Search PubMed⌕ Search

Biomedical subjects

Y Robitaille

Publications and source records attributed to Y Robitaille.

At least 55 records · Page 3Linked to original sources
PubMed1995

Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson's disease and dominantly inherited olivopontocerebellar atrophy.

We measured the levels of dopamine, tyrosine hydroxylase (TH) protein, and dihydroxyphenylalanine (DOPA) decarboxylase (DDC) protein in the striatum of 10 patients with idiopathic Parkinson's disease (PD) and 23 patients with dominantly inherited olivopontocerebellar atrophy (OPCA). The levels of dopamine were markedly reduced (2% of control) in the striatum of the patients with PD, whereas striatal dopamine in the patients with OPCA ranged from normal (> 60% of control) to moderately reduced (20-60% of control) to severely depleted (< 20% of control). Both TH and DDC protein levels were significantly lower than those of the controls in the striatum of all of the patients with PD and in the subgroup of patients with OPCA having severely depleted dopamine. In contradistinction, TH but not DDC protein levels were reduced in those patients with OPCA having moderately reduced dopamine levels. This suggests that in the early stage of nigrostriatal dopamine neurone degeneration, DDC levels may be less susceptible to neurodegenerative influences than is TH synthesis or, alternatively, DDC synthesis may be more aggressively upregulated. Unexpectedly, from the blot immunolabeling analysis an additional DDC-immunoreactive band of slightly lower apparent molecular mass was detected in two of the patients with PD and in 12 of the patients with OPCA. This additional DDC band, which was not present in any of the control subjects, may reflect posttranslational modification(s) of DDC related to the neurodegenerative process.

Aged↗
PubMed1995

Structural and immunocytochemical features of olivopontocerebellar atrophy caused by the spinocerebellar ataxia type 1 (SCA-1) mutation define a unique phenotype.

Neuropathological investigations performed on autopsied brain and spinal cords from 11 patients showed that spinocerebellar ataxia type 1 (SCA-1) can be distinguished from autosomal dominant spinocerebellar ataxia linked to SCA-2 and -3 loci on chromosomes 12 and 14, spinopontine, and the multisystem atrophies. The major diagnostic criteria were: absence of significant pars compacta nigral and locus coeruleus lesions, severe degeneration of olivocerebellar and dentatorubral pathways, extensive loss of Purkinje cells with partial sparing of flocculonodular lobes, severe atrophy of specific cranial nerve nuclei, mostly the third and 12th, extensive loss of motor neurons in anterior horns and Clarke's columns, and lack of oligodendroglial or neuronal cytoplasmic cytoskeletal inclusions. None of the brains displayed any significant immunoreactivity for the amyloid precursor protein or beta-amyloid peptide throughout the cortex. In conclusion, the type and neuroanatomical distribution of structural lesions were similarly reproduced in all probands at the end stage of SCA-1, to the point that they appeared to constitute a unique phenotype.

Adolescent↗
PubMed1995

beta-alanine uptake is upregulated in FeCl3-induced cortical scars.

Glial uptake of beta-[14C]alanine (beta-Ala) was studied in male Sprague-Dawley rats after sub-pial iontophoresis of FeCl3 into the right motor strip. Models bearing a 15-day-old scar were selected because of the presence of strongly reactive glia induced by FeCl3. Behavioral seizures were observed by daily visual inspection in one third of the animals. The effects of intraperitoneal (i.p.) injections of DL-alpha-aminoadipic acid (DLaAA), which exerts specific gliotoxicity through glutamine synthetase (GS) inhibition, and of 3-mercaptoproprionic acid (3MP), a potent inhibitor of glutamic acid decarboxylase (GAD: the rate-limiting enzyme in the biosynthesis of gamma-aminobutyric acid [GABA]), were also examined. There was significant enhancement of beta-Ala uptake in the margins of the scars. Further increases of uptake were triggered by 3MP, and there was extensive recruitment of astrocytes within isocortex even at a distance from the edges of the scar. DL-alpha-Aminoadipic acid caused a slight decrease of beta-Ala uptake, which was selectively localized to the scar margins. Seizure activity was unchanged by high i.p. doses of DL alpha AA. Our results strongly suggest that beta-Ala has high affinity for normal and reactive astrocytes, and that the uptake can be significantly enhanced by lowering endogenous GABA levels in abnormal cortical tissues in and around FeCl3-lesions by inhibition of GAD. Enhancement of glial beta-Ala uptake appeared to depend heavily on increased endothelial transport of small neutral amino acids, in a process modulated by perivascular glia. This model of free radical neurotoxicity may help gain more insight into abnormal neuronal-glial interactions caused by lipid peroxidation.

