Electrophysiological study of working memory in mild cognitive impairment patients.
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Biomedical subjects
Publications and source records attributed to S Blanchet.
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The aging of the population leads to increased awareness of problems associated with age-related degenerative dementias. Given that these dementias are progressive in onset, many clinicians and researchers have proposed criteria that allow for the identification of older subjects manifesting cognitive impairment, but not responding to the criteria for dementia. Our knowledge of subjects with mild cognitive impairment is limited; it is, however, established that they present a high risk of developing dementia in the future. Although it is essential to increase our comprehension of their cognitive and functional decline, the study of subjects presenting mild cognitive impairment is compromised due to the existence of numerous non-converging classifications. The goal of the present article is to conduct a critical review of the different classifications of mild cognitive impairment in the elderly in order to attempt to identify the optimal criteria, allowing for a distinction to be made between subjects with mild cognitive impairment, who remain in a stable state and those whose condition evolves to a dementia. These criteria may enable us to describe a homogenuous group of individuals presenting with different rates of dementia risk factors. We present the classifications most frequently used in clinical and research settings. After listing them according to categorial, clinical or dimensional approaches, we performed a critical analysis for each one. Depending on the diagnostic criteria applied, major variations are revealed for the prevalence of cognitive impairment and the incidence of dementia. They are explained by methodological and theoretical shortcomings that we point out and discuss (e.g., reference group, lack of diagnostic criteria or exclusion criteria, high level of subjectivity). Beyond these criticisms, we discuss the challenges to be met in order to reach the optimal identification criteria. Notably, the impact of mild cognitive impairment on daily living activities should be tested with the use of more specific questionnaires/tasks. The goal of the objective definition of cognitive impairment should be to minimize subjectivity in the diagnosis. It is also suggested that sensitive cognitive measures would be used on all aspects of cognition, while recognizing and taking into account all confounding factors (e.g., age, education level). Given the nature and consequences of mild cognitive impairment, an inter-disciplinary approach is suggested (e.g., neurobiological, psychiatric, and genetic cues). A consensus on optimal diagnostic criteria is essential to propose cognitive and pharmacological treatments for the effective prevention of ementia.
Retinoid signaling has been implicated as an important regulator of retinal development and differentiation. We have used state of the art high-pressure liquid chromatography to identify and quantitate biologically active retinoids, immunohistochemistry to localize the retinoic acid synthetic enzyme retinaldehyde dehydrogenase 2 (RALDH2), and nucleic acid assays to quantitate and localize retinoid receptor gene transcripts in the developing eye and retina of the chicken. Our results demonstrate spatial distinctions in retinoid synthesis and signaling that may be related to laminar differentiation in the developing retina. Retinoic acids (RAs) and their precursor retinols (ROHs) are the predominant retinoids in the developing eye. All-trans-RA and all-trans-3,4-didehydro-RA are present in the neuroepithelium in approximately equal amounts from early stages of neurogenesis until shortly before hatching. The retinoid X receptor (RXR) ligand 9-cis-RA is undetectable at all stages; if present, it cannot exceed a small percentage of the total RA content. RAs are not detected in the pigment epithelium. All-trans-ROH is present in the neuroepithelium and pigment epithelium, whereas all-trans-3,4-didehydro-ROH is detected only in the pigment epithelium and/or the choroid and sclera. RALDH2 immunoreactivity is intense in the choroid, low or absent in the pigment epithelium, and moderate in the neuroepithelium, where it is highest in the outer layers. Transcripts of all five chicken retinoid receptor genes are present in the neural retina and eye throughout development. During the period of neurogenesis, at least three of the receptors (RAR gamma, RXR gamma, RXRalpha), exhibit dynamic patterns of differential localization within the depths of the neural retina.
According to the hemispheric encoding/retrieval asymmetry (HERA) model, based on data obtained through functional neuroimaging, the left and right prefrontal cortices are preferentially, and, respectively, involved in long-term episodic memory encoding and retrieval. In this study, the HERA model was tested from a behavioral perspective using divided visual-field tachistoscopy. A recognition paradigm with both verbal and visuospatial materials was devised to differentiate memory-related effects (encoding vs. retrieval) from effects linked to the materials. The paradigm used lists of 12 and four items to assess long-term episodic memory and short-term memory, respectively. The aim of the latter condition was to test whether the HERA model is applicable in short-term memory. For long-term episodic memory, the data obtained validated the HERA model; the direction of the hemispheric asymmetry was found to depend on the type of materials used, whereas its magnitude was determined by the type of memory process. For verbal short-term memory, the HERA model seems to be confirmed. The pre-existing representations of the material could take into account the similarity of the hemispheric asymmetry pattern between short-term memory and long-term memory. In contrast, for visuospatial short-term memory, Baddeley's working memory model seems to better explain our results insofar as the asymmetries were essentially linked to the material in encoding but not in retrieval. This latter difference between short-term memory and long-term indicates that processes involved in LTM depend on episodic processes per se, hence, lending more support for the HERA model. Accordingly, these two memory systems seem to bring into play two different modes of hemisphere specialization.
