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Biomedical subjects

S Beaulieu

Publications and source records attributed to S Beaulieu.

13 recordsLinked to original sources

Cardiovascular, neuroendocrine, and monoaminergic responses to psychological stressors: possible differences between remitted panic disorder patients and healthy controls.

Both clinical symptomatology and stress research suggest that panic attacks might be partially attributable to exaggerated psychophysiological responses to environmental stressors. In the present study, we aimed to explicitly test this idea by measuring the physiological responses to a mild psychological stressor in both healthy controls (n = 8) and fully remitted, medication-free panic disorder patients (n = 8). One hour before the stressor, former patients, compared to healthy controls, exhibited higher diastolic blood pressure. From a blood sample taken 30 min before the stressor, patients, compared to controls, had lower paroxetine platelet binding site densities. During the stressor, patients, compared to controls, had greater increases in plasma levels of cortisol. These preliminary findings suggest that remitted panic disorder patients might have disturbed physiological responses to mild psychological stressors. These disturbances might be related to the development of future episodes.

Adult

In vitro characterization of purified human thymic dendritic cells infected with human immunodeficiency virus type 1.

In the thymus, dendritic cells (DC) are functionally associated with thymocytes and are recognized to play a major role in the intrathymic differentiation of T cells. Several studies have previously investigated the role of DC during HIV-infection, but the status of thymic DC in HIV-1 pathogenesis remains unclear. In this study, we investigated the susceptibility of purified human thymic DC to HIV-1 infection in vitro. HIV-1 was not detected in cell-free supernatants collected from HIV-infected DC. However, these cultures were shown to transmit HIV-1 infection since coculture with permissive MT4 cells resulted in virus production. The exposure of DC in culture to HIV-1 was shown to promote severe DC morphological changes and killing. We also found that one or several heat labile soluble cytotoxic agents present in the HIV-1-infected DC supernatant mediated the killing of thymocytes. Our observations raise the possibility that (1) the HIV-1-induced DC killing, (2) the capacity of DC to transmit viral infection, and/or (3) the release of HIV-1-mediated cytotoxic agent(s) from DC may contribute to AIDS pathogenesis in vivo.

Animals

An improved method for purifying human thymic dendritic cells.

Thymic dendritic cells (DC) play a prominent role in the immune response as they constitute a key element involved in the maturation of thymocytes in the thymus. Human thymic DC, like DC from other lymphoid organs, represent a minor cell population (< 2%) of the thymus. Since these cells cannot replicate in vitro, the development of efficient purification methods is an essential prerequisite for extensive functional studies. DC express high levels of HLA-DR, a cell surface marker of the MHC class II antigen which is not exclusive to DC. Since no specific human thymic DC marker has been identified so far, DC purification methods are mainly based on depletion of particular subgroups of cells. We report here an improved method for purifying human thymic dendritic cells. In contrast to prior work, CD2+ thymocytes were first depleted by rosetting with neuraminidase treated sheep red blood cells. The nonrosetted cells were separated in a Percoll gradient, and the low-density cells were subsequently depleted of nondendritic cells by using thymocyte and macrophage specific monoclonal antibodies and either magnetic bead depletion or cytofluorometry. Cell populations (18-55 x 10(6) cells) obtained following magnetic bead purification were at least 80% HLA-DR+/CD2- and exhibited ultrastructural morphological features and functional activities such as those described previously for thymic DC. This improved method was compared with different purification approaches that use various combinations of cell density-based separation techniques and cell surface specific markers antibody reactivity. The magnetic beads depletion approach provided higher yields.

Antibodies, Monoclonal

Activation of human immunodeficiency virus 1 gene expression by the src oncoprotein.

Several genes are induced constitutively in cells transformed by the v-src oncoprotein. This induction is generally dependent on the activation of transcription factors binding to src-responsive elements of the promoter. In previous studies, we showed that the induction of the CEF-4/9E3 cytokine gene by pp60v-src is dependent on the PRDII/kappa B domain of the promoter (Dehbi et al., 1992). In this investigation, we describe the activation of the HIV-1 LTR by pp60v-src and show that a region of 30 bp containing the two NF-kappa B binding sites is critical for activation of the promoter. The induction was dependent on transformation since non-transforming forms of pp60v-src had little or no effect on the promoter. The expression of proviral DNA and the release of p24 antigen were also increased by v-src indicating that viral replication was stimulated in src-transformed cells. The effect of v-src on HIV-1 gene expression occurred in the presence or in the absence of the tat viral trans-activator, in fibroblasts and in Jurkat T lymphocytes. These results indicate that several promoters controlled by PRDII/kappa B may be activated constitutively in v-src transformed cells and suggest that oncogenic tyrosine kinases may play a role in the induction of viruses with a PRDII/kappa B-controlled promoter.