Animals↗
PubMed1995

Retained language in dysgenic cortex: case report.

Since the advent of magnetic resonance imaging, there has been renewed interest in disorders of cortical migration in the cause of focal epilepsy. The function of dysplastic cortex is poorly understood. We report a 46-year-old woman in whom this was assessed by intraoperative stimulation. This left-handed patient had a 30-year history of complex partial seizures with secondary generalization. Prolonged electroencephalographic recordings documented an epileptic focus in the right lateral and inferomesiotemporal lobe. Computed tomographic scanning and angiography suggested a right posterotemporal hamartoma. Amytal testing showed major speech representation in the right hemisphere. At craniotomy, an ivory-colored, posterotemporal lesion originating 5 cm from the temporal tip and 4 cm in diameter occupied the posterotemporal region. Electrical stimulation of this lesion produced speech interference. A histological examination of the resected anterotemporal lobe, amygdala, and hippocampus and biopsy specimens of the lesion showed extensive multifocal cortical microdysgenesis and gliovascular and cortical hamartoma. This case shows that grossly dysplastic cortex can remain functional. Cortical mapping under local anesthesia should be performed before resection of dysplastic lesions in putatively functional areas in patients with intractable epilepsy.

Amygdala↗
PubMed1994

Apo E allele frequencies in Alzheimer's disease, Lewy body dementia, Alzheimer's disease with cerebrovascular disease and vascular dementia.

Apolipoprotein (Apo E) was genotyped using a fluorescent PCR-RFLP assay in 187 patients with a probable or possible clinical diagnosis of sporadic Alzheimer's disease (AD) and in 166 autopsied patients with dementia (21 presenile AD, 70 senile AD, 18 Lewy body dementia (LBD), 38 AD with cerebrovascular disease (AD-CVD), 19 vascular dementia). The relative epsilon 4 allele frequency was 0.472 in LBD, 0.513 in AD-CVD, 0.405 in presenile AD, 0.364 in senile AD, and 0.079 in vascular dementia. The relative epsilon 2 allele frequency was 0.211 in vascular dementia, 0.083 in LBD, 0.047 in presenile AD, 0.100 in senile AD and 0.039 in AD with CVD. We infer that apo E is a major risk factor for structural phenotypes of dementia involving AD, alone or in conjunction with another pathology. In addition, the epsilon 2 allele is likely to represent a risk factor for vascular morbidity, as the relative epsilon 2 allele frequency was 0.211 in patients with vascular dementia compared with 0.144 in elderly controls.

Adolescent↗
PubMed1994

Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies.

Apoliprotein E (apoE) is associated with Alzheimer's neurofibrillary tangles and beta-amyloid protein in senile plaques. Recent studies have shown an increased frequency of the epsilon 4 allele of the apoE gene in familial and sporadic cases of Alzheimer's disease (AD). In the present case control study, we have determined the apoE genotype by allele-specific extension of 113 postmortem cases of sporadic AD and 77 control brains shown to be free of AD neuropathological features and then calculated the frequency of the various allelic forms of apoE (epsilon 2, epsilon 3, epsilon 4). The odds ratio associating epsilon 4 with AD was 15.5 (95% confidence interval [CI] 6.2-38.5), and the population attributable risk was 0.53. We have also combined the results of our study and several others to calculate these same parameters in a larger population (570 controls and 961 AD subjects); the odds ratio for this larger group was 6.2 (95% CI 4.9-7.8) and the population attributable risk was 0.57. These results further substantiate and strengthen the association between the epsilon 4 allele of apoE gene and AD. We have also used these results to investigate the usefulness of the determination of epsilon 4 carrier status in the diagnosis of AD.

