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Biomedical subjects

J Gosselin

Publications and source records attributed to J Gosselin.

At least 19 recordsLinked to original sources
PubMed2003

Reference values for an index of fetal aortic isthmus blood flow during the second half of pregnancy.

OBJECTIVE: During fetal life, the parallel position of the two cardiac ventricles confers a special status to the aortic isthmus. Flow through the isthmus reflects the balance between the performances of the two ventricles and their respective peripheral impedances. This study proposes a fetal aortic isthmus flow velocity index and its reference values defined on the basis of gestational age (GA). METHODS: Video recordings of 111 normal fetuses from 18 to 39 weeks of gestation were retrospectively reviewed. An isthmus flow velocity index (IFI) was calculated as follows: IFI = (systolic + diastolic)/systolic velocity integrals. GA-specific reference ranges of IFI were constructed. RESULTS: An IFI of 1.33 +/- 0.03 was found at 18 weeks. This value decreased slightly but steadily with GA to reach 1.23 +/- 0.16 at 39 weeks. This change is mainly related to a decrease in diastolic velocity integrals. CONCLUSION: The proposed IFI provides information on the direction and, indirectly, on the volume of blood flow through the fetal aortic isthmus.

Aorta, Thoracic↗
PubMed2003

Changes in flow velocity patterns of the superior and inferior venae cavae during placental circulatory insufficiency.

OBJECTIVES: Placental circulatory insufficiency, expressed by the disappearance of the diastolic component of the umbilical artery Doppler velocity waveforms, causes blood flow redistribution that could disturb, to different extents, the systemic venous returns to the heart. The purpose of this study was to investigate the effect of an absence of diastolic blood flow in the umbilical artery on the relationship between the Doppler flow velocities of the venae cavae. METHODS: Fifteen normal fetuses (normal group) were matched for gestational age with 11 fetuses with absent diastolic flow in the umbilical artery (abnormal group). In the venae cavae, the following Doppler variables were measured and compared between groups: (a) during ventricular systole: maximum (S(max)) and minimum velocities (S(min)) and velocity integrals (SI); (b) during ventricular diastole: peak velocity of the E-wave and its integral (EI), the A-wave and its integral (AI). A venous velocity index (VVI) was defined as (S(max) + S(min))/S(max). RESULTS: In the normal group, S(min) and VVI were significantly higher in the inferior vena cava (IVC) than in the superior vena cava (SVC). The ratio SVC-VVI/IVC-VVI was therefore always less than one. In the abnormal group, S(min), SI, E, EI and VVI were higher in the SVC compared to those of the IVC. The ratio SVC-VVI/IVC-VVI was always greater than one. CONCLUSION: In the absence of umbilical artery diastolic flow, a reciprocal shift is observed between the IVC and SVC velocity waveforms characterized by a flow profile in the IVC which resembles that of a normal SVC profile and vice versa. These changes are another manifestation of blood flow redistribution towards the brain in the presence of placental circulatory insufficiency. They should be taken into account on Doppler assessment of ventricular diastolic function based on venous flow patterns during placental circulatory impairment.

Blood Flow Velocity↗
PubMed2001

Epstein-Barr virus primes human polymorphonuclear leucocytes for the biosynthesis of leukotriene B4.

In the present study, we have investigated the effect of the short-term incubation of polymorphonuclear leucocytes (PMN) with infectious Epstein-Barr virus (EBV) on leukotriene B(4) (LTB(4)) biosynthesis. Pre-exposure of PMN to EBV led to an increased production of LTB(4) upon stimulation with either the ionophore A23187, the chemotactic peptide fMLP, or phagocytic particles (zymosan). Experiments performed with viral particles pretreated with a neutralizing antibody raised against the gp350 of the viral envelope revealed that a specific interaction between the PMN surface and the viral glycoprotein gp350 is required for the priming effect of EBV. Preincubation of PMN with EBV resulted in an increased release of arachidonic acid upon stimulation with a second agonist. Moreover, LTB(4) biosynthesis in EBV/A23187-treated PMN was greatly diminished in the presence of an inhibitor of the cytosolic phospholipase A2 (cPLA(2)), suggesting that cPLA(2) plays a critical role in the priming effect of EBV. Accordingly, EBV by itself promoted Ser-505 phosphorylation of cPLA(2) and strongly enhanced fMLP-induced phosphorylation of p38 MAP kinase, an enzyme known to phosphorylate cPLA(2) in human PMN. Furthermore, fMLP-induced translocation of cPLA(2) was strongly enhanced when PMN were previously exposed to EBV. These data indicate that binding of EBV to human PMN results in the activation of intracellular events involved in the release of pro-inflammatory lipid mediators.

