression were found for the "CD8-independent" Tg-TCR, indicating that Tg+CD4-CD8- cells are susceptible to tolerance induction involving TCR/CD3 surface down-modulation. Furthermore, different in vitro conditions led to H-2Kb-induced stimulation of Tg+CD4-CD8- cells to differentiate into CTL detected in an anti-TCR clonotypic monoclonal antibody redirected cytolysis assay. Culture in interleukin-2 of H-2k/b Tg+CD4-CD8- cells was sufficient to induced CTL activity in the "CD8-independent" model, whereas stimulation with cells which overexpressed H-2Kb was required in addition to interleukin-2 to induce CTL differentiation in the "CD8-dependent" model. These data suggest that peripheral Tg+CD4-CD8- cells present in a situation of in vivo tolerance to H-2Kb can still be triggered by H-2Kb with a sensitivity correlated with the degree of CD8 dependence.

Animals↗
PubMed1994

Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or beta-globin gene promoters.

We have studied tolerance induction in transgenic CBA mice expressing H-2Kb genes under the influence of guinea-pig alpha-lactalbumin (KAL) or human beta-globin gene promoter (K beta). KAL radio-resistant cells, but not bone marrow derived cells, induce tolerance to H-2Kb in chimeric mice. In contrast, bone marrow derived and radio-resistant cells of K beta mice induce tolerance. Although appropriate, tissue-specific, expression of H-2Kb molecules occurs in KAL and K beta mice, H-2Kb is expressed at low levels in thymus of transgenic mice. In addition, dendritic cells and macrophages express H-2Kb molecules when K beta, but not when KAL bone marrow is cultured in vitro. The mode of tolerance induction was examined in double transgenic mice by mating KAL or K beta mice to mice expressing TCR transgenes (Tg-TCR) derived from a H-2Kb specific, CD8-independent cytotoxic T cell clone. In both cases, a large number of Tg-TCR+ CD8+CD4+ thymocytes develop but mature CD8+CD4- thymocytes fail to appear suggesting that thymocytes are eliminated late in development. Some CD8-CD4- and CD8-CD4+ Tg-TCR+ T cells develop in double transgenic mice and respond to activation through their TCR-CD3 complex in vitro, although no responses to stimulation with H-2Kb expressing cells were detected. Thus, tolerance induction in KAL and K beta mice proceeds via a deletional mechanism that is inefficient due either to low numbers of H-2Kb expressing thymic cells or to the low levels of H-2Kb expressed by thymic cells, or to a combination of these factors.

Animals↗
PubMed1994

Activation of Ras in vitro and in intact fibroblasts by the Vav guanine nucleotide exchange protein.

We recently identified Vav, the product of the vav proto-oncogene, as a guanine nucleotide exchange factor (GEF) for Ras. Vav is enzymatically activated by lymphocyte antigen receptor-coupled protein tyrosine kinases or independently by diglycerides. To further evaluate the physiological role of Vav, we assessed its GDP-GTP exchange activity against several Ras-related proteins in vitro and determined whether Vav activation in transfected NIH 3T3 fibroblasts correlates with the activity status of Ras and mitogen-activated protein (MAP) kinases. In vitro translated purified Vav activated by phorbol myristate acetate (PMA) or phosphorylation with recombinant p56lck displayed GEF activity against Ras but not against recombinant RacI, RacII, Ral, or RhoA proteins. Expression of vav or proto-vav in stably transfected NIH 3T3 cells led to a approximately 10-fold increase in basal or PMA-stimulated Ras exchange activity, respectively, in total-cell lysates and Vav immunoprecipitates. Elevated GEF activity was paralleled in each case by a significant increase in the proportion of active, GTP-bound Ras. PMA had a minimal effect on the low Ras. GTP level in untransfected control fibroblasts but increased it from 20 to 37% in proto-vav-transfected cells. vav-transfected cells displayed a constitutively elevated Ras. GTP level (35%), which was not increased further by PMA treatment. MAP kinases, known downstream intermediates in Ras-dependent signaling pathways, similarly exhibited increased basal or PMA-stimulated activity in Vav-expressing cells by comparison with normal NIH 3T3 cells. These results demonstrate a physiologic interaction between Vav and its target, Ras, leading to MAP kinase activation.

3T3 Cells↗
PubMed1994

Direct stimulation of Vav guanine nucleotide exchange activity for Ras by phorbol esters and diglycerides.

We recently identified Vav as a Ras-activating guanine nucleotide exchange factor (GEF) stimulated by a T-cell antigen receptor-coupled protein tyrosine kinase (PTK). Here, we describe a novel, protein kinase-independent alternative pathway of Vav activation. Phorbol ester, 1,2-diacylglycerol, or ceramide treatment of intact T cells, Vav immunoprecipitates, or partially purified Vav generated by in vitro translation or COS-1 cell transfection stimulated the Ras exchange activity of Vav in the absence of detectable tyrosine phosphorylation. GEF activity of gel-purified Vav was similarly stimulated by phorbol myristate acetate (PMA). Stimulation was resistant to PTK and protein kinase C inhibitors but was blocked by calphostin, a PMA and diacylglycerol antagonist. In vitro-translated Vav lacking its cysteine-rich domain, or mutated at a single cysteine residue within this domain (C528A), was not stimulated by PMA but was fully activated by p56lck. This correlated with increased binding of radiolabeled phorbol ester to COS-1 cells expressing wild-type, but not C528A-mutated, Vav. Thus, Vav itself is a PMA-binding and -activated Ras GEF. Recombinant interleukin-1 alpha stimulated Vav via this pathway, suggesting that diglyceride-mediated Vav activation may couple PTK-independent receptors which stimulate production of lipid second messengers to Ras in hematopoietic cells.

Alkaloids↗
PubMed1992

Electroporation of CTL clones: a useful method to investigate signalling pathways leading to the expression of effector functions.

Signal transduction mechanisms leading to effector functions in mouse cytolytic T lymphocyte (CTL) clones were studied following the introduction of exogenous molecules by electroporation. Conditions were defined in which the application of an electric pulse permeabilized the CTL without affecting functions such as antigen-dependent or antibody-mediated cytotoxicity. When a non-permeant Ca2+ chelator such as EGTA was added in the external medium during the electric pulse, it inhibited subsequent target cell cytolysis carried out in the presence of external Ca2+, thereby indicating the efficiency of EGTA uptake. Results obtained in this system, using a 13 amino-acid protein kinase C (PKC) pseudo-substrate peptide, indicated that it selectively inhibited cytolysis, whereas a substrate peptide with one amino-acid substitution was not inhibitory. This suggests that the technique could be used to study the signal transduction mechanisms of CTL clones which lead to the expression of effector functions.

Amino Acid Sequence↗