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Biomedical subjects

L Lévesque

Publications and source records attributed to L Lévesque.

At least 19 recordsLinked to original sources
PubMed2005

Understanding the outcomes of a psycho-educational group intervention for caregivers of persons with dementia living at home: a process evaluation.

This qualitative process evaluation study aimed to identify the primary processes of a psycho-educational group for caregivers of persons with dementia, in order to better understand intervention outcomes. Semi-structured interviews were conducted with 30 participants recruited from the experimental group of a randomised controlled trial. At pre-test, participants reported their expectations of the group. At post-test, they described their group experience, the most/least helpful aspects of the intervention, their most useful learning and their responses during a recent episode of disturbing behaviour by their relative. Results showed that the group delivered both educational and support processes. Support processes complemented educational processes. Participants learned coping strategies, with reframing playing a more important role than problem-solving or seeking social support. Daughters benefited more than spouses from educational processes. This study of group processes contributes to our understanding of the reported reduction in frequency of disturbing behaviours and of the change in caregivers' behaviours.

Caregivers↗
PubMed2005

Surface plasmon photonic bandgap in azopolymer gratings sputtered with gold.

Surface plasmons (SPs) are generated on a doubly corrugated gold-covered surface. The corrugations were obtained by direct holographic inscription of surface relief gratings on an azopolymer film. This method permits the superposition of multiple surface profiles with easy control of the grating spacing. One grating is inscribed to act as coupler for the incident light to the SP and a second grating is inscribed to generate a gap in the SP dispersion curve. The coupling and the gap can be observed by measuring the reflectivity of the gold surface as a function of the angle of incidence and the wavelength of the probe beam.

Journal Article↗
PubMed2002

The process of a group intervention for caregivers of demented persons living at home: conceptual framework, components, and characteristics.

Most earlier group interventions for caregivers of demented persons lacked a theoretical basis to guide the intervention process and focused on providing information and practical advice and encouraging the expression of feelings. This article presents the process of a group intervention with emphasis on its conceptual framework, components and characteristics. As caregivers are exposed to numerous daily stressful demands, the intervention's conceptual framework was derived from Lazarus and Folkman's transactional theory of stress and coping and Folkman's Coping Effectiveness Training Program. The central aim of the intervention was to improve the ability of caregivers to cope with the stressful demands at the core of caring for a demented person, rather than to focus on information and the task-oriented aspects of caring. The two components of the intervention deal with the cognitive appraisal of stressors and coping strategies, with a view to determining which strategies are most appropriate on the basis of the changeability of stressors. Three coping strategies were proposed: problem solving (problem-focused coping to deal with changeable stressors), reframing (emotion-focused coping to manage the emotional response to unchangeable stressors), and seeking social support (problem- or emotion-focused coping). The most salient characteristics of this group intervention were its intensity (15 meetings) and its focus on the caregivers' daily reality, which provided concrete reference points for the discussion of conceptual notions.

Adaptation, Psychological↗
PubMed2001

RNA export mediated by tap involves NXT1-dependent interactions with the nuclear pore complex.

Nuclear export of ribonucleoprotein complexes requires cis-acting signals and recognition by receptors that mediate translocation through the nuclear pore complex. Translocation is likely to involve a series of physical interactions between the ribonucleoprotein complex and nucleoporins within the nuclear pore complex. Here, we have characterized the function of NXT1 in the context of the Tap-dependent RNA export pathway. Tap has been implicated in the nuclear export of RNA transcripts derived from Mason-Pfizer monkey virus that contain the constitutive transport element. We demonstrate that NXT1 stimulates binding of a Tap-RNA complex to nucleoporins in vitro, and we provide mutational analysis that shows these interactions are necessary for nuclear export of an intron-containing viral mRNA in vivo. Tap contains separate domains for binding to nucleoporins and NXT1, both of which are critical for its export function. RNA export is mediated by a heterodimer of Tap and NXT1, and the function of NXT1 on this pathway is to regulate the affinity of the Tap-RNA complex for nucleoporins within the nuclear pore complex. We propose that NXT1-dependent binding of the Tap-RNA complex to the nucleoporin p62, which we have reconstituted in vitro using recombinant proteins, represents a single step of the translocation reaction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

NXT1 is necessary for the terminal step of Crm1-mediated nuclear export.

