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Biomedical subjects

Y Agid

Publications and source records attributed to Y Agid.

At least 289 records · Page 16Linked to original sources
PubMed1995

Selective impairments in managerial knowledge following pre-frontal cortex damage.

Script generation was investigated in patients with lesions in the prefrontal (n = 9) and posterior (n = 8) cortical regions and in normal subjects (n = 16). Three different activities ranging in degree of familiarity were studied. Frontal patients did not differ from patients with posterior lesion and Normal subjects in the number of actions evoked, mean evocation time, or centrality. Impairments in script information processing were observed only in patients with prefrontal lesions, and for the three types of scripts. Specifically these patients made errors in ordering actions in the correct temporal sequence, failed to close scripts and to remain within the stated boundaries, and made deviant estimates of action importance. The results suggest that pre-frontal cortical lesions provoke a selective impairment in managerial knowledge (Grafman, 1989) that may contribute to difficulties in the formulation and execution of plans.

Adult↗
PubMed1995

Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form.

Huntington's disease (HD) results from the expansion of a polyglutamine encoding CAG repeat in a gene of unknown function. The wide expression of this transcript does not correlate with the pattern of neuropathology in HD. To study the HD gene product (huntingtin), we have developed monoclonal antibodies raised against four different regions of the protein. On western blots, these monoclonals detect the approximately 350 kD huntingtin protein in various human cell lines and in neural and non-neural rodent tissues. In cell lines from HD patients, a doublet protein is detected corresponding to the mutated and normal huntingtin. Immunohistochemical studies in the human brain using two of these antibodies detects the huntingtin in perikarya of some neurons, neuropiles, varicosities and as punctate staining likely to be nerve endings.

Amino Acid Sequence↗
PubMed1995

Long-term induction of tyrosine hydroxylase expression: compensatory response to partial degeneration of the dopaminergic nigrostriatal system in the rat brain.

The present study was undertaken to examine the adaptive changes occurring 1 and 6 months after moderate or severe unilateral 6-hydroxydopamine-induced lesions confined to the lateral part of the rat substantia nigra pars compacta (SNC). The expression of tyrosine hydroxylase (TH) enzyme was analyzed in the remaining dopaminergic nigral cell bodies and in the corresponding striatal nerve endings. In the cell bodies of the lesioned SNC, TH mRNA content was increased (+20 to +30%) 6 months after the lesion without changes in cellular TH protein amounts. The depletion of TH protein in the nerve terminal area was less severe than the percentage of cell loss observed in the SNC at 1- and 6-month postlesion intervals. Moreover, the decrease in TH protein in the ipsilateral striatum was less pronounced 6 months after lesion than 1 month after. That no corresponding change in TH protein content was observed in the cell bodies at a time when TH increased in nerve terminals suggests that the newly synthesized protein is probably rapidly transported to the striatal fibers. These results suggest the existence of a sequence of changes in TH expression between cell bodies and fibers, occurring spontaneously after partial denervation of the nigrostriatal pathway.

Adaptation, Physiological↗
PubMed1995

Does the enhancement of cholinergic neurotransmission influence brain glucose kinetics and clinical symptomatology in progressive supranuclear palsy?

Cholinergic systems are markedly affected both in cortical and subcortical cerebral areas of patients with progressive supranuclear palsy (PSP). To determine whether it is possible to modify the clinical picture of PSP through the enhancement of brain cholinergic neurotransmission, we studied the effects of physostigmine, an anticholinesterase reference drug, on symptoms and brain glucose metabolism using [18F]fluorodeoxyglucose (FDG) and PET. Patients were evaluated blind in a randomized order with both placebo and physostigmine infusions after an individual determination of maximal tolerated dose. Under steady-state physostigmine infusions, although glucose consumption was not significantly modified, the entry of glucose from blood to brain was regionally increased from 8 to 32% of placebo values suggesting an increase in cerebral blood flow (CBF) or an increase in the activity of brain glucose transporter. Following physostigmine administration in the same patients: the errors in antisaccades during ocular movement testing were significantly reduced, a significant reduction in errors or performance was found in four out of seven neuropsychological tests, and motor disability was not significantly altered. Although the precise pathophysiology of these physostigmine-induced effects needs further investigations, our study suggests that part of the clinical symptomatology in PSP could be relieved by the enhancement of brain cholinergic neurotransmission.

Aged↗
PubMed1995

Sequence analysis of the CCG polymorphic region adjacent to the CAG triplet repeat of the HD gene in normal and HD chromosomes.