Arachidonic Acid↗
PubMed2001

Correlation between prenatal velocity waveforms in the aortic isthmus and neurodevelopmental outcome between the ages of 2 and 4 years.

OBJECTIVE: Experimental studies on fetal lambs have shown that during an increase in the resistance to placental flow the delivery of oxygen to the brain is preserved as long as net flow through the aortic isthmus is antegrade. Our purpose was to determine whether the same changes in aortic isthmus flow in human subjects have any impact on neurodevelopmental outcome. STUDY DESIGN: Forty-four fetuses were retrospectively included in this study on the basis of an abnormal Doppler velocity in the umbilical artery. Mean gestational age at delivery was 33.0 +/- 2.0 weeks and mean birth weight 1386 +/- 435 g. The neurodevelopmental condition was assessed between the ages of 2 and 4 years. The developmental score was analyzed in relation to the flow patterns in the fetal aortic isthmus, which were classified as follows: group A, net isthmic flow antegrade (defined as the ratio of the systolic antegrade to the diastolic retrograde velocity integrals) (n = 39); group B, net isthmic flow retrograde (n = 5). RESULTS: Nonoptimal neurodevelopment was observed in 19 (49%) of 39 fetuses in group A and in all 5 fetuses (100%) in group B. This difference is significant and leads to a relative risk of 2.05 (95% confidence interval, 1.49-2.83) for neurodevelopmental deficit when predominantly retrograde flow is observed in the fetal aortic isthmus before birth. CONCLUSION: Measuring the ratio of antegrade to retrograde velocity integrals in the aortic isthmus could help in the indirect assessment of cerebral oxygenation during placental circulatory insufficiency.

Aorta↗
PubMed2001

[Investigation of fetal arrhythmias by simultaneous recording of ascending aortic and superior vena caval blood flow].

In a period of 18 consecutive months, all the foetus referred to our Foetal Cardiology Unit for investigation of arrhythmia were systematically assessed by M mode echocardiography and simultaneous recording of blood flow in the superior vena cava and the aorta (SVC/Ao). This study was undertaken to compare the performance of these two approaches. The foetus were classified into three groups according to the arrhythmia diagnosed: Group 1: irregular arrhythmias, Group 2: bradycardias, Group 3: tachycardias. A surface ECG was recorded in all the neonates in whom the arrhythmias persisted. In Group 1, including 50 cases of extrasystoles (49 atrial and 1 ventricular), M mode echo and the Doppler provided the diagnosis in 42 and 47 cases respectively. This difference was not statistically significant. Group 2 comprised four cases of bradycardia (2 blocked atrial bigeminy, 2 complete atrioventricular blocks); the two methods provided the diagnosis in all 4 cases. Group 3 comprised 11 cases including 7 supraventricular tachycardias (SVT), 2 flutter, 1 chaotic atrial rhythm and 1 ectopic junctional rhythm. Complete analysis of these arrhythmias was possible by M mode in 4 cases and by Doppler in all cases. This difference was significant. The distribution of the 7 cases of SVT with respect to the duration of the ventriculoatrial interval was possible by M mode in 2 cases and in all cases by Doppler. This was a decisive factor in the choice of antiarrhythmic therapy. The authors conclude that Doppler and M mode are two echocardiographic approaches which are equally effective in the investigation of foetal atrial extrasystoles and probably of sustained foetal bradycardia. However, Doppler recording of SVC/Ao gives a more detailed and precise diagnosis of more complex foetal arrhythmias.

Aorta↗
PubMed2000

EBV suppresses prostaglandin E2 biosynthesis in human monocytes.

