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Biomedical subjects

G Laurent

Publications and source records attributed to G Laurent.

At least 127 records · Page 7Linked to original sources
PubMed1996

Central generation of grooming motor patterns and interlimb coordination in locusts.

Coordinated bursts of leg motoneuron activity were evoked in locusts with deefferented legs by tactile stimulation of sites that evoke grooming behavior. This suggests that insect thoracic ganglia contain central pattern generators for directed leg movements. Motoneuron recordings were made from metathoracic and mesothoracic nerves, after eliminating all leg motor innervation, as well as all input from the brain, subesophageal ganglion, and prothoracic ganglion. Strong, brief trochanteral levator motoneuron bursts occurred, together with silence of the slow and fast trochanteral depressor motoneurons and activation of the common inhibitor motoneuron. The metathoracic slow tibial extensor motoneuron was active in a pattern distinct from its activity during walking or during rhythms evoked by the muscarinic agonist pilocarpine. Preparations in which the metathoracic ganglion was isolated from all other ganglia could still produce fictive motor patterns in response to tactile stimulation of metathoracic locations. Bursts of trochanteral levator and depressor motoneurons were clearly coordinated between the left and right metathoracic hemiganglia and also between the mesothoracic and the ipsilateral metathoracic ganglia. These data provide clear evidence for centrally generated interlimb coordination in an insect.

Animals↗
PubMed1996

Odour encoding by temporal sequences of firing in oscillating neural assemblies.

Stimulus-evoked oscillatory synchronization of activity has been observed in many neural systems, including the cerebral cortex of mammals and the brain of insects. The possible functions of such rhythmic synchronization in neural coding, however, remain largely speculative. In the locust, odours evoke activity in dynamic (evolving) ensembles of transiently synchronized neurons. We report here that the active neurons composing these ensembles change in a stimulus-specific manner and with a high degree of reliability on a cycle-by-cycle basis during an odour response. Hence, information about an odour is contained not only in the neural assembly active at each oscillation cycle, but also in the precise temporal sequence in which these assemblies are updated during an odour response. Neural coding with oscillations thus allows combinatorial representations in time as well as in space.

Action Potentials↗
PubMed1996

Distinct mechanisms for synchronization and temporal patterning of odor-encoding neural assemblies.

Stimulus-evoked oscillatory synchronization of neural assemblies and temporal patterns of neuronal activity have been observed in many sensory systems, such as the visual and auditory cortices of mammals or the olfactory system of insects. In the locust olfactory system, single odor puffs cause the immediate formation of odor-specific neural assemblies, defined both by their transient synchronized firing and their progressive transformation over the course of a response. The application of an antagonist of ionotropic gamma-aminobutyric acid (GABA) receptors to the first olfactory relay neuropil selectively blocked the fast inhibitory synapse between local and projection neurons. This manipulation abolished the synchronization of the odor-coding neural ensembles but did not affect each neuron's temporal response patterns to odors, even when these patterns contained periods of inhibition. Fast GABA-mediated inhibition, therefore, appears to underlie neuronal synchronization but not response tuning in this olfactory system. The selective desynchronization of stimulus-evoked oscillating neural assemblies in vivo is now possible, enabling direct functional tests of their significance for sensation and perception.

Animals↗
PubMed1996

GABAergic synapses in the antennal lobe and mushroom body of the locust olfactory system.

