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J Poirier

Publications and source records attributed to J Poirier.

At least 91 records · Page 5Linked to original sources
PubMed1998

Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer's patients.

Apolipoprotein D (apoD) is a member of the lipocalin family of proteins. Most members of this family are transporters of small hydrophobic ligands, although in the case of apoD, neither its physiological function(s) nor its putative ligand(s) have been unequivocally identified. In humans, apoD is expressed in several tissues, including the CNS, and its synthesis is greatly increased during regeneration of rat peripheral nerves. As apoD may have an important function in the nervous system and, particularly, in nerve regeneration, we measured immunoreactive apoD levels in the hippocampus and in CSF of patients with either Alzheimer's disease (AD) or other neuropathologies. In parallel, we determined the concentrations of apolipoprotein E (apoE), another apolipoprotein also implicated in nerve regeneration and in the etiology of AD. Levels of apoD but not apoE were increased in the hippocampus of AD patients compared with controls. ApoD concentrations, as determined by radioimmunoassay, were significantly increased in the CSF of AD patients (4.23 +/- 1.58 microg/ml) and patients with other pathologies (3.29 +/- 1.35 microg/ml) compared with those in the CSF of normal subjects (1.15 +/- 0.71 microg/ml). Although the differences were smaller than for apoD, the mean apoE concentrations in the CSF of both groups of patients were also significantly higher than those of controls. In AD patients, apoD, but not apoE, levels in CSF and hippocampus increased as a function of inheritance of the epsilon4 apoE allele. This study therefore demonstrates that increased apoD levels in the hippocampus and in CSF are a marker of neuropathology, including that associated with AD, and are independent of apoE concentrations.

Aged↗
PubMed1998

Pronounced impact of Th1/E47cs mutation compared with -491 AT mutation on neural APOE gene expression and risk of developing Alzheimer's disease.

Possession of the apolipoprotein E (APOE) epsilon4 allele is the most frequently associated genetic susceptibility factor for Alzheimer's disease (AD). Recently, new polymorphisms in the regulatory region of the APOE gene have been described. We analysed the effects of three of these mutations (-491 AT, -427 CT and Th1/E47cs) on disease risk in a large case-control study, and tested their impacts on APOE allelic expression in brain tissues. The Th1/E47cs T allele was associated with an increased risk of occurrence of AD, while the -491 T allele was associated with a decreased risk, independently of the APOE epsilon2/epsilon3/epsilon4 polymorphism effect. However, the impact of the Th1/E47cs mutation was the strongest. The -427 CT polymorphism was not associated with the disease. In AD subjects heterozygous for the epsilon4 allele, analysis of allelic expression showed that the relative expression levels of the epsilon4 allele were higher than those of the corresponding controls. Consistent with epidemiological data, the relative level of expression of the epsilon4 allele was modified accordingly to the presence or absence of the two main promoter polymorphisms, indicating, in vivo, the deleterious effect of the Th1/E47cs T allele and the protective effect of the -491 T allele in population. These data indicate that in addition to the qualitative effect of the APOE epsilon2/epsilon3/epsilon4 polymorphisms on the AD occurrence, the quantitative variation of expression of these alleles due to functional APOE promoter mutations, is a key determinant of AD development.

Aged↗
PubMed1998

Treatment outcome of tacrine therapy depends on apolipoprotein genotype and gender of the subjects with Alzheimer's disease.

