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P Lefèvre

Publications and source records attributed to P Lefèvre.

At least 19 recordsLinked to original sources
PubMed2006

Influence of cognitive expectation on the initiation of anticipatory and visual pursuit eye movements in the rhesus monkey.

A classic paradigm to study anticipatory pursuit consists in training monkeys to look at a target that appears in the center of a visual display, disappears during a short "gap" period, then reappears and immediately starts to move. To determine the role of prior directional information on anticipatory pursuit eye movements, we trained rhesus monkeys to associate the color of a centrally presented visual cue with the direction of an upcoming target motion. In a first experiment, a gap period occurred randomly in 50% of the trials. Consequently, two possible choices of timing of target motion onset were given to subjects to guide their anticipatory responses. In a second experiment, a gap period occurred during each trial and only a single choice of timing of target motion onset was given to subjects. We found that monkeys used the learned association between the color of the cue and the direction of future target motion to voluntarily initiate anticipatory pursuit movements in the appropriate direction. Anticipatory movements could be classified in two distinct populations: early and late movements. Early movements were most frequent when prior directional information was provided and when two choices of timing of target motion onset were given. The latency of visual pursuit was shortened and its velocity was larger when prior directional information was provided. We conclude that cognitive expectation of future target motion plays a dominant role in determining characteristics of anticipatory pursuit in the monkey.

Animals↗
PubMed2004

Antimycobacterial activity of synthetic pamamycins.

OBJECTIVES: Early studies have indicated that pamamycins, a group of macrodiolides first isolated from Streptomyces alboniger, have potent antimicrobial activity against Gram-positive bacteria, fungi and mycobacteria but not against Gram-negative bacteria. The recent availability of highly purified and reasonable quantities of several pamamycins through their total syntheses has rendered possible more extensive studies on their effects on mycobacteria. METHODS: Bioluminescent strains of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis, expressing the luxA and luxB genes from Vibrio harveyi were used for the comparison of the antimycobacterial activity of the two synthetic macrodiolides pamamycin-607 and pamamycin-621A and a non-naturally occurring cyclic dimer of pamamycin-607, i.e. yukomycin. RESULTS: Pamamycin-607 was the most active of the three macrocycles and was more active against M. tuberculosis than against M. smegmatis. Twenty-five clinical isolates of M. tuberculosis were susceptible to pamamycin-607 in a narrow MIC range of 1.5-2.0 mg/L. The new assay was also validated by comparison with the BACTEC radiometric test. CONCLUSION: Rapid screening of a new class of macrocyclic antimycobacterials using bioluminescent mycobacteria identified pamamycin-607 as a potential antituberculous agent. The latter was active against clinical isolates of M. tuberculosis within a narrow MIC range of 1.5-2.0 mg/L irrespective of their resistance to isoniazid or rifampicin. Our findings warrant further investigations.

Anti-Bacterial Agents↗
PubMed2002

Further evidence that a shared efferent collicular pathway drives separate circuits for smooth eye movements and saccades.

The aim of the present study was to find out whether smooth eye movements (SEMs) evoked by superior colliculus (SC) stimulation are, as suggested by Breznen et al. (1996), artefactual eye movements resulting from a non-physiological response of the saccadic generator. This question was reinvestigated in head-restrained cats. Long-lasting SC stimulation was found to evoke, in a comparable proportion, either a single saccade followed by an uninterrupted SEM or a staircase of two or three saccades interleaved with SEMs. These two different patterns of eye movements could be elicited at a near-threshold current and at low stimulation frequencies. In most cases, SEM direction clearly differed from that of the preceding saccade. This difference between SEM and saccade directions varied in a systematic way as a function of the initial saccade direction. As demonstrated by computer simulation, this observation can be explained if the neural circuit controlling SEMs reaches a saturation level earlier than the saccadic burst-generator. Our results in cats were reminiscent of those reported by Breznen et al. (1996) in the monkey only in some instances, when high frequency stimulation (400-600 Hz) was applied. Indeed, in the case of near-threshold stimulation-elicited staircase saccades, increasing the stimulation frequency led to a progressive disappearance of the smaller subsequent saccades that were substituted by uninterrupted SEM-like movements. Altogether, the present results confirm the view that SEMs are genuine eye movements. These results rule out the hypothesis that SEMs result from a saturation of the saccadic generator and strengthen the hypothesis that SEMs and saccades are distinct movements. We suggest that the same collicular efferent cells carry out the motor command to saccadic and SEM circuits and that the position error originating from the SC may be distributed amongst separate downstream motor systems.