Soluble factors are required to mediate nuclear export of protein and RNA through the nuclear pore complex (NPC). These soluble factors include receptors that bind directly to the transport substrate and regulators that determine the assembly state of receptor-substrate complexes. We recently reported the identification of NXT1, an NTF2-related export factor that stimulates nuclear protein export in permeabilized cells and undergoes nucleocytoplasmic shuttling in vivo (Black, B.E., L. Lévesque, J.M. Holaska, T.C. Wood, and B.M. Paschal. 1999. Mol. Cell. Biol. 19:8616-8624). Here, we describe the molecular characterization of NXT1 in the context of the Crm1-dependent export pathway. We find that NXT1 binds directly to Crm1, and that the interaction is sensitive to the presence of Ran-GTP. Moreover, mutations in NXT1 that reduce binding to Crm1 inhibit the activity of NXT1 in nuclear export assays. We show that recombinant Crm1 and Ran are sufficient to reconstitute nuclear translocation of a Rev reporter protein from the nucleolus to an antibody accessible site on the cytoplasmic side of the NPC. Further progress on the export pathway, including the terminal step of Crm1 and Rev reporter protein release, requires NXT1. We propose that NXT1 engages with the export complex in the nucleoplasm, and that it facilitates delivery of the export complex to a site on the cytoplasmic side of NPC where the receptor and substrate are released into the cytoplasm.

Active Transport, Cell Nucleus↗
PubMed2001

Presenilin function: connections to Alzheimer's disease and signal transduction.

Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are associated with early-onset familial Alzheimer's disease which displays an accelerated deposition of amyloid plaques and neurofibrillary tangles. Presenilins are multi-spanning transmembrane proteins which localize primarily to the endoplasmic reticulum and the Golgi compartments. We have previously demonstrated that PS1 exists as a high-molecular-mass complex that is likely to contain several functional ligands. Potential binding proteins were screened by the yeast two-hybrid system using the cytoplasmically orientated PS1 loop domain which was shown to interact strongly with members of the armadillo family of proteins, including beta-catenin, p0071 and a novel neuron-specific plakophilin-related armadillo protein (NPRAP). Armadillo proteins can have dual functions that encompass the stabilization of cellular junctions/synapses and the mediation of signal transduction pathways. Our observations suggest that PS1 may contribute to both aspects of armadillo-related pathways involving neurite outgrowth and nuclear translocation of beta-catenin upon activation of the wingless (Wnt) pathway. Alzheimer's disease (AD)-related presenilin mutations exhibit a dominant gain of aberrant function resulting in the prevention of beta-catenin translocation following Wnt signalling. These findings indicate a functional role for PS1 in signalling and suggest that mistrafficking of selected presenilin ligands may be a potential mechanism in the genesis of AD.

Alzheimer Disease↗
PubMed2001

Mental health, stress correlates and psychotropic drug use or non-use among aged caregivers to elders with dementia.

The goal of the study was to compare caregivers who used psychotropic drugs with caregivers who were non-users in order to pinpoint differences in coping styles between the two groups. We performed a secondary analysis of a study on the stress and psychological well-being of persons caring for relatives with dementia. We compared elderly caregivers, as either psychotropic drug users (n = 61) or non-users (n = 133), over various psychosocial characteristics relating to the care-giving context. Results reveal that users, as compared to non-users were: (a) more disturbed (appraised a greater stress) by the relative's dysfunctional behaviours, after controlling for the frequency of the behaviours; and (b) experienced more conflict during interpersonal interactions, although their appraisal of self-satisfaction with formal and informal support to their care-giving activities did not differ significantly. Strikingly, users combined and called on a greater number of problem-focused and emotion-reducing coping strategies than did non-users. They more frequently used affective regulation and information seeking coping styles. Stress-related measures (especially stress appraisal and conflict) contributed more to the variation in mental distress of users than of non-users. Results provide a theoretical and empirical rationale for therapeutic interventions such as the cognitive behavioural approach.

