Biomedical subjects

Y Robitaille

Publications and source records attributed to Y Robitaille.

At least 109 records · Page 6Linked to original sources

PubMed1990

Morphologic heterogeneity of human adult astrocytes in culture: correlation with HLA-DR expression.

Human adult astrocytes derived from brain surgical resections showed marked morphologic heterogeneity when cultured in vitro, ranging from a flat, fibroblast-like appearance to process-bearing cells with little soma cytoplasm. The majority of cells were intermediate in morphology, bearing a prominent cytoplasmic cell body with processes radiating from them. The morphologic heterogeneity was more extensive than that of adult rat astrocytes, and was not correlated with the extent of attendant gliosis in the surgical specimens, or the site of the surgical resection. None of the human astrocytes expressed A2B5, thus preventing their classification on basis of lineage into type 1 or type 2 astrocytes. However, functional differences appear to exist between subpopulations of human astrocytes, since the proportion of process-bearing human astrocytes that expressed HLA-DR in vitro was significantly greater than that found for flat astrocytes.

Adolescent↗

PubMed1990

Spinal synovial cyst: case report using magnetic resonance imaging.

The case of a 65-year-old woman who developed a spinal synovial cyst at the L4-5 disk space is reported. Her clinical signs and symptoms are presented. A comparison among her preoperative myelogram, computed tomography scan, and magnetic resonance imaging showed magnetic resonance imaging to be more accurate in detailing both the intraoperative and pathological findings.

Aged↗

PubMed1990

Neurochemical deficits in pathological brain aging: specificity and possible relevance for treatment strategies.

Normal brain aging is accompanied by the losses of certain neuronal populations and the appearance of structures such as neuronal plaques and neurofibrillary tangles. Additionally, various neurotransmitter systems are altered in the elderly, although marked variations are observed between individuals, suggesting important differences between successful and unsuccessful aging. In certain pathological conditions, only certain features of normal aging are exacerbated. For example, the densities of forebrain cholinergic neurons are markedly decreased in cortical and hippocampal (but not striatal) areas in Alzheimer's disease. We discuss here the comparative alterations of cholinergic markers in certain neurological disorders such as Alzheimer's disease, Parkinson's disease, and the combined pathology. Differential alterations of brain cholinergic profile are observed in each disorder, this most likely having functional significance. We also found that muscarinic receptors of the M2 subtype act as negative autoreceptors to decrease brain acetylcholine release, whereas nicotinic agonists induced the opposite effect. This suggests that blockade of negative M2 or stimulation of positive nicotinic autoreceptors could have beneficial effects in Alzheimer's disease. Additionally, modulation of heteroreceptor activation such as the serotonergic or interleukin-2 sites located on or in proximity to cholinergic nerve terminals could offer alternate strategies for the treatment of cholinergic deficits in pathological brain aging.

Aging↗

PubMed1990

Substitution of the U3 long terminal repeat region of the neurotropic Cas-Br-E retrovirus affects its disease-inducing potential.

The Cas-Br-E and ts-Mo BA-1 murine leukemia viruses (MuLV) induce a spongiform neurodegenerative disease with different clinical manifestations, namely, either hind limb paralysis (Cas-Br-E) or tremors, spasticity, and hind limb weakness (ts-Mo Ba-1). We constructed the chimeric NEBA-1 MuLV by replacing the long terminal repeat of Cas-Br-E MuLV with that of ts-Mo BA-1 MuLV. In SWR/J or CFW/D mice, NEBA-1 MuLV induced an ataxic neurological disease characterized by clinical signs different from those induced by both parents. Although NEBA-1 MuLV did not induce lesions in novel brain areas, the spongiform lesions were more severe in deep cerebellar nuclei and in the spinal cord than those found in paralyzed mice inoculated with Cas-Br-E MuLV. By in situ hybridization, we found that the distribution of the spongiform lesions closely correlated with the distribution of the infected central nervous system cells. In the spinal cord, a close correlation was found between the number of infected cells and the severity of the spongiform degeneration. Sequencing of the substituted ts-BA-1 MuLV fragment and comparison with homologous sequences of Cas-Br-E and Moloney MuLV showed differences mainly in the U3 tandem direct repeats. Our results show that a few modifications within the U3 long terminal repeat allow the virus to cause more severe lesions in some central nervous system regions and that the severity of the spongiform degeneration correlates with the level of viral replication.

Animals↗

PubMed1989

Cerebellar [3H]inositol 1,4,5-trisphosphate binding is markedly decreased in human olivopontocerebellar atrophy.

