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Biomedical subjects

F Gros

Publications and source records attributed to F Gros.

At least 19 recordsLinked to original sources
PubMed2007

Elevated levels of soluble non-classical major histocompatibility class I molecule human leucocyte antigen (HLA)-G in the blood of HIV-infected patients with or without visceral leishmaniasis.

The non-classical class I major histocompatibility complex molecules human leucocyte antigen (HLA)-G have been shown to play a role in HIV persistence, but no data are available on the expression of the soluble forms HLA-G5 and sHLA-G1 in HIV-infected patients with and without opportunistic infections. The soluble HLA-G isoform was measured with an enzyme-linked immunosorbent assay (ELISA) method in plasma from 94 subjects: 31 HIV-1-seropositive, 17 with visceral leishmaniasis (VL), seven with both VL and HIV-1 infection and 39 healthy HIV-seronegative subjects. Between groups, the frequency of sHLA-G positivity was statistically different: 81% of HIV-infected patients were positive, as were 57% of HIV-Leishmania infantum co-infected patients, 35% of HIV-seronegative patients with VL and 3% of healthy controls. Levels of the soluble forms of the immunomodulatory molecules HLA-G are elevated during HIV infection. In HIV-Leishmania co-infected patients, sHLA-G secretion could contribute to the tolerogenic environment and to Leishmania immune evasion.

AIDS-Related Opportunistic Infections↗
PubMed2005

Diencephalic and mesencephalic influences on ponto-medullary respiratory control in normoxic and hypoxic conditions: an in vitro study on central nervous system preparations from newborn rat.

We investigated the effects of the diencephalon and mesencephalon on the central respiratory drive originating from ponto-medullary regions in normoxic and hypoxic conditions, using central nervous system preparations from newborn rats. We used two approaches: 1) electrophysiological analysis of respiratory frequency and the amplitude of inspiratory C4 activity and 2) immunohistochemical detection of Fos protein, an activity-dependent neuronal marker. We found that, in normoxic conditions, the mesencephalon moderated respiratory frequency, probably by means of an inhibitory effect on ventral medullary respiratory neurons. Diencephalic inputs restored respiratory frequency. Moreover, O(2)-sensing areas in the diencephalon (caudal lateral and posterior hypothalamic areas) and mesencephalon (ventrolateral and dorsolateral periaqueductal gray) seem to increase the amplitude of respiratory bursts during adaptation of the central respiratory drive to hypoxia. In contrast, decrease in respiratory frequency during hypoxia is thought to be mediated by a cluster of ventral hypothalamic neurons.

Animals↗
PubMed2004

Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure. a study on brainstem-spinal cord preparations isolated from newborn rats.

Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure has been investigated on pontomedullary-spinal cord, caudal pons-medullary-spinal cord and medullary-spinal cord preparations isolated from newborn rats. According to the drinking fluid of dams (tap water or 0.02% caffeine), two groups of preparations were distinguished, no-caffeine and caffeine. In the no-caffeine group, adenosine A1 receptor activation induces a decrease in respiratory frequency (Rf) in caudal pons-medullary-spinal cord and medullary-spinal cord preparations whereas, in presence of the rostral pons, an increase is observed. A parallel Fos detection indicates that this discrepancy may be due to the excitatory action of the medial parabrachial nucleus at the rostral pontine level that surpasses inhibitory influence of the adenosine A1 receptor activation at the medullary level particularly in the ventrolateral reticular nucleus of the medulla. In caffeine group, an increase in the baseline Rf in presence of the pons and no change in medullary-spinal cord preparations have been observed. Depending on Fos detection, we assume that the medial parabrachial nucleus is the main region involved in the exaggeration of Rf. Moreover, adenosine A1 receptor activation was modified by in utero caffeine exposure with an overcharge of the Rf increase in pontomedullary-spinal cord preparations and an exaggeration of the Rf decrease in medullary-spinal cord preparations. Based on Fos detection, we link the overcharge in Rf of pontomedullary spinal cord preparations to an increase in the medial parabrachial nucleus neuronal activity. Similarly, exaggeration of Rf decrease observed without the pons is linked with a decrease in activity of the ventrolateral reticular neurons. This study brings evidence for the involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations in newborns following in utero caffeine exposure and the importance of rostral pons in the adenosinergic A1 modulation of the respiratory control.