Aged↗
PubMed1994

Biochemical mapping of neurofibrillary degeneration in a case of progressive supranuclear palsy: evidence for general cortical involvement.

A biochemical study was performed to quantify and map the neurodegenerating process in cortical and subcortical brain areas from a case of progressive supranuclear palsy (PSP). Our approach was based on a Western blot analysis of pathological Tau proteins, which are the basic components of neurofibrillary lesions. We found that: (i) the abnormal Tau proteins can be detected in all cortical areas, sometimes in larger amounts than in some subcortical areas; (ii) these abnormal Tau proteins consist of a doublet called Tau 64 and 69, except for in the entorhinal cortex where we detected, as for Alzheimer brains, the triplet of Tau proteins called Tau 55, 64 and 69; (iii) the amounts of abnormal Tau proteins were higher in some neocortical regions, especially in the frontal lobe, than in the hippocampal formation. Our results show that the neocortical pathology in PSP, as revealed by the presence of pathological proteins, is more extended than thought so far. Our biochemical approach appears to be more sensitive than the immunohistochemical one and can clearly differentiates between two types of neurofibrillary pathology, the Alzheimer type with a triplet of abnormal Tau proteins (Tau 55, 64 and 69) and the PSP type with a characteristic doublet (Tau 64 and 69).

Aged↗
PubMed1994

Cerebellar glutamate metabolizing enzymes in spinocerebellar ataxia type I.

We measured the levels of three glutamate metabolizing enzymes, namely, glutamate dehydrogenase (GDH), aspartate aminotransferase (AAT), and glutamine synthetase (GS) in cerebellar and occipital cortices of nine patients with dominantly-inherited olivopontocerebellar atrophy (OPCA; spinocerebellar ataxia type I). As compared with the controls, mean GDH activities in cerebellar cortex of the OPCA patients were normal whereas levels of AAT (-17%) and the glial enzyme GS (-27%) were significantly reduced. No statistically significant changes were observed in occipital cortex, a morphologically unaffected brain area. We suggest that the decreased GS levels could reflect impaired capacity of astrocytes to metabolize glutamate which might contribute to the degenerative processes in OPCA cerebellum.

Adult↗
PubMed1994

Operative strategies for patients with cortical dysplastic lesions and intractable epilepsy.

Cortical dysplastic lesions (CDLs) are usually identified by magnetic resonance imaging (MRI). Clinical, electrographic and histologic findings suggest that focal CDLs (FCDLs) are highly epileptogenic, often involve the rolandic cortex, and can present variable degrees of histopathologic abnormalities. An ictal or "ictal-like" bursting pattern of electrographic activity was recorded over dysplastic cortex in 65% of our patients. Resective surgery can eliminate or significantly reduce seizure frequency in many medically intractable patients, depending on lesion location, degree, and extent of histopathologic abnormalities. Best results are achieved when complete or major excision of both the MRI-visible lesion and the cortical areas displaying ictal electrographic activity can be performed. This is more likely when the degree of histopathologic abnormality is mild to moderate or when the lesion is in a temporal lobe. More severe histopathologic abnormalities and central insular or multilobar lesions usually lead to less favorable results: either major excision of the visualized lesion is impractical or the lesion is microscopically more extensive than shown by MRI. Multilobar resection or hemispherectomy for patients with infantile spasms associated with CDLs and for patients with hemimegalencephaly are often associated with dramatic improvement in seizure control. Callosotomy can be performed in selected patients with diffuse CDLs who have intractable drop attacks.

Adolescent↗
PubMed1994

Expression of human immunodeficiency virus type 1 in the nervous system of transgenic mice leads to neurological disease.

