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Biomedical subjects

S Rousseau

Publications and source records attributed to S Rousseau.

At least 19 recordsLinked to original sources
PubMed2003

[Indications of vasopressin in the management of septic shock].

OBJECTIVE: Vasopressin (antidiuretic hormone) is emerging as a potentially major advancement in the treatment of septic shock. Vasopressin is both a vasopressor and an antidiuretic hormone. It also has haemostatic, gastrointestinal, and thermoregulatory effects. This article reviews the physiology of vasopressin and all the relevant clinical literature on its use in the treatment of septic shock. DATA SOURCES AND EXTRACTION: Extraction from Pubmed database of French and English articles on the physiology and clinical use of vasopressin. The following key words were selected: vasodilatory shock, vasopressin, septic shock, catecholamines, norepinephrine, renal function, diuresis, mesenteric haemodynamic. The collected articles were reviewed and selected according to their quality and originality. DATA SYNTHESIS: Vasopressin mediates vasoconstriction via V1-receptor activation on vascular smooth muscle. Septic shock causes first a transient early increase in blood vasopressin concentrations that decreases later to very low concentrations compared to other causes of hypotension. Vasopressin infusion of 0.01-0.04 U min(-1) in septic shock patients increases plasma vasopressin concentrations. This increase is associated with a lesser need for other vasopressors. Vasopressin has been shown to produce greater blood flow diversion from non-vital to vital organ beds than does adrenaline. A large randomized clinical trial should be performed to assess its place as a therapeutic agent of septic shock patient.

Clinical Trials as Topic↗
PubMed2001

Diagnosis of human parvovirus B19 infections by detection of epitope-type-specific VP2 IgG.

In the B19 VP2 molecule an immunodominant heptapeptide epitope has been detected, recently for which IgG antibodies are synthesized exclusively in the acute phase of B19 infection. Using this acute-phase-specific epitope (KYVTGIN) a 2(nd)-generation epitope-type EIA was developed, which compares serum IgG activity for native VP2 capsids exhibiting conformational VP2 epitopes with IgG activity for the KYVTGIN epitope. In this study the diagnostic performance (clinical sensitivity and specificity) of the 1st and 2nd-generation epitope-type EIAs and of a peptide-based EIA utilising as antigen the KYVTGIN epitope alone was assessed in comparison with various high-quality IgM- and IgG- based B19 assays. Serum samples from 489 patients with B19-related symptoms and asymptomatic controls from three countries were studied. Among 323 patients with B19-IgG, 20% were diagnosed as acute infection, 73% had past immunity and 7% were not classified due to contradictory results among the different assays. The unclassified samples were explored for viral strain diversity by PCR and DNA sequencing but all sequences obtained were B19-like with variance of only a few per cent. The 2nd-generation epitope-type EIA had a diagnostic sensitivity of 98% and a diagnostic specificity of 94%. In combination with conventional approaches, the epitope-type assays increase greatly the accuracy of B19 serodiagnosis.

Acute Disease↗
PubMed2001

Surveillance of HIV infection and related risk behaviour in European prisons. A multicentre pilot study.

BACKGROUND: In order to demonstrate the feasibility of human immunodeficiency virus (HIV) infection and related risk behaviour surveillance in European prisons, a multicentre pilot study was undertaken. METHODS: A cross-sectional survey was carried out in six European prisons (France, Germany, Italy, The Netherlands, Scotland and Sweden). Inmates were invited to complete a self-administered and anonymous questionnaire and to give a saliva sample in order to test for HIV antibodies. RESULTS: Eight hundred and forty-seven out of 1,124 inmates participated in the survey (response rate 75%). Saliva from 817 inmates (73%) was collected and processed for HIV antibodies. Twenty-seven per cent reported that they had ever injected drugs and 49% of these reported they had injected whilst in prison. Eighteen per cent of inmates reported that they had been tattooed whilst in prison, which was found to be higher among injecting drug users (IDUs). One and sixteen per cent reported that they had ever had homosexual and heterosexual intercourse in prison respectively. The HIV prevalence among IDUs was 4% (versus 1% among non-IDUs) (p = 0.02). The proportions of inmates previously tested for hepatitis C and vaccinated against hepatitis B were 24 and 16% respectively. CONCLUSION: This survey demonstrates the feasibility of cross-sectional surveys in European prison inmates and highlights the importance of surveillance of HIV prevalence and related risk behaviour among inmates. The continuing high HIV prevalence and potential for HIV spread in prisons should encourage decision makers in implementing or enhancing harm reduction and education programmes and substance abuse treatment services in prison.

Cross-Sectional Studies↗
PubMed2000

Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase.

