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R Bossé

Publications and source records attributed to R Bossé.

At least 19 recordsLinked to original sources
PubMed2005

Regulation of membrane trafficking by a novel Cdc42-related protein in Caenorhabditis elegans epithelial cells.

Rho GTPases are mainly known for their implication in cytoskeleton remodeling. They have also been recently shown to regulate various aspects of membrane trafficking. Here, we report the identification and the characterization of a novel Caenorhabditis elegans Cdc42-related protein, CRP-1, that shows atypical enzymatic characteristics in vitro. Expression in mouse fibroblasts revealed that, in contrast with CDC-42, CRP-1 was unable to reorganize the actin cytoskeleton and mainly localized to trans-Golgi network and recycling endosomes. This subcellular localization, as well as its expression profile restricted to a subset of epithelial-like cells in C. elegans, suggested a potential function for this protein in polarized membrane trafficking. Consistent with this hypothesis, alteration of CRP-1 expression affected the apical trafficking of CHE-14 in vulval and rectal epithelial cells and sphingolipids (C(6)-NBD-ceramide) uptake and/or trafficking in intestinal cells. However, it did not affect basolateral trafficking of myotactin in the pharynx and the targeting of IFB-2 and AJM-1, two cytosolic apical markers of intestine epithelial cells. Hence, our data demonstrate a function for CRP-1 in the regulation of membrane trafficking in a subset of cells with epithelial characteristics.

Actins↗
PubMed2000

Employment and health among older bereaved men in the normative aging study: one year and three years following a bereavement event.

Research has indicated that the negative effects of bereavement on health among elderly men occur within the first six to twelve months following a bereavement event while other studies indicate that the death of a loved one can have long-term effects on social functioning and mental health (Arbuckle & DeVries, 1995; Vinick, 1983a). However, employment has been found to buffer the strain produced by stressful life events. The purpose of this study was to examine the differential effects of employment on physical and mental health between elderly men bereaved for one year and elderly men bereaved for two to three years. We selected two groups of men from the Normative Aging Study: those bereaved within the past year (N = 248) and those bereaved from two to three years (N = 262). Ordinary least squares multiple regression analyses examined the direct effect of employment, controlling for age, education, income, marital status, and stress, on physical and mental health among the two groups of men. Although there were no significant differences between the two groups of men, the results from the separate analyses indicated that employment had a direct positive effect on physical health among those bereaved for one year and those bereaved from two to three years, but no significant effects were observed on mental health. The results suggest that employment can benefit men soon after a bereavement event and also over a longer period of time, especially on physical health. Implications for clinical practice and future research are discussed.

Adult↗
PubMed2000

Relations between health-related quality of life and well-being: the gerontologist's new clothes?

Is the recent construct of health-related quality of life (HQL) distinct from what gerontologists have long referred to as "well-being" or "life satisfaction?" We addressed this question using data from men in the VA Normative Aging Study to examine relations among twelve scales assessing HQL and seven scales of well-being (WB). We hypothesized that these two constructs would be distinct factorially, and that the derived factors would have different correlates. Correlations between scales of HQL and WB were moderate. When the nineteen scales were factored, four factors were extracted with HQL and WB scales generally loading on separate factors. The factors had distinct patterns of relations with general quality of life, personality, and the presence of a health problem, controlling for sociodemographics. These results suggest that HQL is distinct from the older construct of well-being. Although the two constructs are conceptually related, there is only a moderate amount of statistical overlap between them. Gerontologists should readily adopt health-related quality of life, which maintains continuity with such classics as well-being. This new construct, although needing slight alterations to broaden its assessment of well-being and life satisfaction, holds promise as more than an accessory in the study of health and well-being among older persons.

Activities of Daily Living↗
PubMed1998

Gonadal hormones modulate 5-hydroxytryptamine2A receptors: emphasis on the rat frontal cortex.