We studied the effects of apolipoprotein E (APOE) genotype and gender on clinical response to tacrine in patients with mild to moderate Alzheimer's disease (AD). We analyzed data from a previously reported 30-week, double-blind, placebo-controlled trial of tacrine, in which APOE genotypes were determined from previously collected plasma samples. Patients were assigned to placebo or tacrine with daily dosages of 80, 120, or 160 mg/day. The outcome measures were Alzheimer's Disease Assessment Scale-Cognitive Component, Clinician Interview Based Impression, Mini-Mental State Examination, and the Caregiver-rated Clinical Global Impression of Change. An intent-to-treat (ITT) analysis of patients with available genotypes (n = 528) did not reveal response differences by genotype, although the effect size was twice as large in the epsilon2-3 as the epsilon4 group (-2.62 versus -1.25). The association of treatment effect with APOE genotype varied significantly according to gender (p < 0.002 for ITT; p < 0.05 for evaluables). The treatment effect was larger in the epsilon2-3 compared with epsilon4 women (ITT, 4.24 points, p = 0.03; evaluable, 7.20 points, p = 0.01). In contrast, treatment effect size was not different between epsilon2-3 and epsilon4 of men with AD. APOE genotype and gender may predict response to tacrine in patients with AD.

Aged↗
PubMed1998

[Arachnoid cysts: histologic, embryologic and physiopathologic review].

Arachnoid cysts form a cavity containing a cerebrospinal-like fluid, the wall of which is composed of arachnoidal cells. Other types of intracranial cysts have been described, they differ from arachnoid cysts by the histological characteristics of their wall. To analyze homogeneous series, it is thus necessary to differentiate arachnoid cysts from the other types of cysts. Several localizations of these lesions have been described: the most frequent being the temporo-sylvian area. Arachnoid cysts are considered as resulting from congenital malformations that can change during postnatal life. They can no longer be considered as resulting from cerebral atrophy. This arachnoid malformation could be the primary event or be explained by an impairment of the cerebrospinal fluid drainage generated by venous agenesis. Several mechanisms could account for the inflation of these cysts: secretion by the cells forming the cyst walls, unidirectional valve, liquid movements secondary to pulsations of the veins.

Arachnoid↗
PubMed1997

Alzheimer's disease: current knowledge, management and research.

Alzheimer's disease is a common neurological condition, appearing as early as age 40 but increasing dramatically in incidence over age 85. Different genetic factors are at play, modified by events over a lifetime. Clinical diagnosis is possible through careful history taking with a reliable informant and a minimum number of laboratory tests. A relatively predictable natural history can be observed, with progression through stages of cognitive loss, functional impairment and behavioural disinhibition or apathy. New medications such as donepezil offer hope for improving or stabilizing symptoms. Such treatment can be administered by primary care physicians with experience in the diagnosis and management of Alzheimer's disease. Disease stabilization, or even prevention, may be possible in the future.

Adult↗
PubMed1997

The effect of L-deprenyl, D-deprenyl and MDL72974 on mitochondrial respiration: a possible mechanism leading to an adaptive increase in superoxide dismutase activity.

L-Deprenyl is an irreversible monoamine oxidase-B inhibitor with a complex pharmacological profile. For instance, L-deprenyl administration to rat and mice increases cytosolic CuZn- and mitochondrial Mn-superoxide dismutase activities in the striatum. CuZn- and Mn-superoxide dismutase are enzymes involved in defense against superoxide (O2.) radicals. Hence, an increase in CuZn- and Mn-superoxide dismutase activities is suggestive of oxidative stress. The major intracellular site of O2. radicals formation is the mitochondrial respiratory chain. Several reports indicated that alterations in mitochondrial respiratory functions enhances O2. production. We observed that L-deprenyl induced a dose-dependent inhibition of oxygen (O2) consumption (state 3) during ATP synthesis in presence of complex I (pyruvate and malate) and complex II (succinate) substrates in fresh mitochondrial preparations. D-Deprenyl produced a similar inhibitory profile whereas MDL72974, a selective monoamine oxidase-B inhibitor, was less effective. Administration of D-deprenyl or MDL72974 to mice resulted in an increase in both striatal CuZn- and -Mn-superoxide dismutase activities. Accordingly, we propose that the impairment of mitochondrial respiratory functions which stimulates O2. formation could modulate CuZn- and Mn-superoxide dismutase activities, through a mechanism that appears to be independent of monoamine oxidase-B inhibition.

