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Biomedical subjects

N Bruneau

Publications and source records attributed to N Bruneau.

At least 37 records · Page 2Linked to original sources
PubMed1997

Temporal prominence of auditory evoked potentials (N1 wave) in 4-8-year-old children.

Cortical auditory evoked potentials (N1 wave) were studied in 24 adults (12 men, 12 women) and 20 children (12 boys, 8 girls; age: 4-8 years). In adults, this wave was recorded with maximal amplitude at frontocentral sites, peaking at about 100 ms poststimulation, whereas in children the auditory response displayed maximal amplitude at the midtemporal sites, with a positive wave at about 100 ms and a large negative wave at approximately 170 ms. Moreover, the modulatory effects of intensity on N1 amplitude were prominent at frontocentral sites in adults and at temporal sites in children. Frontocentral negative response was also recorded in children but was smaller in amplitude and longer in peak latency (around 140 ms) than in adults; responses were of greater amplitude at the frontal site than at the vertex before 6 years of age, whereas the reverse was more often found after this age. These data suggest great differences with age in the neural generators contributing to auditory evoked potentials recorded in the N1 latency range.

Adult↗
PubMed1995

Association of bile-salt-dependent lipase with membranes of human pancreatic microsomes.

Immunolocalization studies indicated that, in contrast to other enzyme markers of human pancreatic secretion, bile-salt-dependent lipase (BSDL) was partly but specifically associated with endoplasmic reticulum membranes. In microsomes, temperature-induced phase separation using Triton X-114 elucidated the partition of BSDL between the aqueous phase and the detergent-rich phase containing hydrophilic and membrane proteins, respectively. The size of the membrane-associated BSDL (approx. 100 kDa) is compatible with that of the fully processed enzyme. Fucosylated O- and N-linked oligosaccharide structures were detected by means of specific lectins. The membrane-associated BSDL might therefore be released from membranes between the trans-Golgi compartment (where terminal fucose residues were added) and the zymogen granules where BSDL was mainly found in the soluble fraction. Even though BSDL associated with membranes was enzymically active, it appeared less efficient than the soluble form. The association of BSDL with membranes was pH-dependent and optimal association occurred between pH 5-6. The membrane-associated BSDL was released by KBr which suggests that the association of BSDL with microsomal membranes involves ionic interactions. Lipid-protein interactions are probably not involved in this association as BSDL did not associate with liver microsome membranes. We attempted to characterize the putative ligand and showed that BSDL and a 94-kDa protein, immunologically related to a glucose-regulated protein of 94 kDa (Grp94), were co-immunoprecipitated by specific antibodies directed against each individual species. It is suggested that the biogenesis of the human pancreatic BSDL involves an association with intracellular membranes and that its folding may be assisted by molecular chaperones.

Adult↗
PubMed1995

Chaperone function of a Grp 94-related protein for folding and transport of the pancreatic bile salt-dependent lipase.

In its fundamental attributes, the secretion pathway of the pancreatic bile salt-dependent lipase (BSDL) followed that described for all enzymes involved in regulated secretion. This route was inhibited by drugs that affect protein synthesis and intracellular transport. In the presence of monensin, BSDL was solely detected in microsome membrane fractions. The association of BSDL with intracellular membranes involved a protein complex, formed by at least two proteins of 94 and 56 kDa. In cells experiencing the metabolic stress due to azetidine-2-carboxylic acid, BSDL was additionally associated with a protein of 46 kDa. Affinity blotting showed that BSDL bound directly to the 94-kDa protein (p94). It was suggested that p94 could be a molecular chaperone, further identified as related to the 94-kDa glucose regulated protein (Grp 94). The membrane-associated BSDL (i.e. BSDL bound to the Grp 94-related p94) was O- and N-glycosylated and consequently appeared released from membranes in the trans-Golgi compartment. Therefore and for the first time, it is suggested that a multiprotein complex including the chaperone Grp 94-related p94 protein may play an essential role in the folding and transport of BSDL. One hypothesis is that the association of BSDL with membrane via the Grp 94-related p94 along its secretion pathway is required for its complete O-glycosylation, which occurs on the extended mucin-like structures present on the C-terminal part of the protein.

Animals↗
PubMed1995

Identification of behaviour profiles with a population of autistic children using multivariate statistical methods.

