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F Chollet

Publications and source records attributed to F Chollet.

18 recordsLinked to original sources

Supplementary and primary sensory motor area activity in Parkinson's disease. Regional cerebral blood flow changes during finger movements and effects of apomorphine.

We have measured with single-photon emission tomography the regional cerebral blood flow changes that occurred in the supplementary motor areas and in the primary sensory motor areas during sequential finger-to-thumb opposition movements of the right hand in seven akinetic patients with Parkinson's disease and in nine normal volunteers. Parkinsonian patients were studied before ("off" condition) and after a subcutaneous injection of apomorphine hydrochloride which was able to switch them "on" (on condition). In normal volunteers and parkinsonian patients in the on condition, regional cerebral blood flow significantly increased in the supplementary motor areas and in the contralateral primary sensory motor cortex but not in the ipsilateral primary sensory motor cortex. On the contrary, no significant regional cerebral blood flow change was observed in these areas in parkinsonian patients in the off condition. These results support the hypothesis that a functional cortical motor area deafferentation is involved in the pathophysiological makeup of akinesia and that this abnormality is reversed by dopaminergic drugs.

Aged

Functional reorganization of the brain in recovery from striatocapsular infarction in man.

We used positron emission tomography (PET) to study organizational changes in the functional anatomy of the brain in 10 patients following recovery from striatocapsular motor strokes. Comparisons of regional cerebral blood flow maps at rest between the patients and 10 normal subjects revealed significantly lower regional cerebral blood flow in the basal ganglia, thalamus, sensorimotor, insular, and dorsolateral prefrontal cortices, in the brainstem, and in the ipsilateral cerebellum in patients, contralateral to the side of the recovered hand. These deficits reflect the distribution of dysfunction caused by the ischemic lesion. Regional cerebral blood flow was significantly increased in the contralateral posterior cingulate and premotor cortices, and in the caudate nucleus ipsilateral to the recovered hand. During the performance of a motor task by the recovered hand, patients activated the contralateral cortical motor areas and ipsilateral cerebellum to the same extent as did normal subjects. However, activation was greater than in normal subjects in both insulae; in the inferior parietal (area 40), prefrontal and anterior cingulate cortices; in the ipsilateral premotor cortex and basal ganglia; and in the contralateral cerebellum. The pattern of cortical activation was also abnormal when the unaffected hand, contralateral to the hemiplegia, performed the task. We showed that bilateral activation of motor pathways and the recruitment of additional sensorimotor areas and of other specific cortical areas are associated with recovery from motor stroke due to striatocapsular infarction. Activation of anterior and posterior cingulate and prefrontal cortices suggests that selective attentional and intentional mechanisms may be important in the recovery process. Our findings suggest that there is considerable scope for functional plasticity in the adult human cerebral cortex.

Adult

The anatomy of phonological and semantic processing in normal subjects.

We assessed brain activation of nine normal right-handed volunteers in a positron emission tomography study designed to differentiate the functional anatomy of the two major components of auditory comprehension of language, namely phonological versus lexico-semantic processing. The activation paradigm included three tasks. In the reference task, subjects were asked to detect rising pitch within a series of pure tones. In the phonological task, they had to monitor the sequential phonemic organization of non-words. In the lexico-semantic task, they monitored concrete nouns according to semantic criteria. We found highly significant and different patterns of activation. Phonological processing was associated with activation in the left superior temporal gyrus (mainly Wernicke's area) and, to a lesser extent, in Broca's area and in the right superior temporal regions. Lexico-semantic processing was associated with activity in the left middle and inferior temporal gyri, the left inferior parietal region and the left superior prefrontal region, in addition to the superior temporal regions. A comparison of the pattern of activation obtained with the lexico-semantic task to that obtained with the phonological task was made in order to account for the contribution of lower stage components to semantic processing. No difference in activation was found in Broca's area and superior temporal areas which suggests that these areas are activated by the phonological component of both tasks, but activation was noted in the temporal, parietal and frontal multi-modal association areas. These constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language.