It is well known that EBV has developed strategies to evade immune surveillance. Previously, EBV was shown to bind specifically to monocytes and regulate expression of proinflammatory mediators such as IL-1, IL-6, TNF-alpha, and leukotrienes. EBV was also found to affect phagocytosis of monocytes. In this study, we show that in addition to these effects, EBV suppresses the biosynthesis of PGE2, a pleiotropic immunomodulatory molecule that is synthesized by the dioxygenation of arachidonic acid via the cyclooxygenase (COX) pathway. This down-regulation of PGE2 formation involved the inhibition of the inducible COX-2 isoform expression both at the transcriptional and translational levels, whereas expression of the constitutive COX-1 isoform was unaltered. Furthermore, exposure of monocytes to EBV was found to impact on the NF-kappaB activation pathway, which plays an essential role in the induction of COX-2 in monocytes. The inhibition of PGE2 biosynthesis was relieved when the experiments were conducted in presence of phosphonoacetic acid, an inhibitor of herpesviruses DNA polymerase, indicating that viral replication and/or neosynthesized viral proteins were involved in this process. Thus, inhibition of PGE2 biosynthesis in monocytes may represent an additional mechanism underlying EBV pathogenicity.

Biological Transport↗
PubMed2000

Altered expression of laminins in Crohn's disease small intestinal mucosa.

Laminins are a large family of heterotrimeric basement membrane molecules that mediate crucial cell functions such as adhesion, proliferation, migration, and differentiation. Up to now, three distinct laminins have been identified in the normal human small intestinal epithelium. Laminin-1 (alpha1beta1gamma1) and laminin-5 (alpha3beta3gamma2) are mainly expressed at the base of villus cells, whereas laminin-2 (alpha2beta1gamma1) is restricted to the bottom of the crypts. The expression of these molecules has not yet been studied in Crohn's disease (CD), but it could be altered, in light of the important changes occurring in the architecture of the crypt-villus axis under the active state of the disease. To test this hypothesis, the expression of laminin alpha1, alpha2, and alpha3 subunits was analyzed in control, inflamed, and corresponding uninflamed CD small intestinal specimens by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. Surprisingly, alpha1 and alpha3 remained strongly expressed by all villus cells, whereas alpha2, normally expressed in the bottom of the crypts in control and uninflamed CD specimens, was lacking in inflamed CD specimens. However, this loss of alpha2 expression was associated with a significant up-regulation of both alpha1 and alpha3 expression in the crypts of inflamed CD specimens. A significant up-regulation of the alpha1 subunit was also observed in the crypts of uninflamed CD specimens. At the transcript levels, alpha1 was found significantly higher in inflamed than uninflamed CD specimens. Taken together, these observations identify important alterations in laminin expression in the small intestine with CD and suggest that compositional changes in the epithelial basement membrane may play a role in this disease.

Adult↗
PubMed2000

Doppler and M-mode ultrasonography to time fetal atrial and ventricular contractions.

OBJECTIVE: To compare ease of recording and reliability of ultrasonographic approaches used to time fetal heart atrial and ventricular contractions. METHODS: Seventeen consecutive fetuses seen at our fetal cardiology unit for possible fetal cardiac arrhythmia were included in this study. The same ultrasonographer obtained M-mode tracings of atrial and ventricular free walls, atrial wall and opening of the aortic valves, a peak of the mitral valve, and the opening of the aortic valves; and Doppler signals of flow-velocity waveforms in the outflow tract of the left ventricle and simultaneous flow-velocity waveforms in the aorta and superior vena cava. The outcome measures were rate of successful attempts and intra- and interobserver reliability coefficients. RESULTS: Valid recordings were made for all patients with one M-mode (atrial and ventricular free walls) and two Doppler (intraventricular, superior vena cava, and ascending aorta) approaches. Atrioventricular intervals were significantly longer with M-mode compared with Doppler ultrasonography. Reliability coefficients were excellent (at least 0.89) for all intraobserver measurements. Comparisons of atrioventricular and ventriculoatrial interval measurements made by two observers gave the following intraclass correlation coefficients (95% confidence interval): atrioventricular = M-mode: 0.87 (0.79, 0. 91), left ventricular outflow: 0.93 (0.89, 0.96), superior vena cava-aorta: 0.98 (0.97, 0.99); ventriculoatrial = M-mode: 0.79 (0.67, 0.87), left ventricular outflow: 0.97 (0.95, 0.98); superior vena cava-aorta: 0.99 (0.98, 0.99). CONCLUSION: Fetal atrioventricular intervals measured indirectly from M-mode or Doppler tracings were equally reliable when measured by the same observer; the Doppler approaches had better correlation between measurements made by two different observers.