We examined the behaviour of [3H]inositol-1,4,5-trisphosphate (IP3) binding in autopsied cerebellar and cerebral cortex of 10 neurologically normal controls and 8 patients with end-stage olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder characterized histologically by severe degeneration of Purkinje cells. [3H]IP3 binding to normal human cerebellar cortex was 6-15 times higher than in cerebral cortex. As compared with the controls, mean [3H]IP3 binding to cerebellar cortex was markedly reduced by 61% in the OPCA patients whereas levels were normal in frontal and occipital cortices. Since the Purkinje cell dendrite receives neuronal input from granule cells and climbing fibers utilizing glutamate and aspartate, respectively, as neurotransmitters, the reduced IP3 binding in OPCA cerebellar cortex may reflect a loss of Purkinje cells containing these excitatory amino acid receptors linked to the phosphatidylinositide second messenger system. Our data suggest that in humans, IP3 receptors may be highly localized to the Purkinje cell dendrite.

Adult↗

PubMed1989

DNA synthesis by young adult human-derived astrocytes in vitro.

We have assessed whether adult human non-neoplastic astrocytes exhibit DNA synthesis in vitro, as measured using a double immunofluorescence technique to detect incorporation of 5-bromodeoxyuridine (BrdU) by nuclei of glial fibrillary acidic protein (GFAP)-containing cells. Dissociated cell cultures containing GFAP+ cells were established from surgically resected temporal lobe tissue from 3 young adult individuals operated upon to remove epileptogenic foci. In 5-18-day-old cultures from each of the 3 individuals, we observed GFAP+ cells whose nuclei had incorporated BrdU. BrdU nuclear staining was found in GFAP+ cells with either flat or process-bearing morphologies. The mean mitotic index for the GFAP+ cells was 6% (range 2-12%) as compared to a mean mitotic index of 29% for the GMK-7 glioma cell line. Our results do indicate that astrocytes derived from young adult donors, unlike such cells derived at autopsy from elderly adults, are capable of DNA synthesis in vitro, albeit to a markedly lesser extent than reported for fetal human astrocytes.

Adult↗

PubMed1989

Generalized cortical dysplasia manifested by diffusely thick cerebral cortex.

Unilateral or bilateral rolandic macrogyria has been described as a cause of epilepsy and, in some cases, retardation. Tissue from the periphery of these lesions shows the changes of focal cortical dysplasia. Evidence reported herein suggests that cortical dysplasia may also be generalized. Two patients with intractable epilepsy and mental retardation had diffusely abnormal, thick cortex, shallow gyri, and poor demarcation of gray and white matter. One patient had an anterior callosotomy that led to considerable improvement of the epilepsy. Cortical layers 5 and 6 could not be differentiated on biopsy material. The white matter was poorly myelinated and contained clusters of heterotopic neurons. This syndrome, a congenital disorder of neuronal migration, with prolonged survival, represents a mild form of lissencephaly. It can be diagnosed during life by computed tomography or magnetic resonance scanning.

Adolescent↗

PubMed1989

Non-Alzheimer-type pattern of brain cholineacetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy.

We recently reported reduced activity of the cholinergic marker enzyme cholineacetyltransferase (ChAT) in several brain regions of patients with dominantly inherited olivopontocerebellar atrophy (OPCA). To document the regional extent of these changes we performed a comprehensive examination of the behavior of ChAT throughout both cerebral cortical and subcortical brain areas in 5 patients from one large OPCA pedigree. As compared with the controls, mean ChAT activities in OPCA were reduced by 39 to 72% in all (n = 27) cerebral cortical areas examined and in several thalamic subdivisions, caudate head, globus pallidus, red nucleus, and medial olfactory area. In contradistinction to findings in Alzheimer's disease (AD), mean ChAT levels in OPCA amygdala and hippocampal subdivisions were either normal or only mildly reduced. The lack of severe disabling dementia in our OPCA patients compared with AD patients having a similar cortical cholinergic reduction could be explained by an absence of either a marked cholinergic loss in amygdala or hippocampus or significant loss of noncholinergic cerebral cortical and limbic neurons as occurs in AD brain. We suggest that this and other OPCA pedigrees having a cortical cholinergic reduction represent a unique model for the study of behavioral consequences of a more selective cerebral cortical cholinergic lesion rather than a limbic cholinergic lesion.

Adult↗

PubMed1989

Immunohistochemical studies of adult human glial cells.