Allyl Compounds↗
PubMed1997

Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein.

Proteolytic processing of amyloid precursor protein (APP) through an endosomal/lysosomal pathway generates carboxy-terminal polypeptides that contain an intact beta-amyloid domain. Cleavage by as-yet unidentified proteases releases the beta-amyloid peptide in soluble form. In Alzheimer's disease, aggregated beta-amyloid is deposited in extracellular neuritic plaques. Although most of the molecular mechanisms involving beta-amyloid and APP in the aetiology of Alzheimer's disease are still unclear, changes in APP metabolism may be important in the pathogenesis of the disease. Here we show that transgenic mice expressing the amyloidogenic carboxy-terminal 104 amino acids of APP develop, with ageing, extracellular beta-amyloid immunoreactivity, increased gliosis and microglial reactivity, as well as cell loss in the CA1 region of the hippocampus. Adult transgenic mice demonstrate spatial-learning deficits in the Morris water maze and in maintenance of long-term potentiation (LTP). Our results indicate that alterations in the processing of APP may have considerable physiological effects on synaptic plasticity.

Aging↗
PubMed1997

Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion.

We studied genotype-phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and in three groups of patients with atypical clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), and 6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA, carried two copies of the FRDA-associated GAA triplet repeat expansion. Overall, the phenotypic spectrum of FRDA appeared to be wider than defined by the currently used diagnostic criteria. Our study indicated the existence of several sources of variability in FRDA. Patients with larger GAA expansions tended to have earlier onset and were more likely to show additional manifestations of the disease. Mitotic instability of the expanded GAA repeats may partially account for the limited degree of correlation between expansion sizes as determined in lymphocytes and clinical parameters. Some clinical variants associated with specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be unrelated to expansion sizes. No polymorphism in the frataxin coding sequence could be associated with these clinical variants.

Adolescent↗
PubMed1997

L-Deprenyl and MDL72974 do not improve the recovery of dopaminergic cells following systemic administration of MPTP in mouse.

L-Deprenyl, a monoamine oxidase B (MAO-B) inhibitor, administered prior to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) protects dopaminergic neurons against degeneration in several animal species including mice. L-Deprenyl inhibits MPP+ formation, the mediator of MPTP toxicity. In addition, L-deprenyl, administered 72 h following MPTP, improves the recovery of tyrosine hydroxylase (TH) immunopositive neurons in the substantia nigra (SN) of mice. This observation lead to the proposal that L-deprenyl exerts a 'neurorescue' effect. However, clinical trials failed to demonstrate that L-deprenyl can effectively 'rescues' degenerating dopaminergic neurons in early untreated Parkinson's disease (PD) patients. These observations prompted us to reevaluate the long-term impact of L-deprenyl on MPTP-induced dopaminergic cell loss in mice. In addition, we made use of another MAO-B inhibitor, MDL72974, to assess MAO-B participation in this paradigm. Our results suggest that L-deprenyl does not improve the recovery of TH immunopositive neurons in MPTP-treated mice. An apparent reduction in TH+ neurons is observed in the SN of MDL72974 and L-deprenyl/MPTP-treated mice at 30 days post-treatment. The possible implication of these findings in relation to the used of MAO-B inhibitors in PD is discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

[The first nurses school at "La Salpêtrière Hospital" in Paris].

In 1870, D.M. Bourneville organized municipal lectures for parisian hospital staff in order to improve their inadequate training. It was carried on with that teaching till 1914, but owing to imperfected knowledge it was compelled to enlarge the project in opening the first nurses school inside "La Salpêtrière (1907). Following the hospital staff reform (1903), a preliminary Commission was settled. That commitee was inspired by british or french experiments (private, parisian and provincial initiatives) for its accomplishement. The opening speech, in 1908, pointed out democratic recruiting and professional feature of the scool. A new career was offered to women where nurses would became physician assistants, devoted to him, but of necessity for their own skills.