Adenosine↗
PubMed2001

5-HT(2A/2C) receptor-mediated hypopnea in the newborn rat: relationship to Fos immunoreactivity.

Previous data derived from anesthetized, decerebrate, or in vitro preparations suggested that 5-HT(2) receptor activation might be responsible for respiratory dysfunction. Such a mechanism has not yet been documented in the intact animal, but might be of clinical relevance to the apneic spells of the premature infant. In the present investigation on conscious newborn rats we analyzed the respiratory response to the activation of 5-HT(2A/2C) receptors by the agonist 1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and we delineated central structures possibly involved in this response, using Fos expression as a marker of neuronal activation. We demonstrated that intraperitoneal injection of 5 mg/kg DOI produced a long-lasting decrease in respiratory frequency and tidal volume, which could be blocked by the antagonist ritanserin. Fos immunohistochemistry suggested that the rostral ventrolateral medulla and the lateral paragigantocellular nucleus might have a key role in the respiratory response to 5-HT(2) receptor activation. In addition, double immunostaining for Fos and tyrosine hydroxylase suggested that the contribution of catecholaminergic neurons to this response might be modest and indirect.

Animals↗
PubMed2000

Postnatal changes in Fos-like immunoreactivity evoked by hypoxia in the rat brainstem and hypothalamus.

We have recently used Fos expression in adult rats to map neuronal populations activated in the brainstem and hypothalamus during the acute ventilatory response to moderate hypoxia (O(2) 11%). Although present at birth, this response evolves postnatally. The present investigation aimed at a better understanding of these maturational processes by delineating structures that might functionally develop after birth. The developmental pattern Fos expression evoked by hypoxia was analysed in rats aged from 0 to 26 postnatal days. The numbers of Fos positive neurons markedly increased with the age in the medullary areas related to respiratory control during the 2 first postnatal weeks. Thereafter, the response plateaued in the nucleus tractus solitarius and attenuated in the ventral medulla. In the upper brainstem (parabrachial area, central grey) and the hypothalamus (posterior and dorsomedial nuclei, ventral zone), Fos response to hypoxia was absent or weak at birth and increased until late development. The significance of the development of evoked Fos expression in these rostral sites is discussed together with their possible contribution to the maturation of O(2)-sensitive chemoreflex pathways.

Age Factors↗
PubMed2000

Brainstem and hypothalamic areas involved in respiratory chemoreflexes: a Fos study in adult rats.

The adaptation to hypoxia and hypercapnia requires the activation of several anatomical structures along the neuraxis. In this study, using Fos immunoreactivity, we sought to map neuronal populations involved in chemoreflex networks activated during the responses to moderate hypoxia (O(2) 11%), and hypercapnia (CO(2) 5%) in the brainstem and the hypothalamus of the rat. In the medulla, hypoxia elicited marked and significant staining in the nucleus of the solitary tract (NTS), and in parapyramidal neurons located near the ventral surface, whereas hypercapnia evoked significantly c-fos only near the ventral surface in paraolivar neurons. In contrast, within pontine and suprapontine structures, both hypoxia and hypercapnia evoked similarly Fos immunoreactivity in the lateral parabrachialis area, the central grey, the caudal hypothalamus (dorsomedial and posterior hypothalamic nuclei), and in a ventro-lateral hypothalamic area, extending from the rostral limit of the mammillary nuclei to the retrochiasmatic area. More rostrally, labelling was observed in the paraventricular nucleus of the hypothalamus in response to hypercapnia, and in the supraoptic nucleus in response to hypoxia. These results support the hypothesis that chemoreflexes pathways are not only restricted to medulla and pons but also involved mesencephalic and hypothalamic regions. The parabrachialis area and the central grey may be key relays between caudal and ventral hypothalamic neurons, and medullary neurons involved in the response to hypoxia and hypercapnia.

Animals↗
PubMed1999

Structure modelling and site-directed mutagenesis of the rat aromatic L-amino acid pyridoxal 5'-phosphate-dependent decarboxylase: a functional study.