Patients infected with the human immunodeficiency virus type 1 (HIV-1) frequently develop central and peripheral nervous system complications, some of which may reflect the effect of the virus itself. In order to elucidate the pathogenic mechanisms of HIV in neurological disease in a small animal model, we generated transgenic mice expressing the entire HIV genome under control of the promoter for the human neurofilament NF-L gene. The transgene was predominantly expressed in anterior thalamic and spinal motor neurons. Animals developed a neurological syndrome characterized by hypoactivity and weakness and by axonal degeneration in peripheral nerves. These results provide evidence for a role of HIV in affecting both the central and peripheral nervous systems. This animal model may also facilitate the development of therapeutic agents against the human disease.

Animals↗
PubMed1993

Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2-macroglobulin and C-reactive protein.

Recent immunocytochemical data have demonstrated increases in interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and the IL-6-inducible acute phase protein, alpha 2-macroglobulin (alpha 2-M), in Alzheimer's disease (AD) brains. We investigated the levels of these proteins quantitatively using ELISA procedures and determined if increases in IL-1 beta were compensated for by a parallel increase in the endogenous interleukin-1 receptor antagonist (IL-1RA). Comparing control vs. Alzheimer's temporal cortex, we examined mature IL-1 beta, IL-1RA, IL-6, alpha 2-M and C-reactive protein (CRP). The specificities of the ELISA procedures were verified by serial dilutions of the samples; by chromatofocusing, and by Sephadex G-150 gel filtration. There were no differences in the levels of mature IL-1 beta or IL-1RA in AD and control brains. However, IL-6 levels were detectable in 14 of the 16 Alzheimer samples but only 2 of the 14 control samples. There were also significant increases seen in alpha 2-M and CRP levels in the Alzheimer's group compared to controls. These data support previous studies demonstrating a possible up-regulation of neuroimmune function in Alzheimer's cortex; however, we cannot determine, at this time, if this immune reaction is initiated by IL-1 beta.

Acute-Phase Proteins↗
PubMed1993

Phospholipid metabolite levels are altered in cerebral cortex of patients with dominantly inherited olivopontocerebellar atrophy.

We measured metabolic precursors and breakdown products of phosphatidylcholine (choline, glycerophosphocholine (GPC) and phosphatidylethanolamine (ethanolamine, glycerophosphoethanolamine (GPE)) as well as the amino acid serine, a precursor of phosphatidylserine, in four morphologically unaffected cerebral cortical areas obtained at autopsy from 14 patients with dominantly inherited olivopontocerebellar atrophy (OPCA) and 13 controls matched for age and postmortem interval. As compared with the controls, mean GPE levels were elevated by 49-57% in frontal and parietal cortices of OPCA brains whereas concentrations of ethanolamine were significantly reduced in temporal, occipital and parietal cortex (-40 to -54%). This resulted in increased GPE/ethanolamine ratios (+80 to +146%). GPC levels were significantly increased (by 53%) in the frontal cortex of OPCA patients relative to controls. Free serine levels were reduced by 20 to 28% in frontal, parietal, temporal, and occipital cortices. These abnormalities in phospholipid metabolite levels in OPCA resemble those seen in Alzheimer's disease, although the changes in GPC are less pronounced. These changes in phospholipid metabolism in OPCA cerebral cortex, a brain area spared from neurodegenerative changes, points to generalized disturbances in cellular membrane function in this disease.

Adult↗
PubMed1993

NGF level of is not decreased in the serum, brain-spinal fluid, hippocampus, or parietal cortex of individuals with Alzheimer's disease.

Although the cause of Alzheimer's disease (AD) is unknown, nerve growth factor (NGF) has gained attention as a therapeutic agent for the disease. Because NGF maintains the magnocellular cholinergic neurons that are damaged in AD, research interests have been focused on the change in NGF level in patients with AD. This is the first reported study in which human NGF levels were accurately measured and compared between normal and AD samples. We measured NGF levels using enzyme immunoassay (EIA) system for human NGF and found no difference in NGF level in serum, brain-spinal fluid, or brain (hippocampus and parietal cortex) obtained from normal people and patients with AD. These results suggest that a decrease in the NGF level is not a causative factor of AD.