Animals

An analysis of frequencies of surgical procedures in Canada.

This paper reports preliminary and selected results of an analysis of the frequencies of 36 common surgical procedures in hospitals across Canada during the period April 1985 to March 1987. Age-sex-specific and age-sex-standardized procedure rates were calculated for each procedure for each of 245 Census Divisions (CDs) across Canada, as well as for 338 smaller urban areas (FSAs) within the province of Ontario. Special attention was given to adjusting the rates for differing population sizes of the geographical regions. Procedure rates were computed based on the residence of the patient, not on the location of the hospital. Graphical techniques, analysis of variance, and other statistical techniques were used to identify unusually high or low procedure rates and to determine effects due to differences in age, sex, and geographical region. The relationship of procedure rate to the socio-economic level of a region (as measured by the proportion of low-income individuals in the region) was analyzed.

Canada

Differential regulation by dexamethasone of glucocorticoid receptor messenger RNA concentrations in neuronal cultures derived from fetal rat hypothalamus and cerebral cortex.

1. Differential regulation, by dexamethasone, of glucocorticoid receptor gene expression was studied in three different neuronal cultures derived from hypothalamus amygdala, and cerebral cortex. 2. Cellular glucocorticoid receptor (GR) mRNA concentration was measured by hybridization using a 32P-labeled RNA probe complementary to a 2.2-kb fragment of the glucocorticoid receptor mRNA. Changes in the amount of GR mRNA were evaluated in relation to the content of beta-actin mRNA. 3. In cells derived from either hypothalamus or cerebral cortex, we observed a complex pattern of GR mRNA concentrations which were characterized by cyclic variations of GR mRNA content during continuous treatment with dexamethasone for up to 72 hr. 4. In contrast to cells derived from the hypothalamus where a persistent 30-40% reduction in GR mRNA levels was seen for up to a least 72 hr, we observed, in cells derived from the cerebral cortex, a sustained increased (1.4-fold) of the GR mRNA at this same time interval.

Animals

Antidepressants regulate glucocorticoid receptor messenger RNA concentrations in primary neuronal cultures.

Increased cortisol secretion, caused by hyperactivity of the brain-pituitary-adrenal axis, and non-suppression of cortisol secretion following dexamethasone administration are two characteristics frequently associated with major depression or the depressed phase of bipolar illness. Antidepressants, irrespective of their selective inhibitory actions on the re-uptake of serotonin or of norepinephrine, modify glucocorticoid receptor messenger RNA concentrations in primary cultures of rat hypothalamic or amygdaloid neurons in a biphasic manner, with predominant stimulatory effects. This suggests a mechanism whereby antidepressants, by restoring the sensitivity of the limbic-hypothalamic system to glucocorticoid feedback inhibition, reverse the hyperactivity of the brain-pituitary-adrenal axis.

Amygdala

Influence of the central nucleus of the amygdala on the content of corticotropin-releasing factor in the median eminence.

The central nucleus of the amygdala possesses numerous neurons containing corticotropin-releasing factor (CRF). This study demonstrates a striking decrease of the CRF-like immunoreactivity in the median eminence at both 1 and 2 weeks after bilateral lesions of the amygdaloid central nucleus. Lesion of the amygdaloid central nucleus did not alter the neurophysin-like immunoreactivity in the internal zone of the median eminence, indicating the integrity of the efferent neurophysin-containing fibers of the supraoptic and paraventricular hypothalamic nuclei. However, there was a concomitant decrease of neurophysin and CRF-like immunoreactivity in the external zone of the median eminence. These results substantiate the hypothesis that the amygdaloid central nucleus can influence the content of CRF-like material in the median eminence via a multisynaptic pathway involving the synthesis of CRF at the level of the paraventricular nucleus of the hypothalamus. The exact mechanism by which lesion of the amygdaloid central nucleus influences the CRF content in the median eminence remains to be determined.

Amygdala

Glucocorticoid regulation of proopiomelanocortin messenger ribonucleic acid content of rat hypothalamus.

We have verified the possibility that the POMC gene of the rat hypothalamus might be subject to regulation by glucocorticoids. Adrenalectomy increased the concentration of POMC mRNA in anterior pituitary and in hypothalamus, but not in the neurointermediate lobe of the pituitary gland. Dexamethasone and, to a slightly lesser extent, corticosterone treatments reversed the adrenalectomy-induced increase in POMC mRNA concentrations in both anterior pituitary and hypothalamus. Dexamethasone caused a slight decrease of POMC mRNA levels in the neurointermediate lobe of the pituitary gland, while corticosterone had no effect. These results indicate that the POMC gene of the rat brain hypothalamus is also under negative control by glucocorticoids.