Adult↗
PubMed2000

Infection of primary human monocytes by Epstein-Barr virus.

Previous studies have reported that infection of monocytes by viruses such as cytomegalovirus and human immunodeficiency virus weakens host natural immunity. In the present study, we demonstrated the capability of Epstein-Barr virus (EBV) to infect and replicate in freshly isolated human monocytes. Using electron microscopy analysis, we observed the presence of EBV virions in the cytoplasm and nuclei of approximately 20% of monocytes. This was confirmed by Southern blot analysis of EBV genomic DNA sequences in isolated nuclei from monocytes. Infection of monocytes by EBV leads to the activation of the replicative cycle. This was supported by the detection of immediate-early lytic mRNA BZLF-1 transcripts, and by the presence of two early lytic transcripts (BALF-2, which appears to function in DNA replication, and BHRF-1, also associated with the replicative cycle). The late lytic BcLF-1 transcripts, which code for the major nucleocapsid protein, were also detected, as well as EBNA-1 transcripts. However, attempts to detect EBNA-2 transcripts have yielded negative results. Viral replication was also confirmed by the release of newly synthesized infectious viral particles in supernatants of EBV-infected monocytes. EBV-infected monocytes were found to have significantly reduced phagocytic activity, as evaluated by the quantification of ingested carboxylated fluoresceinated latex beads. Taken together, our results suggest that EBV infection of monocytes and alteration of their biological functions might represent a new mechanism to disrupt the immune response and promote viral propagation during the early stages of infection.

Cell Nucleus↗
PubMed2000

[Comparison of behavior characteristics of the spontaneously alert state and the liberated state in the term newborn].

Occupational therapists evaluate the capacities of infants at younger ages than ever before. The variability of the infants' state has an inevitable influence on the expression of their behaviours. In order to counter the effect of this instability, Grenier (1985) suggests inducing the "liberated state," which optimizes the infant's level of attention. The aim of this study was to identify the behaviours that discriminate this liberated state from the alert state (state 4) as described by Brazelton (1973). Some of the parameters that were defined in the Synactive Theory of Development Model (Als, 1982) were used in order to document the behaviours of the infants observed in the two different states. The average age of the infants, at the time of observation, was 62 hours. The duration of the observation was 5 minutes. Among the 54 newborns that were evaluated, 21 were observed in the two states under study; 33 were evaluated in one state only. The results confirm a greater stability of the "liberated state". Stress and self-regulation behaviours, and the need for external regulation are less frequent in this state; these differences are statistically significant (p < 0.05). Goal-directed movements are more frequent in the "liberated state" (p < 0.001). The authors suggest the use of the "liberated state" to further document the early capacities of infants.

Attention↗
PubMed1999

Interleukin-15 as an activator of natural killer cell-mediated antiviral response.

Natural killer (NK) cells are large granular lymphocytes capable of efficient killing of virus-infected and tumor cells in a major histocompatibility complex-independent manner. The cytotoxic killing potential of NK cells can be modulated by a variety of factors, including cytokines such as interleukin-12 (IL-12), IL-15, and interferon (IFN). IL-15 also plays an important role in NK cell development and survival. Killing of virally infected cells by NK cells is likely to represent an important antiviral defense mechanism, especially during the early phase of infection when antigen-specific immunity has yet to be generated. In the present work, we studied the potential of IL-15 to act as a modulator of NK cell-mediated antiviral defense. Our results clearly indicate that IL-15 can curtail infections by 3 human herpesviruses: Herpes simplex virus type 1, Epstein-Barr virus, and human herpesvirus 6. The antiviral activity of IL-15 is dose-, time-, and NK cell-dependent. IL-15-treated NK cells showed an increased killing potential against a variety of cells, including virus-infected target cells. Lastly, using highly purified cell population, we report that IL-15 triggers the synthesis of IFN-gamma from both CD4(+) and NK cells, which can act in both autocrine and paracrine fashion to modulate NK cells cytotoxic potential. In conclusion, IL-15 is a cytokine that can contribute to the establishment of an antiviral state in 2 ways: first by increasing the killing ability of NK cells and second by stimulating the synthesis and secretion of IFN.