Using immunohistochemical techniques, we examined major histocompatibility complex (MHC) antigen expression on astrocytes, oligodendrocytes, and macrophages-microglia derived from surgically resected tissue from young adults and maintained in dissociated cell cultures supplemented with either fetal calf or human AB serum. The majority of these cells in culture expressed class I MHC antigens. MHC class II expression was observed on only a restricted proportion of astrocytes either under basal or induction conditions (gamma-interferon, activated lymphocyte supernatants), on the majority of macrophages-microglia under inducing conditions, and not on oligodendrocytes. MHC class II expression on astrocytes in culture did not correlate with the extent of in situ gliosis or with in vitro cell morphology. MHC antigen expression was not detected in situ immunohistochemically. These data extend observations on the dissociation of in vivo and in vitro expression of MHC antigens on glial cells. The apparent greater expression of MHC class II antigens on macrophages-microglia compared to astrocytes raises the issue of the relative roles of each of these cell types in promoting immune reactivity under pathologic conditions.

Adolescent↗

PubMed1989

Ascertainment of informative Alzheimer disease families from the IMAGE Project registry for genetic linkage analysis studies.

Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population-based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SOREP. We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.

Alzheimer Disease↗

PubMed1989

Retrovirus-induced murine motor neuron disease: mapping the determinant of spongiform degeneration within the envelope gene.

The Cas-Br-E murine leukemia virus (MuLV) induces a degenerative myeloencephalopathy leading to hind-limb paralysis when inoculated into newborn mice. To map the viral DNA sequences encoding the determinant of neurological degeneration, we constructed chimeric viruses in vitro with parental genomes from Cas-Br-E MuLV and from nonparalytogenic MuLVs. We found that a 1.5-kilobase-pair env Cas-Br-E fragment was sufficient to confer the full paralysis-inducing potential to chimeric viruses. This region encodes the 19 carboxyl-terminal residues of the leader sequence, all of gp70, and the 45 amino-terminal residues of the transmembrane protein (p15E). Within this env region, we identified a 372-base-pair fragment which was necessary for the full paralysis-inducing potential of the virus and which influenced the development of the disease in a strain-dependent manner. This domain encodes the 19 carboxyl-terminal residues of the leader peptide and the first 67 amino-terminal residues of gp70. We propose that Cas-Br-E MuLV induces spongiform degeneration through binding of its gp70 to a specific cellular receptor.

Animals↗

PubMed1989

Familial factors in Alzheimer's disease (IMAGE project). A case-control study in the Saguenay-Lac-St-Jean region (Quebec, Canada).

Alzheimer's disease is now recognized as a major public health problem. Many hypotheses have tried to explain the etiology of Alzheimer's disease and, among them, genetic factors are considered one of the most plausible. A case-control study of familial factors, including sex distribution, age at onset, birth order, parental age, fertility, mortality, inbreeding and kindship, was conducted on 130 clinically diagnosed patients born in the Saguenay-Lac-St-Jean region (Quebec, Canada). The cases were screened by the IMAGE project. Our results showed that most factors studied are not associated with Alzheimer's disease. Inbreeding was found to be slightly increased in the Alzheimer group. Kindship was higher in the Alzheimer group than in the control groups, therefore confirming that familial predisposition is a very important risk factor.

Adult↗

PubMed1988

Focal cortical myoclonus and rolandic cortical dysplasia: clarification by magnetic resonance imaging.

Focal cortical myoclonus is rare. Obvious causes include tumor or atrophy involving the motor strip, but in some cases no cause is apparent. We present 4 patients who started to have focal myoclonus in childhood. All had focal motor seizures as well, and one had recurrent focal motor status epilepticus. All 4 had a mild progressive hemiparesis. Electrographic investigations showed focal epileptic discharges in the contralateral rolandic areas. Radiological studies were unrevealing, but magnetic resonance showed rolandic lesions in 3 patients. At surgery, abnormally wide gyri were found in the distribution demonstrated by magnetic resonance. The pathological substrate was focal cortical dysplasia. All patients have improved considerably following surgery. These findings suggest that focal myoclonus may be due to a rolandic neuronal migration disorder. Visualization of these lesions by magnetic resonance permits development of a surgical strategy leading to optimal treatment of these medically intractable epileptic disorders.

Adolescent↗

PubMed1988

Neuronal transformations in Alzheimer's disease.

Brains of nine early and four advanced Alzheimer patients have been investigated, utilizing three approaches to specify the threshold state of Alzheimer's disease (AD). Extensive thin sectioning electron microscopy (EM) of frontal lobe biopsies, correlated with stringent clinical assessment, has demonstrated that the neuronal cytoskeleton undergoes specific transformations into paired helical filament-like (PHF-like) strands, which lead to the formation of the insoluble paracrystalline paired helical filaments (PHFs). The neurofilamentous network (NFN) transformation plays an important role in this process, whereby segregation, posttranslational modifications and reassembly of the modified components through autocrosslinking, and phase transition occur. According to our data, the threshold state can be defined as the state of irreversible segregation and posttranslational modification of the NFN and the microtubule-associated proteins. At this state, therapeutic intervention to reverse the disease process may be possible. The results indicate similarities between the formation of the paracrystals of the PHFs and the formation of the tropomyosin-like crystals of the Hirano bodies. Close relationships among PHFs and smooth endoplasmic reticulum and plasma membrane do exist. Enveloped virus-like particles have been observed in neurons containing PHFs. A possible role of these virus-like particles as an etiological agent for AD is discussed.