The Revised Behaviour Summarized Evaluation Scale (BSE-R) was developed for the objective evaluation of autistic behaviours in order to facilitate the recording of the evolution of developmentally disabled children. Among its 29 items, 13 items that precisely describe the degree of autistic behaviours were extracted by Principal Component Analysis. We hypothesised that these relevant behaviours could differentiate autistic behaviour profiles in a population of children previously diagnosed as typically autistic. For this purpose, we used an original multivariate descriptive statistical approach, Correspondence Analysis, which can help in detecting structural relationships among variables. In a population of autistic children initially diagnosed using DSM-III-R criteria, this procedure proved effective in identifying new main dimensions of behaviours among the 13 previously defined core autistic symptoms. Cluster analysis, which followed factorial analysis, allowed the identification of three meaningful behaviour profiles separated principally on the basis of two main functions, perception and imitation, which have been always considered to be fundamentally involved in autistic syndrome. The individualisation of homogeneous subgroups of children on the basis of the behavioural evaluation provides a potentially useful starting point for further biological and therapeutic studies.

Autistic Disorder↗
PubMed1995

Disorders of regulation of cognitive activity in autistic children.

Infantile autism is a pervasive developmental disorder characterized by disturbances concerning not only the areas of socialization and communication ("aloneness") but also the ability to modify and change behavior ("need for sameness"). In most recent studies, various abnormal and deviant cognitive activities, such as the ability to regulate one's behavior, were considered as accounting for these signs. In this report, we examined the regulation of cognitive activity, from a developmental perspective in comparing autistic with mentally retarded children matched in a pairwise manner by global, verbal, and nonverbal developmental ages. All children were tested with tasks adapted from the Object Permanence Test which corresponds to Piaget's sensorimotor development Stages IV to VI. Results showed that autistic children had a pervasive difficulty in maintenance set, made more perseverative errors when the abstraction degree of task was higher, and were more variable in their behavioral strategies. Discussion is focused on the interests and limits of these tasks for the examination of regulation activity from diagnostic and developmental perspectives. Finally, interpretations about recent neuropsychological and neurophysiological works, and additional interdisciplinary studies are suggested.

Attention↗
PubMed1993

Bile salt-dependent lipase biosynthesis in rat pancreatic AR 4-2 J cells. Essential requirement of N-linked oligosaccharide for secretion and expression of a fully active enzyme.

This study used the rat pancreatic AR 4-2 J cell line as a model system to investigate the role of glycosylation in bile salt-dependent lipase (BSDL) secretion and esterolytic activity. Results indicated that AR 4-2 J cells synthesized BSDL, the esterolytic activity of which was the greater part of the cell activity toward 4-nitrophenylcaproate. The protein thus expressed was glycosylated and had a molecular mass approximately 74 kDa. Exposure of these cells to tunicamycin significantly decreased [3H]mannose incorporation, while [35S]methionine incorporation in trichloroacetic acid-precipitable material was not modified. Tunicamycin treatment of AR 4-2 J cells lead to a lower molecular mass form (approximately 70 kDa) of BSDL which did not incorporate [3H]mannose. The nonglycosylated low M(r) form of the enzyme was not secreted as shown by the decreasing activity in cell-free medium which paralleled the time-dependent secretion of the enzyme. Tunicamycin had no effect on BSDL synthesis. Nevertheless, the nonglycosylated BSDL was apparently not degraded in any cell compartment as shown in part by the enzyme activity accumulation within cells upon brefeldin A treatment. The BSDL expressed by AR 4-2 J cells was characterized by a Km of 68 +/- 30 microM and a kcat of 106 +/- 19 min-1. The sequestrated BSDL due to tunicamycin treatment of cells presents a significant increase of Km of over 10 times to 757 +/- 303 microM. kcat was affected by a factor of approximately 4-445 +/- 22 min-1. These data correlated with an approximately 2.5-fold decrease of the esterolytic activity following inhibition of the N-glycosylation of the protein. The nonglycosylated BSDL was less stable to temperature than the native form. Processing inhibitors (castanospermine, 1-deoxymannojirimycin, and swainsonine) had no effect either on the enzyme activity or on its secretion. Results suggested first that the transfer of the oligosaccharide precursor to the nascent BSDL is essential for the folding of the fully active BSDL. Second that the glycan structure is required for the enzyme secretion.

1-Deoxynojirimycin↗
PubMed1993

Auditory stimulus intensity responses and frontal midline theta rhythm.

The influence of stimulus intensity on the N1 component of auditory evoked potentials recorded at fronto-central sites was investigated in respect to the spectral components of the EEG recorded at Cz, Fz and Oz. The study was performed on 14 healthy adult subjects. The only EEG frequency bandwidth that was strongly correlated with the N1 amplitude-intensity slope was the theta rhythm, particularly the 5-7 Hz frequencies recorded at Cz and Fz. This frequency bandwidth corresponds to the previously described frontal midline theta rhythm related to performance of tests that require continuous concentration of attention. Our results show that the steeper the slope, the greater the amount of Fm theta. This suggests that the interindividual differences in the N1 amplitude/intensity slope could be related to interindividual differences in attentional readiness toward the auditory stimuli, even when delivered in "passive" conditions.