The CAG expansion responsible for Huntington's disease (HD) is followed by an adjacent polymorphic CCG repeat region which may interfere with a PCR based diagnosis. We have sequenced this region in 52 unrelated HD patients, from both normal and HD chromosomes. Fifty percent of the normal alleles were (CCG)7(CCT)2, 48% (CCG)10(CCT)2, and 2% (CCG)7(CCT)3. In contrast (CCG)7(CCT)2 was found in 85% of the HD alleles which represents significant linkage disequilibrium with the HD mutation.

Alleles↗
PubMed1995

Neuropsychological pattern of striatonigral degeneration: comparison with Parkinson's disease and progressive supranuclear palsy.

To study the neuropsychological pattern of striatonigral degeneration (SND), 14 consecutive patients with probable SND were submitted to an extensive battery of neuropsychological tests. Compared with controls the performance of patients with SND was impaired on category and phonemic fluency, frontal behaviours, trail making test A and B, and free recall of the Grober and Buschke test, but normal on the revised WAIS verbal scale, Raven 47 coloured progressive matrices, Wechsler memory scale, California verbal learning test, Wisconsin card sorting test, and the Stroop interference condition. The performance of patients with SND was also compared with that of 14 patients with Parkinson's disease and 14 patients with progressive supranuclear palsy (PSP) matched for age at onset, duration of disease, severity of intellectual deterioration, and depression. The results showed that the dysexecutive syndrome of SND is similar to that of Parkinson's disease and less severe than in PSP.

Analysis of Variance↗
PubMed1995

Memory disorders in probable Alzheimer's disease: the role of hippocampal atrophy as shown with MRI.

Magnetic resonance based volumetric measures of hippocampal formation, amygdala (A), caudate nucleus (CN), normalised for total intracranial volume (TIV), were analysed in relation to measures of cognitive deterioration and specific features of memory functions in 18 patients with probable Alzheimer's disease. Neuropsychological examination included the mini mental state examination (MMSE), the Mattis dementia rating scale (DRS), tests of executive functions, assessment of language abilities and praxis, the Wechsler memory scale (WMS), the California verbal learning test (CVLT) and the Grober and Buschke test. The volume of the hippocampal formation (HF/TIV) was correlated with specific memory variables: memory quotient and paired associates of the WMS; intrusions and discriminability at recognition for the Grober and Buschke test. By contrast, except for intrusions, no correlations were found between memory variables and the volume of amygdala (A/TIV). No correlations were found between the volume of caudate nuclei (CN/TIV) and any neuropsychological score. The volume of the hippocampal formation was therefore selectively related to quantitative and qualitative aspects of memory performance in patients with probable Alzheimer's disease.

Aged↗
PubMed1995

Alterations of GABAergic neurons in the basal ganglia of patients with progressive supranuclear palsy: an in situ hybridization study of GAD67 messenger RNA.

We analyzed postmortem GABAergic neurons in the basal ganglia of three patients with progressive supranuclear palsy (PSP) and four matched controls by means of glutamic acid decarboxylase (M(r) 67,000 [GAD67]) mRNA in situ hybridization. In PSP, we found a 50 to 60% decrease in the number of neurons expressing GAD67 mRNA in the caudate nucleus, ventral striatum, and the external and internal pallidum. The expression of GAD67 mRNA per neuron was reduced in the caudate nucleus and putamen (-43%), the ventral striatum (-55%), and the external and internal pallidum (-59% and -68%). Our data indicate that striatal and pallidal GABAergic neurotransmission is markedly reduced in PSP and we suggest that this alteration may account for the motor and cognitive symptoms observed in PSP. Furthermore, the destruction of the basal ganglia output systems may explain the lack of responsiveness to L-dopa therapy of PSP patients.

Aged↗
PubMed1995

Levodopa-induced dyskinesias are improved by fluoxetine.

We evaluated the severity of motor disability and dyskinesias in seven levodopa-responsive patients with Parkinson's disease after an acute challenge with the mixed dopamine agonist, apomorphine, before and after the administration of fluoxetine (20 mg twice per day) for 11 +/- 1 days. After fluoxetine treatment, there was a significant 47% improvement (p < 0.05) of apomorphine-induced dyskinesias without modification of parkinsonian motor disability. The dyskinesias were reduced predominantly in the lower limbs during the onset and disappearance of dystonic dyskinesias (onset- and end-of-dose dyskinesias) and in the upper limbs during choreic mid-dose dyskinesias. The results suggest that increased brain serotoninergic transmission with fluoxetine may reduce levodopa- or dopamine agonist-induced dyskinesias without aggravating parkinsonian motor disability.