To help elucidate the role of inhibitory feedback in the genesis of odour-evoked synchronization of neural activity, we investigated the distribution of gamma-aminobutyric acid (GABA)ergic synaptic terminals in the antennal lobes (AL) and mushroom bodies (MB) of the locust olfactory system. Electron-microscopy, intracellular horseradish peroxidase labelling, and immunocytochemistry were combined to assess the distribution of GABAergic synapses, using established methods (Leitch and Laurent [1993] J. Comp. Neurol. 337:461-470). In the AL, GABA-immunoreactive presynaptic terminals contacted both immunoreactive and immunonegative profiles. Conversely, GABA-immunoreactive profiles received direct input from both reactive and negative terminals. The tract containing the axons of the projection neurons that run from the AL to the MB contained about 830 axons of fairly uniform size, none of which was immunoreactive for GABA. In the calyx of the MB, large immunoreactive terminals contacted very-small-diameter profiles thought to belong to the Kenyon cells (KCs). This was confirmed by combining immunocytochemistry with intracellular HRP-labelling of KCs. KCs were not immunoreactive for GABA. Although some GABAergic contacts were made onto the spiny profiles of KCs, others were made onto their dendritic shafts. Large GABA-immunoreactive profiles were also found to contact large negative profiles that were presynaptic to KC terminals. This suggests that KC dendrites can be both pre- and post-synaptically inhibited in the calyx. The MB pedunculus contained ca. 50,000 tightly packed KC axons, showing conspicuous en passant and often reciprocal synaptic contacts between neighbouring axons. KC axons were immunonegative, but received direct input from, and contacted directly, large immunoreactive profiles running across or along the KC axons. In the alpha- and beta-lobes of the MB, connections similar to those in the pedunculus were seen with two main differences: (1) The density of synaptic profiles was higher, giving on occasion numerous serially connected profiles in a single section; (2) large immunonegative profiles with dense-core vesicles were abundant and were frequently presynaptic to GABAergic processes and to very-small-diameter profiles which possibly belong to KCs. These results are discussed in the context of the known physiological data on olfactory processing in these complex circuits.

Animals↗
PubMed1996

Opposite effects of tumor necrosis factor alpha on the sphingomyelin-ceramide pathway in two myeloid leukemia cell lines: role of transverse sphingomyelin distribution in the plasma membrane.

Tumor necrosis factor alpha (TNF alpha) mediates proliferation, functional activation, and apoptotic cell death depending on the target cell type. Although sphingomyelin (SPM) hydrolysis and ceramide generation may function as an important mediator in TNF alpha signaling, the molecular mechanisms of the signaling pathway(s) are still not well understood. The aim of the present study is to compare the effect of TNF alpha on SPM metabolism and cell growth in two myeloid leukemic cell lines (U937 and KG1a) that differ in their sensitivity to TNF alpha. Our results show that TNF alpha induced apoptosis in U937 but not in KG1a cells. TNF alpha triggered in KG1a cells neither SPM hydrolysis nor ceramide generation, but induced SPM synthesis and ceramide breakdown as well as dose-dependent cell proliferation. In contrast, TNF alpha induced in U937 SPM hydrolysis and ceramide generation as well as dose-dependent cell death. Synthetic cell permeant ceramide, as well as natural ceramide, generated by treatment with bacterial sphingomyelinase (SPMase), all induced apoptosis in both U937 and KG1a cells. These findings indicate that the SPM-ceramide pathway is altered in KG1a cells upstream of the ceramide generation. Analysis of the transverse distribution of SPM in the plasma membrane showed that the SPM pool involved in cell signaling (inner leaflet) was markedly reduced in KG1a cells; it is 7-fold lower than that found in the inner leaflet of U937 cells. Therefore, our study strongly suggests that the different responses induced by TNF alpha in myeloid cells are dependent on the SPM plasma membrane transverse asymmetry.

Animals↗
PubMed1996

Temporal representations of odors in an olfactory network.

The responses of projection neurons in the antennal lobe of the locust brain (the functional analog of mitral-tufted cells in the vertebrate olfactory bulb) to natural blends and simple odors were studied with multiple intra- and extracellular recordings in vivo. Individual odors evoked complex temporal response patterns in many neurons. These patterns differed across odors for a given neuron and across neurons for a given odor, but were stable for each neuron over repeated presentations (separated by seconds to minutes) of the same odor. The response of individual neurons to an odor was superimposed on an odor-specific coherent oscillatory population activity. Each neuron usually participated in the coherent oscillations during one or more specific epochs of the ensemble activity. These epochs of phase locking were reliable for each neuron over tens of repeated presentations of one odor. The timing of these epochs of synchronization differed across neurons and odors. Correlated activity of specific pairs of neurons, hence, generally occurred transiently during the population response, at times that were specific to these pairs and to the odor smelled. The field potential oscillations, therefore, fail to reveal a progressive transformation of the synchronized ensemble as the response to the odor unfolds. We propose that (1) odors are represented by spatially and temporally distributed ensembles of coherently firing neurons, and (2) the field potential oscillations that characterize odor responses in the olfactory system occur, at least in this animal, in parallel with a slower dynamic odor representation.

Animals↗
PubMed1996

Daunorubicin-induced apoptosis: triggering of ceramide generation through sphingomyelin hydrolysis.