In endothelial cells, vascular endothelial growth factor (VEGF) induces an accumulation of stress fibers associated with new actin polymerization and rapid formation of focal adhesions at the ventral surface of the cells. This cytoskeletal reorganization results in an intense motogenic activity. Using porcine endothelial cells expressing one or the other type of the VEGF receptors, VEGFR1 or VEGFR2, or human umbilical vein endothelial cells pretreated with a VEGFR2 neutralizing antibody, we show that VEGFR2 is responsible for VEGF-induced activation of the stress-activated protein kinase-2/p38 (SAPK2/p38), phosphorylation of focal adhesion kinase (FAK), and enhanced migratory activity. Activation of SAPK2/p38 triggered actin polymerization whereas FAK, which was phosphorylated independently of SAPK2/p38, initiated assembly of focal adhesions. Both processes contributed to the formation of stress fibers. Geldanamycin, an inhibitor of HSP90 blocked tyrosine phosphorylation of FAK, assembly of focal adhesions, actin reorganization, and cell migration, all of which were reversed by overexpressing HSP90. We conclude that VEGFR2 mediates the physiological effect of VEGF on cell migration and that two independent pathways downstream of VEGFR2 regulate actin-based motility. One pathway involves SAPK2/p38 and leads to enhanced actin polymerization activity. The other involves HSP90 as a permissive signal transduction factor implicated in FAK phosphorylation and assembly of focal adhesions.

Actins↗
PubMed2000

Theoretical Study of the Electronic Structure of the KRb Molecule.

Upon request of experimentalists now engaged in high-resolution spectroscopic investigations of the molecule KRb, we have determined the potential energy of electronic states (2S+1)Lambda((+)) correlating up to the limit K(5p) + Rb(5s) and of electronic states Omega((+/-)) correlating up to the limit K(4s) + Rb(4d(2)D(3/2)) in a large range of internuclear distance R. For the five states so far observed, the agreement between calculated and experimental molecular constants is good with DeltaR(e) < 0.08 Å, Deltaomega(e) < 6 cm(-1), and DeltaT(e) < 140 cm(-1). Extensive numerical data for energies versus R have been listed in a data base available at http://www.idealibrary.com. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

An ecological approach to planning dysfunction: script execution.

Planning, which concerns many activities in everyday life, is a two-stage process. The first one predetermines a course of actions aimed at achieving some specific goals. It is founded on managerial knowledge or overlearned sequences of events and may be tested by script generation. The second stage entails monitoring and guiding the execution of the plan to a successful conclusion. It must take into account environmental contingencies and may be tested by script execution. If the frontal lobes intervene not only in managerial knowledge (Grafman, 1989) but also in binding the plan with contextual environment (Damasio, Tranel and Damasio, 1991; Shallice and Burgess, 1991), script execution would be more sensitive than script generation to planning deficits. To test this hypothesis, script execution and script generation were compared in 11 patients with a dysexecutive syndrome and 10 matched controls, using three scripts of daily life activities: (1) 'shopping for groceries'; (2) 'cooking'; (3) 'answering a letter and finding the way to post the reply'. Two way ANOVAs showed more errors in execution than in generation, more errors in patients than in controls, and a greater difference between execution and generation in patients than in controls. Furthermore, 'context neglect' and 'environmental adherence' were the two types of errors that best differentiated patients from controls. Finally, the total number of errors in execution correlated with the score on behavioral questionnaires answered by occupational therapists. These results confirm our hypothesis and suggest that script execution may be a valid ecological approach to estimate the severity of deficits in daily life activities.

Activities of Daily Living↗
PubMed2000

Transient enhancing of cone electroretinograms following exposure to brighter photopic backgrounds.

Normal subjects were first light adapted to a standard photopic background and a control photopic ERG was obtained. The subjects were then light adapted to a brighter background for 5 min at the end of which the luminance was returned to the control background and ERGs were taken at regular intervals. Most of the ERG/OP components were transiently enhanced following the above procedure. Given that the previously reported photopic light adaptation effect occurred following an increase in the luminance of the adapting field (from dark adaptation to light adaptation) while that reported in the present study is triggered following a decrease in the level of light adaptation, the opposite effects noted might suggest that the two retinal events result from the same, not yet identified, cone adaptation mechanisms which are solicited in an opposite way.

Adaptation, Ocular↗
PubMed2000

Integrating the VEGF signals leading to actin-based motility in vascular endothelial cells.

Vascular endothelial growth factor (VEGF) is a potent pro-angiogenic factor that stimulates endothelial cell proliferation and migration, two key events of the angiogenic process. The intracellular signals leading to these events have recently been investigated and a better understanding on how VEGF induces its angiogenic functions is emerging. Herein, we summarize recent findings on how VEGF stimulates endothelial cell migration and contributes to angiogenesis. In particular, the role of the VEGF receptors involved in initiating the coordinated signals that leads to actin-based motility is discussed.

Actins↗
PubMed1999

Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta.