The effect of short-term (Sprague-Dawley rats, two weeks) and long-term ovariectomy (Sprague-Dawley and Fischer rats, three months) on serotonin 5-hydroxytryptamine2A receptors in different regions of the brain and its possible correction with an 17 beta-estradiol treatment (10 micrograms, b.i.d., two weeks) were studied in comparison to intact rats. Saturation binding assays were performed using [3H]ketanserin to estimate 5-hydroxytryptamine2A receptor density and affinity in tissue homogenates of frontal cortex of Fischer rats and quantitative autoradiography was performed to evaluate receptor specific binding in frontoparietal cortex, nucleus accumbens, striatum and dorsal raphe nucleus of Fischer rats, and in frontal cortex of the two strains of rats. Messenger RNA levels of 5-hydroxytryptamine2A receptors were measured by in situ hybridization in frontal cortex of the two strains of rats. An overall decrease of 5-hydroxytryptamine2A receptor densities was found in all the brain regions of ovariectomized Fischer rats assayed, and this could be restored towards control levels by estradiol treatment. No change in the 5-hydroxytryptamine2A receptor affinity was measured in the frontal cortex. A similar pattern of changes was observed for the messenger RNA levels encoding the 5-hydroxytryptamine2A receptors and receptor density, suggesting the implication of a genomic mechanism. Experiments in Sprague-Dawley rats confirmed and extended the results obtained with Fischer rats. By analogy, in humans, this 5-hydroxytryptamine2A receptor modulation may underlie the mood and movement disorders associated with menopause.

Animals↗
PubMed1997

Ovariectomy and estradiol treatment affect the dopamine transporter and its gene expression in the rat brain.

The impact of gonadal hormone withdrawal and estrogen therapy was investigated on the rat dopamine transporter (DAT). Short-term ovariectomized (ST-OVX, 2 weeks) and long-term ovariectomized (LT-OVX, 3 months) rats were treated or not with 17beta-estradiol (E2) for 2 weeks. DAT mRNA expression was measured by in situ hybridization in the substantia nigra pars compacta (SNc) for the nigrostriatal pathway and the ventral tegmental area (VTA) for the mesolimbic pathway whereas DAT levels were assessed by [3H]GBR-12935 autoradiography, respectively, in the striatum and the nucleus accumbens. Ovariectomy produced a time-dependent decrease of the DAT density in the striatum and the nucleus accumbens and the E2 treatment did not significantly restore these DAT levels. Neither ST-OVX nor E2 treatment of the ST-OVX animals altered the DAT mRNA expression in the SNc and the VTA. However, LT-OVX animals showed increased DAT mRNA levels in these regions. E2 treatment of LT-OVX animals partially restored DAT mRNA levels in the SNc and left these levels unchanged in the VTA. These opposite variations induced by OVX on the DAT density and their mRNA levels suggest the involvement of non-genomic mechanisms, such as post-transcriptional events and/or membrane effects. Altered neurotransmission following gonadal hormone withdrawal may contribute to CNS disorders occurring at menopause in predisposed women. Ovariectomized rats constitute a useful model to study the changes in neurotransmitters balance occurring after menopause.

Animals↗
PubMed1997

Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter.

Deletion of the dopamine transporter (DAT) results in increased dopaminergic tone, anterior pituitary hypoplasia, dwarfism, and an inability to lactate. DAT elimination alters the spatial distribution and dramatically reduces the numbers of lactotrophs and somatotrophs in the pituitary. Despite having normal circulating levels of growth hormone and prolactin in blood, hypoplastic glands from DAT-/- mice fail to respond to secretagog stimulation. The effects of DAT deletion on pituitary function result from elevated DA levels that down-regulate the lactotroph D2 DA receptors and depress hypothalamic growth hormone-releasing hormone content. These results reveal an unexpected and important role or DA in the control of developmental events in the pituitary gland and assign a critical role for hypothalamic DA reuptake in regulating these events.

Animals↗
PubMed1996

The modulation of brain dopamine and GABAA receptors by estradiol: a clue for CNS changes occurring at menopause.