Adaptation, Psychological↗
PubMed2000

Ligand specific effects on aluminum incorporation and toxicity in neurons and astrocytes.

Aluminum is present in many manufactured foods and medicines and is added to drinking water for purification purposes. It has been proposed that aluminum is a contributing factors to several neurodegenerative disorders such as Alzheimer's disease. However, this remains controversial primarily due to the unusual properties of aluminum and a lack of information on its cellular sites of action. To resolve some of these questions, we have examined aluminum uptake in both neuronal and astroglial cells as well as the role of metal speciation. The relative accumulation of four aluminum salts, aluminum maltolate, aluminum lactate, aluminum chloride and aluminum fluoride, was investigated and correlated with cell viability and intracellular distribution as determined by morin staining. Significant differences in aluminum incorporation and toxicity were observed in both neuronal and glia cells with the largest effects exhibited by the maltol species. This was accompanied by a nuclear accumulation in the neuronal cell line that was contrasted by the perinuclear, vesicular distribution in astrocytes that partially co-localized with cathepsin D, a lysosomal marker. These findings demonstrate differences in aluminum species and highlights the importance of these factors in modulating the toxic effect of aluminum.

Aluminum Chloride↗
PubMed2000

Presenilin structure, function and role in Alzheimer disease.

Numerous missense mutations in the presenilins are associated with the autosomal dominant form of familial Alzheimer disease. Presenilin genes encode polytopic transmembrane proteins, which are processed by proteolytic cleavage and form high-molecular-weight complexes under physiological conditions. The presenilins have been suggested to be functionally involved in developmental morphogenesis, unfolded protein responses and processing of selected proteins including the beta-amyloid precursor protein. Although the underlying mechanism by which presenilin mutations lead to development of Alzheimer disease remains elusive, one consistent mutational effect is an overproduction of long-tailed amyloid beta-peptides. Furthermore, presenilins interact with beta-catenin to form presenilin complexes, and the physiological and mutational effects are also observed in the catenin signal transduction pathway.

Alzheimer Disease↗
PubMed2000

Resolution of allelic and non-allelic variants of histone H1 by cation-exchange-hydrophilic-interaction chromatography.

A mixed-mode high-performance liquid chromatography (HPLC) method that resolves the six known non-allelic variants of chicken erythrocyte histone H1 is described. Common, but previously unknown, allelic variants of H1 that comigrate in polyacrylamide gel electrophoresis are also resolved. The resolution of H1 variants achieved by this method should be useful in determining the functional significance of H1 sequence heterogeneity and in analyses of post-translational modification of H1. Furthermore, the principles behind the separation should be applicable to analyses of polymorphism in other proteins.

Acetonitriles↗
PubMed2000

RanGTP-binding protein NXT1 facilitates nuclear export of different classes of RNA in vitro.

To better characterize the mechanisms responsible for RNA export from the nucleus, we developed an in vitro assay based on the use of permeabilized HeLa cells. This new assay supports nuclear export of U1 snRNA, tRNA, and mRNA in an energy- and Xenopus extract-dependent manner. U1 snRNA export requires a 5' monomethylated cap structure, the nuclear export signal receptor CRM1, and the small GTPase Ran. In contrast, mRNA export does not require the participation of CRM1. We show here that NXT1, an NTF2-related protein that binds directly to RanGTP, strongly stimulates export of U1 snRNA, tRNA, and mRNA. The ability of NXT1 to promote export is dependent on its capacity to bind RanGTP. These results support the emerging view that NXT1 is a general export factor, functioning on both CRM1-dependent and CRM1-independent pathways of RNA export.

Animals↗
PubMed2000

Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease.