Mek is a dual-specificity kinase that activates the extracellular-signal-regulated (Erk) mitogen-activated protein (MAP) kinases upon agonist binding to receptors. The Erk MAP kinase cascade is involved in cell-fate determination in many organisms. In mammals, this pathway is proposed to regulate cell growth and differentiation. Genetic studies have shown that although a single mek gene is present in Caenorhabditis elegans, Drosophila and Xenopus, two mek homologs, Mek1 and Mek2, are present in the mammalian cascade. In the present study, we describe a mutant mouse line in which the mek1 gene has been disrupted by insertional mutagenesis. The null mutation was recessive lethal, as the homozygous mutant embryos died at 10.5 days of gestation. Histopathological analyses revealed a reduction in vascularization of the placenta that was due to a marked decrease of vascular endothelial cells in the labyrinthine region. The failure to establish a functional placenta probably explains the death of the mek1-/- embryos. Cell-migration assays indicated that mek1-/- fibroblasts could not be induced to migrate by fibronectin, although the levels of Mek2 protein and Erk activation were normal. Re-expression of Mek1 in the mutant mouse embryonic fibroblasts (MEFs) restored their ability to migrate. Our findings provide genetic evidence that establishes the unique role played by Mek1 in signal transduction. They also suggest that mek1 function is required for normal response to angiogenic signals that might promote vascularization of the labyrinthine region of the placenta.

Animals↗
PubMed1999

The electroretinogram recorded at the onset of dark-adaptation: understanding the origin of the scotopic oscillatory potentials.

The purpose of this study was to examine the origin of the oscillatory potentials (OPs) recorded at the onset of dark-adaptation. Our results show that following pre-exposure of the retina to progressively brighter photopic backgrounds there is a complete abolition of OP4 and approximately 50% of OP3, while OP2 is not affected in responses evoked to dim flashes of white light and recorded at the onset of dark-adaptation. These results bring further support to the claim that the short latency OP2 is cone-mediated while the OP3 and OP4 would have a significant rod contribution. However, a more complex picture of OP genesis arises when flicker and response to brighter white light flashes, also obtained within the first minute of dark-adaptation are considered. The latter would suggest that our understanding of the origin of the OPs cannot be exclusively based on which of the two class of photoreceptors is preferentially stimulated at the time the response is recorded.

Adolescent↗
PubMed1998

SAPK2/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis.

In endothelial cells, H2O2 induces the rapid formation of focal adhesion complexes at the ventral face of the cells and a major reorganization of the actin cytoskeleton into dense transcytoplasmic stress fibers. This change in actin dynamics results from the activation of the mitogen-activated protein (MAP) kinase stress-activated protein kinase-2/p38 (SAPK2/p38), which, via MAP kinase-activated protein (MAPKAP) kinase-2/3, leads to the phosphorylation of the actin polymerization modulator heat shock protein of 27 kD (HSP27). Here we show that the concomitant activation of the extracellular signal-regulated kinase (ERK) MAP kinase pathway by H2O2 accomplishes an essential survival function during this process. When the activation of ERK was blocked with PD098059, the focal adhesion complexes formed under the plasma membrane, and the actin polymerization activity led to a rapid and intense membrane blebbing. The blebs were delimited by a thin F-actin ring and contained enhanced levels of HSP27. Later, the cells displayed hallmarks of apoptosis, such as DEVD protease activities and internucleosomal DNA fragmentation. Bleb formation but not apoptosis was blocked by extremely low concentrations of the actin polymerization inhibitor cytochalasin D or by the SAPK2 inhibitor SB203580, indicating that the two processes are not in the same linear cascade. The role of HSP27 in mediating membrane blebbing was assessed in fibroblastic cells. In control fibroblasts expressing a low level of endogenous HSP27 or in fibroblasts expressing a high level of a nonphosphorylatable HSP27, H2O2 did not induce F-actin accumulation, nor did it generate membrane blebbing activity in the presence or absence of PD098059. In contrast, in fibroblasts that expressed wild-type HSP27 to a level similar to that found in endothelial cells, H2O2 induced accumulation of F-actin and caused bleb formation when the ERK pathway was inhibited. Cis-platinum, which activated SAPK2 but induced little ERK activity, also induced membrane blebbing that was dependent on the expression of HSP27. In these cells, membrane blebbing was not followed by caspase activation or DNA fragmentation. We conclude that the HSP27-dependent actin polymerization-generating activity of SAPK2 associated with a misassembly of the focal adhesions is responsible for induction of membrane blebbing by stressing agents.

