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Biomedical subjects

V Michaud

Publications and source records attributed to V Michaud.

10 recordsLinked to original sources

Differential histopathology and chemokine gene expression in lung tissues following respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV- or BBG2Na-immunized mice.

A BALB/c mouse model of enhanced pulmonary pathology following vaccination with formalin-inactivated alum-adsorbed respiratory syncytial virus (FI-RSV) and live RSV challenge was used to determine the type and kinetics of histopathologic lesions induced and chemokine gene expression profiles in lung tissues. These data were compared and contrasted with data generated following primary and/or secondary RSV infection or RSV challenge following vaccination with a promising subunit vaccine, BBG2Na. Severe peribronchiolitis and perivascularitis coupled with alveolitis and interstitial inflammation were the hallmarks of lesions in the lungs of FI-RSV-primed mice, with peak histopathology evident on days 5 and 9. In contrast, primary RSV infection resulted in no discernible lesions, while challenge of RSV-primed mice resulted in rare but mild peribronchiolitis and perivascularitis, with no evidence of alveolitis or interstitial inflammation. Importantly, mice vaccinated with a broad dose range (20 to 0.02 microg) of a clinical formulation of BBG2Na in aluminium phosphate demonstrated histopathology similar to that observed in secondary RSV infection. At the molecular level, FI-RSV priming was characterized by a rapid and strong up-regulation of eotaxin and monocyte chemotactic protein 3 (MCP-3) relative gene expression (potent lymphocyte and eosinophil chemoattractants) that was sustained through late time points, early but intermittent up-regulation of GRO/melanoma growth stimulatory activity gene and inducible protein 10 gene expression, while macrophage inflammatory protein 2 (MIP-2) and especially MCP-1 were up-regulated only at late time points. By comparison, primary RSV infection or BBG2Na priming resulted in considerably lower eotaxin and MCP-3 gene expression increases postchallenge, while expression of lymphocyte or monocyte chemoattractant chemokine genes (MIP-1beta, MCP-1, and MIP-2) were of higher magnitude and kinetics at early, but not late, time points. Our combined histopathologic and chemokine gene expression data provide a basis for differentiating between aberrant FI-RSV-induced immune responses and normal responses associated with RSV infection in the mouse model. Consequently, our data suggest that BBG2Na may constitute a safe RSV subunit vaccine for use in seronegative infants.

Animals↗

Problem and probable pathological gambling: considerations from a community survey.

OBJECTIVE: To investigate the nature and extent of gambling problems in a region of Canada in which legalized gambling activities were expanded during the 1990s. METHOD: A standardized telephone interview was conducted with a random sample of 738 community-dwelling adults (response rate 74%) in Winnipeg, Manitoba. RESULTS: According to traditional classification criteria, the lifetime prevalence of "probable pathological gambling" was 2.6%. A further 3.0% of the sample met criteria for traditionally defined "problem gambling," and evidence suggests that both types of gamblers share several characteristics. Social or recreational gamblers significantly differed on several variables from individuals who reported gambling problems. CONCLUSIONS: The 2.6% prevalence figure is the highest yet reported in a Canadian epidemiological survey and was obtained in a region that developed a more liberal attitude toward gambling in the 1990s. Further, a continuum of severity was demonstrated by scores on the South Oaks Gambling Screen (SOGS), and a clear and consistent distinction between problem and probable pathological gambling was not apparent. Frequenting casinos and using video poker and slot machines, rather than buying lottery tickets, distinguishes problem or pathological gamblers from recreational gamblers.

Adult↗

[Facial hemangioma associated with arterial anomalies, coarctation of the aorta, and eye abnormalities: PHACES syndrome].