BACKGROUND: Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD). MATERIALS AND METHODS: We characterized the cellular localization and endoproteolysis of presenilin 2 (PS2) and presenilin 1 (PS1) in brains from 25 individuals with presenilin-mutations causing FAD, as well as neurologically normal individuals and individuals with sporadic Alzheimer's disease (AD). RESULTS: Amino-terminal antibodies to both presenilins predominantly decorated large neurons. Regional differences between the broad distributions of the two presenilins were greatest in the cerebellum, where most Purkinje cells showed high levels of only PS2 immunoreactivity. PS2 endoproteolysis in brain yielded multiple amino-terminal fragments similar in size to the PS1 amino-terminal fragments detected in brain. In addition, two different PS2 amino-terminal antibodies also detected a prominent 42 kDa band that may represent a novel PS2 form in human brain. Similar to PS1 findings, neither amino-terminal nor antiloop PS2 antibodies revealed substantial full-length PS2 in brain. Immunocytochemical examination of brains from individuals with the N141I PS2 mutation or eight different PS1 mutations, spanning the molecule from the second transmembrane domain to the large cytoplasmic loop domain, revealed immunodecoration of no senile plaques and only neurofibrillary tangles in the M139I PS1 mutation stained with PS1 antibodies. CONCLUSIONS: Overall presenilin expression and the relative abundance of full-length and amino-terminal fragments in presenilin FAD cases were similar to control cases and sporadic AD cases. Thus, accumulation of full-length protein or other gross mismetabolism of neither PS2 nor PS1 is a consequence of the FAD mutations examined.

Age of Onset↗
PubMed1999

Identification of an NTF2-related factor that binds Ran-GTP and regulates nuclear protein export.

Active transport of macromolecules between the nucleus and cytoplasm requires signals for import and export and their recognition by shuttling receptors. Each class of macromolecule is thought to have a distinct receptor that mediates the transport reaction. Assembly and disassembly reactions of receptor-substrate complexes are coordinated by Ran, a GTP-binding protein whose nucleotide state is regulated catalytically by effector proteins. Ran function is modulated in a noncatalytic fashion by NTF2, a protein that mediates nuclear import of Ran-GDP. Here we characterize a novel component of the Ran system that is 26% identical to NTF2, which based on its function we refer to as NTF2-related export protein 1 (NXT1). In contrast to NTF2, NXT1 preferentially binds Ran-GTP, and it colocalizes with the nuclear pore complex (NPC) in mammalian cells. These properties, together with the fact that NXT1 shuttles between the nucleus and the cytoplasm, suggest an active role in nuclear transport. Indeed, NXT1 stimulates nuclear protein export of the NES-containing protein PKI in vitro. The export function of NXT1 is blocked by the addition of leptomycin B, a compound that selectively inhibits the NES receptor Crm1. Thus, NXT1 regulates the Crm1-dependent export pathway through its direct interaction with Ran-GTP.

Amino Acid Sequence↗
PubMed1999

Is there a difference between family caregiving of institutionalized elders with or without dementia?

Based on the stress and coping model of Lazarus and Folkman, the aim of this comparative study was to determine whether the caregiving experience of the caregivers of an institutionalized demented relative is different from the one of the caregivers whose relative does not suffer from dementia. Five dimensions of the caregiving experience were considered: stressors, cognitive appraisal of the stressors, social support, coping strategies and well-being. The sample consisted of primary caregivers of a demented and a nondemented relative. Results revealed that the caregivers of a demented relative were exposed to more stressors than the caregivers of a nondemented relative. Functional impairment as well as depressive behaviors were appraised as more disturbing. According to MANCOVA analysis, formal and informal social support seems to play a protective role in the psychological distress of the caregivers of a demented relative. There was no difference between the two groups with regard to their coping strategies. Overall, the caregivers of a demented relative seemed to experience some dimensions of caregiving in a different way compared with their counterparts, and the nature of dementia in itself helps to explain this difference.