Adult

[Is there any desensitization of presynaptic alpha 2-adrenergic receptors in hypertension? Experimental and clinical studies].

Several authors have discussed an alteration of adrenergic receptivity in arterial hypertension. De Champlain (Hypertension 1990; 8: S77-S85) suggested that postsynaptic alpha 1-adrenergic functions became dominant while beta-adrenergic functions are attenuated in arterial hypertension. However, the status of presynaptic alpha 2-adrenoceptors remains unknown. The present study investigates presynaptic alpha 2-adrenoceptors in hypertension through the measurement of plasma levels of noradrenaline after administration of yohimbine, an alpha 2-adrenoceptor antagonist, in essential hypertension. Yohimbine (0.2 mg/kg per os) induced a 73% increase of plasma levels of noradrenaline in hypertensive patients (n = 12) and a 178% one in normotensive subjects (n = 6, p < 0.05). A similar significant difference was found in experimental neurogenic hypertension observed in awake dogs 3 weeks after sinoaortic denervation: the increase in plasma concentrations of noradrenaline after yohimbine (0.5 mg/kg i.v.) was +279% in hypertensive versus +642% in normotensive dogs (p < 0.05). The results show that the magnitude of the yohimbine-induced sympathetic activation is lower in hypertensives than in normotensives. They suggest the existence of a presynaptic alpha 2-adrenoceptor desensitization in arterial hypertension. The abnormality of this presynaptic inhibitory mechanism can increase the sympathetic tone and help to develop and maintain arterial hypertension.

Adrenergic alpha-Antagonists

The functional anatomy of recovery from brain injury.

The functional neuroanatomical basis for recovery from ischaemic brain injury is not known. We have used positron emission tomography (PET) to study changes in the functional organization of the brain in patients recovering from striatocapsular motor strokes. Significant changes in regional cerebral blood flow (rCBF) were found during repetitive sequential opposition movements of the fingers in normal subjects and in patients with recovery from motor deficits. There was a difference in the pattern of cerebral activation when patients performed the motor task with the unaffected hand (when the activation was lateralized to contralateral sensorimotor and premotor cortex and ipsilateral cerebellum) and when the task was performed with the recovered, previously plegic hand (when the activation was bilateral and involved novel areas of cortex, especially area 40). Comparisons of rCBF maps at rest in the patient group and in normal subjects showed areas with significantly decreased rCBF in the patients (contralateral to the plegic hand in the basal ganglia, thalamus, insular cortex, brainstem and ipsilateral cerebellum), which reflected the distribution of dysfunction caused by the ischaemic lesions. A significantly increased activation over and above that in normal subjects was found in patients during movement of the recovered fingers in ipsilateral premotor cortex and bilateral frontal opercular/insular regions and area 40, the ipsilateral basal ganglia (the ischaemic lesion lying contralaterally) and the contralateral cerebellum. We postulate that these findings may be explained by the generation of movements by pathways that are different from those that normal subjects use to perform what are ordinarily fairly simple, automated tasks. We suggest that this is a direct demonstration of cerebral plasticity resulting in the resolution of acquired motor deficits.

Brain Ischemia

The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography.

We have studied regional cerebral blood flow changes in 6 patients after their recovery from a first hemiplegic stroke. All had a single well-defined hemispheric lesion and at least a brachial monoparesis that subsequently recovered. Each patient had 6 measurements of cerebral blood flow by positron tomography with 2 scans at rest, 2 during movement of fingers of the recovered hand, and 2 during movement of fingers of the normal hand. When the normal fingers were moved, regional cerebral blood flow increased significantly in contralateral primary sensorimotor cortex and in the ipsilateral cerebellar hemisphere. When the fingers of the recovered hand were moved, significant regional cerebral blood flow increases were observed in both contralateral and ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres. Other regions, namely, insula, inferior parietal, and premotor cortex, were also bilaterally activated with movement of the recovered hand. We have also demonstrated, by using a new technique of image analysis, different functional connections between the thalamic nuclei and specific cortical and cerebellar regions during these movements. Our results suggest that ipsilateral motor pathways may play a role in the recovery of motor function after ischemic stroke.