BACKGROUND: Hemangiomas are frequent in childhood. Their association with dysmorphic anomalies is rare. Recently, the acronym "PHACES syndrome" was proposed to emphasize the association of Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and cardiac defects, Eye abnormalities, and Sternal malformations. CASE REPORT: A female child, 3 months old, had a large facial hemangioma. The physical examination was normal otherwise. A choroidal hemangioma and a papillary abnormality, causing amblyopia, were detected. The brain magnetic resonance imaging was normal. A subglottic hemangioma was found at endoscopy. At the age of 16 months, physical examination disclosed a heart murmur and coarctation of the aorta was detected. Moreover, the cardiac angiography showed diffuse arterial lesions. Strict surveillance was decided as there were no manifestations. DISCUSSION: Different abnormalities have been described to be associated with large facial hemangiomas. Frieden has grouped these abnormalities under the acronym PHACES. She described 43 hemangiomas and found 74 p. 100 Dandy Walker malformations and other posterior fossa malformations, 41 p. 100 arterial anomalies, 26 p. 100 cardiac or aortic malformations, 23 p. 100 ophthalmologic abnormalities. There is a high risk for the hemangiomas to develop in an airway localization. The prevalence of facial hemangiomas associated with other malformations is, to our knowledge, not known. In our department, 56 children were treated with corticosteroid therapy for severe facial hemangioma. 11 p. 100 had a cerebral abnormality. There were no cases with cardiac malformation or dysmorphism. PHACES syndrome is very rare but easy to remember. Thus in patients presenting a large facial hemangioma, it is important to conduct an attentive neurological examination completed by brain imaging and an extensive cardiovascular exploration. Special attention should be given to the ophthalmologic and sternal examinations as well as the search for hemangiomas in an airway localization.

Aortic Coarctation↗

Detection of JC virus DNA in the peripheral blood leukocytes of HIV-infected patients.

OBJECTIVES: To assess whether JC virus (JCV) DNA is frequently harboured by peripheral blood leukocytes (PBL) in HIV-positive patients, before the onset of progressive multifocal leukoencephalopathy (PML). DESIGN: The polyomavirus JCV induces PML in immunocompromised persons and particularly AIDS patients. Leukocytes may play a central part in the onset of PML, but their precise role in JCV latency and reactivation still remains hypothetical. The controversial presence of JCV DNA in PBL has been, until now, investigated only among small groups of patients. We therefore studied 157 HIV-positive persons and compared them with 65 HIV-negative immunocompromised patients. METHODS: DNA was extracted from PBL. The presence of JCV DNA was demonstrated by the polymerase chain reaction (PCR) alone or combined with a molecular hybridization assay. RESULTS. The presence of JCV DNA was ascertained by PCR and hybridization in 28.9% of 135 HIV-infected persons at all stages of HIV infection and only 16.4% of 61 HIV-negative immunocompromised patients. No correlation could be drawn between the detection of JCV DNA and the clinical or biological status of the HIV-positive patients. CONCLUSIONS: JCV DNA is detectable in the PBL of 28.9% of HIV-infected persons, even in the early stages of infection. JCV is more seldomly amplified in HIV-negative immunocompromised patients. Further work is in progress to determine the prognostic value of the presence of JCV DNA in the blood of HIV-positive patients.

Adult↗

Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone.

The objective was to identify the major cytochrome P450 enzyme(s) involved in the metabolism of domperidone. Experiments were performed using human liver microsomes (HLMs), recombinant human cytochrome P450 enzymes, cytochrome P450 chemical inhibitors and monoclonal antibodies directed against cytochrome P450 enzymes. Four metabolites were identified from incubations performed with HLMs and excellent correlations were observed between the formation of domperidone hydroxylated metabolites (M1, M3 and M4), N-desalkylated domperidone metabolite (M2) and enzymatic markers of CYP3A4/5 (r2 = 0.9427, 0.951, 0.9497 and 0.8304, respectively). Ketoconazole (1 microM) decreased the formation rate of M1, M2, M3 and M4 by 83, 78, 75 and 88%, respectively, whereas the effect of other inhibitors (quinidine, furafylline and sulfaphenazole) was minimal. Important decreases in the formation rate of M1 (68%), M2 (64%) and M3 (54%) were observed with anti-CYP3A4 antibodies. Formation of M1, M2 and M3 in HLMs exhibited Michaelis-Menten kinetics (Km: 166, 248 and 36 microM, respectively). Similar Km values were observed for M1, M2 and M3 when incubations were performed with recombinant human CYP3A4 (Km: 107, 273 and 34 microM, respectively). The data suggest that CYP3As are the major enzymes involved in the metabolism of domperidone.

Cells, Cultured↗