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C Michel

Publications and source records attributed to C Michel.

At least 73 records · Page 4Linked to original sources

Functional imaging of visual semantic processing in the human brain.

Previous neuroimaging studies have identified a large network of cortical areas involved in semantic processing in the human brain, which includes left occipito-temporal and inferofrontal areas. Most studies, however, investigated exclusively the associative/functional semantic knowledge by using mainly words and/or language related tasks, and this factor may have contributed to the large left hemisphere superiority found in semantic processing and to the controversial involvement of left prefrontal structures. The present study investigates the neural basis of visual objects knowledge, accessed exclusively through pictorial information. Regional cerebral blood flow (rCBF) was assessed using positron emission tomography (PET) during 3 conditions in right-handed normal volunteers: resting with eyes closed, retrieval of semantic information related to visual properties of objects (real size), and visual categorization based on physical properties of the image. Confirming previous experiments and neuropsychological findings, most activations were found in left occipito-temporal areas during retrieval of visual semantic knowledge. The absence of any activation in the left prefrontal inferior cortex for visual semantic processing confirms recent observations which suggest that this region would not be involved in retrieval of visual semantic knowledge from living entities. Rather, such knowledge about visual properties of objects, situated closely to cortical regions mediating perception of the visual attributes, can be retrieved directly from these regions when visual images are used as entry level stimuli.

Adult↗

Internally driven vs. externally cued movement selection: a study on the timing of brain activity.

Brain imaging studies in man and single cell recordings in monkey have suggested that medial supplementary motor areas (SMA) and lateral pre-motor areas (PMA) are functionally dissociated concerning their involvement in internally driven and externally cued movements. This dichotomy, however, seems to be relative rather than absolute. Here, we searched for further evidence of relative differences and aimed to determine by what aspect of brain activity (duration, strength, or both) these might be accounted for. Event-related potentials (ERPs) were recorded while healthy, right-handed subjects selected one of three possible right hand digit movements based either on 'internal' choice or 'external' cues. The results obtained from ERP mapping suggest that movement selection evokes the same electrical brain activity patterns in terms of surface potential configurations in the same order and at the same strength independent of the selection mode. These identical configurations, however, differed in their duration. Combined with the results of a distributed source localization procedure, our data are suggestive of longer lasting activity in SMA during the 'internal' and longer lasting activity in PMA during the 'external' condition. Our results confirm previous findings in showing that SMA and PMA are distinctively involved in the two tasks and that this functional dichotomy is relative rather than absolute but indicate that such a dissociation can result from differences in duration rather than pure strength of activation.

Adult↗

Arguments against the significance of the Fenton reaction contributing to signal pathways under in vivo conditions.

One of the common explanations for oxidative stress in the physiological milieu is based on the Fenton reaction, i.e. the assumption that radical chain reactions are initiated by metal-catalyzed electron transfer to hydrogen peroxide yielding hydroxyl radicals. On the other hand - especially in the context of so-called "iron switches" - it is postulated that cellular signaling pathways originate from the interaction of reduced iron with hydrogen peroxide. Using fluorescence detection and EPR for identification of radical intermediates, we determined the rate of iron complexation by physiological buffer together with the reaction rate of concomitant hydroxylations of aromatic compounds under aerobic and anaerobic conditions. With the obtained overall reaction rate of 1,700 M(-1)s(-1) for the buffer-dependent reactions and the known rates for Fenton reactions, we derive estimates for the relative reaction probabilities of both processes. As a consequence we suggest that under in vivo conditions initiation of chain reactions by hydroxyl radicals generated by the Fenton reaction is of minor importance and hence metal-dependent oxidative stress must be rather independent of the so-called "peroxide tone". Furthermore, it is proposed that - in the low (subtoxic) concentration range - hydroxylated compounds derived from reactions of "non-free" (crypto) OH radicals are better candidates for iron-dependent sensing of redox-states and for explaining the origin of cellular signals than the generation of "free" hydroxyl radicals.

Buffers↗

Effects of atorvastatin on dyslipidaemia in uraemic patients on peritoneal dialysis.