The nature of the signaling pathway(s) which initiate drug-triggered apoptosis remains largely unknown and is of fundamental importance in understanding cell death induced by chemotherapeutic agents. Here we show that in the leukemic cell lines U937 and HL-60, daunorubicin, at concentrations which trigger apoptosis, stimulated two distinct cycles of sphingomyelin hydrolysis (approximately 20% decrease at 1 microM) within 4-10 min and 60-75 min with concomitant ceramide generation. We demonstrate that the increase in ceramide levels, which precedes apoptosis, is mediated by a neutral sphingomyelinase and not by ceramide synthase. Indeed, potent ceramide synthase inhibitors such as fumonisin B1 did not affect daunorubicin-triggered sphingomyelin hydrolysis, ceramide generation or apoptosis. In conclusion, we provide evidence that daunorubicin-triggered apoptosis is mediated by a signaling pathway which is initiated by an early sphingomyelin-derived ceramide production.

Amidohydrolases↗
PubMed1996

Frequent expression of the cell death-inducing gene Bax in Reed-Sternberg cells of Hodgkin's disease.

The expression of a cell death-inducing gene, Bax, was investigated in 52 cases of Hodgkin's disease in parallel with Epstein-Barr virus and was compared with the immunodetection of other apoptosis-regulating proteins, Mcl-1, Bcl-2, and Bcl-x. Bax immunostaining was found in 92% of the cases, among them 28% with a strong signal in more than 75% of the Reed-Sternberg cells. Mcl-1 was positive in 80% of the cases, whereas Bcl-2 and Bcl-x were found in 53% and 88% of the cases, respectively. Of 48 (89%) Bax-positive tumors, 43 were found to express apoptosis-inhibiting proteins such as Mcl-1 or Bcl-2. With the exception of 1 case, all Bax-positive tumors also expressed either Bcl-2, Bcl-x, Mcl-1, or combinations of these anti-apoptotic proteins. No correlation was found between Bax expression and the presence of apoptotic cells as detected by morphology and the in situ 3' OH-DNA end-labeling technique. Our findings show that the apoptosis-inducing gene Bax expression is frequently expressed in Hodgkin's disease, providing a potential explanation for the good chemoresponses generally obtained for patients with this neoplastic disorder.

Apoptosis↗
PubMed1996

Dynamical representation of odors by oscillating and evolving neural assemblies.

Although smells are some of the most evocative and emotionally charged sensory inputs known to us, we still understand relatively little about olfactory processing and odor representation in the brain. This review summarizes physiological results obtained from an insect olfactory system and presents a functional scheme for odor coding that is compatible with data from other animals, including mammals. This coding scheme consists of three main and concurrent odor-induced phenomena: 20-30 Hz oscillatory mass activity; patterned and odor-specific neuronal responses; and transient, dynamic synchronization of odor-specific neural assemblies. When these phenomena are considered together, odors appear to be represented combinatorially by dynamical neural assemblies, defined partly by the transient but stimulus-specific synchronization of their neuronal components.

Animals↗
PubMed1996

Clinical assessment of dry weight.

Unsatisfactory control of blood pressure (BP) leading to an increased rate of cardiovascular events is the main cause of mortality in haemodialysis. BP control has deteriorated since haemodialysis session times have been reduced. Inadequate BP control most often is due to a failure to achieve and maintain dry weight. Dry weight and normotension have been gradually omitted in the goals of dialysis, satisfactory dialysis being reduced to an 'adequate' urea Kt/V. Ideal dry body weight needs a reappraisal. What is dry weight? How should it be clinically assessed, established and maintained in patients? The problems encountered in estimating dry weight can be solved at the bedside in most cases. The additional laboratory, echography and impedancemetry methods are research tools that hopefully can be made simpler and lower in cost so they can be used everyday at the bedside. In the mean time, with the exception of ambulatory blood pressure measurement, one must rely on careful and repeated clinical observation to determine and maintain dry weight.

Blood Pressure↗
PubMed1996

Multifrequency bioimpedance in assessment of dry weight in haemodialysis.