Animals↗
PubMed2002

A quantitative analysis of the correlations between eye movements and neural activity in the pretectum.

The study of the saccadic system has focused mainly on neurons active before the beginning of saccades, in order to determine their contribution in movement planning and execution. However, most oculomotor structures contain also neurons whose activity starts only after the onset of saccades, the maximum of their activity sometimes occurring near saccade end. Their characteristics are still largely unknown. We investigated pretectal neurons with saccade-related activity in the alert cat during eye movements towards a moving target. They emitted a high-frequency burst of action potentials after the onset of saccades, irrespective of their direction, and will be referred to as "pretectal saccade-related neurons". The delay between saccade onset and cell activity varied from 17 to 66 ms on average. We found that burst parameters were correlated with the parameters of saccades; the peak eye velocity was correlated with the peak of the spike density function, the saccade amplitude with the number of spikes in the burst, and burst duration increased with saccade duration. The activity of six pretectal saccade-related neurons was studied during smooth pursuit at different velocities. A correlation was found between smooth pursuit velocity and mean firing rate. A minority of these neurons (2/6) were also visually responsive. Their visual activity was proportional to the difference between eye and target velocity during smooth pursuit (retinal slip). These results indicate that the activity of pretectal saccade-related neurons is correlated with the characteristics of eye movements. This finding is in agreement with the known anatomical projections from premotor regions of the saccadic system to the pretectum.

Action Potentials↗
PubMed2001

Role of retinal slip in the prediction of target motion during smooth and saccadic pursuit.

Visual tracking of moving targets requires the combination of smooth pursuit eye movements with catch-up saccades. In primates, catch-up saccades usually take place only during pursuit initiation because pursuit gain is close to unity. This contrasts with the lower and more variable gain of smooth pursuit in cats, where smooth eye movements are intermingled with catch-up saccades during steady-state pursuit. In this paper, we studied in detail the role of retinal slip in the prediction of target motion during smooth and saccadic pursuit in the cat. We found that the typical pattern of pursuit in the cat was a combination of smooth eye movements with saccades. During smooth pursuit initiation, there was a correlation between peak eye acceleration and target velocity. During pursuit maintenance, eye velocity oscillated at approximately 3 Hz around a steady-state value. The average gain of smooth pursuit was approximately 0.5. Trained cats were able to continue pursuing in the absence of a visible target, suggesting a role of the prediction of future target motion in this species. The analysis of catch-up saccades showed that the smooth-pursuit motor command is added to the saccadic command during catch-up saccades and that both position error and retinal slip are taken into account in their programming. The influence of retinal slip on catch-up saccades showed that prediction about future target motion is used in the programming of catch-up saccades. Altogether, these results suggest that pursuit systems in primates and cats are qualitatively similar, with a lower average gain in the cat and that prediction affects both saccades and smooth eye movements during pursuit.

Animals↗
PubMed2000

What are the immunologically active components of bacille Calmette-Guérin in therapy of superficial bladder cancer?

The subcomponents of bacille Calmette-Guérin (BCG) involved in the mechanism of action of intravesical BCG immunotherapy used for prophylaxis of superficial bladder cancer recurrences have been poorly investigated. We purified various BCG subcomponents and analyzed in vitro their ability to enhance a Th1 polarized immune response as well as to increase lymphocyte-mediated cytotoxicity against bladder tumors. Human peripheral blood mononuclear cells (PBMCs) from healthy purified protein derivative-positive subjects were incubated for 7 days with whole BCG and various fractions (BCG cell wall, plasma membrane, cytosol, purified polysaccharides as glucan or arabinomannan, purified native proteins from BCG culture filtrate, recombinant 22 kDa protein, phosphate transporter PstS-2 and -3 proteins). IFN-gamma, IL-12, IL-2, and IL-6 production by stimulated PBMCs was compared to unstimulated controls and the phenotype of expanded cells analyzed by flow cytometry (FACS analysis). A (51)Cr-release assay monitored the cytotoxicity of amplified effector cells against T24 bladder tumor cells. Live BCG and most of its subcomponents (with the exception of cytosol, PstS-2 and -3) significantly enhanced IFN-gamma and IL-12 secretion, expanded CD3(-)CD56(+) cells and the non-MHC-restricted cytotoxicity against bladder tumor cells compared to unstimulated controls (all P < 0.001, t-test). IL-2 receptor blockage resulted in a clear reduction in the cytotoxic activity of stimulated PBMCs. Numerous BCG subcomponents thus provide positive stimuli for Th1 cell differentiation and enhance in vitro, non-MHC-restricted cytotoxicity against bladder tumor cells. Our findings provide the basis for the therapeutic use of several of these subfractions in experimental animal models bearing bladder tumors.