BACKGROUND: Our purpose was to evaluate the efficacy and safety of atorvastatin, a potent cholesterol- and triglyceride-lowering agent, in peritoneal dialysis patients with dyslipidaemia. METHODS: Peritoneal dialysis patients with hypercholesterolaemia were treated for 4 months with atorvastatin at a starting dose of 10 mg. The dose could be increased to 20 or 40 mg in order to achieve the following targets: plasma LDL-cholesterol of 130 mg/dl for primary prevention of coronary heart disease, plasma LDL cholesterol of 100 mg/dl for secondary prevention, and plasma triglycerides of 200 mg/dl. Plasma lipid profile and liver and muscle enzyme levels were assessed at baseline and then monthly during treatment. RESULTS: Thirty-one patients with hypercholesterolaemia were included (16 males and 15 females; mean age 57+/-16 years; mean duration of peritoneal dialysis 27+/-17 months). Nineteen of the patients also had hypertriglyceridaemia and seven had diabetes. Twenty patients had no coronary history (primary prevention), whereas nine had experienced a coronary event (secondary prevention). In the primary and the secondary prevention patients, mean LDL-cholesterol levels (mg/dl) decreased significantly by 42 and 46% from 204+/-23 to 119+/-27 (P<0. 001) and 198+/-37 to 104+/-21 (P<0.001), and mean triglyceride levels (mg/dl) decreased by 37 and 26% from 289+/-132 to 186+/-92 (P<0.001) and 201+/-62 to 150+/-54 (P<0.001 respectively). Nineteen primary prevention and seven secondary prevention patients achieved the LDL-cholesterol target. The triglyceride target was achieved by 15 of the 19 hypertriglyceridaemic patients. Two patients stopped treatment (one because of gastrointestinal disturbances, the other because of an allergic skin reaction). After 4 months, there were no changes in enzyme levels. CONCLUSION: Atorvastatin is an effective and safe lipid-lowering agent for peritoneal dialysis patients with mixed dyslipidaemia.

Adult↗

N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study.

OBJECTIVE: In septic shock, decreased splanchnic blood flow is reported, despite adequate systemic hemodynamics. Aacetylcysteine (NAC) was found to increase hepatosplanchnic blood flow in experimental settings. In septic shock patients, NAC improved the clearance of indocyanine green and the relationship of systemic oxygen consumption to oxygen demand. We investigated the influence of NAC on liver blood flow, hepatosplanchnic oxygen transport-related variables, and liver function during early septic shock. DESIGN: Prospective, randomized, double-blind study. SETTING: Septic shock patients admitted to an interdisciplinary surgical intensive care unit. PATIENTS: We examined 60 septic shock patients within 24 hrs after onset of sepsis. They were conventionally resuscitated with volume and inotropes and were in stable condition. A gastric tonometer was inserted into the stomach and a catheter into the hepatic vein. Microsomal liver function was assessed by using the plasma appearance of monoethylglycinexylidide (MEGX). INTERVENTIONS: Subjects randomly received either a bolus of 150 mg/kg iv NAC over 15 mins and a subsequent continuous infusion of 12.5 mg/kg/hr NAC over 90 mins (n = 30) or placebo (n = 30). MEASUREMENTS AND MAIN RESULTS: Measurements were performed before (baseline) and 60 mins after beginning the infusion (infusion). After NAC, a significant increase in absolute liver blood flow index (2.7 vs. 3.3 L/min/m2; p = .01) and cardiac index (5.0 vs. 5.7 L/min/m2; p = .02) was observed. Fractional liver blood flow index (cardiac index-related liver blood flow index) did not change. The difference between arterial and gastric mucosal carbon dioxide tension decreased (p = .05) and MEGX increased (p = .04). Liver blood flow index and MEGX correlated significantly (r(s) = .57; p < or = .01). CONCLUSIONS: After NAC treatment, hepatosplanchnic flow and function improved and may, therefore, suggest enhanced nutritive blood flow. The increase of liver blood flow index was not caused by redistribution to the hepatosplanchnic area, but by an increase of cardiac index. Because of its correlation with liver blood flow index, MEGX may be helpful in identifying patients who benefit from NAC treatment in early septic shock.

Acetylcysteine↗

Differential stress responsivity in diet-induced obese and resistant rats.

The relationship between stress and obesity was assessed in male rats selectively bred to develop either diet-induced obesity (DIO) or diet resistance (DR) when fed a high-energy, 31% fat diet for 3 wk followed by 2 wk on a hyperphagic liquid diet (Ensure). One-half of the rats of each phenotype were subjected to moderate daily, unpredictable stress (cage changing, exposure to conspecific, swim, and immobilization stress, intraperitoneal saline injection) during the 5 wk. Both stressed and unstressed DIO rats were 26% heavier and ate 27% more than comparable DR rats at onset and had 48% lower basal morning plasma corticosterone levels. Stressed DR rats gained less weight and had significant elevations of basal morning corticosterone but reduced basal sympathetic activity (24-h urine norepinephrine) over 5 wk compared with their unstressed DR controls. Terminally, there was a 35% increase in the paraventricular nucleus corticotropin-releasing hormone mRNA expression. On the other hand, stressed DIO rats showed only a transient early increase in open-field activity and a terminal increase in basal corticosterone levels as the only effects of stress. Thus DIO rats are hyporesponsive to chronic stress compared with DR rats. This is in keeping with several other known differences in hypothalamopituitary and autonomic function in this model.

