Biomedical subjects

L Petit

Publications and source records attributed to L Petit.

At least 55 records · Page 3Linked to original sources

PubMed1998

The role of prefrontal cortex in working memory: examining the contents of consciousness.

Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory.

Animals↗

PubMed1998

Sustained activity in the medial wall during working memory delays.

We have taken advantage of the temporal resolution afforded by functional magnetic resonance imaging (fMRI) to investigate the role played by medial wall areas in humans during working memory tasks. We demarcated the medial motor areas activated during simple manual movement, namely the supplementary motor area (SMA) and the cingulate motor area (CMA), and those activated during visually guided saccadic eye movements, namely the supplementary eye field (SEF). We determined the location of sustained activity over working memory delays in the medial wall in relation to these functional landmarks during both spatial and face working memory tasks. We identified two distinct areas, namely the pre-SMA and the caudal part of the anterior cingulate cortex (caudal-AC), that showed similar sustained activity during both spatial and face working memory delays. These areas were distinct from and anterior to the SMA, CMA, and SEF. Both the pre-SMA and caudal-AC activation were identified by a contrast between sustained activity during working memory delays as compared with sustained activity during control delays in which subjects were waiting for a cue to make a simple manual motor response. Thus, the present findings suggest that sustained activity during working memory delays in both the pre-SMA and caudal-AC does not reflect simple motor preparation but rather a state of preparedness for selecting a motor response based on the information held on-line.

Adult↗

PubMed1998

An area specialized for spatial working memory in human frontal cortex.

Working memory is the process of maintaining an active representation of information so that it is available for use. In monkeys, a prefrontal cortical region important for spatial working memory lies in and around the principal sulcus, but in humans the location, and even the existence, of a region for spatial working memory is in dispute. By using functional magnetic resonance imaging in humans, an area in the superior frontal sulcus was identified that is specialized for spatial working memory. This area is located more superiorly and posteriorly in the human than in the monkey brain, which may explain why it was not recognized previously.

Animals↗

PubMed1998

Reopening the mental imagery debate: lessons from functional anatomy.

Over the past few years, the neural bases of mental imagery have been both a topic of intense debate and a domain of extensive investigations using either PET or fMRI that have provided new insights into the cortical anatomy of this cognitive function. Several studies have in fact demonstrated that there exist types of mental imagery that do not rely on primary/early visual areas, whereas a consensus now exists on the validity of the dorsal/ventral-route model in the imagery domain. More importantly, these studies have provided evidence that, in addition to higher order visual areas, mental imagery shares common brain areas with other major cognitive functions, such as language, memory, and movement, depending on the nature of the imagery task. This body of recent results indicates that there is no unique mental imagery cortical network; rather, it reflects the high degree of interaction between mental imagery and other cognitive functions.

Brain Mapping↗

PubMed1998

[Structure and function of melatonin receptors].

Melatonin receptors belong to the super-family of G protein-coupled receptors. They modulate a large spectrum of physiological functions including regulation of circadian rhythms and seasonal reproduction. Pharmacological evidence suggests the expression of two types of receptors, called Mel1 and Mel2. So far, only Mel1 receptors have been cloned and classified into three subtypes (Mel1A, Mel1B, Mel1C). Mel1 receptors are expressed in the brain, the retina and several other peripheral tissues. All Mel1 subtypes show comparable pharmacological profiles including inhibition of adenylyl cyclase. Cloning and expression of two allelic isoforms of the Mel1 receptor from Xenopus laevis has revealed another signalling pathway, inhibition of cGMP levels via the soluble guanylyl cyclase pathway. The two isoforms are differentially coupled to the cAMP and cGMP pathways indicating the existence of functional differences between melatonin receptors. Future research topics will include cloning of the Mel2 receptor, receptor regulation and the elucidation of melatonin receptor's function in peripheral tissues.

Adenylyl Cyclases↗

PubMed1997

Clostridium perfringens epsilon-toxin acts on MDCK cells by forming a large membrane complex.

