Biomedical subjects

T Lefrançois

Publications and source records attributed to T Lefrançois.

10 recordsLinked to original sources

PubMed2001

Migration pathways of human glioblastoma cells xenografted into the immunosuppressed rat brain.

Diffuse invasion of the brain by tumor cells is a hallmark of human glioblastomas and a major cause for the poor prognosis of these tumors. This phenomenon is only partially reproduced by rodent models of gliomas that display a very high rate of proliferation and limited cell migration. We have analyzed the development of human glioblastoma cells (GL15) xenografted into the brain of immunosuppressed rats, in order to define the characteristics of tumor cell invasion. As identified by the specific immunolabeling of the tumor cells for the human HLA-ABC antigen, GL15 tumors reproduced the three types of intraparenchymal invasion observed in patients. First, a majority of multipolar tumor cells intermingled rapidly and profusely with host neural cells in the margin of the injection site. This progressively enlarging area was principally responsible for the tumor growth over time. Second, in the gray matter, columns of thin bipolar tumor cells aligned along capillary walls. Third, in the white matter, elongated bipolar isolated tumor cells were observed scattered between axonal fibers. The maximum migration distances along white matter fibers remained significantly higher than the maximum migration distances along blood vessels, up to two months after injection. Development of the tumor was associated with a significant increase of vascularization in the area of tumor spread. Xenografting of human GL15 glioblastoma cells into the immunosuppressed rat brain allowed to differentiate between the three classical types of invasion identified in the clinic, to quantify precisely the distances of migration, and to evaluate cell morphology for each of these routes. The present results support the existence of host/tumor cells interactions with specific characteristics for each type of invasion.

Animals↗

PubMed2000

Effects of retinoic acid and tumor necrosis factor alpha on GL-15 glioblastoma cells.

Glioblastomas are particularly resistant to classical antitumor treatments. Retinoids, which proved effective in the treatment of promyelocytic leukemia, have been used for clinical assays on glioma tumors with only moderate effects; however in some cases they were active in combination with another therapy. These observations prompted us to analyse the efficacy of combining retinoic acid (RA) with a cytokine on a clonal human glioma cell line. On GL-15 cells, RA and tumor necrosis factor alpha (TNFalpha) both reduced the glial fibrillary acidic protein level and DNA synthesis and induced apoptotic pathways, but they were significantly more effective when used together. The up-regulation of the p55 TNF receptors observed during RA exposure might explain this cooperative effect.

Antigens, CD↗

PubMed1999

Polymerase chain reaction as a diagnosis tool for detecting trypanosomes in naturally infected cattle in Burkina Faso.

African animal trypanosomoses constitute the most important vector-borne cattle diseases in sub-Saharan Africa. Generally it is considered that there is a great lack of accurate tools for the diagnosis of the disease. During a trypanosomosis survey in the agro-pastoral zone of Sideradougou, Burkina Faso, 1036 cattle were examined for trypanosomes using microscopy. The PCR was applied on a subset of 260 buffy-coat samples using primers specific for Trypanosoma congolense savannah and riverine-forest groups, T. vivax, and T. brucei. Parasitological examination and the molecular technique were compared, showing a better efficiency of the latter. In the near future, the PCR is likely to become an efficient tool to estimate the prevalence of African trypanosomoses in affected areas.

Animals↗

PubMed1999

Polymerase chain reaction characterization of trypanosomes in Glossina morsitans submorsitans and G. tachinoides collected on the game ranch of Nazinga, Burkina Faso.

The polymerase chain reaction was used to characterize the trypanosomes infecting Glossina morsitans submorsitans and G. tachinoides in the game ranch of Nazinga, Burkina Faso, situated near an agropastoral zone. Dissection of 435 tsetse flies, and PCR analysis of 166 infected flies were conducted to assess the epidemiological situation. Trypanosomes of the Nannomonas subgenus were the most abundant in the two tsetse species (80.4% and 73.7% of identified infections in G. m. submorsitans and G. tachinoides respectively). T. vivax and T. brucei infection rates were comparable between the two tsetse species. Mature infection pattern identified by PCR differed from overall infections, mainly because T. simiae infections did not mature, whereas T. vivax represented the predominant taxon. Parasitological and PCR results showed some discrepancies; possibly some typical Duttonella strains could not be recognized by the sets of primers used. The technologies used in this work helped to determine the high trypanosomosis risk in this area.

Animals↗

PubMed1998

New epidemiological features on animal trypanosomiasis by molecular analysis in the pastoral zone of Sideradougou, Burkina Faso.

A multidisciplinary work was undertaken in the agropastoral zone of Sidéradougou, Burkina Faso to try to elucidate the key factors determining the presence of tsetse flies. In this study the PCR was used to characterize trypanosomes infecting the vector (Glossina tachinoides and Glossina palpalis gambiensis) and the host, i.e. cattle. A 2-year survey involved dissecting 2211 tsetse of the two Glossina species. A total of 298 parasitologically infected tsetse were analysed by PCR. Trypanosoma vivax was the most frequently identified trypanosome followed by the savannah type of T. congolense and, to a lesser extent, the riverine forest type of T. congolense, and by T brucei. No cases of T. simiae were found. From the 107 identified infections in cattle, the taxa were the same, but T. congolense savannah type was more frequent, whereas T. vivax and T. congolense riverine forest types were found less frequently. A correlation was found between midgut infection rates of tsetse, nonidentified infections and reptile bloodmeals. These rates were higher in G.p. gambiensis, and in the western part of the study area. T. vivax infections were related to cattle bloodmeals, and were more frequent in G. tachinoides and in the eastern study area. The PCR results combined with bloodmeal analysis helped us to establish the relationships between the vector and the host, to assess the trypanosome challenge in the two parts of the area, to elucidate the differences between the two types of T. congolense, and to suspect that most midgut infections were originating from reptilian trypanosomes.