Activities of Daily Living↗
PubMed1999

Developmental expression of wild-type and mutant presenilin-1 in hippocampal neurons from transgenic mice: evidence for novel species-specific properties of human presenilin-1.

Presenilins 1 (PS1) and 2 (PS2) are multispanning transmembrane proteins associated with familial Alzheimer disease (FAD). They are developmentally regulated, being expressed at highest levels during neuronal differentiation and are sustained at a lower level throughout life. We investigated the distribution and metabolism of endogenous murine PS1 as well as human wild-type (wtPS1) and the familial AD Met146Leu (M146L) mutant presenilins in dissociated cultures of hippocampal neurons derived from control and transgenic mice. We found that the PS1 endoproteolytic fragments and, to a lesser extent, the full-length protein, were expressed as early as day 3 post-plating. Both species increased until the cells were fully differentiated at day 12. Confocal microscopy revealed that presenilin is present in the Golgi and endoplasmic reticulum and, as in punctate, vesicle-like structures within developing neurites and growth cones. Using a human-specific PS1 antibody, we were able to independently examine the distribution of the transgenic protein which, although similar to the endogenous, showed some unique qualities. These included (i) some heterogeneity in the proteolytic fragments of human PS1; (ii) significantly reduced levels of full-length human PS1, possibly as a result of preferential processing; and (iii) a more discrete intracellular distribution of human PS1. Colocalization with organelle-specific proteins revealed that PS1 was located in a diffuse staining pattern in the MAP2-positive dendrites and in a punctate manner in GAP43-positive axons. PS1 showed considerable overlap with GAP43, particularly at the growth cones. Similar patterns of PS1 distribution were detected in cultures derived from transgenic animals expressing human wild-type or mutant presenilins. The studies demonstrate that mutant presenilins are not grossly different in their processing or distribution within cultured neurons, which may represent more physiological models as compared to transfection systems. Our data also suggest that the molecular pathology associated with PS1 mutations results from subtle alterations in presenilin function, which can be further investigated using these transgenic neuronal cell culture models.

Aging↗
PubMed1998

Empirical verification of a theoretical model derived from the Roy adaptation model: findings from five studies.

This article presents a theoretical model derived from the Roy adaptation model and the findings of an empirical verification of this model from five studies. Four groups of subjects were included in the studies: informal caregivers of demented relatives at home, informal caregivers of psychiatrically ill relatives at home, professional caregivers of elderly institutionalized patients, and aged spouses in the community. In at least three studies, a number of theoretical propositions derived from the Roy adaptation model were supported using LISREL VIII, thus adding credence to some tenets of Roy's model. Particularly, the focal stimulus of perceived stress, the contextual stimulus of conflicts in the exchange of social support, and one component of the coping mechanisms (the passive/avoidance coping strategies) were positively linked directly or indirectly with psychological distress, which is an indicator of adaptation in the self-concept mode. Given their importance, these elements should be considered in the development of a middle-range theory of psychological adaptation derived from the Roy adaptation model.

Adaptation, Psychological↗
PubMed1998

Empirical testing of a longitudinal model derived from the Roy adaptation model.

This article presents the steps and results of the empirical testing of a theoretical longitudinal model, derived from Roy's nursing conceptual model, of the psychosocial determinants of adaptation in different target groups. The model was elaborated and empirically verified based on the integrated results of four longitudinal studies involving groups vulnerable to mental health problems. By means of structural equation analyses, the cross-sectional model was verified at two points in time. The results showed that the model was relatively stable over time. The model was also tested using longitudinal data. Results showed little consistency in the patterns of relationships across studies. The significant links that emerged from the analyses shed some light on the complexity of the process of adaptation to different types of stressors. They underscore the importance for nursing practice to develop interventions aimed at certain variables: perceived stress, conflicts in the exchange of support, and passive and avoidance coping strategies. The results also highlight the importance of the relationship between perceived stress, passive/avoidance coping strategies and psychological distress.

Adaptation, Psychological↗