The use of multifrequency bioimpedance (MFB) for determination of dry weight (DW) in haemodialysis (HD) patients was evaluated in three studies. In Study 1, the fluid state [total body water (TBW) and extracellular volume (ECV)] was measured by MFB in 82 normotensive patients. 41 hypertensive patients and in 30 healthy subjects. TBW and ECV were expressed as per cent of body weight (BW). In Study 2, DW of five hypertensive HD patients was gradually decreased during 3 months and ECV (MFB) and blood pressure (48 h ambulatory blood pressure monitoring) were measured at the beginning and end of study. In Study 3, we measured the fluid status repeatedly by MFB and the diameter of the inferior vena cava (DIVC) by ultrasound before, during and 2 h post-HD. In Study 1, the hypertensive patients had significantly greater TBW (P < 0.05) than the normotensive patients before (50.3 +/- 6.5% vs 47.6 +/- 5.8%) and after HD (48.8 +/- 7.8% vs 45.7 +/- 6.4%) and ECV (P < 0.001) before (29.4 +/- 3.6% vs 26.8 +/- 3.5%) and after HD (27.0 +/- 4.0% vs 24.6 +/- 3.5%), Post-HD ECV in the normotensive patients was similar to that in the healthy subjects. In Study 2, more efficient ultrafiltration resulted in reduction of BW and ECV along with a decrease in blood pressure and need for antihypertensive medication. In Study 3, both ECV and DIVC decreased following the removal of fluid during HD. ECV maintained stable values during the post-HD period, unlike DIVC which increased significantly (P < 0.005) due to refilling from the interstitial space. We conclude that MFB is an appropriate non-invasive method for DW determination, which is highly reproducible and technically simple to use.

Adult↗
PubMed1996

In situ demonstration of germinal cell apoptosis during diethylstilbestrol-induced testis regression in adult male Syrian hamsters.

Testis regression was induced in male Syrian hamsters by chronic exposure to diethylstilbestrol (DES), and estradiol-17 beta agonist. Experimental groups (n = 4-5) were killed at increasing time intervals over a period of 6 mo after initiation of treatment. Apoptosis in testes was demonstrated by in situ analysis of DNA fragmentation. Cell proliferation was monitored by immunostaining nuclei of S-phase cells after pulse labeling with 5-bromo-2'-deoxyuridine. Levels of FSH and testosterone, measured by RIA fell rapidly in DES-treated hamsters. In parallel, testis weight and seminiferous tubule area underwent an 80% decrease during the first 2 wk of DES administration. The composition of seminiferous epithelium was also drastically affected by DES, since it became progressively confined to Sertoli cells, spermatogonia, and spermatocytes. Testis regression was associated with an important increase of apoptosis, which started 3 days after the beginning of DES administration. Apoptosis was still 10- to 50-fold higher than in control testes by the end of treatment; it affected primarily spermatocytes and, to a much lesser extent, spermatogonia. Cell proliferation was not inhibited by chronic DES administration. In conclusion, these data indicate that apoptosis can by itself account for estrogen-induced testis regression.

Animals↗
PubMed1996

Importance of treatment time and blood pressure control in achieving long-term survival on dialysis.

A drastic reduction in hemodialysis (HD) time has been based on the dialysis dose measurement in terms of urea Kt/V exclusively and on the use of high efficiency dialysers. It was subtly coupled to a de-emphasis of the use of HD to normalize blood pressure. In Tassin we have maintained long slow HD with an overall excellent patient survival. We analyze the influence of the different factors of this survival: the place of dry weight and blood pressure control without use of antihypertensive medication is emphasized, and the role of dialysis dose and nutrition is discussed. Adequacy should be defined in terms of these additive conditions. Long slow HD allows one to fulfill these conditions easily. Shortening of dialysis time should not interfere with the control of blood pressure.

Adult↗
PubMed1996

Vincristine degradation by serum from leukemic patients: role of myeloperoxidase.

Myeloperoxidase (MPO) has been shown to catalyze the in vitro degradation of vincristine (VCR). Given that MPO is a lysosomal enzyme that can be released into the circulation by both normal activated and leukemic myeloid cells, we investigated the possibility that sera from patients with acute myeloblastic leukemia (AML) might exhibit an increased capacity to degrade VCR. 31 serum samples (23 from patients with acute myeloblastic leukemia and 8 from patients with other conditions) were analyzed after incubation with ((3)H)VCR by using HPLC. Sera from patients with AML demonstrated an increased ability to breakdown VCR when compared to either normal sera or to sera from patients with lymphoid leukemias. VCR degradation was significantly increased by adding hydrogen peroxide, an electron donor for MPO, to the sera and was almost completely inhibited by adding 1 mM acetaminophen, an inhibitor of MPO. VCR peroxidation in the presence of hydrogen peroxide correlated both with the number of leukemic blasts in the circulation at the time the sera were obtained and with serum MPO concentrations determined by an immunoassay. These data suggest that the inactivity of VCR in AML may be due in part to its rapid peroxidation to inactive species by the MPO of leukemic myeloblasts.