Antigens, Bacterial↗
PubMed2000

Stearoyl-CoA desaturase 1 coding sequences and antisense RNA affect lipid secretion in transfected chicken LMH hepatoma cells.

Hepatic stearoyl CoA desaturase (SCD) activity in chickens from a fat line is higher than that of chickens from a lean line and correlates with plasma triacylglycerol concentrations. Furthermore, in these lines, the hepatic SCD1 mRNA level is positively correlated with the adipose tissue weight. To analyze the contribution of the SCD1 gene in the regulation of adiposity in the early stages of triacylglycerol secretion, SCD1 coding sequence and antisense RNA expression vectors were transfected in LMH cells. After selection, these cells were analyzed with regard to SCD1 expression and lipid secretion. The amounts of secreted triacylglycerols and phospholipids were shown to be higher in LMH cells transfected with the SCD1 gene, but reduced in those transfected with the SCD1 antisense sequences when compared to cells transfected with the vector alone (without SCD1 sequences). These results provide direct evidence that the expression of the SCD1 gene plays a major role in the triacylglycerol and phospholipid secretion process.

Animals↗
PubMed2000

[Idiopathic thrombotic thrombocytopenic purpura or Moschowitz syndrome: current physiopathologic and therapeutic perspectives].

INTRODUCTION: The objective of this work was to review current data about the physiopathology, clinical features, and treatment of thrombotic thrombocytopenic purpura (Moschowitz's syndrome). CURRENT KNOWLEDGE AND KEY POINTS: Thrombotic thrombocytopenic purpura is a rare disorder characterized by widespread thrombotic injuries of platelets in the microcirculation. Its physiopathology has been elucidated recently. Evidence of a deficiency of Von Willebrand's factor-cleaving protease would be due to either IgG antibodies in the acute form of the disease or constitutional deficiency in the chronic form of the disease. FUTURE PROSPECTS AND PROJECTS: Plasma exchange is the current reference treatment. However, in the light of recent publications, either infusions of concentrates of purified enzyme or more intensive immunosuppressive therapy would be more specific.

ADAM Proteins↗
PubMed2000

Mycobacterium intracellulare as a cause of a recurrent granulomatous tenosynovitis of the hand.

We report a case of recurrent granulomatous tenosynovitis with M. intracellulare in a 55-year-old HIV negative diabetic woman. Identification of the causative agent further than belonging to the M. avium-intracellulare complex is provided by specific PCR-amplification of genomic DNA and sequencing of an hypervariable region within its 16S RNA gene. Sixteen months antibiotic regimen of rifabutin and clarithromycin led to a complete resolution of the tenosynovitis.

Female↗
PubMed2000

Cloning of the gene encoding a 22-kilodalton cell surface antigen of Mycobacterium bovis BCG and analysis of its potential for DNA vaccination against tuberculosis.

Using spleen cells from mice vaccinated with live Mycobacterium bovis BCG, we previously generated three monoclonal antibodies reactive against a 22-kDa protein present in mycobacterial culture filtrate (CF) (K. Huygen et al., Infect. Immun. 61:2687-2693, 1993). These monoclonal antibodies were used to screen an M. bovis BCG genomic library made in phage lambdagt11. The gene encoding a 233-amino-acid (aa) protein, including a putative 26-aa signal sequence, was isolated, and sequence analysis indicated that the protein was 98% identical with the M. tuberculosis Lppx protein and that it contained a sequence 94% identical with the M. leprae 38-mer polypeptide 13B3 recognized by T cells from killed M. leprae-immunized subjects. Flow cytometry and cell fractionation demonstrated that the 22-kDa CF protein is also highly expressed in the bacterial cell wall and membrane compartment but not in the cytosol. C57BL/6, C3H, and BALB/c mice were vaccinated with plasmid DNA encoding the 22-kDa protein and analyzed for immune response and protection against intravenous M. tuberculosis challenge. Whereas DNA vaccination induced elevated antibody responses in C57BL/6 and particularly in C3H mice, Th1-type cytokine response, as measured by interleukin-2 and gamma interferon secretion, was only modest, and no protection against intravenous M. tuberculosis challenge was observed in any of the three mouse strains tested. Therefore, the 22-kDa antigen seems to have little potential for a DNA vaccine against tuberculosis, but it may be a good candidate for a mycobacterial antigen detection test.