Adult

Distribution of cortical neural networks involved in word comprehension and word retrieval.

Six normal volunteers were studied with positron emission tomography to identify the cortical neural networks that participate in the processing of single words. Activity-related changes in regional cerebral blood flow were measured consecutively on 6 occasions in each subject, 2 while the subject was at rest and 4 while single word language tasks were being performed. The data from each subject were standardized for brain shape and size, reconstructed parallel to the intercommissural line, normalized for global flow differences, and then averaged for each activation condition across the 6 subjects. Significant areas of change in rCBF (P less than 0.05, with appropriate Bonferroni corrections) between task and rest conditions were displayed with reference to the coordinates of a standard neuroanatomical atlas. We have demonstrated that categorical judgements on heard pairs of real words activate neural networks along both superior temporal gyri, but with an anatomical distribution no different from that seen when the subjects listened to nonwords: the tasks would appear to be very different in cognitive demands but not in terms of the distribution of activation. However, during a verb generation task that involved thinking of verbs appropriate to heard nouns presented at a slow rate, the only temporal region activated was the left posterior superior temporal association cortex (Wernicke's area). Further analysis showed that whereas activation in other superior temporal regions, both left and right, correlated with rates of word presentation during the 4 tasks, there was no such correlation in Wernicke's area; evidence that this site is responsible for more than early acoustic processing. During verb generation there was also activation of left premotor and prefrontal cortex (including Broca's area and the supplementary motor area). The supplementary motor area is thought to be involved in the motor planning of speech. The subjects did not vocalize during the task, and therefore it would appear that the act of retrieving words from semantic memory activates networks concerned with the production of speech sounds. We conclude that single word comprehension and retrieval activate very different distributed regions of cerebral cortex, with Wernicke's area the only region engaged by both processes and with participation during silent word generation of networks involved in vocalization.

Adult

[Cerebral blood volume, endarterectomy and SPECT].

Cerebral blood flow and cerebral blood volume were measured and quantified using single photon emission computed tomography before and after unilateral endarterectomy in 3 patients with bilateral severe lesions of the internal carotid artery. These parameters were measured using an intravenous injection of 133 Xenon and 99m Technetium respectively. Before endarterectomy cerebral blood volume was high in all patients suggesting a focal vasodilatation in response to a reduced cerebral perfusion pressure. After endarterectomy a decrease of cerebral blood volume and an increase of cerebral blood flow were observed. These preliminary results confirm that the hemodynamic adaptative mechanisms secondary to carotid occlusion are reversible when the stenosis is removed and demonstrate that these changes can be accurately measured using single photon emission computed tomography. Positron emission tomography was previously considered to be the only method able to quantify cerebral blood volume in man. Single photon emission computed tomography can also be considered a reliable technique to measure both cerebral blood flow and cerebral blood volume. This technique can then be used to assess individual cerebral vascular adaptative states and to evaluate the influence of cerebral hemodynamic changes on stroke occurrence in large longitudinal studies.

Aged

The functional nature of cerebellar diaschisis.