Alzheimer Disease↗
PubMed1993

Neurological disease induced in transgenic mice expressing the env gene of the Cas-Br-E murine retrovirus.

The Cas-Br-E murine leukemia virus induces a spongiform myeloencephalopathy in susceptible mice. We constructed transgenic mice harboring either the viral genome (in a replication-defective form) or only its env gene. Low levels of expression of either transgene resulted in mild neuropathology and/or signs of neurological disease in more than half of these mice. These results indicate that the disease can occur in the absence of virus replication and strongly suggest that the env gp70/p15E complex is sufficient to induce disease.

Animals↗
PubMed1993

Incidence of and risk factors for falls and injurious falls among the community-dwelling elderly.

To determine the frequency of and risk factors for falls and injurious falls in the noninstitutionalized elderly, the authors conducted a follow-up study of 409 community-dwelling persons aged 65 years or more in west-central Montreal, Quebec, Canada, from May 1987 to October 1988. Following an initial at-home interview, each subject was telephoned every 4 weeks for 48 weeks for collection of data on falls experienced since the last contact. Each of the 12 follow-up interviews was completed by at least 90% of the subjects eligible for interview. Data were also collected in the follow-up interviews on time-varying exposures. Twenty-nine percent of the subjects fell during follow-up; 17.6% fell once, and 11.5% fell two or more times. The incidence rate for falls was 41.4 falls per 1,000 person-months. The majority of falls resulted in no injury or in minor injury only. Potential risk factors investigated included sociodemographic variables, physical activity, alcohol consumption, acute and chronic health problems, dizziness, mobility, and medications. Multivariate analyses showed that the following factors were statistically significantly associated with an increased rate of falls: dizziness (incidence rate ratio (IRR) = 2.0), frequent physical activity (IRR = 2.0), having days on which activities were limited because of a health problem (IRR = 1.8), having trouble walking 400 m (IRR = 1.6), and having trouble bending down (IRR = 1.4). Factors which were protective included diversity of physical activities (IRR = 0.6), daily alcohol consumption (IRR = 0.5), having days spent in bed because of a health problem (IRR = 0.5), and taking heart medication (IRR = 0.6). Risk factors for injurious falls were similar.

Accidental Falls↗
PubMed1993

Life-threatening focal status epilepticus due to occult cortical dysplasia.

OBJECTIVE: Neuronal migration disorders are usually, but not necessarily, demonstrated by magnetic resonance imaging. Preoperative suspicion of these anomalies in the presence of normal magnetic resonance studies has important practical implications. This study delineates some clinical features that permit early suspicion of focal cortical dysplasia localized in the central and precentral regions. DESIGN: In a retrospective case series, we studied the clinical presentation of four consecutive patients with normal preoperative magnetic resonance images in whom focal cortical dysplasia was found in the surgical specimen. SETTING: Patients were seen in three referral centers specializing in epilepsy surgery. PATIENTS: Four patients (three female), between the ages of 4 and 21 years, had intractable partial seizures leading to resective brain surgery. INTERVENTION: Three patients had corticectomies in the central (two patients) or frontal (one patient) regions. One underwent an en bloc resection of the central area after two unsuccessful corticectomies and cortical transection. RESULTS: Three patients presented with life-threatening focal motor status epilepticus necessitating intubation, and one had epilepsia partialis continua. All had had seizures previously, and the attacks progressed to intractability after 1 1/2 to 3 years. Surgery led to control of the seizures, but only two patients became seizure free (mean follow-up, 15.7 months). All but one developed a postoperative deficit, which eventually improved. CONCLUSIONS: Focal cortical dysplasia should be suspected when life-threatening focal motor status epilepticus or epilepsia partialis continua occur in children or young persons without another obvious cause. Normal magnetic resonance studies do not exclude neuronal migration disorders.

Adolescent↗