Animals↗
PubMed2000

Difference between visually and electrically evoked gaze saccades disclosed by altering the head moment of inertia.

Differences between gaze shifts evoked by collicular electrical stimulation and those triggered by the presentation of a visual stimulus were studied in head-free cats by increasing the head moment of inertia. This maneuver modified the dynamics of these two types of gaze shifts by slowing down head movements. Such an increase in the head moment of inertia did not affect the metrics of visually evoked gaze saccades because their duration was precisely adjusted to compensate for these changes in movement dynamics. In contrast, the duration of electrically evoked gaze shifts remained constant irrespective of the head moment of inertia, and therefore their amplitude was significantly reduced. These results suggest that visually and electrically evoked gaze saccades are controlled by different mechanisms. Whereas the accuracy of visually evoked saccades is likely to be assured by on-line feedback information, the absence of duration adjustment in electrically evoked gaze shifts suggests that feedback information necessary to maintain their metrics is not accessible or is corrupted during collicular stimulation. This is of great importance when these two types of movements are compared to infer the role of the superior colliculus in the control of orienting gaze shifts.

Animals↗
PubMed2000

Activity of mesencephalic vertical burst neurons during saccades and smooth pursuit.

The activity of vertical burst neurons (BNs) was recorded in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF-BNs) and in the interstitial nucleus of Cajal (NIC-BNs) in head-restrained cats while performing saccades or smooth pursuit. BNs emitted a high-frequency burst of action potentials before and during vertical saccades. On average, these bursts led saccade onset by 14 +/- 4 ms (mean +/- SD, n = 23), and this value was in the range of latencies ( approximately 5-15 ms) of medium-lead burst neurons (MLBNs). All NIC-BNs (n = 15) had a downward preferred direction, whereas riMLF-BNs showed either a downward (n = 3) or an upward (n = 5) preferred direction. We found significant correlations between saccade and burst parameters in all BNs: vertical amplitude was correlated with the number of spikes, maximum vertical velocity with maximum of the spike density, and saccade duration with burst duration. A correlation was also found between instantaneous vertical velocity and neuronal activity during saccades. During fixation, all riMLF-BNs and approximately 50% of NIC-BNs (7/15) were silent. Among NIC-BNs active during fixation (8/15), only two cells had an activity correlated with the eye position in the orbit. During smooth pursuit, most riMLF-BNs were silent (7/8), but all NIC-BNs showed an activity that was significantly correlated with the eye velocity. This activity was unaltered during temporary disappearance of the visual target, demonstrating that it was not visual in origin. For a given neuron, its ON-direction during smooth pursuit and saccades remained identical. The activity of NIC-BNs during both saccades and smooth pursuit can be described by a nonlinear exponential function using the velocity of the eye as independent variable. We suggest that riMLF-BNs, which were not active during smooth pursuit, are vertical MLBNs responsible for the generation of vertical saccades. Because NIC-BNs discharged during both saccades and pursuit, they cannot be regarded as MLBNs as usually defined. NIC-BNs could, however, be the site of convergence of both the saccadic and smooth pursuit signals at the premotoneuronal level. Alternatively, NIC-BNs could participate in the integration of eye velocity to eye position signals and represent input neurons to a common integrator.

Action Potentials↗
PubMed1999

Characterization of a Mycobacterium bovis BCG insertion sequence related to the IS21 family.

The structure and distribution of a Mycobacterium bovis BCG insertion element of the IS21 family were investigated. Several IS21-like elements found in mycobacterial genomes were separated in four types, following their nucleic acid similarities. The M. bovis BCG IS21 element is highly similar to IS1533 (class I), 70% similar to IS1534 (class II), 52% similar to IS1532 (class III) of Mycobacterium tuberculosis, and 54% similar to both an Mycobacterium avium serovar 2 and an M. avium silvaticum IS (class IV). The M. bovis BCG IS21 element of the class I appears to be present in a single copy in the genome of M. bovis BCG, M. bovis, M. tuberculosis and Mycobacterium africanum and to be absent from all other tested species of the Corynebacteria-Mycobacteria-Nocardia group.