Animals↗

gamma-aminobutyric acid type B receptor splice variant proteins GBR1a and GBR1b are both associated with GBR2 in situ and display differential regional and subcellular distribution.

The subunit architecture of gamma-aminobutyric acid, type B (GABA(B)), receptors in situ is largely unknown. The GABA(B) receptor variants, characterized by the constituents GBR1a and GBR1b, were therefore analyzed with regard to their subunit composition as well as their regional and subcellular distribution in situ. The analysis was based on the use of antisera recognizing selectively GBR1a, GBR1b, and GBR2. Following their solubilization, GBR1a and GBR1b were both found by immunoprecipitation to occur as heterodimers associated with GBR2. Furthermore, monomers of GBR1a, GBR1b, or GBR2 were not detectable, suggesting that practically all GABA(B) receptors are heterodimers in situ. Finally, there was no evidence for an association of GBR1a with GBR1b indicating that these two constituents represent two different receptor populations. A size determination of solubilized GABA(B) receptors by sucrose density centrifugation revealed two distinct peaks of which one corresponded to dimeric receptors, and the higher molecular weight peak pointed to the presence of yet unknown receptor-associated proteins. The distribution and relative abundance of GBR2 immunoreactivity corresponded in all brain regions to that of the sum of GBR1a and GBR1b, supporting the view that most if not all GBR1 proteins are associated with GBR2. However, GBR1a was present preferentially at postsynaptic densities, whereas GBR1b may be mainly attributed to presynaptic or extrasynaptic sites. Thus, GBR1a and GBR1b are both associated with GBR2 to form heterodimers at mainly different subcellular locations where they are expected to subserve different functions.

Alternative Splicing↗

Redox components of cytochrome bc-type enzymes in acidophilic prokaryotes. I. Characterization of the cytochrome bc1-type complex of the acidophilic ferrous ion-oxidizing bacterium Thiobacillus ferrooxidans.

The redox components of the cytochrome bc1 complex from the acidophilic chemolithotrophic organism Thiobacillus ferrooxidans were investigated by potentiometric and spectroscopic techniques. Optical redox titrations demonstrated the presence of two b-type hemes with differing redox midpoint potentials at pH 7.4 (-169 and + 20 mV for bL and bH, respectively). At pH 3.5, by contrast, both hemes appeared to titrate at about +20 mV. Antimycin A, 2-heptyl-4-hydroxyquinoline N-oxide, and stigmatellin induced distinguishable shifts of the b hemes' alpha-bands, providing evidence for the binding of antimycin A and 2-heptyl-4-hydroxyquinoline N-oxide near heme bH (located on the cytosolic side of the membrane) and of stigmatellin near heme bL (located on the periplasmic side of the membrane). The inhibitors stigmatellin, 5-(n-undecyl)-6-hydroxy-4,7-dioxobenzothiazole, and 2, 5-dibromo-3-methyl-6-isopropyl-p-benzoquinone affected the EPR spectrum of the Rieske iron-sulfur center in a way that differs from what has been observed for cytochrome bc1 or b6f complexes. The results obtained demonstrate that the T. ferrooxidans complex, although showing most of the features characteristic for bc1 complexes, contains unique properties that are most probably related to the chemolithotrophicity and/or acidophilicity of its parent organism. A speculative model for reverse electron transfer through the T. ferrooxidans complex is proposed.

Antimycin A↗

Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sézary syndrome. The French Study Group on Cutaneous Lymphomas.

Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sézary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution (ie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension (ie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator.

Adolescent↗

Changes in occipital cortex activity in early blind humans using a sensory substitution device.

The purpose of this study was to investigate the neural networks involved when using an ultrasonic echolocation device, which is a substitution prosthesis for blindness through audition. Using positron emission tomography with fluorodeoxyglucose, regional brain glucose metabolism was measured in the occipital cortex of early blind subjects and blindfolded controls who were trained to use this prosthesis. All subjects were studied under two different activation conditions: (i) during an auditory control task, (ii) using the ultrasonic echolocation device in a spatial distance and direction evaluation task. Results showed that the abnormally high metabolism already observed in early blind occipital cortex at rest [C. Veraart, A.G. De Volder, M.C. Wanet-Defalque, A. Bol, C. Michel, A.M. Goffinet, Glucose utilization in human visual cortex is, respectively elevated and decreased in early versus late blindness, Brain Res. 510 (1990) 115-121.] was also present during the control task and showed a trend to further increase during the use of the ultrasonic echolocation device. This specific difference in occipital cortex activity between the two tasks was not observed in control subjects. The metabolic recruitment of the occipital cortex in early blind subjects using a substitution prosthesis could reflect a concurrent stimulation of functional cross-modal sensory connections. Given the unfamiliarity of the task, it could be interpreted as a prolonged plasticity in the occipital cortex early deprived of visual afferences.