Animals↗
PubMed1999

Ambulatory care transitioning for the rural hospital.

As rural community hospitals continue their transition of health care delivery to predominantly outpatient and ambulatory services, many factors are being considered in design, planning, and operations to enact this change both efficiently and effectively. The following examines strategies that allow these changes to be incorporated successfully while maintaining the flexibility for the continued transition that these organizations will experience in the future.

Ambulatory Care Facilities↗
PubMed1998

Epstein-Barr virus infects and induces apoptosis in human neutrophils.

The role of neutrophils during Epstein-Barr virus (EBV) infection is not known. Disruption of the initial and nonspecific immune response may favor the spread of EBV infection. We have previously shown that EBV interacts with human neutrophils and modulates protein expression. In this study we have investigated the ability of EBV to infect neutrophils. Electron microscopy studies showed penetration of virus and its subsequent localization to the nucleus. The presence of viral genomes in isolated nuclei from neutrophils was also shown by polymerase chain reaction (PCR). Expression of viral transcripts like EBNA-2 (Epstein-Barr nuclear antigen-2) and ZEBRA (BamHI Z EBV replication activator) was not detected by reverse transcriptase (RT)-PCR, suggesting that EBV does not seem to establish a latent or a lytic infection in neutrophils. However, at 20 hours post-EBV infection, 77% of cells were apoptotic as compared to 22% in uninfected cell cultures, as evaluated by flow cytometry. This EBV-induced apoptosis was prevented by the addition of granulocyte-macrophage colony-stimulating factor to the cell cultures. Apoptotic cell death seems to implicate the Fas/Fas ligand (L) pathway, as reflected by an increase of Fas/Fas L expression on neutrophils treated with EBV and an increase of soluble Fas L, which may function in an autocrine/paracrine pathway to mediate cell death. Lastly, EBV genome was detected from neutrophils of infectious mononucleosis (IM) patients in contrast to neutrophils obtained from healthy EBV-seropositive donors. Our findings on the interactions of EBV with neutrophils will then provide new insights on the immunosuppressive effects associated with EBV infection.

Apoptosis↗
PubMed1998

Expression of the alpha9beta1 integrin in human colonic epithelial cells: resurgence of the fetal phenotype in a subset of colon cancers and adenocarcinoma cell lines.

Cell-matrix interactions are thought to be of critical importance in the regulation of various cell functions, including proliferation, migration and control of gene expression. The integrins, a large family of specific receptors for the macromolecules of the extracellular matrix, are important mediators of these interactions. The integrin alpha9beta1 is one of the integrins whose expression is restricted to specialized tissues. Its exact function is unknown. In the present study, we have analyzed expression of the alpha9 subunit in human colonic epithelial cells by indirect immuno-fluorescence and Western and Northern blots. In normal intact tissues, the antigen was detected at the basolateral domain of epithelial cells in colonic glands at the fetal stage but was absent in adults. Strong staining was detected constitutively in contractile cells at both stages. In adenocarcinomas, the alpha9 subunit was detected at the basolateral domain of epithelial cells in 6 of the 10 tumors tested, while a reduction of the staining was observed in the sub-epithelial myofibroblasts in parallel with peri-glandular stroma disorganization. The potential for colon adenocarcinoma cells to express the integrin alpha9 subunit was confirmed at both the protein and transcript levels in Caco-2 and T84 cell lines, 2 well-characterized cell lines known to exhibit polarization features. The 5 other cell lines tested were negative for expression of the alpha9 subunit. Taken together, our observations suggest that the alpha9 integrin subunit is subject to an onco-fetal pattern of expression in human colonic epithelium.

Adenocarcinoma↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor enhances EBV-induced synthesis of chemotactic factors in human neutrophils.