Acetaminophen↗
PubMed1996

Bcl-x gene expression in Hodgkin's disease.

Bcl-x is a Bcl-2-family protein that has been previously detected in cortical thymocytes, plasma cells, and activated lymphocytes. We report here on the high detection rate of the Bcl-x protein found in 86% of Hodgkin's disease samples and on the significance regarding its complex role among the Bcl-2-family of proteins: Bcl-x is known to heterodimerize with Bcl-2 (an anti-apoptosis protein) and with Bax, a potent inducer of cell death. Moreover, recent evidences show that Bcl-x may induce multiple drug resistance in vitro, suggesting that chemical or biological interactions with this protein may have potential therapeutic value in Hodgkin's disease.

Apoptosis↗
PubMed1996

DNA repair activity in protein extracts of fresh human malignant lymphoid cells.

Nucleotide excision repair (NER) activity was investigated in lymphocytes from patients with chronic lymphocytic leukemia (CLL). The NER process consists of two broad stages: incision/excision of the damaged oligonucleotide and resynthesis of the repair patch. NER in CLL lymphocytes was monitored with the use of in vitro biochemical assays, allowing the determination of either the extent of repair synthesis or the incision activity on damaged plasmid DNA during incubation with whole-cell protein extracts. Fresh CLL tumor cells were purified from the blood of 7 untreated patients and 11 patients who had been treated with chemotherapy. No repair activity was found in 14 extracts (7 treated and 7 untreated) or in normal blood peripheral lymphocytes. The defect was at the level of both repair synthesis and incision/excision activity of DNA damage. In contrast, 4 of the extracts exhibited 25-60% of the repair activity measured in an extract from a control repair-proficient cell line. A linear relationship was found between the values of DNA-repair synthesis and incision activities, which indicates that the extent of significant incision was the limiting factor in these protein extracts. All of the extracts that exhibited DNA-repair activity were purified from lymphocytes of treated patients. These data suggest that chemotherapy might exert an effect on the status of repair activity in the lymphoid tumor cells of patients.

Aged↗
PubMed1996

Daunorubicin-induced internucleosomal DNA fragmentation in acute myeloid cell lines.

The study was designed to evaluate the implication of apoptosis in myeloid leukemic cell death induced by daunorubicin (DNR) and to identify the possible factors which may influence this process. DNR-induced apoptosis was characterized by morphology and DNA fragmentation in six leukemic myeloid cell lines which expressed different differentiation phenotypes. In phenotypically mature HL-60 and U937 cells, DNR induced typical apoptosis with characteristic morphological changes and intense internucleosomal DNA fragmentation within a narrow concentration range (0.5-2 microM). When these cells were treated with higher doses of DNR, large DNA fragments (100 kbp), but not internucleosomal fragments, were identified. DNR-induced DNA fragmentation in HL-60 and U937 was inhibited by antioxidants such as N-acetylcysteine (N-ac) or pyrrolidine-dithiocarbamate (PDTC). In the phenotypically immature KG1a, KG1, HEL and ML1 cell lines DNR induced no characteristic apoptotic morphological features as well as very low levels of internucleosomal DNA fragmentation, whereas large DNA fragments (200 kbp) were observed in KG1a treated with 7 microM DNR. Since the latter expressed P-glycoprotein (P-gp), the role of P-gp in the lack of apoptotic response to DNR was investigated. One P-gp inhibitor (verapamil) slightly improved DNR-induced DNA fragmentation in KG1a cells whereas the combination of verapamil and buthionine-sulfoximine (BSO), which depletes glutathion store, further increased internucleosomal DNA fragmentation. In conclusion, DNR induced internucleosomal DNA fragmentation in some but not all AML cells; the magnitude of this process being influenced by both intracellular drug concentration and oxidative balance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