We report a patient who presented with transient clumsiness of his right hand due to a small hemorrhage in the left globus pallidus. Ten days later, positron emission tomography performed at rest showed decreased oxygen metabolism and blood flow at the site of the anatomic lesion and in remote areas such as the ipsilateral frontotemporoparietal cortex and the contralateral cerebellar hemisphere. Cerebellar hypometabolism has been ascribed to functional disconnection of the contralateral hemisphere from the cerebral cortex and has been termed crossed cerebellar diaschisis. One month later, positron emission tomography performed during unilateral motor activation (finger opposition) showed increased blood flow in the sensorimotor and supplementary motor areas contralateral to the hand engaged in the motor task. An at-rest study at this time showed resolution of the crossed cerebellar diaschisis observed acutely, but cerebellar asymmetry was demonstrated during performance of the motor task with the normal as well as with the previously paretic hand. Our activation study demonstrated cerebellar asymmetry in the chronic phase during a motor task, even though resting cerebellar blood flow was symmetrical. This observation reveals the dynamic, functional nature of crossed cerebellar diaschisis and may partially explain the lack of any clinical counterpart in functional studies of the cerebellum performed with the patient at rest.

Brain

SPECT study of cerebral blood flow reactivity after acetazolamide in patients with transient ischemic attacks.

We investigated 15 patients with one or more transient ischemic attacks (TIAs) in the internal carotid artery territory within the month following the most recent TIA. Cerebral blood flow (CBF) was measured by single-photon emission computed tomography, using intravenous xenon-133 before and after injection of 1 g acetazolamide. Six patients had severe carotid stenosis or occlusion; the other nine patients had no significant carotid lesions. Twenty age-matched volunteers free of neurologic symptoms or history were used as controls. Mean CBF in the sylvian region was not significantly different between patients and controls. Seven patients exhibited a focal hypoperfusion at rest in the symptomatic hemisphere, and their hypoperfused areas were hyporeactive after administration of acetazolamide. Seven other patients exhibited hyporeactive areas after acetazolamide administration while their CBF tomograms at rest were normal. Thus, CBF abnormalities were detected in 14 of the 15 patients. Our findings suggest that CBF measured early after acetazolamide administration could be useful to confirm the clinical diagnosis of TIA. In the nine patients with no significant lesion of the internal carotid artery, the areas of hypoperfusion were small and were probably related to the focal ischemic event. In the six patients with severe lesions of the internal carotid artery, abnormalities were of variable size and intensity but were often large and pronounced. The discrepancy between these two subgroups of patients could be ascribed to the hemodynamic influence of the internal carotid artery lesions. Moreover, our findings may provide some insight into the pathophysiology of TIAs.

Acetazolamide

Uptake of HDL unesterified and esterified cholesterol by human endothelial cells. Modulation by HDL phospholipolysis and cell cholesterol content.

Human HDL (1.070-1.210), doubly labelled with 3H/14C-labelled unesterified cholesterol and 3H-labelled esterified cholesterol were incubated for 1-5 h with monolayer cultures of human endothelial cells. HDL were preincubated for 60-120 min the presence of albumin and with/without purified phospholipase A2 (control HDL, phospholipase A2 HDL) before dilution in the cell culture medium. Average phosphatidylcholine (PC) degradation was 62.10% +/- 2.57% (range 45-80%). A purified lipase/phospholipase A1 from guinea pig pancreas was used in some experiments (range of PC hydrolysis: 16-70%). (1) 3H/14C-labelled unesterified cholesterol and 3H-labelled esterified cholesterol appeared in cells during 0-5 h incubations. Trypsin treatment allowed a simple adsorption of HDL onto the cell surface to be avoided, and most of the 3H-labelled esterified cholesterol transferred to cells was hydrolysed. Cell uptake of radioactive cholesterol increased as a function of HDL concentration but no saturation was achieved at the highest lipoprotein concentration used (200 micrograms cholesterol/ml). Flux of 3H/14C-labelled unesterified cholesterol was related to the cell cholesterol content, suggesting that it might partly represent an exchange process. The cell cholesterol content was slightly increased after 5 h incubation with HDL (+16%). (2) Pretreatment of HDL with purified phospholipase A2 doubled on average the amount of cell recovered 3H-labelled esterified cholesterol, while the flux of 3H/14C-labelled unesterified cholesterol was enhanced by 15-25%. Both transfer and cell hydrolysis of 3H-labelled esterified cholesterol were increased. A stimulation was also observed using purified lipase/phospholipase A1, provided that a threshold phospholipid degradation was achieved (between 27 and 45%). (3) Endothelial cells were conditioned in different media so as to modulate their charge in cholesterol. The uptake of 3H-labelled esterified cholesterol was found to be significantly higher in cholesterol-enriched cells compared to the sterol-depleted state. Finally, movements of 3H-labelled esterified cholesterol from HDL to endothelial cells were essentially unaffected by cell density or by the presence of partially purified cholesterol ester transfer protein. The possible roles of the transfer of HDL esterified cholesterol to endothelial cells and its modulation by phospholipases are discussed.