The pyridoxal-5'-phosphate-dependent enzymes (B6 enzymes) are grouped into three main families named alpha, beta, and gamma. Proteins in the alpha and gamma families share the same fold and might be distantly related, while those in the beta family exhibit specific structural features. The rat aromatic L-amino acid decarboxylase (AADC; EC(4.1.1.28)) catalyzes the synthesis of two important neurotransmitters: dopamine and serotonin. It binds the cofactor pyridoxal-5'-phosphate and belongs to the alpha family. Despite the low level of sequence identity (approximately 10%) shared by the rat AADC and the sequences of the enzymes belonging to the B6 enzymes family, including the known three-dimensional structures, a multiple sequence alignment was deduced. A model was built using segments belonging to seven of the eleven known structures. By homology, and based on knowledge of the biochemistry of the aspartate aminotransferase, structurally and functionally important residues were identified in the rat AADC. Site-directed mutagenesis of the conserved residues D271, T246, and C311 was carried out in order to confirm our predictions and highlight their functional role. Mutation of D271A and D271N resulted in complete loss of enzyme activity, while the D271E mutant exhibited 2% of the wild-type activity. Substitution of T246A resulted in 5% of the wild-type activity while the C311A mutant conserved 42% of the wild-type activity. A functional model of the AADC is discussed in view of the structural model and the complementary mutagenesis and labelling studies.

Amino Acid Sequence↗
PubMed1997

Changes in Fos-like immunoreactivity evoked by maturation of the sneeze reflex triggered by nasal air puff stimulation in kittens.

The sneeze reflex is a valuable tool for exploring the maturation of the respiratory control in the newborn as it alters both inspiratory and expiratory activities. Air puff stimulation of the superior nasal meatus innervated by ethmoidal afferents consistently evokes sneeze in adult cats. Such stimulation evokes only a reinforcement of expiratory activities in newborn kittens. This study demonstrates that the pattern of Fos-like immunoreactivity evoked by nasal stimulation changes during functional maturation of sneeze. Nasal stimulation evoked immunoreactivity (i) in the trigeminal sensory complex, at the levels where nasal afferents project, (ii) in the reticular formation, (iii) in the solitary complex and (iv) in the parabrachial area of mature kittens. The evoked immunoreactivity was the same in newborn kittens as in mature kittens in the projection areas of the nasal primary afferents. Fos response was less than half that in mature kittens in the reticular formation and absent in the solitary complex or the parabrachial area. Sneeze can be elicited from the time when evoked immunoreactivity in the solitary complex and the parabrachial area is above control levels. These data provide evidence that the maturation of sneeze is dependent on the development of central relays allowing peripheral inputs to be integrated by neurons engaged in respiratory control.

Aging↗
PubMed1997

Biochemical characterization of the mouse muscle-specific enolase: developmental changes in electrophoretic variants and selective binding to other proteins.

The glycolytic enzyme enolase (EC 4.2.1.11) is active as dimers formed from three subunits encoded by different genes. The embryonic alphaalpha isoform remains distributed in many adult cell types, whereas a transition towards betabeta and gammagamma isoforms occurs in striated muscle cells and neurons respectively. It is not understood why enolase exhibits tissue-specific isoforms with very close functional properties. We approached this problem by the purification of native betabeta-enolase from mouse hindlimb muscles and by raising specific antibodies of high titre against this protein. These reagents have been useful in revealing a heterogeneity of the beta-enolase subunit that changes with in vivo and in vitro maturation. A basic carboxypeptidase appears to be involved in generating an acidic beta-enolase variant, and may regulate plasminogen binding by this subunit. We show for the first time that pure betabeta-enolase binds with high affinity the adjacent enzymes in the glycolytic pathway (pyruvate kinase and phosphoglycerate mutase), favouring the hypothesis that these three enzymes form a functional glycolytic segment. betabeta-Enolase binds with high affinity sarcomeric troponin but not actin and tropomyosin. Some of these binding properties are shared by the alphaalpha-isoenolase, which is also expressed in striated muscle, but not by the neuron-specific gammagamma-enolase. These results support the idea that specific interactions with macromolecules will address muscle enolase isoforms at the subcellular site where ATP, produced through glycolysis, is most needed for contraction. Such a specific targeting could be modulated by post-translational modifications.

Animals↗
PubMed1997

Expression, purification, and characterization of rat aromatic L-amino acid decarboxylase in Escherichia coli.