Acoustic Stimulation↗

PET study of the human foveal fixation system.

Positron emission tomography (PET) was used to investigate the functional anatomy of the foveal fixation system in 10 subjects scanned under three different conditions: at rest (REST), during the fixation of a central point (FIX), and while fixating the same foveal target during the presentation of peripheral visual distractors (DIS). Compared with the REST condition, both FIX and DIS tasks activated a common set of cortical areas. First, in addition to the involvement of the occipital visual cortex, both the frontal eye field (FEF) and the intraparietal sulcus (IPS) were bilaterally activated. Right frontal activation was also found in the dorsolateral prefrontal cortex, the inferior part of the precentral gyrus, and the inferior frontal gyrus. These results suggest that both FEF and IPS may constitute the main cortical regions subserving bilaterally the foveal fixation system in humans. The remaining right frontal activations may be considered as part of the anterior attentional network, supporting a role for the right frontal lobe in the allocation of the attentional mechanisms. Compared with the FIX condition, the DIS task also revealed the perceptual and cognitive processes related to the presence of peripheral visual distractors during foveal fixation. In addition to a bilateral activation of the V5/MT motion-sensitive area, a right FEF-IPS network was activated which may correspond to the engagement of the visuospatial attention. Finally, normalized regional cerebral blood flow (NrCBF) decreases were also observed during both DIS and FIX condition performance. Such NrCBF decreases were centered in the superior and middle temporal gyri, the prefrontal cortex, and the precuneus and the posterior retrosplenial part of the cingulate gyrus.

Adult↗

Poly(ADP-ribose) polymerase alleles in French Caucasians are associated neither with lupus nor with primary antiphospholipid syndrome. GRAID Research Group. Group for Research on Auto-Immune Disorders.

OBJECTIVE: To investigate the putative involvement of poly(ADP-ribose) polymerase (PARP) alleles in systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: This study of French Caucasians included 171 unrelated patients with SLE, 88 unrelated patients with primary APS, and 193 ethnically matched healthy controls. The SLE group comprised 89 patients with sporadic SLE and 82 patients with familial SLE. Patients' and controls' DNA were genotyped for the various alleles of a polymorphic CA dinucleotide repeat located within the promoter region of PARP. RESULTS: No statistically significant difference was observed for the distribution of PARP alleles between the healthy control group and each patient group or the pooled SLE patient group. CONCLUSION: The study findings strongly suggest that these alleles do not influence susceptibility to SLE or primary APS in French Caucasians.

Alleles↗

Neuronal mechanisms of perceptual learning: changes in human brain activity with training in orientation discrimination.

Using 15O-water 3D positron emission tomography, regional cerebral blood flow was measured twice in six human subjects: before and after extensive training in orientation discrimination. In each session subjects performed two orientation discrimination tasks, during which they discriminated the orientation of a grating at either the trained or untrained reference orientation, and a control task, during which they detected a randomly textured pattern. By comparing the discrimination to the detection tasks, we observed a main effect of task bilaterally in the posterior occipital cortex, extending into the left posterior fusiform gyrus and the right inferior occipital gyrus, bilaterally in the intraparietal sulcus, as well as in the cerebellum, thalamus, and brainstem. When we compared the activation pattern before and after the training period, all the changes observed were activity decreases. The nonspecific changes, which were not related to the orientation used during the training, were situated in the cerebellum and bilaterally in the extrastriate visual cortex. The orientation-specific changes, on the other hand, were restricted to the striate and extrastriate visual cortex, more precisely the right calcarine sulcus, the left lingual gyrus, the left middle occipital, and the right inferior occipital gyrus. These findings confirm our hypothesis concerning the existence of learning related changes at early levels of visual processing in human adults and suggest that mechanisms resulting in neuronal activity decreases might be involved in the present kind of learning.

Adult↗

Effect of familiarity on the processing of human faces.