France↗
PubMed1996

Apolipoprotein E genotype and gender influence response to tacrine therapy.

Our objective is to evaluate the effects of apolipoprotein E genotype (APOE) on clinical response to treatment with tacrine, in patients with Alzheimer's disease (AD). Only 25 to 50% of patients with AD, depending on dose and design, have been responders in previous tacrine trials. AD autopsy studies have suggested that APOE epsilon 4 is associated with decreased numbers of cholinergic markers in temporal cortex and the hippocampus. Our hypothesis was that cholinergic therapy might be less effective in epsilon 4 carriers. APOE phenotypes were determined from plasma samples previously saved from a large 30-week, randomized, double-blind placebo-controlled, parallel-group, multicenter trial of tacrine at dosages of 80, 120, or 160 mg/day. Outcome measures included Alzheimer's Disease Assessment Scale (ADAS) and its cognitive component (ADAS-Cog), Clinician's Interview-Based Impression (CIBI), Global Deterioration Scale (GDS), and the caregiver-rated Clinical Global Impression of Change (CGIC). Analyses were performed on the change in scores from baseline to last observation on 460 patients having APOE results available. There were 291 patients heterozygous or homozygous for APOE epsilon 4 and 169 patients with only APOE epsilon 2 or epsilon 3 alleles. Analysis of variance showed non-APOE epsilon 4 carriers (E2,3) on tacrine improved more versus placebo than patients with APOE epsilon 4 (E4) on tacrine versus placebo as measured by the ADAS (p = 0.04) and the ADAS-Cog (p = 0.05). A trend toward greater treatment effect in the E2,3 patients was seen with CIBI, GDS, and CGIC, but these differences did not achieve significance. APOE genotype may be a predictor for clinical response to tacrine in AD patients, APOE epsilon 4 associated with a lower probability of cognitive improvement. When the groups were further divided by gender, most of the effect of APOE on treatment response was seen in women. E2-3 women improved more than any other group, and E4 women the least. The interaction of gender and APOE genotype on treatment response as measured by ADAS-Cog was significant (p = 0.03). Future trials of cholinergic therapy in AD should include APOE genotyping.

Aged↗
PubMed1996

Friedreich ataxia in Acadian families from eastern Canada: clinical diversity with conserved haplotypes.

The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodegenerative disease, remains elusive. The current candidate region of about 150 kb lies between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1. Linkage homogeneity between classical FRDA and a milder, slowly progressive Acadian variant (FRDA-Acad) has been demonstrated. An extended D9S15-D9S5 haplotype (C6) predominates in FRDA-Acad chromosomes from Louisiana. We studied 10 Acadian families from New Brunswick, Canada. In eight families, affected individuals conformed to the clinical description of FRDA-Acad; in one, 2 sibs presented with spastic ataxia (SPA-Acad). In the last family, 2 sibs had FRDA-Acad, and one had SPA-Acad. We found that SPA-Acad is linked to the FRDA gene region. The C6 haplotype and a second major haplotype (B7) were identified. The same ataxia-linked haplotypes segregated with both FRDA-Acad and SPA-Acad in two unrelated families. The parental origins of these haplotypes were different. Our observation of different phenotypes associated with the same combination of haplotypes may point to the influence of the parent of origin on gene expression, indicate the effect of modifier genes, or reflect the presence of different mutations on the same haplotypes. Our findings underline the need to investigate families with autosomal-recessive ataxias for linkage to the FRDA region, despite lack of key diagnostic manifestations such as cardiomyopathy or absent deep-tendon reflexes.

Canada↗
PubMed1996

[Histopathology of brain tumors. Histoprognosis and its limitations].