Analysis of velum-forming yeast cell wall components released by beta-1,3-glucanase treatment were compared with those of a non velum-forming yeast. SDS-PAGE electrophoresis and Western blotting with ConA-peroxidase staining of mannoproteins allowed us to identify a 49-kDa mannoprotein present in the cell wall of the velum-forming yeast and hardly visible in the control. The cell wall nature of this protein was confirmed by labelling with the non-permeable sulfosuccinimydiyl-6-(biotinamido)hexanoate reagent. A partial purification of this mannoprotein by anion exchange HPLC followed by surface hydrophobicity determination revealed that the fraction containing the 49-kDa mannoprotein was the most hydrophobic. Since cell surface hydrophobicity plays an important role in aggregate formation, it is likely that this mannoprotein is involved in velum formation.
Visual recognition memory was assessed in terms of delay duration, memory load and amount of interference(s) in non-demented patients with Parkinson's disease (PD) using an automated delayed non-matching-to-sample (DNMS) task with trial-unique stimuli. Special attention was focused on the different cognitive functions engaged by these patients in solving this recognition memory task. Thirteen patients with PD, carefully selected according to their stable regimen and anticholinergic medication, were compared to 12 controls matched by age and educational level. Besides the DNMS task, a neuropsychological battery that included tasks carefully selected according to processes potentially required to perform the DNMS task (e.g. attention, executive functions, visual discrimination and motor speed) was administered to the subjects. As compared with controls, patients with PD showed a deficit on most DNMS subscores, except those requiring the least cognitive load. The correlative analysis between the DNMS and other neuropsychological tasks suggests involvement of long-term memory mainly in the DNMS performance for the control group, contrasting with a major involvement of executive functions for the patients with PD. These data indicate that visual recognition memory impairment in non-demented patients with PD is largely due to an executive dysfunction, notably in working memory. Several hypotheses are proposed concerning the neuronal substrates underlying the impairment on the visual DNMS task in PD.
Vitamin A requirement for early embryonic development is clearly evident in the gross cardiovascular and central nervous system abnormalities and an early death of the vitamin A-deficient quail embryo. This retinoid knockout model system was used to examine the biological activity of various natural retinoids in early cardiovascular development. We demonstrate that all-trans-, 9-cis-, 4-oxo-, and didehydroretinoic acids, and didehydroretinol and all-trans-retinol induce and maintain normal cardiovascular development as well as induce expression of the retinoic acid receptor beta2 in the vitamin A-deficient quail embryo. The expression of RARbeta2 is at the same level and at the same sites where it is expressed in the normal embryo. Retinoids provided to the vitamin A-deficient embryo up to the 5-somite stage of development, but not later, completely rescue embryonic development, suggesting the 5-somite stage as a critical retinoid-sensitive time point during early avian embryogenesis. Retinoid receptors RARalpha, RARgamma, and RXRalpha are expressed in both the precardiac endoderm and mesoderm in the normal and the vitamin A-deficient quail embryo, while the expression of RXRgamma is restricted to precardiac endoderm. Vitamin A deficiency downregulates the expression of RARalpha and RARbeta. Our studies provide strong evidence for a narrow retinoid-requiring developmental window during early embryogenesis, in which the presence of bioactive retinoids and their receptors is essential for a subsequent normal embryonic development.