Amino Acid Sequence↗
PubMed1999

Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding putative phosphate transport receptors.

Using culture filtrate Ag-specific mAbs generated from mycobacteria-infected H-2b haplotype mice, we have previously identified three genes in the Mycobacterium tuberculosis genome, encoding proteins homologous to the periplasmic ATP-binding cassette phosphate-binding receptor PstS of the phosphate-specific transport system of E. coli. To define the potential vaccinal properties of these phosphate-binding proteins, female C57BL/6 mice were injected i.m. with plasmid DNA encoding PstS-1, PstS-2, or PstS-3 proteins from M. tuberculosis and immunogenicity and protective efficacy against i.v. challenge with M. tuberculosis H37Rv was analyzed. Significant levels of highly Ag-specific Abs and Th1-type cytokines IL-2 and IFN-gamma could be detected following vaccination with each of the three genes. However, only mice vaccinated with PstS-3 DNA demonstrated significant and sustained reduction in bacterial CFU numbers in spleen and lungs for 3 mo after M. tuberculosis challenge, as compared with CFU counts in mice vaccinated with control DNA. Vaccination with PstS-2 DNA induced a modest reduction in CFU counts in spleen only, whereas vaccination with PstS-1 DNA was completely ineffective in reducing bacterial multiplication. In conclusion, our results indicate that DNA vaccination is a powerful and easy method for comparative screening of potentially protective Ags from M. tuberculosis and that the PstS-3 protein is a promising new subunit vaccine candidate.

ATP-Binding Cassette Transporters↗
PubMed1999

Model of the control of saccades by superior colliculus and cerebellum.

Experimental evidence indicates that the superior colliculus (SC) is important but neither necessary nor sufficient to produce accurate saccadic eye movements. Furthermore both clinical and experimental evidence points to the cerebellum as an indispensable component of the saccadic system. Accordingly, we have devised a new model of the saccadic system in which the characteristics of saccades are determined by the cooperation of two pathways, one through the SC and the other through the cerebellum. Both pathways are influenced by feedback information: the feedback determines the decay of activity for collicular neurons and the timing of the activation for cerebellar neurons. We have modeled three types of cells (burst, buildup, and fixation neurons) found in the intermediate layers of the superior colliculus. We propose that, from the point of view of motor execution, the burst neurons and the buildup neurons are not functionally distinct with both providing a directional drive to the brain stem circuitry. The fixation neurons determine the onset of the saccade by disfacilitating the omnipause neurons in the brain stem. Excluding noise-related variations, the ratio of the horizontal to the vertical components of the collicular drive is fixed throughout the saccade (i.e., its direction is fixed); the duration of the drive is such that it always would produce hypermetric movements. The cerebellum plays three roles: first, it provides an additional directional drive, which improves the acceleration of the eyes; second, it keeps track of the progress of the saccade toward the target; and third, it ends the saccade by choking off the collicular drive. The drive provided by the cerebellum can be adjusted in direction to exert a directional control over the saccadic trajectory. We propose here a control mechanism that incorporates a spatial displacement integrator in the cerebellum; under such conditions, we show that a partial directional control arises automatically. Our scheme preserves the advantages of several previous models of the saccadic system (e.g., the lack of a spatial-to-temporal transformation between the SC and the brain stem; the use of efference copy feedback to control the saccade), without incurring many of their drawbacks, and it accounts for a large amount of experimental data.

Action Potentials↗
PubMed1998

[Heparin-induced thrombopenia: rapid regression of thrombopenia and thrombosis after plasma exchange. Case report].

INTRODUCTION: Heparin-induced thrombocytopenia with thrombosis is a rare but severe adverse reaction to heparin therapy, whose management is difficult. After heparin withdrawal, the initiation of an alternative anticoagulant therapy, such as recombinant hirudin or danaparoid, is strongly recommended before vitamin K antagonists are effective. Several reports of the efficacity of plasma exchanges in patients with life-threatening thrombosis have been made. EXEGESIS: We report on a patient with severe aortic thrombosis related to heparin therapy in whom a unique plasma exchange resulted in both dramatic improvement in the platelet count and marked reduction of the thrombosis. CONCLUSION: This case provides further evidence that plasma exchanges can be useful in the management of heparin-induced thrombocytopenia with thrombosis. They are rapidly efficient and can be used before heparin alternative treatment is effective.

Anticoagulants↗