Most brain imaging studies on face perception have investigated the processing of unknown faces and addressed mainly the question of specific face processing in the human brain. The goal of this study was to highlight the effects of familiarity on the visual processing of faces. Using [15O]water 3D Positron Emission Tomography, regional cerebral blood flow distribution was measured in 11 human subjects performing an identical task (gender categorization) on both unknown and known faces. Subjects also performed two control tasks (a face recognition task and a visual pattern discrimination task). They were scanned after a training phase using videotapes during which they had been familiarized with and learned to recognize a set of faces. Two major results were obtained. On the one hand, we found bilateral activations of the fusiform gyri in the three face conditions, including the so-called fusiform-face area, a region in the right fusiform gyrus specifically devoted to face processing. This common activation suggests that different cognitive tasks performed on known and unknown faces require the involvement of this fusiform region. On the other hand, specific regional cerebral blood flow changes were related to the processing of known and unknown faces. The left amygdala, a structure involved in implicit learning of visual representations, was activated by the categorization task on unknown faces. The same task on known faces induced a relative decrease of activity in early visual areas. These differences between the two categorization tasks reveal that the human brain processes known and unknown faces differently.

Adult↗

Evidence for interhemispheric motor-level transfer in a simple reaction time task: an EEG study.

Simple visuomanual reaction time tasks require interhemispheric communication when stimuli are presented in the hemifield opposite the responding hand. Although confirmed in many studies, it is still a matter of debate when, at what functional level and at what site this interhemispheric transfer takes place. To address these questions, we recorded event-related potentials (ERPs) in 12 healthy subjects performing such a task and analyzed the data using techniques based on topographic ERP map characteristics. A method which has proved useful for associating ERP map configurations of different time periods with functional states of the brain was supplemented by a source localization procedure. The results suggest that transfer occurs late in time, on a functional motor level and at frontal sites, at least for left-to-right interhemispheric direction of transfer.

Adult↗

Attenuation correction in whole-body FDG oncological studies: the role of statistical reconstruction.

Whole-body fluorine-18 fluoro-2-d-deoxyglucose positron emission tomography (FDG-PET) is widely used in clinical centres for diagnosis, staging and therapy monitoring in oncology. Images are usually not corrected for attenuation since filtered backprojection (FBP) reconstruction methods require a 10 to 15-min transmission scan per bed position on most current PET devices equipped with germanium-68 rod transmission sources. Such an acquisition protocol would increase the total scanning time beyond acceptable limits. The aim of this work is to validate the use of iterative reconstruction methods, on both transmission and emission scans, in order to obtain a fully corrected whole-body study within a reasonable scanning time of 60 min. Five minute emission and 3-min transmission scans are acquired at each of the seven bed positions. The transmission data are reconstructed with OSEM (ordered subsets expectation maximization) and the last iteration is reprojected to obtain consistent attenuation correction factors (ACFs). The emission image is then also reconstructed with OSEM, using the emission scan corrected for normalization, scatter and decay together with the set of consistent ACFs as inputs. The total processing time is about 35 min, which is acceptable in a clinical environment. The image quality, readability and accuracy of uptake quantification were assessed in 38 patients scanned for various malignancies. The sensitivity for tumour detection was the same for the non-attenuation-corrected (NAC-FBP) and the attenuation-corrected (AC-OSEM) images. The AC-OSEM images were less noisy and easier to interpret. The interobserver reproducibility was significantly increased when compared with non-corrected images (96.1% vs 81.1%, P<0.01). Standardized uptake values (SUVs) measured on images reconstructed with OSEM (AC-OSEM) and filtered backprojection (AC-FBP) were similar in all body regions except in the pelvic area, where SUVs were higher on AC-FBP images (mean increase 7.74%, P<0. 01). Our results show that, when statistical reconstruction is applied to both transmission and emission data, high quality quantitative whole-body images are obtained within a reasonable scanning (60 min) and processing time, making it applicable in clinical practice.

Adult↗

Lipectomy, body weight, and body weight set point in rats.

Adult, Wistar male rats were lipectomized or sham lipectomized. The food-hoarding behavior was measured repeatedly and plotted against the animals' body weights. Body weight set point was estimated as the intercept of regression line of hoarding with the X axis. Body fat content was measured with a TOBEC body composition analyzer. Body weight set point, fat content, and girth were obtained initially, after surgery, and after recovery. The hoarding threshold was lowered for 2 weeks after surgery, from 561 +/- 20 to 512 +/- 19 g (lipectomized), and from 582 +/- 15 to 558 +/- 14 g (sham lipectomized). After a 4-week recovery, all rats reached their prelipectomy body weight set point and regained their initial body fat. Five weeks after surgery, no significant difference was found between the body weight set points of lipectomized and sham-lipectomized rats. This indicates that the body weight set point was not mainly modulated by fat depots. The transient lowering of the set point is thought to be due to surgical stress.

Adipose Tissue↗