Although the current radiological imaging is really performing, histologic examination remains essential in as much regarding the diagnosis as the pronostical assessment of cerebral tumors pronostic. The difficulties of histological diagnosis are not the same according to the various processes such as cerebral biopsy, extemporaneous examination or routine examination. Grading of gliomatous tumors is one among all the components that might enable pronostical assessment. Predictivity of meningiomas and pituitary adenomas recurrences remain unreliable despite numerous histological techniques that can be used (proliferative markers, bromodeoxyuridine incorporation, nucleolar organizers, flow cytometry).

Adult↗
PubMed1996

Apolipoprotein E, plaques, tangles and cholinergic dysfunction in Alzheimer's disease.

Apolipoprotein E is a plasma cholesterol and phospholipid transporter which plays a central role in lipoprotein metabolism in the brain. Apolipoprotein E is a polymorphic protein with three common alleles in the general population, designated epsilon 2, epsilon 3 and epsilon 4 coding for proteins ApoE2, ApoE3 and ApoE4, respectively. Recent findings have demonstrated a significant relationship between the epsilon 4 allele and late onset familial and sporadic Alzheimer's disease. We examined several classical neuropathological hallmarks of Alzheimer's disease to determine whether they might be related to apolipoprotein E genotype: the presence of intracellular neurofibrillary tangles, extracellular senile plaques, and the attenuation of choline acetyltransferase activity. Significant correlations were found between epsilon 4 allele copy number and senile plaque density in the frontal, parietal and fusiform cortical areas. Similarly, significant correlations were also found with increased neurofibrillary tangle number in the frontal and fusiform cortex. Interestingly, there was an inverse correlation between the epsilon 4 allele with temporal cortical choline acetyltransferase activity. To further define the specific function of ApoE4, cultured rat hippocampal neurons were used to investigate interactions involving beta-amyloid protein. In this model, ApoE4 (but not ApoE2) was able to reverse the neuroprotective effects of beta-amyloid. ApoE3 was demonstrated to increase the internalization of beta-amyloid peptide into these neurons. Taken together, these results support the involvement of ApoE4 in the pathogenesis of Alzheimer's disease and also provide some explanations for the possible function of this protein.

Aged↗
PubMed1996

Apolipoprotein E and low-density lipoprotein binding and internalization in primary cultures of rat astrocytes: isoform-specific alterations.

Apolipoprotein (apo) E is likely involved in redistributing cholesterol and phospholipids during compensatory synaptogenesis in the injured CNS. Three common isoforms of apoE exist in human (E2, E3, and E4). The apoE4 allele frequency is markedly increased in both late-onset sporadic and familial Alzheimer's disease (AD). ApoE concentration in the brain of AD subjects follows a gradient: ApoE levels decrease as a function of E2 > E3 >> E4. It has been proposed that the poor reinnervation capacity reported in AD may be caused by impairment of the apoE/low-density lipoprotein (LDL) receptor activity. To understand further the role of this particular axis in lipid homeostasis in the CNS, we have characterized binding, internalization, and degradation of human 125I-LDL to primary cultures of rat astrocytes. Specific binding was saturable, with a KD of 1.8 nM and a Bmax of 0.14 pmol/mg of proteins. Excess unlabeled human LDL or very LDL (VLDL) displaced 70% of total binding. Studies at 37 degrees C confirmed that astrocytes bind, internalize, and degrade 125I-LDL by a specific, saturable mechanism. Reconstituted apoE (E2, E3, and E4)-liposomes were labeled with 125I and incubated with primary cultures of rat astrocytes and hippocampal neurons to examine specific binding. Human LDL and VLDL displaced binding and internalization of all apoE isoforms similarly in both astrocytes and neurons. 125I-ApoE2 binding was significantly lower than that of the other 125I-apoE isoforms in both cell types. 125I-ApoE4 binding was similar to that of 125I-apoE3 in both astrocytes and neurons. On the other hand, 125I-apoE3 binding was significantly higher in neurons than in astrocytes. These isoform-specific alterations in apoE-lipoprotein pathway could explain some of the differences reported in the pathophysiology of AD subjects carrying different apoE alleles.

Animals↗