Alzheimer Disease↗

PubMed1988

Evidence for increased amyloid enhancing factor activity in Alzheimer brain extract.

Soluble brain extracts containing 0.1 to 16 mg of protein from 3 normal human brain and 11 patients with Alzheimer's disease, Down's syndrome and other neurological disorders were assayed for amyloid enhancing factor (AEF) activity in the mouse bioassay. At the 0.1 mg dosage, five of seven brain extracts from amyloid-positive samples and only one of four amyloid-negative samples demonstrated AEF activity. Marginal AEF activity was detected in the normal brain extracts at 8 or 16 mg protein dosage. Alzheimer-AEF was aggregated by exhaustive dialysis against 0.01 M phosphate buffer, pH 6 or distilled water and the solubilized aggregate was fractionated on a BioGel P-60 column. Of the two protein peaks, AEF activity was present only in the low mol.wt second fraction, which on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining showed two discrete and three minor peptide bands between 60 and 66 kDa and one of these was periodic acid-Schiff positive, and three fuzzy bands near 14 kDa. Pretreatment of the crude and second fraction with 10 mM phenylmethylsulfonyl fluoride (PMSF) nearly completely abolished the in vivo AEF bioactivity. It is suggested that (a) a higher AEF concentration is present in amyloid-positive brain samples than those negative for amyloid or normal brain tissues, (b) AEF-positive fraction contains at least five dominant peptides ranging between 14 to 66 kDa, and (c) abolition of PMSF-treated Alzheimer-AEF activity, similar to that of murine AEF, might be due to its serine/thiol proteinase nature. To our knowledge, this is the first time that AEF activity has been demonstrated in Alzheimer brain samples.

Adult↗

PubMed1988

Paired helical filaments and the cytoplasmic-nuclear interface in Alzheimer's disease.

The cytoplasmic-nuclear interface has been investigated by conventional thin sectioning electron microscopy of neurons from frontal lobe biopsies of 13 patients with Alzheimer's disease. Nine patients were in the early and intermediate stages of the disease and four patients in the advanced stage. Fascicles of paired helical filament-like strands and paired helical filaments appose the nuclear envelope, the nuclear pore complexes and the perinuclear polysomes. Paired helical filament profiles have also been identified in the nucleoplasm. These observations indicate that the cytoplasmic-nuclear interface and, consequently, the relationships between the cytoplasm and the nucleus, might be impaired in Alzheimer's disease.

Alzheimer Disease↗

PubMed1988

Magnetic resonance imaging of meningio-angiomatosis.

We report the case of a patient with meningio-angiomatosis, a rare disorder of the cerebral cortex often associated with Von Recklinghausen's neurofibromatosis. Previous reports have described a variety of radiological findings but in general they have been of little value in the diagnosis of this disorder. We describe the magnetic resonance image, which identified a well-defined lesion. The imaging techniques are reviewed.

Adolescent↗

PubMed1988

Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer's disease.

The main objective of the present study was to determine whether cholinergic markers (choline acetyltransferase activity and nicotinic and muscarinic receptors) are altered in Alzheimer's disease. Choline acetyltransferase activity in Alzheimer's brains was markedly reduced in various cortical areas, in the hippocampus, and in the nucleus basalis of Meynert. The maximal density of nicotinic sites, measured using the novel nicotinic radioligand N-[3H]methylcarbamylcholine, was decreased in cortical areas and hippocampus but not in subcortical regions. M1 muscarinic cholinergic receptor sites were assessed using [3H]pirenzepine as a selective ligand; [3H]pirenzepine binding parameters were not altered in most cortical and subcortical structures, although the density of sites was modestly increased in the hippocampus and striatum. Finally, M2-like muscarinic sites were studied using [3H]-acetylcholine, under muscarinic conditions. In contrast to M1 muscarinic sites, the maximal density of M2-like muscarinic sites was markedly reduced in all cortical areas and hippocampus but was not altered in subcortical structures. These findings reveal an apparently selective alteration in the densities of putative nicotinic and muscarinic M2, but not M1, receptor sites in cortical areas and in the hippocampus in Alzheimer's disease.

Acetylcholine↗