Adult↗
PubMed1993

[Surgical and metabolic aspects of liver transplantation for tyrosinemia].

Tyrosinemia represents a very small percentage of patients undergoing liver transplantation world-wide. This disease is endemic within our referral area however, one-third of the liver transplantations at our institution are done for this disease. Since 1986, 16 patients with tyrosinemia and 34 patients with various other indications (non-tyrosinemic) have undergone a total of 55 liver transplantation. The survival rate for tyrosinemic patients is 87%, compared to 75% for non-tyrosinemic patients. Liver transplantation for hereditary tyrosinemia and other metabolic disorders without portal hypertension or previous portohepatic operations is notably easier to perform. Intraoperative blood loss was less, length of hospital stay was shorter and incidence of infections was lower in tyrosinemic than in non-tyrosinemic patients. Less than 10% of tyrosinemic patients had foci of hepatocellular carcinoma at the time of transplantation. For this reason, and while most patients with tyrosinemia will eventually require liver transplantation, our results do not support systematic early transplantation.

Adolescent↗
PubMed1992

Blood flow response to auditory stimulations in normal, mentally retarded, and autistic children: a preliminary transcranial Doppler ultrasonographic study of the middle cerebral arteries.

Using the noninvasive transcranial ultrasonic Doppler method, flow dynamics of the middle cerebral arteries were investigated in relation to auditory stimulations in 12 children with autistic behavior compared with 12 normal controls and 10 mentally retarded children. In normal children, auditory stimulation evoked lateralized modifications: blood flow increased and resistance index decreased on the left side; such modifications were not recorded on the right side. This pattern should indicate vasodilatation mechanisms induced by changes in the metabolism of the brain areas supplied by the left middle cerebral arteries (MCA). Although less asymmetrical, this pattern was also found in the mentally retarded children. Autistic children significantly differed from these two groups. They displayed a symmetric pattern of responses with a blood flow decrease and resistance-index increase on both sides; this could suggest abnormal metabolic mechanisms induced by auditory stimulation in autistic children and could be related to the previous hypothesis of impairment in the development of cerebral lateralization in autism. These preliminary results show that transcranial Doppler ultrasonography may be a valuable and practicable tool for the noninvasive study of evoked blood flow responses in psychopathology.

Arousal↗
PubMed1992

[Demonstration of cerebral lateralisation disorder in autistic children: study of auditory reactivity by transcranial pulsed Doppler].

Transcranial Doppler Ultrasonographic recordings of the middle cerebral arteries were performed on children with autistic behavior (AUT), compared to retarded children without autistic behavior (NON-AUT) and normal children (NOR). Blood flow measurements (resistance index) were performed at rest and during auditory stimulations. Compared to NOR and NON-AUT, significant differences of the resistance index were found in AUT on the left side, thus suggesting differences in metabolic mechanisms evoked by auditory stimulations. This result confirms the hypothesis of abnormal development of cerebral lateralization in autism.

Autistic Disorder↗
PubMed1991

Auditory evoked responses (AER) and augmenting-reducing phenomenon in patients with progressive supranuclear palsy (PSP).

Variations in amplitude and latency of P1, N1 and P2 waves of AER induced by increasing the stimulus intensity (augmenting-reducing) were measured in PSP patients and compared to those observed in normal subjects. The studied population included 17 patients (10 male, 7 female, mean age 66 +/- 8 yr) with a typical PSP symptomatology and 17 normal subjects (10 male, 7 female, mean age 66 +/- 9 yr). All subjects from both the groups showed a normal auditory threshold (less than 30 db SPL or a moderately increased threshold never exceeding 10 db SPL). Nine patients had normal BAER; 4 patients showed an abnormal III wave; 3 patients showed an abnormal V wave. One patient had a poorly individualized BAER. Latencies and amplitudes of P1, N1 and P2 waves derived from Cz and Fz (linked ear reference) were studied with 50, 60, 70 and 80 db intensities and for each patient slopes of amplitude-stimulus intensity and latency-stimulus intensity curves were studied. Although patients showed decreased AER amplitudes, the augmenting-reducing phenomenon was not different from controls regarding either latency or amplitude changes with increasing stimulus intensity. Previous studies had established a negative correlation between the augmenting-reducing responses and HVA levels in the cerebrospinal fluid (CSF). Similarity of augmenting-reducing mechanisms in PSP and normal subjects favors the hypothesis of unimpaired mesocortical and mesolimbic dopaminergic pathways in PSP. This hypothesis is also supported by postmortem studies using biochemical markers.

Aged↗
PubMed1989

Urinary dopamine metabolites as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior.

