Biomedical subjects

Thierry Lefrançois

Publications and source records attributed to Thierry Lefrançois.

7 recordsLinked to original sources

PubMed2006

Optimisation of the inactivated vaccine dose against heartwater and in vitro quantification of Ehrlichia ruminantium challenge material.

The aim of this work was to evaluate the minimal protective dose of the inactivated vaccine against heartwater. In order to conduct a reliable vaccination trial, an in vitro quantification method of Ehrlichia ruminantium (ER) challenge doses was developed. In experimental conditions, homologous Gardel challenges with 2.1 x 10(4) to 9.4 x 10(4) live ER elementary bodies were reproducible and mimicked a natural challenge. Similar results were obtained when animals were challenged with 3 x 10(4) live elementary bodies from five different ER strains. A 28-fold reduction of the vaccine dose did not decrease protection when compared to the conventional dose of inactivated vaccine. Two injections of 35 microg of ER antigen induced good protection against heartwater. Moreover, we found that the amount of IFNgamma secreted in blood from vaccinated animals after in vitro stimulation with ER antigen was not a reliable predictor of survival and could not be used to test the potency of the inactivated vaccine.

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PubMed2006

West Nile virus in Guadeloupe: introduction, spread, and decrease in circulation level: 2002-2005.

In July 2002, a surveillance system was implemented on Guadeloupe to detect for the potential introduction and monitor the spread of West Nile virus (WNV). From 2002 to 2004, equines and chickens were serologically assayed for antibodies to WNV by IgG and IgM enzyme-linked immunosorbent assay (ELISA), epitope-blocking ELISA, and plaque reduction neutralization tests. After introduction, probably through migratory birds at the end of 2001, many seroconversions occurred between July and October 2002 resulting in a high seroprevalence (19.3%) in equines in 2003. WNV circulation levels decreased dramatically in 2003 and 2004 as assessed by the absence of seroconversion in equine and the very low prevalence in chickens. This decrease coincided with a 7-month drought that presumably caused a decrease in vector populations. In 2005, a sentinel survey was implemented in equines and chickens placed in areas at high risk and the very low rate of seroconversion (1 equine out of 106, no chicken) demonstrated that WNV circulation is now occurring at a very low level.

Age Factors↗

PubMed2006

Understanding the mechanisms of transmission of Ehrlichia ruminantium and its influence on the structure of pathogen populations in the field.

The understanding of the structure of Ehrlichia ruminantium stock population in the field was highlighted by experiments done in controlled conditions on the goat model. The mixture of strains observed in ticks seemed to be due to simultaneous infections rather than successive infections of the carrier. During a dual infection, the timing of Ehrlichia ruminantium circulation of the two stocks in hosts influenced their selection by ticks.

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PubMed2005

West Nile virus surveillance, Guadeloupe, 2003-2004.

We conducted extensive surveillance for West Nile virus infection in equines and chickens in Guadeloupe in 2003-2004. We showed a high seroprevalence in equines in 2003 related to biome, followed by a major decrease in virus circulation in 2004. No human or equine cases were reported during the study.

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PubMed2004

West Nile virus, Guadeloupe.

To determine whether West Nile virus (WNV) had reached the archipelago of Guadeloupe, a serologic study in horses and birds was conducted in 2002. Immunoglobulin (Ig) G, IgM, enzyme-linked immunosorbent assay, and seroneutralization tests identified WNV infection in horses and chickens. Six months later, a high rate of seroconversion was observed in horses.

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PubMed2002

Astroglial permissivity for neuritic outgrowth in neuron-astrocyte cocultures depends on regulation of laminin bioavailability.

The molecular determinants underlying the failure of axons to regenerate in the CNS after injury were studied in an in vitro model of astrogliosis and neuronal coculture. Mechanically lesioned neuron-astrocyte mouse cortical cocultures were treated with antisense glial fibrillary acidic protein (GFAP)-mRNA in order to inhibit the formation of gliofilaments that occurs in response to injury. This inhibition relieves the blockage of neuron migration and neuritic outgrowth observed after lesion, and migrating neurons reappeared, supported by a laminin-labeled extracellular network (permissive conditions). We then questioned the relationship between this permissivity and laminin production. Follow-up studies on the concentration of laminin indicated that, after antisense treatment, the laminin level was increased in the cocultures and was under the control of astrocyte-neuron interactions. The addition of exogenous laminin favored neuronal migration and neurite outgrowth, whereas neutralizing laminin bioavailability with antibodies recognizing the astroglial laminin resulted in an inhibition of both neuronal access to the lesion site and neurite outgrowth, suggesting an active role for laminin in the permissive process. This permissive process could be associated with modulation of extracellular matrix (ECM) molecule degradation by proteinases. Among the latter, matrix metalloproteinases (MMPs) are involved in the breakdown of the ECM component. Our investigation showed a net decrease of the matrix metalloproteinase MMP-2 expression and activity and an increase of its endogenous inhibitor TIMP-2 expression. Both proteins associated with permissivity should be involved in the laminin stabilization and cell-matrix interactions. High levels of laminin and laminin bioavailability, consequent to a reduction in astrogliosis, may be important permissive elements for neuronal migration and neurite outgrowth postlesion.

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PubMed2002

Invasion of human glioma biopsy specimens in cultures of rodent brain slices: a quantitative analysis.

OBJECT: The reliable assessment of the invasiveness of gliomas in vitro has proved elusive, because most invasion assays inadequately model in vivo invasion in its complexity. Recently, organotypical brain cultures were successfully used in short-term invasion studies on glioma cell lines. In this paper the authors report that the invasiveness of human glioma biopsy specimens directly implanted into rodent brain slices by using the intraslice implantation system (ISIS) can be quantified with precision. The model was first validated by the demonstration that, in long-term studies, established glioma cells survive in the ISIS and follow pathways of invasion similar to those in vivo. METHODS: Brain slices (400 microm thick) from newborn mice were maintained on millicell membranes for 15 days. Cells from two human and one rodent glioblastoma multiforme (GBM) cell lines injected into the ISIS were detected by immunohistochemistry or after transfection with green fluorescent protein-containing vectors. Preferential migration along blood vessels was identified using confocal and fluorescent microscopy. Freshly isolated (< or = 24 hours after removal) 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-prelabeled human glioma biopsy specimens were successfully implanted in 19 (83%) of 23 cases, including 12 GBMs and seven lower grade gliomas (LGGs). Morphometric quantification of distance and density of tumor cell invasion showed that the GBMs were two to four times more invasive than the LGGs. Heterogeneity of invasion was also observed among GBMs and LGGs. Directly implanted glioma fragments were more invasive than spheroids derived from the same biopsy specimen. CONCLUSIONS: The ISIS combines a high success rate, technical simplicity, and detailed quantitative measurements and may, therefore, be used to study the invasiveness of biopsy specimens of gliomas of different grades.

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