1. Tardive dyskinesia is more important in postmenopausal women than men of comparable age and a peak of first episodes of schizophrenia is observed in postmenopausal women. The effect of ovariectomy (2 weeks or 3 months) in rats was investigated as a model of decreased gonadal function associated with menopause. 2. Frontal cortex D1 receptor density and affinity were similar in intact male compared to intact female rats and progressively decreased in density with time after ovariectomy, with no change of affinity. Striatal D1 and D2 receptors also decreased in density after ovariectomy for both receptor subtypes, with no change of affinity. Striatal D1 receptor density and affinity were similar in intact male and female rats, whereas the density of D2 receptors was higher in females. Treatment with estradiol for 2 weeks restored the D2 but not the D1 receptor changes. 3. In the substantia nigra pars reticulata, striatum, nucleus accumbens, and entopeduncular nucleus, a progressive increase in [3H]flunitrazepam specific binding associated with GABAA receptors was observed as a function of time following ovariectomy; this was corrected with estradiol treatment. In contrast, the opposite was observed for [3H] flunitrazepam binding in the globus pallidus, where ovariectomy decreased binding, which was corrected with estradiol replacement therapy. 4. Low prefrontal cortex dopamine activity with implications of D1 receptors in negative symptoms of schizophrenia is hypothesized. Furthermore, GABAergic overactivity in the internal globus pallidus-substantia nigra pars reticulata complex is hypothesized in tardive dyskinesia. 5. The present data suggest that gonadal hormone withdrawal by reducing brain dopamine receptors and producing an imbalance of GABAA receptors in the output pathways of the striatum may predispose to schizophrenia and dyskinesia.

Animals↗
PubMed1995

Dopamine and GABAA receptor imbalance after ovariectomy in rats: model of menopause.

A peak of first episodes of schizophrenia can occur in postmenopausal women. Furthermore, tardive dyskinesia is more common in postmenopausal women than in men of comparable age. This study investigated the effect of ovariectomy (2 weeks or 3 months) in rats as a model of decreased gonadal function associated with menopause. After ovariectomy, frontal cortex D1 receptors progressively decreased in density with no change of affinity over time. Striatal D1 and D2 receptors also had decreased density after ovariectomy with no change of affinity. In the substantia nigra pars reticulata, a progressive increase in [3H]flunitrazepam-specific binding associated with GABAA receptors was observed as a function of time following ovariectomy. It is hypothesized that low prefrontal cortex dopamine activity has implications in negative symptoms of schizophrenia and, furthermore, that GABAergic overactivity in the internal globus pallidus-substantia nigra pars reticulata complex plays a role in tardive dyskinesia. The present results suggest that, by reducing brain dopamine receptors and increasing GABAA receptors, gonadal hormone withdrawal may predispose to schizophrenia and dyskinesia.

Adult↗
PubMed1994

Methylation in positions 1 and 7 of angiotensin II. A structure-activity relationship study.

Six analogues of angiotensin II (Ang) were synthesized with modifications in positions 1 and 7. The study was undertaken in order to learn more about the influence of alkylations in positions 1 and 7 and their interdependence. Previous studies have shown that alpha, alpha-dimethylation of Gly (aminoisobutyric acid, Aib) in position 1 produces quite potent analogues, as does N-methylation of Gly (sarcosine). Combination of both C alpha- and N alpha-methylations to N-Me-Aib1, however, did not produce an affinity increase. Decyclisation of the Pro7-residue produced moderately active analogues with position 7 N-methylation and inactive analogues if the N-alkylation was suppressed. In order to investigate a possible stereochemical interdependence of positions 1 and 7, a group of peptides with combinations of position 1 and 7 alkylations were investigated. The following analogues were prepared: [Sar1,Aib7]Ang, [Sar1,Aib,Leu8]Ang, [Aib1,7,Leu8]Ang, [Aib1,7,Leu8]Ang, [N-Me-Aib1,Aib7]Ang, [N-Me-Aib1,Aib7,Leu8]Ang. They were synthesized by classical solid phase synthesis using the BOC-TFA-HF scheme. The biological properties of these peptides were assessed on the rabbit aorta preparation and their binding potencies were measured on bovine adrenal membranes. Both on agonistic and antagonistic [Leu8]Ang analogues single Aib substitutions in position 1 or 7 induced affinity reduction in both bioassays. Simultaneous Aib modifications in positions 1 and 7 induced more important affinity loss in a synergic manner in both bioassays and as well for agonists and antagonists. The N-Me-Aib1 modifications induce similar affinity loss with or without concomitant Aib7 modification.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Discrimination between putative bradykinin B2 receptor subtypes in guinea pig ileum smooth muscle membranes with a selective, iodinatable, bradykinin analogue.