Epsilon-toxin is produced by Clostridium perfringens types B and D and is responsible for a rapidly fatal enterotoxemia in animals, which is characterized by edema in several organs due to an increase in blood vessel permeability. The Madin-Darby canine kidney (MDCK) cell line has been found to be susceptible to epsilon-toxin (D. W. Payne, E. D. Williamson, H. Havard, N. Modi, and J. Brown, FEMS Microbiol. Lett. 116:161-168, 1994). Here we present evidence that epsilon-toxin cytotoxic activity is correlated with the formation of a large membrane complex (about 155 kDa) and efflux of intracellular K+ without entry of the toxin into the cytosol. Epsilon-toxin induced swelling, blebbing, and lysis of MDCK cells. Iodolabeled epsilon-toxin bound specifically to MDCK cell membranes at 4 and 37 labeled C and was associated with a large complex (about 155 kDa). The binding of epsilon-toxin to the cell surface was corroborated by immunofluorescence staining. The complex formed at 37 degrees C was more stable than that formed at 4 degrees C, since it was not dissociated by 5% sodium dodecyl sulfate and boiling.

Animals↗

PubMed1997

Dissociation of saccade-related and pursuit-related activation in human frontal eye fields as revealed by fMRI.

The location of the human frontal eye fields (FEFs) underlying horizontal visually guided saccadic and pursuit eye movements was investigated with the use of functional magnetic resonance imaging in five healthy humans. Execution of both saccadic and pursuit eye movements induced bilateral FEF activation located medially at the junction of the precentral sulcus and the superior frontal sulcus and extending laterally to the precentral gyrus. These findings extend previous functional imaging studies by providing the first functional imaging evidence of a specific activation in the FEF during smooth pursuit eye movements in healthy humans. FEF activation during smooth pursuit performance was smaller than during saccades. This finding, which may reflect the presence of a smaller pursuit-related region area in human FEF than the saccade-related region, is consistent with their relative size observed in the monkey. The mean location of the pursuit-related FEF was more inferior and lateral than the location of the saccade-related FEF. These results provide the first evidence that there are different subregions in the human FEF that are involved in the execution of two different types of eye movements, namely saccadic and pursuit eye movements. Moreover, this study provides additional evidence that the human FEF is located in Brodmann's area 6, unlike the monkey FEF which is located in the posterior part of Brodmann's area 8.

Adult↗

PubMed1997

Impact of a combination of a calcium antagonist and a beta-blocker on cell- and copper-mediated oxidation of LDL and on the accumulation and efflux of cholesterol in human macrophages and murine J774 cells.

Calcium antagonists and beta-blockers may retard or inhibit atherogenesis. In the absence of data pertaining to the potential cardioprotective action of an association of such agents, we have investigated the impact of nifedipine and atenolol, alone or in combination, on the capacity of monocyte-macrophages (ex vivo) and copper ions (in vitro) to oxidize LDL and on intracellular metabolism and efflux of free and esterified forms of cholesterol in human macrophages and foam cells. At concentrations up to 100 micromol/L, atenolol had no effect on the oxidative resistance of LDL; on the contrary, nifedipine displayed a significant dose-dependent capacity to protect LDL during copper-mediated oxidation (100 micromol/L; P<.001). Using a DPPH radical generating system, nifedipine was shown to exert free radical-trapping activity (molar ratio of scavenging activity, nifedipine:alpha-tocopherol, 1:114). The addition of atenolol to nifedipine was without effect on the antioxidant activity of the calcium antagonist. In experiments in which oxidative modification was mediated by monocyte-macrophages, nifedipine but not atenolol conserved its antioxidant capacity. Furthermore, we demonstrated that association of atenolol with nifedipine did not modify the antioxidant properties of nifedipine itself. Using a human monocyte-derived macrophage culture system, nifedipine, atenolol, or a combination of the two drugs was ineffective in inhibiting foam cell formation induced by acetylated LDL or oxidized LDL. However, atenolol (100 micromol/L) increased cellular accumulation of cholesteryl ester (+17%; P<.05), whereas nifedipine (100 micromol/L) decreased total cholesterol (-37.4%; P<.05) accumulation induced by acetylated LDL in the mouse macrophage cell line J774. A combination of the two drugs neutralized these antagonistic effects. None of these results were reproduced during the oxidized LDL-induced transformation of murine J774 cells into foam cells. Furthermore, cholesterol efflux from preloaded human macrophages was equally unaffected by the addition of the drugs alone or in combination. It therefore seems unlikely that the beneficial effect of atenolol on coronary heart disease is mediated by changes in either LDL oxidizability or cholesterol metabolism in human macrophages and foam cells. Our findings with nifedipine suggest, however, that this calcium antagonist may potentially exert antiatherosclerotic properties via a reduction of the oxidative modification of LDL, thereby affecting a reduction in foam cell formation and in the pathophysiological cellular activities of oxidized lipids, rather than by inducing a direct reduction in cholesterol accumulation in human foam cells of macrophage origin.