Biological Transport

Platelet alpha 2- and leucocyte beta 2-adrenoceptors in phaeochromocytoma: effect of tumour removal.

Platelet alpha 2- and leucocyte beta 2-adrenoceptors (as well as noradrenaline and adrenaline plasma levels) were studied in five patients with confirmed phaeochromocytoma using tritiated yohimbine and iodated cyanopindolol, respectively, before and after tumour removal. Patients with phaeochromocytoma had a lower leucocyte iodated cyanopindolol binding than control subjects, but no change in platelet tritiated yohimbine binding. Plasma catecholamine levels were higher than controls. Tumour removal induced a return to normal values of leucocyte iodated cyanopindolol binding and a decrease in plasma catecholamine levels. These results underline the potential interest of leucocyte beta-adrenoceptor quantification in the diagnosis and the follow-up of phaeochromocytoma. Pharmacologically, they show that down-regulation occurs in vivo for leucocyte beta 2-adrenoceptors but not for platelet alpha 2-adrenoceptors.

Adrenal Gland Neoplasms

Distribution of high-density lipoprotein 2 and 3 constituents during in vitro phospholipid hydrolysis.

Human high-density lipoproteins HDL2 (d = 1.068-1.125) and HDL3 (d = 1.125-1.210) doubly labelled with [3H]cholesterol/cholesteryl ester and with [acyl-14C]phosphatidylcholine were further incubated with phospholipases. Highly purified phospholipase A2 from Crotalus adamanteus allowed gradual degrees of lipolysis (30-90%) on both HDL2 and HDL3. Moderate phospholipid hydrolyses were achieved using hepatic triacylglycerol lipase, partially purified from post-heparin plasma. Moreover, the latter enzyme seemed to exert a lysophospholipase activity, acting on the 2-acyl-sn-glycero-3-phosphocholine generated. A purified sphingomyelinase C from Staphylococcus aureus was also used and completely hydrolysed HDL sphingomyelin. After incubation, doubly labelled HDL2/HDL3 were reisolated in their appropriate density interval. In the presence of albumin, which bound most of the lipolysis products, phospholipolysis induced a phospholipid depletion of the particles and a heterogeneous partition of all HDL2 constituents between the HDL2 and HDL3 density intervals. Radioactivity distributions correlated with mass movements. The 'HDL3-like' particles isolated after HDL2 lipolysis were twice as rich in cholesterol as plasma HDL3. No loss of apoprotein A1 was recorded due to phospholipolysis. In the absence of albumin, the density distributions of HDL2 or HDL3 constituents were unaffected by phospholipolysis, the products of lipolysis being reisolated with the stable particles. Control and treated HDL were also reisolated by equilibrium density gradient ultracentrifugation, gel chromatography or by gradient gel electrophoresis. Phospholipase treatment in the presence of albumin induced a shift of the HDL2 or HDL3 whole distribution towards particles of higher density and lower apparent size. Lipolysed HDL2 thus showed characteristics intermediate between those of HDL2 and HDL3. So, phospholipolysis may affect the physical parameters of HDL particles, but additional pathways such as cholesterol movements and apoprotein loss must be linked to achieve the HDL2----HDL3 interconversion.

Humans

Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase-induced removal of cellular cholesterol.

Cholesterol