We have recently demonstrated that EBV binds to human neutrophils and stimulates a wide range of activities, including homeotypic aggregation, total RNA synthesis, and expression of the chemokines IL-8 and macrophage inflammatory protein-1alpha (MIP-1alpha). Neutrophil function is also known to be modulated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have therefore investigated the modulation of EBV-induced activation of human neutrophils by GM-CSF. Treatment of neutrophils with GM-CSF before EBV activation enhanced the production of both MIP-1alpha and IL-8. The IL-8 produced under these conditions was biologically active as determined in the calcium mobilization assay. GM-CSF was also found to increase the ability of EBV to prime neutrophils for increased leukotriene B4 (LTB4) synthesis. Prior treatment of GM-CSF with neutralizing Abs inhibited these effects. GM-CSF also increased the specific binding of FITC-EBV to the neutrophil surface, as evaluated by fluorocytometry. Local production of GM-CSF in tissues invaded by EBV could therefore serve to potentiate a host defense mechanism directed toward the destruction of the infectious virus via increased production of chemotactic factors. Since both IL-8 and MIP-1alpha are reported to be chemoattractants in vitro for T cells and T and B cells, respectively, the ability of EBV to induce their production by neutrophils may enhance its ability to infect B and T lymphocytes via increased recruitment to sites of infection.

Adjuvants, Immunologic↗
PubMed1997

EBV induces the production and release of IL-8 and macrophage inflammatory protein-1 alpha in human neutrophils.

As the first line of defense in the immune system, neutrophils may release a variety of potent agents upon exposure to infectious agents. In this study we have investigated the ability of human neutrophils to produce chemotactic cytokines, or chemokine in response to EBV. Exposure of neutrophils to EBV led to an increase in accumulation of mRNA for IL-8 and macrophage inflammatory protein-1alpha (MIP-1alpha). EBV stimulated a time-dependent production of immunoreactive IL-8 and MIP-1alpha by neutrophils. The ability of EBV to stimulate the synthesis of IL-8 and MIP-1alpha protein was reflected by both an accumulation of the protein in the intracellular compartment as well as increased secretion. A variety of control studies support the idea that infectious EBV is not required for induction of chemokine gene expression; however, the response is dependent on the interaction between the glycoprotein gp350 of the viral envelope and the neutrophil surface. Since both IL-8 and MIP-1alpha are reported to be chemoattractants in vitro for T cells and for T and B cells, respectively, the ability of EBV to induce their production by neutrophils may enhance the ability of this virus to infect B and T lymphocytes via increased recruitment to sites of infection.

Chemokine CCL3↗
PubMed1997

Epstein-Barr virus induces GM-CSF synthesis by monocytes: effect on EBV-induced IL-1 and IL-1 receptor antagonist production in neutrophils.

Neutrophils play an important role in the control of viral infections by releasing a variety of potent agents. We previously demonstrated that Epstein-Barr virus (EBV) binds to human neutrophils and stimulates cytokine synthesis including interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1Ra). Since neutrophil functions are known to be modulated by the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), we therefore investigated the cellular source of GM-CSF synthesis following treatment of leukocytes with EBV and the effect of GM-CSF on the production of IL-1, IL-1Ra, and superoxide by EBV-treated neutrophils. In enriched-cell populations, only monocytes were found to produce GM-CSF in response to EBV, which was maximal after 12 h of incubation. The results obtained with UV-irradiated particles or EBV neutralized with monoclonal antibody 72A1 suggest that contact between the cell and the gp350 of the viral envelope is sufficient to induce the release of GM-CSF. On the other hand, GM-CSF differentially upregulated EBV-induced IL-1 and IL-1Ra production by neutrophils. Pretreatment of neutrophils with GM-CSF prior to EBV activation synergistically enhanced the production of IL-1 alpha and IL-1 beta, but only marginally affected IL-1Ra synthesis. In addition, GM-CSF was also found to synergistically enhance the superoxide production by neutrophils in response to EBV. Molecular analysis showed that GM-CSF did not alter the IL-1 beta and IL-1Ra mRNA synthesis induced by EBV, suggesting that GM-CSF could act at a posttranslational level. Local production of GM-CSF by monocytes in tissues invaded by EBV could serve to potentiate the host defense mechanisms directed toward the destruction of the infectious virus.

Animals↗