Adrenergic beta-Antagonists↗

PubMed1997

Novel isoforms of Mel1c melatonin receptors modulating intracellular cyclic guanosine 3',5'-monophosphate levels.

Two cDNAs encoding novel isoforms of Xenopus laevis melatonin receptors were cloned using PCR primers specific for the X. laevis-melanophore Mel1c melatonin receptor described in a recent publication. The novel isoforms were highly homologous to the described frog Mel1c cDNA, although the C-terminal tail of both was shorter by 65 amino acid residues. Nucleotide sequences of these novel isoforms, called Mel1c(alpha) and Mel1c(beta), differed from each other by only 35 nucleotides and six amino acid residues. Studies on several animals of various Xenopus species indicate that Mel1c(alpha) and Mel1c(beta) receptors may correspond to allelic variants of the same locus. Studies on cells transfected with both receptor cDNAs showed the expression of high-affinity 2-[125I]iodomelatonin binding sites. Agonist stimulation of Mel1c(alpha) receptor was associated with the inhibition of cAMP accumulation stimulated by forskolin (IC50 approximately 10(-10) M) in HeLa, Ltk-, and human embryonic kidney 293 (HEK 293) cells. Mel1c(beta) receptor modulated cAMP in HeLa and HEK 293 cells but not in Ltk- cells. Both receptors inhibited, in a dose-dependent manner, cGMP accumulation in all three cell lines incubated with a phosphodiesterase inhibitor. This effect was localized upstream of soluble guanylyl cyclase and was blocked by pertussis toxin treatment. However, IC50 values (approximately 10(-10) M for Mel1c(beta) and 10(-9) to 10(-7) M for Mel1c(alpha)) and maximal inhibition levels showed that Mel1c(alpha) receptors are much less efficiently coupled to the cGMP pathway. Coupling differences may be explained by the fact that five of the six amino acid substitutions between Mel1c(alpha) and Mel1c(beta) receptors are located within cytoplasmic regions potentially involved in signal transduction. The existence of coupling differences is in agreement with the observation that expression of both receptors is evolutionally conserved in native tissue. In conclusion, two novel, potentially allelic, isoforms of Xenopus Mel1c melatonin receptors display identical ligand-binding characteristics, but different potencies in modulating cAMP and cGMP levels through G(i)/G(o)-dependent pathways. Furthermore, to our knowledge, this study provides the first data on the modulation of intracellular cGMP levels by cloned melatonin receptors.

Adenylyl Cyclases↗

PubMed1996

Functional anatomy of a prelearned sequence of horizontal saccades in humans.

We have used positron emission tomography (PET) to study the functional anatomy of the repetition of a prelearned sequence of horizontal saccadic eye movements. Five subjects had to memorize a sequence of six successive horizontal saccades. The subjects were scanned in total darkness under three different conditions: at rest, during the execution of self-paced horizontal saccades, and while repeating a prelearned saccades sequence. The repetition of the prelearned saccades sequence led to specific normalized regional cerebral blood flow (NrCBF) increases at the depth of the superior frontal sulcus as well as at the rostral part of the supplementary motor area, whereas at the parietal level an important activation was observed in the intraparietal sulcus extending up to the precuneus. In addition, it was noticed that compared with the resting control condition, both oculomotor tasks activated a common set of cortical and subcortical areas. At the cortical level, this network was composed of the frontal eye fields, the supplementary eye fields, the median part of the cingulate gyrus, and the insula. At the subcortical level, the lenticular nucleus and the thalamus as well as the cerebellar vermis were activated consistently. A direct comparison of our results with those of other PET studies on spatial vision suggest that the dorsal visuospatial pathway could be extended toward the frontal premotor region. In such a scheme, visuospatial information computed in the intraparietal sulcus would be transmitted to the frontal premotor cortex to optimize a spatial-oriented behavior. This is consistent with the early proposal that perceptual and intentional components of spatial information are mediated through superior parietal and frontal areas, respectively.

Adult↗

PubMed1996

Combinatorial peptide libraries: robotic synthesis and analysis by nuclear magnetic resonance, mass spectrometry, tandem mass spectrometry, and high-performance capillary electrophoresis techniques.