Modifications in serotonin and dopamine metabolism were evaluated in 13 children with autistic behavior and related to their responsiveness to fenfluramine treatment. A double-blind medication-placebo crossover design was used. Each patient received 1.5 mg/kg fenfluramine daily for 3 months followed and preceded by placebo for 1 month. Clinical improvement was observed in 6 children (responders). It included reduction of behavioral symptoms such as motor activity, anxiety, mood disturbances, and distractibility. Modifications of serotonin (5-HT), dopamine (DA), and DA metabolites [homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC)] were assessed at urinary levels. Responders and nonresponders showed a significant decrease of urinary 5-HT levels on fenfluramine. The main differences between the two groups of subjects were found with HVA, the major metabolite of DA. Fenfluramine significantly increased HVA levels in responders whereas no significant modification was found in nonresponders. Moreover the initial level of HVA (lower in responders) significantly differentiated the two groups. These results suggest that the clinical response to fenfluramine could be related to the dopaminergic action of this drug and that urinary DA metabolite levels could be considered as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Effect of age on auditory evoked responses (AER) and augmenting-reducing.

Auditory evoked responses (AER) were obtained from Cz and Fz in 30 adults (14 male, 16 female) from 20-80 years old. Sound bursts (1000 Hz-200 msec) of four different intensities were used. Peak to trough amplitudes of P1N1 and N1P2 and latencies of P1, N1 and P2 peaks were measured with increasing stimulus intensity and slopes of amplitude - intensity and latency - intensity curves were analysed for assessment of an age effect. The main result is that the increase in P1N1 amplitude with increasing stimulus intensity is more pronounced in older persons. Previous studies have established a negative correlation between the augmenting-reducing responses and HVA levels in the CSF (with lower amounts of HVA in the CSF of "augmenters"). Decreased dopamine metabolism in old subjects could account for our results, so further studies should focus on patients with pathological dopamine deficiencies.

Acoustic Stimulation↗
PubMed1989

Auditory evoked potential modifications according to clinical and biochemical responsiveness to fenfluramine treatment in children with autistic behavior.

Evoked potentials to auditory stimulations varying in intensity were studied in 13 children with autistic behavior treated with fenfluramine. Modifications of both amplitude and single-trial potential variability were considered according to the clinical and biochemical responsiveness to this drug. Six children (responders) were clinically improved by the treatment. Electrophysiological data were affected according to the clinical and biochemical responsiveness to fenfluramine: the auditory evoked potential amplitude increased, and the single-trial potential variability decreased at each intensity level only in responders whose dopaminergic metabolism was significantly modified by fenfluramine treatment. No modification was found in nonresponders. Both biochemical and electrophysiological results argued for an amphetamine-like action of fenfluramine in those autistic children whose attention deficits are associated with motor disturbances including hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

[Measurement of cerebral blood flow by transcranial Doppler ultrasonography in children presenting with autistic behavior. Preliminary results].

Transcranial Doppler ultrasonographic recordings of the middle cerebral arteries were performed on eight children with autistic behavior compared to eight controls. Blood flow measurements were assessed at rest and during auditory and visual stimulations. The main result was obtained during the auditory stimulations and concerned the left artery blood flow which is lower in autistics than in controls in these conditions (p less than .02). This result confirms the possibility of a left hemisphere dysfunctioning in autistics and may be related to clinical features as language disabilities and paradoxical reactivity to auditory stimuli.

Acoustic Stimulation↗
PubMed1988

Urinary free and conjugated catecholamines and metabolites in autistic children.

Urinary catecholamines (DA, NE, E) and their main metabolites (HVA, DOPAC, MHPG) were analyzed both as free and conjugates in eight children diagnosed as autistic according to DSM-III criteria and eight normal children. Significant differences appeared for the urinary excretion of both DA and NE and their respective metabolites: Autistic children showed low DA, high HVA, high NE, low MHPG urinary levels. These results are consistent with previous findings on altered catecholamine metabolism in autistic children. They suggest that autistic behaviors might be related to an abnormal functional imbalance among monoamines either at a molecular level or at a system level. Furthermore, they emphasize the special interest of urinary assays in pediatric research.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Urinary homovanillic acid levels of autistic children.

Anomalies in dopamine metabolism were investigated by assaying total homovanillic acid, and its free and conjugated fractions, in the urine of 34 autistic, 34 normal and 34 mentally retarded children. An increase in total homovanillic acid in autistic and retarded children is apparently due to an increase of free homovanillic acid in the autistic group and to an increase of conjugated homovanillic acid in the retarded group. Further research needs to be carried out into the central origin of homovanillic acid and to establish its relevance to autistic children.

Autistic Disorder↗