Embryonic mouse upper-lip skin explants treated with 16.7 microM all-trans retinoic acid (tRA) give rise to a glandular metaplasia of hair vibrissa follicles; however, at this concentration, tRA can activate not only the three retinoic acid receptors (RARalpha, beta, and gamma), but also the retinoid X receptors (RXRalpha, beta, and gamma) as a consequence of its isomerization to 9-cis retinoic acid. We therefore studied the respective roles of the RXR and RAR by treating RARalpha(-/-), beta(-/-), and gamma(-/-) skin explants with tRA and wild-type explants with synthetic retinoids specific for RXR or for each of the RAR. The null mutation of the RARalpha, RARbeta, and RARgamma genes did not prevent tRA-induced hair glandular metaplasia, but RARgamma inactivation dramatically reduced its ratio. As demonstrated by treating explants with a RAR- or a RXR-specific panagonist (CD367 and Ro25-7386, respectively), RAR are primarily responsible for this metaplasia. The use of two retinoids (Ro40-6055, 8 x 10(-3) microM, or CD437, 7.7 x 10(-2) microM) that are believed to act, respectively, as a RARalpha- or a RARgamma-specific agonist showed that both these receptors can initiate a metaplasia. In contrast, BMS453, a RARbeta-specific agonist, was unable to give rise to any metaplasia. Nevertheless, the highest degrees and ratios of metaplasia were only obtained after treatment with the CD367 RAR panagonist, or with either Ro40-6055 or CD437 at a concentration sufficient to allow the activation of the three RAR, suggesting that RARbeta activation is required for a metaplasia of all vibrissae.
We report a patient who presented with clinical symptoms suggesting giant cell arteritis. A diagnosis of AL amyloidosis was made on temporal artery biopsy. Temporal artery involvement is unusual in AL amyloidosis, but its frequency may be underestimated. Another uncommon finding was the presence of an IgD monoclonal gammopathy without diagnostic features of multiple myeloma.
We report the isolation and characterization of a chicken cDNA which putatively encodes an actin-like protein (chACTL). This 394-amino-acid (aa) polypeptide shares sequence homology (81, 70 and 67% identical aa, respectively) with three actin-related proteins (ARP) described for Drosophila melanogaster (ARP14D), Caenorhabditis elegans (ACTL) and Saccharomyces cerevisiae (ACT2). At least six chACTL transcripts were detected in different tissues during chick embryogenesis. Sequence analysis suggests that at least three groups of ARP have been evolutionarily conserved.
The amino acid sequence of the retinoic acid receptors alpha, beta and gamma (RAR alpha, beta and gamma) can be divided into six functional domains (A-F), different isoforms arising from the presence of different A domains by differential splicing. In order to address the respective roles of the different RARs during skin morphogenesis in birds, cDNAs encoding two chick RAR alpha isoforms (alpha1 and alpha2) have been isolated. While the A1 and B-F domains of the RAR alpha are highly conserved across species, the chick A2 domain contains 50% specific amino acids. The three RAR alpha, beta and gamma genes display specific patterns of expression during chick skin morphogenesis. As in mouse, RAR alpha and gamma transcripts are present in both the dermis and epidermis during the first stages of skin appendage formation. Furthermore, Northern blot analysis suggests that different RAR alpha and gamma isoforms could be successively required during feather formation. The RAR gamma gene, continuously expressed in the epidermal cells in both chick and mouse, is thus likely to play a similar role in skin development in these two species. However, RAR alpha transcripts, only transiently detected during mouse skin development, still accumulate in epidermis during the later stages of chick skin differentiation. Furthermore, RAR beta transcripts, never detected during normal development in mouse skin, are actually present at the early stages of chick skin morphogenesis. Thus, our results suggest that the role of the three RAR in skin development has not been strictly conserved in the different classes of vertebrates.
Retinoic acid receptors alpha, beta and gamma (RAR alpha, beta and gamma) are ligand-inductible transcriptional activators which belong to the steroid/thyroid hormone receptor superfamily. At least two major isoforms (1 and 2) of each RAR arise by differential use of two promoters and alternative splicing. In mouse, the three RAR genes are expressed in stage- and tissue-specific patterns during embryonic development. In order to understand the role of the different RARs in chick, RAR gamma 2 cDNAs were isolated from an 8.5-day (stage 35 of Hamburger and Hamilton) chick embryo skin library. The deduced chick RAR gamma 2 amino acid sequence displays uncommon features such as 21 specific amino acid replacements, 12 of them being clustered in the amino-terminal region (domains A2 and B), and a truncated acidic carboxy-terminal region (F domain). However, the pattern of RAR gamma expression in chick embryo resembles that reported in mouse, particularly in skin where RAR gamma expression occurs in both the dermal and epidermal layers at the beginning of feather formation, and is subsequently restricted to the differentiating epidermal cells. Northern blot analysis suggests that different RAR gamma isoforms could be successively required during chick development.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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