Combinatorial peptide libraries are a new source of compounds from which a large number of pharmacological leads will emerge in the next few years. A large body of literature shows that this approach is of considerable interest in many areas of biological sciences for the search of enzyme substrates and inhibitors, of receptor agonists or antagonists, or of antigen sequences. Nevertheless, the analytical investigation of such complex mixtures as libraries which contain up to millions of individual molecules is still poorly documented. In this work, we present analytical solutions for their characterization. NMR and tandem mass spectrometry (MS/MS) can provide an in deep description of any type of combinatorial libraries, while MS and high-performance capillary electrophoresis can bring a rapid and overall information at the routine level, sufficient to ensure a first assessment of their composition. MS in the fast atom bombardment mode was used to describe the libraries O1X2X3X4X5 or O1X2X3X4 (Oi and Xi are fixed and random residue in position i, respectively). Advantage was taken of the high proton affinity of arginine and of its induction of charge remote fragmentation to interpret the MS spectra of whole libraries and neutral losses (MS/MS) in the model sublibraries ArgGlyX3X4 and NipValX3X4 (Nip,4-nitrophenylalanine). Two-dimensional NMR allowed the incorporation of the individual residues during synthesis to be tested in 24 sublibraries O1X2X3X4. While from the pharmacological point of view, impressive discoveries made with combinatorial peptide libraries have already been reported, our results show that they should be complemented by appropriate analytical tools, crucial for the proper characterization and exploitation of these libraries.

Amino Acid Sequence↗

PubMed1995

Functional neuroanatomy of the human visual fixation system.

The regional cerebral blood flow correlates of the active fixation of an imagined target were studied in five healthy humans using the positron emission tomography activation paradigm. The fixation task was contrasted to a passive control condition, both tasks being performed in total darkness. Blood flow increases were observed in the frontal eye fields and supplementary eye fields and in the median cingulate gyrus. We suggest that the network of these activated regions mediates the interactions between ocular fixation, eye movements and directed visual attention.

Adult↗

PubMed1995

[Quantification of aortic insufficiencies. Comparison between Doppler echocardiography and qualitative angiographic methods: apropos of a series of 60 consecutive patients].

Many doppler echocardiographic indices have been described for quantifying aortic regurgitation, posing the problem of the relative value of each. Therefore, the authors assessed the severity of aortic regurgitation in 60 consecutive patients (16 women and 44 men, mean age 56.7 years, range 7 to 84 years) by the four grades of Seller's classification with selective aortography. These results were compared with Doppler echocardiographic measurement of anterograde cardiac output (Qao), the pressure half time (PHT), diameter of the jet at its origin in M mode colour Doppler (DTM) and calculation of the regurgitant fraction (RF) by comparison of flow at the different cardiac orifices by a method previously described and validated in the author's laboratory with an interorifice correlation of 0.91 to 0.96 and confidence intervals at 95% of the order of 12%. The feasibility of doppler echocardiographic methods was good: 87.8% for PHT (58/66 patients), 90% for DTM (36/40 patients), 90.9% for Qao and RF (60/66 patients). The correlation with aortography was -0.65 (p < 0.01) for PHT; 0.91 (p < 0.01) for DTM, 0.80 (p < 0.01) for Qao and 0.92 (p < 0.005) for RF. However, there was a number of overlaps between Grades I and II and Grades III and IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

A positron emission tomography study of oculomotor imagery.

Focal increases of regional cerebral blood flow (rCBF) were measured by positron emission tomography in order to study the anatomo-functional analogies between imagined and executed saccadic eye movements. Oculomotor imagery was performed in the absence of overt eye movements. Compared with a control state the two conditions were associated with normalized rCBF increases in the median cingulate gyrus, and the supplementary and frontal eye fields of both hemispheres. Therefore in the human brain execution and mental imagery of eye movement appear to be functionally linked and mediated by a common network of frontal structures.

Adult↗

PubMed1994

[Quantification of mitral valve insufficiency by Doppler echocardiography. Correlation with cine-angiography in 60 patients].

Non-invasive quantification of mitral regurgitation remains a clinical problem. The aim of this study was to assess a new methodology of Doppler echocardiographic assessment of the mitral regurgitant fraction. The study included 60 patients (average age 61 years) in sinus rhythm with mitral regurgitation. The cardiac output was measured by Doppler echocardiography at four sites: the aortic, pulmonary and mitral rings and at the tips of the mitral leaflets by a method previously validated and published. Using the average of the aortic and pulmonary cardiac outputs on the hand and the mitral cardiac output on the other, it was possible to calculate the regurgitant fraction: (mean mitral flow-mean aortic/pulmonary flow)/mean mitral flow. This was correlated with the Sellers angiographic grades of regurgitation. The results confirm this validated procedure: the correlation of aortic and pulmonary flows was good: r = 0.94. This also held true for mitral flow at the two sites: r = 0.96. The correlation between the Doppler echocardiographic regurgitant fraction and the angiographic estimation of the severity of mitral regurgitation was good: r = 0.89. There was a statistically significant difference between the Doppler echocardiographic regurgitant fractions corresponding to Sellers Grades I, II and III mitral regurgitation (p = 0.0001). This study shows that Doppler echocardiographic measurements of blood flow at different orifices of the heart applied to the quantification of mitral regurgitation is a reliable method, the use of which, with strict methodological criteria, may be proposed in everyday clinical practice.