A cDNA encoding rat aromatic L-amino acid decarboxylase (AADC) was successfully expressed in Escherichia coli using a T7 RNA polymerase expression system. Two types of expression vectors were tested and revealed to be equivalent to produce AADC. The enzyme was purified in both cases. The ratio of recovery of the pure active recombinant protein was better when the purification of the protein was made easier by addition of a short His-Tag at the C-terminal moiety of AADC, as achieved in the case of pET-20b+ vector expression. Spectral characteristics of the bound pyridoxal-5'-phosphate were essentially identical to the spectral properties of rat AADC. Kinetic constants Km and Vmax of recombinant AADC for the natural substrates L-dihydroxyphenylalanine and 5-hydroxytryptamine were 0.14 mM and 8444 U/mg, and 0.066 mM and 1813 U/mg, respectively. These values were in good agreement with previously reported values for AADC of the rat and other mammalian species.

5-Hydroxytryptophan↗
PubMed1997

[Developmental genes].

In the present review article, we have attempted to define and class the so called "developmental genes". This designation applies to genes whose activity is involved in lineage determination, in differentiation pathways or in the modes of tissue or organ formation. A special emphasis has been given to genes controlling the body plan in the course of development. Three main subclasses of such genes are described: genes involved in very early development by establishing the anteroposterior or dorso-ventral axes of the embryo (or of the insect larva); segmentation genes; homeotic genes containing an homeodomain (HD) motif and homeotic-related genes (with a "LIM" or "PAX" motif). While classical (HD containing) homeotic genes were initially discovered and studied in drosophila, their general occurrence in many other species, particularly in vertebrates was soon reported. They are characterized phylogenetically speaking, by a high degree of sequence similarities and chromosomal organization, although their number appears much greater in vertebrates than in insects due to successive duplication and chromosomal distribution events. In vertebrates they are essentially involved in the development of the central nervous system. Large varieties of genes with "LIM" or "PAX" motifs have been reported, and many subclasses can be distinguished depending upon the presence or absence of distinct peptidic motifs within the genes under concern. The peptidic domains encoded by the LIM motifs include "Zn finger" containing varieties which are involved in protein-protein interactions. The roles of genes with a LIM motif vary according to the type of sub-variety (organization of the central nervous system; axonal distribution of peripheric nerves at distinct levels of the spinal cord, control of tissue differentiation, etc.). "Pax" genes include a DNA binding domain (encoded by the "paired" motif) with variable sequences and organization, which is sometime in the vicinity of an homeodomain. Generally speaking "Pax" genes behave like controlling elements in the development of the brain or of tissues derived from the neural crest.

Animals↗
PubMed1996

Interaction of kinesin motor domains with alpha- and beta-tubulin subunits at a tau-independent binding site. Regulation by polyglutamylation.

Interaction of rat kinesin and Drosophila nonclaret disjunctional motor domains with tubulin was studied by a blot overlay assay. Either plus-end or minus-end-directed motor domain binds at the same extent to both alpha- and beta-tubulin subunits, suggesting that kinesin binding is an intrinsic property of each tubulin subunit and that motor directionality cannot be related to a preferential interaction with a given tubulin subunit. Binding features of dimeric versus monomeric rat kinesin heads suggest that dimerization could drive conformational changes to enhance binding to tubulin. Competition experiments have indicated that kinesin interacts with tubulin at a Tau-independent binding site. Complementary experiments have shown that kinesin does not interact with the same efficiency with the different tubulin isoforms. Masking the polyglutamyl chains with a specific monoclonal antibody leads to a complete inhibition of kinesin binding. These results are consistent with a model in which polyglutamylation of tubulin regulates kinesin binding through progressive conformational changes of the whole carboxyl-terminal domain of tubulin as a function of the polyglutamyl chain length, thus modulating the affinity of tubulin for kinesin and Tau as well. These results indicate that microtubules, through tubulin polymorphism, do have the ability to control microtubule-associated protein binding.

Animals↗
PubMed1996

Autonomous differentiation in the mouse myogenic cell line, C2, involves a mutual positive control between insulin-like growth factor II and MyoD, operating as early as at the myoblast stage.