Animals↗

PubMed1997

Neuritic outgrowth associated with astroglial phenotypic changes induced by antisense glial fibrillary acidic protein (GFAP) mRNA in injured neuron-astrocyte cocultures.

In the adult CNS, axons fail to regenerate after injury. Among the cell interactions that lead to this failure are those developed with astrocytes. In an effort to elucidate the mechanisms underlying these negative interactions, we have used astrocytes treated with antisense glial fibrillary acidic protein (GFAP) mRNA to inhibit the formation of gliofilaments, indispensable for the astroglial morphological response to injury, and have studied their permissivity for neuritic outgrowth. In a neuron-astrocyte coculture, a mechanical lesion led to hypertrophy of astrocytes neighboring the lesion. Neuronal cell bodies and neurites were absent both from the area of lesion and from its surroundings. Reactive astrocytes appeared, therefore, to be a nonpermissive substrate. Transfection that used antisense GFAP mRNA blocked astroglial morphological changes and was characterized by both a persistence of neuronal cell bodies in the vicinity of the lesion site and a growth of neurites into the same region. These morphological differences were associated with a 46% decrease in the GFAP translation capacity and a 50% increase in the concentration of GAP-43 in the treated cultures. Neurons were associated mainly with an extracellular laminin network, which was predominant at the lesion site in treated cocultures. In contrast, those astrocytes highly laminin-immunoreactive appeared to be a nonpermissive substrate for neurons. These results show that inhibition in GFAP synthesis, leading to a reduction of astroglial hypertrophy, relieves the blockade of neuritic outgrowth that normally is observed after a lesion. The mechanisms may involve changes in the secretion of extracellular matrix molecules by astrocytes.

Animals↗

PubMed1995

Apolipoprotein E gene expression in astrocytes: developmental pattern and regulation.

Apolipoprotein E (ApoE) is involved in brain development and repair. In order to investigate the contribution of astrocytes to ApoE gene expression, we investigated ApoE mRNA levels in mouse brain and in astroglial primary cultures during postnatal development and in two different trauma models. A biphasic developmental pattern was observed consisting in an increased expression during the first 2 weeks and a decrease in the later stages. A similar pattern was obtained in highly enriched primary cultures, suggesting ApoE mRNA location in the astroglial population and an important role for ApoE in astroglial development and/or function. ApoE gene expression could be modulated in culture by administration of lipopolysaccharides (LPS) which mimics a bacterial infection, or in reactive astrocytes consequent to a chemically induced lesion, suggesting that ApoE might be involved in the inflammatory events consequent to both situations. These results underline the importance of astrocytes in regenerative processes.

Animals↗

PubMed1995

Glutamine synthetase (GS) expression is reduced in senile dementia of the Alzheimer type.

Glutamine synthetase (GS), a metabolic marker of the mature astrocyte, was investigated in the temporal neocortex of postmortem brain samples of 8 cases, either not demented or affected by senile dementia of the Alzheimer type. A negative correlation between the GS protein level and the density of both classical beta A4 deposits and senile plaques was evidenced. Such a correlation for GS underlies a dysfunction of the astroglial metabolism and particularly of the glutamate and ammonia neutralization. Since GS is sensitive to oxidative lesioning, the changes in GS level that were observed, occurring at the posttranslational stage, might reflect oxidative damage and have severe consequences on the pathological cascade of events.

Aged↗

PubMed1994

Astroglial reactivity in natural scrapie of sheep.

Astrogliosis is known to be a common histological feature in experimental scrapie, but astroglial reactivity in natural scrapie of sheep has not yet been precisely studied. We investigated the expression of two markers of glial plasticity, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS), by Western and Northern blotting, in different areas of the sheep brain. We report that both GFAP-mRNA and GFAP are overexpressed in the cerebellum and the pons. In the thalamus, overexpression of GS was demonstrated for the first time in this disease. The enhancement of this astroglial metabolic marker, essential for glutamate and ammonia neutralization, cellular function and brain detoxification, could represent an attempt by astrocytes to maintain and control the cerebral homeostasis in this area. Our results show that astrocytes: (i) are a target for the scrapie agent even in the early temporal evolution of the disease; (ii) react by overexpressing their intermediate filament major protein, changing their phenotypic appearance and stabilizing their processes in precise brain areas; (iii) overexpress key elements of their metabolism. These changes clearly implicate astrocytes in the pathogenesis of the disease.

Animals↗

PubMedDate not supplied

Review on the molecular tools for the understanding of the epidemiology of animal trypanosomosis in West Africa.

The epidemiology of animal trypanosomosis around Bobo-Dioulasso (Burkina Faso, West Africa) benefited a lot in the last years from the progress of molecular tools. The two most used molecular techniques were the polymerase chain reaction for the diagnosis of the disease in cattle and the characterization of the trypanosomes in the host and the vector on one hand, and the microsatellite DNA polymorphism in tsetse flies to study the intraspecific genetic variability of the vector on the other hand. The results obtained in the Sideradougou area during a recent two year survey with these techniques, associated with many other georeferenced informations concerning vector and cattle distribution, natural environment, landuse, ground occupation, livestock management, were combined in a Geographical Information System. This new approach of a complex pathogenic system led to a better evaluation of the risk of trypanosome transmission.

Africa, Western↗