Adult↗

PubMed1993

PET study of voluntary saccadic eye movements in humans: basal ganglia-thalamocortical system and cingulate cortex involvement.

1. The purpose of this work was to explore the cortical and subcortical mechanisms underlying the execution of voluntary saccadic eye movements in humans. 2. Normalized regional cerebral blood flow (NrCBF) was measured using positron emission tomography (PET) and H2(15O) bolus intravenous injections in four right-handed healthy volunteers at rest and while performing self-paced voluntary horizontal saccadic eye movements in total darkness. 3. Magnetic resonance imaging of each subject's brain was matched to PET images, allowing the detection of activation in individually defined anatomic regions of interest. Cortical regions were drawn according to gyri limits; subcortical structures were also defined. 4. Self-paced saccadic eye movements elicited bilateral NrCBF increases in the lenticular nuclei, including putamen and globus pallidus, and in the thalamus. At the cortical level, we found bilateral NrCBF increases in the precentral gyrus, the superior part of the median frontal gyrus that corresponds to the supplementary motor area. There was also a significant NrCBF increase in the cerebellar vermis. 5. Right fusiform and lingual gyri, right insula, and left cingulate gyrus were also activated during the execution of saccades. 6. These results indicate that the classical basal ganglia-thalamocortical motor loop previously described for skeletal movements may also be involved in simple saccadic eye movements in humans.

Adult↗

PubMed1993

[Myocardial infarction treated within 4 hrs: comparison of the cost-benefit ratio of 3 thrombolytic treatments: APSAC, rt-PA and streptokinase in 270 patients].

Two hundred and seventy patients under 71 years of age with myocardial infarction less than 4 hours old, defined by clinical and electrocardiographic criteria, were included in this trial and followed up for 1 year: two groups of 89 and 92 patients were randomised to receive APSAC (30 mg i.v. over 5 minutes) or rt-PA (10 mg bolus + 5000 IU of heparin as a bolus, followed by 90 mg rt-PA over 3 hours) and compared with a control series of 89 consecutive patients treated with streptokinase (1.5 MU in 1 hour). Heparin and aspirin (250 mg/day) were prescribed systematically. A score of efficacy was established from the following 4 parameters: patency of the infarct-related artery on coronary angiography at day 6 +/- 2 (N = 252), dyssynergic score on radiological ventriculography, infarct size on resting Thallium myocardial scintigraphy performed between day 15 and 21 (N = 242) and radionuclide ejection fraction performed at the same time. This score (0-24) was respectively 17.8 +/- 6.4 for rt-PA, 17.7 +/- 6.0 for APSAC and 18.1 +/- 6.0 for streptokinase (NS). The costs of hospital treatment were assessed by including: the cost of thrombolytic therapy (ranging from 1.7% of total cost for streptokinase to 16% for rt-PA), the cost of other treatments and biological investigations (10% of total cost); the cost of followed coronary angiography, in 33% of patients, by an angioplasty (21% of total cost), the cost of hospital stay averaging 17 days (49% of total cost in the rt-PA and APSAC groups and 56% in the streptokinase group NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗

PubMed1992

[Evaluation of cardiac output by Doppler echocardiography. Correlation of aortic, pulmonary and mitral ring flow rates. Study of 103 subjects free of valve leak].

Measurement by Doppler-echocardiography of blood flow rates has the advantage over techniques for the measurement of cardiac output of determining the latter for each valve orifice, and of opening up an approach to the quantification of aortic and mitral regurgitation. This prospective study involving 103 subjects free of any valve leak showed the absence of an significant difference between aortic, pulmonary and mitral ring flow rates in a given individual. Correlations between results obtained at the three measurement sites were: r = 0.92 between aorta and pulmonary artery, r = 0.90 between aorta and mitral ring and r = 0.90 between pulmonary artery and mitral ring. These results support the validation of this technique and would justify its use in the evaluation, quantification and monitoring of mitral and aortic valve leaks.

Adolescent↗