Actins↗
PubMed1998

Analytical Formulas for Long-Range Energies of the 16 Omega(+/-)g,u States of Alkali Dimers Dissociating into M(ns) + M(np 2PJ)

Analytical formulas for long-range energies of the 16 Omega(+/-)g,u states of alkali dimers dissociating into M(ns) + M(np 2PJ) are displayed in terms of the long-range Cn coefficients for the 2S+1Lambda(+)g,u corresponding states, and including exchange interaction energy contributions. Corrections due to retardation effects for resonant-dipole interactions are also included. For values of the internuclear distance R large enough so that only Coulombic interactions in R-3 are nonnegligible, the variation with R of the long-range energy is seen to be different from the usually assumed C3/R3 form. Present formulas can be used both to predict accurately long-range energies and to fit experimental energies now available in such long-range of R from photoassociative spectroscopy. As an example, they have been used, together with more accurate values of Cn coefficients than those used some 10 years ago, to predict again the three states of Rb2 displaying structures (well and barrier) at long range, i.e., 0(-)g(3/2), 1u(3/2), and 1u(1/2). Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Evidence supportive of a functional discrimination between photopic oscillatory potentials as revealed with cone and rod mediated retinopathies.

We report on a family where four of the eleven children presented with reduced visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test, normal appearing fundi and unexpected electroretinographic findings. Light- (photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory potentials (OPs) were obtained following an accepted standard protocol. The b-wave of their photopic ERG was significantly more attenuated than the a-wave due to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within the normal range, giving to the b-wave a truncated appearance reminiscent of that seen in congenital stationary night blindness (CSNB) with myopia. Interestingly in the latter condition, which is believed to result from an ON-retinal pathway anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of normal amplitude thus resulting in an OP response pattern which complements that seen with our patients. Also of interest is the fact that, in our patients, the amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured in light-adaptation while, in normal, a non-significant 14% increase is noted; a finding which is in keeping with other studies reporting supernormal scotopic ERGs in some forms of cone dystrophies. Based on the photopic OP response pattern, our patients represent the electrophysiological complement of patients affected with CSNB. Interestingly their symptoms are also complementary, a finding which could support a functional discrimination between the photopic OPs.

Adolescent↗
PubMed1998

International health training in family practice residency programs.

BACKGROUND AND OBJECTIVES: This survey determined the extent of involvement in and support of international health training by family practice residency programs. METHODS: We mailed a 17-item survey about four areas of international health training (curriculum, faculty, financial support, and international health sites) to the 192 family practice residency programs that answered affirmatively to the American Academy of Family Physicians (AAFP) 1996 survey question, "Does your program offer or encourage an elective in an international setting?" RESULTS: Of the surveyed programs, 75% (144/192) responded. Fifty-four percent of programs offered some form of international health curriculum, and 15.3% (22/144) provided significant support for resident involvement in international health, defined as having 1) an international health curriculum, 2) funding support (other than paid salary while away), and 3) at least one faculty member who had done health care work in a developing country in the past 2 years. Of the responding programs, 24.3% (35/144) had none of the three criteria. The number of residents who worked in developing countries most strongly correlated with the number of faculty who have done such work in the past 2 years. Logistic regression suggested that the factors associated with a program having residents who have worked in developing countries in the past 2 years included the number of faculty who worked in developing countries in the past 2 years, the number of months of salary paid while on an international health elective, the length of time a program had offered an international health experience, and paid living expenses while at the international site. CONCLUSIONS: A wide range of support is offered for international health education by programs that are self-identified as offering or encouraging international health rotations. This survey begins to clarify the specific factors associated with placing residents in international training opportunities.

Curriculum↗
PubMed1997

p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells.

Vascular endothelial growth factor (VEGF) is a potent chemotactic agent for endothelial cells. Yet the signalling pathways that modulate the motogenic effects of VEGF in vascular endothelial cells are still ill defined. In the present study, we found in primary cultures of human umbilical vein endothelial cells (HUVEC) that VEGF increased cell migration and induced a marked reorganization of the microfilament network that was characterized by the formation of stress fibers and the recruitment of vinculin to focal adhesions. VEGF also stimulated the mitogen activated protein (MAP) kinases ERK (extracellular signal-regulated kinase) and p38 (stress activated protein kinase-2), but not SAPK1/JNK (stress activated protein kinase-1/c-Jun NH2-terminal kinase). Activation of p38 resulted in activation of MAP kinase activated protein kinase-2/3 and phosphorylation of the F-actin polymerization modulator, heat shock protein 27 (HSP27). Inhibiting the VEGF-induced activation of ERK with PD098059 did not influence actin organization or cell migration but totally inhibited the VEGF-induced incorporation of thymidine into DNA. Inhibition of p38 activity by the specific inhibitor SB203580 led to an inhibition of HSP27 phosphorylation, actin reorganization and cell migration. The results indicate that the p38 pathway conveys the VEGF signal to microfilaments inducing rearrangements of the actin cytoskeleton that regulate cell migration. By modulating cell migration, p38 may thus be an important regulator of angiogenesis.

Actins↗