We have synthesized a potent, selective, radioiodinated bradykinin (BK) analogue with high specific radioactivity (1000-1500 Ci/mmol). The new tracer, 125I-[p-Phe5]BK, was prepared carrier-free from the corresponding nitro precursor, [p-NO2-Phe5]BK, via catalytic hydrogenation and halodediazotation. This peptide bound to guinea pig ileum membranes in a biphasic pattern, with a high affinity dissociation constant of 3 pM (Bmax = 22 fmol/mg of protein) and a low affinity dissociation constant of 192 pM (Bmax = 245 fmol/mg of protein). The kinetically determined Kd values were 2 pM and 910 pM, respectively. The properties of the new tracer and of the peptide analogues [p-iodo-Phe5]BK and [p-NO2-Phe5]BK were compared with those of [3,4-3H(N)] [2,3-prolyl]BK as label in both saturation and inhibition studies. The results indicated that [p-iodo-Phe5]BK possessed increased affinity for the high affinity site and decreased affinity for the low affinity site, relative to BK. In rat myometrial membranes, in contrast, [p-iodo-Phe5]BK failed to reveal a high affinity site and displayed reduced affinity for the low affinity site, compared with BK. The nitro precursor was a nonselective ligand with nanomolar affinity for all labeled binding sites in both membrane preparations. Measuring the influence of BK and its analogues on guanosine-5'-O-(3-[35S]thio)triphosphate binding to guinea pig ileum membranes, we showed that G proteins were separately activated via both binding sites, qualifying these sites as constituents of signal transduction pathways and, therefore, real membrane receptors. With the new tracer as label, the B2 receptor antagonists D-Arg0-[Hyp3,Thi5,D-Tic7,Oic8]BK and D-Arg0-[Hyp3,Thi5,8,D-Phe7]BK recognized both binding sites with very high affinity in guinea pig ileum membranes, classifying these sites as B2 receptors. The BK-induced contraction in guinea pig ileum is obviously mediated via the receptor with nanomolar affinity, but the physiological role of the high affinity receptor is still unknown.

Amino Acid Sequence↗
PubMed1993

Sar1-p-benzoylphenylalanine-angiotensin, a new photoaffinity probe for selective labeling of the type 2 angiotensin receptor.

Previous photoaffinity labeling of angiotensin II (Ang) receptors with azidophenylalanine containing Ang analogs produced high yield labeling of a 60 kDa protein on bovine adrenocortical membranes. This preparation is mostly enriched in the type 1 Ang receptor (AT1) and AT1 selective ligands (L158,809) totally prevented labeling, therefore confirming the AT1 nature of the labeled protein. Our attempt to photolabel the type 2 Ang receptor (AT2) of human myometrium with [Sar1,D-Phe(N3)8]Ang was unsuccessful, revealing a high degree of photolabeling selectivity. An Ang analog, [Sar1,Bpa8]Ang (or BpaAng) was prepared containing the photosensitive amino acid p-benzoylphenylalanine (Bpa). This compound was a specific but non-competitive Ang antagonist on rabbit aorta with a pA2 of 8.5. It displayed good binding affinities for bovine adrenocortical membranes (Kd = 6.5 nM), a predominantly AT1 preparation, and for human myometrium membranes (Kd = 0.39 nM), a predominantly AT2 preparation. Photolabeling experiments with iodinated BpaAng showed that AT1 was not covalently labeled whereas AT2 was covalently labeled with high yield. Labeling specificity was verified with the AT2-selective ligand PD123319 and with the AT1-selective antagonist L158,809. Our results indicate that 125I-BpaAng is exclusively labeling AT2 sites. This compound should be a useful tool for further biochemical characterization of the AT2 binding site.

Adrenal Cortex↗
PubMed1993

Construct validation of optimism and pessimism in older men: findings from the normative aging study.

Validation of Scheier and Carver's (1985) Life Orientation Test (LOT) has identified associations between bipolar optimism and several external constructs. However, optimism and pessimism may be not bipolar, but rather separate constructs. Furthermore, these constructs may be indistinguishable from personality traits, such as neuroticism and extraversion. This study examined the associations of separate optimism and pessimism measures with self-reports of hassles, psychological symptoms, and illness severity, controlling for personality. Ss were 1,192 men from the Normative Aging Study. Findings suggest that optimism and pessimism are separate and that their relations to external criteria remain, although attenuated, when neuroticism and extraversion are controlled.