We have studied the contribution of the endogenous production of insulin-like growth factor II (IGFII) and of the muscle regulatory factor, MyoD, to the autonomy of differentiation in isolated skeletal myoblasts. Inhibition of MyoD and IGFII gene expression in myoblasts of the mouse myogenic cell line, C2, was achieved by transfection and selection of stably transfected cells (anti-MyoD and anti-IGFII cells) with vectors producing MyoD or IGFII antisense RNA. We observed that inhibiting either MyoD or IGFII has multiple and similar consequences. In addition to the inhibition of the target gene, expression of MyoD transcripts in anti-IGFII myoblasts and expression of IGFII in anti-MyoD myoblasts were also abolished, whereas accumulation of transcripts for the muscle regulatory factor, Myf5, was markedly increased in both cell types. However, despite this Myf5 up-regulation, both anti-IGFII and anti-MyoD myoblasts lost the ability to undergo autonomous differentiation (differentiation in the absence of added IGF), further indicating that Myf5 and MyoD are not strictly interchangeable. Additional evidence of a link between MyoD and IGFII was obtained: (1) forced expression of the MyoD cDNA stimulated IGFII gene expression, and (2) treatment of C2 myoblasts with fibroblast growth factor, not only diminished MyoD expression and compromised differentiation as previously shown by others, but also abolished IGFII expression. These experiments showing loss or gain of function argue in favor of a mutual positive control between IGFII and MyoD operating as early as the myoblast stage.

Animals↗
PubMed1995

C-Fos-like immunoreactivity in the cat brainstem evoked by sneeze-inducing air puff stimulation of the nasal mucosa.

Sneeze is one of the most important protective reflex of the respiratory tract. It is elicited from trigeminal peripheral fields and results in major changes in the discharge patterns of the medullary respiratory-related neurons. The pattern of c-Fos-like immunoreactivity evoked by sneezing was explored as a structural approach to the networks involved in this particular model of trigemino--respiratory interactions. Sneezes were elicited in anaesthetized adult cats by driving air puffs to the superior nasal meatus through a catheter. Additional cats were used as controls for anaesthesia and for catheter insertion into the nostril. In sneezing cats, immunoreactivity was evoked in projection areas of the ethmoidal afferents which innervate the superior nasal meatus, e.g. the subnuclei caudalis, interpolaris and in the interstitial islands of the trigeminal sensory complex. Immunoreactivity was also markedly enhanced in the areas devoted to respiratory control in the medulla (solitary complex, nucleus retroambiguus) and in the pontine parabrachial area. C-Fos expression was also evoked in the lateral aspect of the parvicellular reticular formation in sneezing cats. This area might be of major importance in the adaptation of the ventilatory system to expulsive functions.

Anesthesia↗
PubMed1995

Transcriptional up-regulation of the mouse gene for the muscle-specific subunit of enolase during terminal differentiation of myogenic cells.

The glycolytic enzyme enolase (EC 4.2.1.11) exists as dimers formed from three structurally related subunits alpha, beta, and gamma, encoded by separate genes. The gene encoding the beta-subunit is expressed only in striated muscles. We have previously shown that the beta-enolase gene belongs to a small subset of muscle-specific genes showing transcriptional activity in cultured myoblasts, prior to withdrawal from the cell cycle. An increase in the level of beta-enolase mRNA occurs during terminal differentiation of myoblasts. To investigate the mechanisms underlying this increase, we have simultaneously estimated, under steady state conditions, the rate of synthesis and the stability of beta-enolase mRNA in proliferating C2.7 myoblasts as well as in differentiating myotubes. The method used is based on the isolation of newly synthesized RNA from the total RNA pool, following pulse-labeling of intact cells in the presence of 4-thiouridine. The results described here demonstrate a coordinate increase in newly synthesized and total beta-enolase mRNA, while the mRNA half-life, about 4 hr, remains unchanged in the course of terminal differentiation. The expression of the gene for insulin-like growth factor-II (IGF-II), a major positive regulator of myogenesis, was analyzed using the same approach. It is concluded that the up-regulation of beta-enolase as well as IGF-II gene expression in differentiating muscle cells reflects an increased rate of entry of newly synthesized mRNAs into the general pool of transcripts without changes in their respective half-lives.

Animals↗