Antiparkinson Agents↗
PubMed1995

Clinical, electrophysiologic, and molecular correlations in 13 families with hereditary neuropathy with liability to pressure palsies and a chromosome 17p11.2 deletion.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease characterized by recurrent episodes of acute nerve palsies. We performed a clinical, electrophysiologic, and molecular study of 13 French families with HNPP associated with a chromosome 17p11.2 deletion in 36 individuals. There were electrophysiologic abnormalities in all symptomatic (n = 28) and asymptomatic (n = 8) deletion carriers, even in childhood. Bilateral delayed distal motor latency of the median nerve at the wrist, reduced sensory velocity in the palm-wrist segment, and delayed distal motor latency or reduced motor velocity in the peroneal nerve was diagnostic in at-risk relatives. This large series confirms the reliability of molecular analysis combined with a simplified electrophysiologic examination for the diagnosis of HNPP associated with 17p11.2 deletion.

Adolescent↗
PubMed1995

The neuropsychological pattern of corticobasal degeneration: comparison with progressive supranuclear palsy and Alzheimer's disease.

The pattern of cortical and subcortical neuropathologic lesions in corticobasal degeneration (CBD) should predict a specific cognitive profile in this disease. To characterize this profile and to determine its specificity by comparison with progressive supranuclear palsy (PSP) and senile dementia of the Alzheimer's type (SDAT), we used an extensive neuropsychological battery assessing global efficiency, executive functions, various tests of encoding and retrieval, dynamic motor organization, and upper limb praxis. We compared the performance of patients with CBD (n = 15) with that of controls (n = 19) matched for age and education, and with that of patients with PSP and SDAT (15 in each group), matched for severity of dementia and depression. Patients with CBD showed: (1) a moderate global deterioration; (2) a dysexecutive syndrome similar to that of patients with PSP and more severe than in SDAT; (3) explicit learning deficits, without retention difficulties and easily compensated by using the same semantic cues at encoding and retrieval as in PSP; this was in contrast with SDAT where cued recall and recognition were also impaired; (4) disorders of dynamic motor execution (temporal organization, bimanual coordination, control, and inhibition) similar to those of patients with PSP and not in SDAT; (5) asymmetric praxis disorders (posture imitation, symbolic gesture execution, and object utilization) that were not observed in PSP or SDAT. Patients with CBD show a specific neuropsychological pattern associating a dysexecutive syndrome, likely due to degeneration of the basal ganglia and prefrontal cortex, and asymmetric praxis disorders, which might be related to premotor and parietal lobe lesions. This neuropsychological profile may help to distinguish this condition clinically from other neurodegenerative diseases.

Aged↗
PubMed1995

Marked phenotypic heterogeneity associated with expansion of a CAG repeat sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus.

The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with those with Machado-Joseph disease (MJD), the gene of which maps to the same region. We show here that the disease gene segregating in each of three French ADCA type I kindreds and in a French family with neuropathological findings suggesting the ataxochoreic form of dentatorubropallidoluysian atrophy carries an expanded CAG repeat sequence located at the same locus as that for MJD. Analysis of the mutation in these families shows a strong negative correlation between size of the expanded CAG repeat and age at onset of clinical disease. Instability of the expanded triplet repeat was not found to be affected by sex of the parent transmitting the mutation. Evidence was found for somatic and gonadal mosaicism for alleles carrying expanded trinucleotide repeats.

Adolescent↗
PubMed1995

Autosomal dominant cerebellar ataxia type I linked to chromosome 12q (SCA2: spinocerebellar ataxia type 2).

Spinocerebellar ataxia 2 (SCA2) is one of the loci for the clinically and genetically heterogeneous group of autosomal dominant type I cerebellar ataxias. After initial linkage to chromosome 12q in Cuban families, SCA2 was shown to be the gene responsible for the disease in Italian, Tunisian, French-Canadian, Austrian-Canadian and Martinican kindreds with dominant ataxia, and the candidate interval was reduced to 6.4 cM between markers D12S84 and D12S79. Comparison of patients from families of different geographical origins clearly demonstrates the clinical interfamilial variability of the clinical signs which reaches statistical significance for the frequency of extrapyramidal rigidity, postural tremor and dementia. The most striking difference between the 29 Martinican SCA2 patients and those with SCA1 on chromosome 6p or SCA3/MJD on chromosome 14q is the greater frequency of hyporeflexia in the former. A mean 12.5 year anticipation is observed, with a more rapid clinical course of the disease in successive generations, indicating that an expanded trinucleotide repeat probably constitutes the underlying molecular mechanism.

Adolescent↗