Adrenalectomy

Participation of the central amygdaloid nucleus in the response of adrenocorticotropin secretion to immobilization stress: opposing roles of the noradrenergic and dopaminergic systems.

Bilateral lesions of the amygdaloid central nucleus (ACE) significantly diminished the secretion of ACTH in response to immobilization stress. Stress is associated with increased noradrenergic activity in the ACE and in the anterior and lateral hypothalamic areas. In comparison with intact stressed animals, lesion of the ACE reduced the noradrenergic activity in response to stress within the anterior and lateral hypothalamic areas, the arcuate and paraventricular nuclei of the hypothalamus and the bed nucleus of the stria terminalis. These results support the hypothesis of a stimulatory role for the noradrenergic system in the ACE on ACTH secretion. Stress decreased dopaminergic activity in the ACE, the cortical nucleus of the amygdala, the dorsomedial and ventromedial nuclei of the hypothalamus and the ventral tegmental area. In comparison with intact stressed rats, lesion of the ACE reduced dopaminergic activity in the anterior and lateral hypothalamic areas. Our results support the hypothesis of an inhibitory role of the dopaminergic system, particularly in the ACE, on ACTH secretion. This study also indicates that, in the control of ACTH secretion in response to immobilization stress, the noradrenergic and dopaminergic systems act in opposition to one another in certain brain structures such as the anterior and lateral hypothalamic areas and the ACE.

Adrenocorticotropic Hormone

Control of ACTH secretion by the central nucleus of the amygdala: implication of the serotoninergic system and its relevance to the glucocorticoid delayed negative feedback mechanism.

The possible implication of the amygdaloid central nucleus (ACE) of the rat in the control of ACTH secretion in response to immobilization stress was assessed. The ACTH secretion, in response to stress and/or bilateral lesions of the ACE, was correlated with the serotoninergic activity in specific hypothalamic and amygdaloid nuclei. Bilateral lesions of the ACE produced a striking decrease of plasma ACTH levels in response to stress. However, basal plasma ACTH levels measured between 7 and 11 a.m. were identical in both control and lesioned groups. Stress, applied to intact animals, did not modify the serotoninergic activity in any of the following areas: hypothalamic paraventricular (PVH), ventromedial (VMH) and dorsomedial (DMH) nuclei; the anterior hypothalamic area (AHA); the lateral part of the basal amygdaloid nucleus (ABL), the amygdaloid medial (AME) and cortical (ACO) nuclei. However, lesion of the ACE increased the serotoninergic activity in all these structures except for the VMH. Immobilization stress applied to lesioned animals decreased the serotoninergic activity to control levels in the PVH, AHA and DMH and decreased the activity to below control levels in the VMH. The serotoninergic activity remained at an increased level in the glucocorticoid receptor-rich areas of the amygdala, namely the AME, ACO and ABL nuclei. These results provide evidence for a stimulatory role of the central nucleus of the amygdala in the control of ACTH secretion. Moreover, they substantiate an implication of the amygdaloid complex in the control of the delayed negative feedback of glucocorticoids on ACTH secretion via interaction with the serotoninergic system.

Adrenocorticotropic Hormone

Implication of the serotoninergic system in the decreased ACTH response to stress after lesion of the amygdaloid central nucleus.

The present study was designed to ascertain the possible implication of the serotoninergic system and the central amygdaloid nucleus in the control of ACTH secretion in response to immobilization stress. The response to immobilization stress of intact and lesioned animals was studied by monitoring the plasma and pituitary ACTH concentration and the activity of the serotoninergic system within specific hypothalamic and amygdaloid nuclei. Bilateral lesions of the central nucleus of the amygdala significantly decreased the secretion of ACTH in response to immobilization. Moreover, the serotoninergic activity in most of the hypothalamic and in all the amygdaloid nuclei studied was greatly increased. A 60-min immobilization stress prevented this increase in the hypothalamic nuclei but not in the amygdala. These results indicate that the central nucleus of the amygdala participates in the regulation of ACTH secretion in response to immobilization stress. Furthermore, they substantiate the hypothesis of a participation of the serotoninergic system in limbic areas, particularly in nuclei which contain neurons possessing glucocorticoid receptors such as the medial, basomedial and cortical amygdaloid nuclei.

Adrenocorticotropic Hormone