Age Factors↗
PubMed1993

Change in social support after retirement: longitudinal findings from the Normative Aging Study.

Although retirement is generally thought to lead to a decline in social support due to a loss of social contacts with coworkers, the evidence for this is at best contradictory. This longitudinal study examined change in social support among 1,311 men, participants in the Veterans Administration Normative Aging Study, over a 3-year period. In general, long-term retirees reported the least quantitative social support, and the continuing full-time workers the most; however, change in workforce status produced no apparent effect on quantitative support over the duration of this study. In general, qualitative support showed no retirement effects. We also examined more specific patterns of coworker friendship and again found a pattern similar to that of general quantitative support. The findings support our earlier suggestion of a distinction between retirement as a transition and retirement as a state, and also support the convoy model of social support in late life and the selectivity theory of developmental adaptation to aging.

Adult↗
PubMed1993

Photoaffinity labeling of subtype 2 angiotensin receptor of human myometrium.

Angiotensin II (AII) binding sites were characterized in human myometrium membrane preparations. The sites were saturable and of high affinity (Kd of 0.09 nM and Bmax of about 200 fmol/mg of protein). PD 123319 completely inhibited 125I-AII binding, with an IC50 of 30 nM, whereas L-158,809 (1 microM) had no significant effect on 125I-AII binding. These results indicate that human myometrium contains almost exclusively the AT2 receptor subtype. Association and dissociation studies performed with 125I-AII on human myometrium membranes revealed that AII had a very high affinity for AT2 receptors, with a Kd of 0.01 nM (association rate constant K1 = 1.056 x 10(12) mol-1 min-1; dissociation rate constant K2 = 0.003 min-1). The photoactivable AII analogue [Sar1, Val5, D-Phe8(N3)]AII displayed a high affinity for AT2 receptors (IC50 of 0.18 nM), but its radioiodinated form showed poor efficiency in photoaffinity labeling experiments. A newly synthesized photoactivatable analogue of AII, [Sar1, p-benzoyl-Phe8]AII, (AII-Bpa), also displayed a high affinity for AT2 receptors of human myometrium (IC50 of 0.3 nM). Photoaffinity labeling experiments were performed with 125I-AII-Bpa, and a high yield (70%) of covalent incorporation to human myometrium membranes was obtained upon photolysis. Covalently labeled receptors were solubilized, denatured, and subjected to polyacrylamide gel electrophoresis. Autoradiography of the polyacrylamide gel revealed a single band, of 68 kDa, and the labeling of this band was completely abolished in the presence of 1 microM PD 123319, indicating selective labeling of the AT2 receptor subtype. These results demonstrate that AII-Bpa is a very efficient tool for selective photoaffinity labeling of the AT2 receptor.

Adrenal Cortex↗
PubMed1991

Personality and aging: a study of the MMPI-2 among older men.

We examined whether separate norms for older men are necessary for the revised Minnesota Multiphasic Personality Inventory (MMPI-2). Scores from 1,459 men in the Normative Aging Study (NAS) (age: M = 61.27, SD = 8.37) were contrasted with those from 1,138 men from the MMPI Restandardization Study (age: M = 41.71, SD = 15.32). Results showed that scores on the MMPI-2 validity, clinical, and content scales for the NAS men were highly similar to those from the MMPI-2 Restandardization sample. There were also few differences between the two groups at the item level. Within-sample analyses revealed some differences between age groups. However, the magnitudes of these differences were small and may represent the single or combined effects of cohort factors and age-related changes in physical health status rather than age-related changes in psychopathology per se. We concluded that special, age-related norms for the MMPI-2 are not needed for older men.

Adolescent↗
PubMed1991

How stressful is retirement? Findings from the Normative Aging Study.

The stressfulness of retirement both as a transitional event experienced during the past year and as a life stage was investigated. Transitional stress was assessed using a life events approach, and stage stress using a "hassles" approach. Respondents were 1,516 male participants in the Normative Aging Study, 45% of whom were retired. Among those retiring in the past year, respondents' own and spouse's retirement were rated the least stressful from a list of 31 possible events. Only 30% found retirement stressful. Retirement hassles were also less frequently reported and were rated less stressful than the work hassles of men still in the labor force. The only consistent predictors of both transitional and stage retirement stress were poor health and family finances; personality did not predict retirement stress.

Adult↗