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Biomedical subjects

F Mathieu-Daude

Publications and source records attributed to F Mathieu-Daude.

7 recordsLinked to original sources
PubMed2006

Advances and perspectives in Leishmania cell based drug-screening procedures.

Efforts for the development of new therapeutics, essential for the control of leishmaniasis rely mainly on screening of potentially effective compounds in pathogen growth/multiplication assays, both in vitro and in vivo. Screenings designed to closely reflect the situation in vivo are currently labor-intensive and expensive, since they require intracellular amastigotes and animal models. Screenings designed to facilitate rapid testing of a large number of drugs are not performed on the clinically relevant parasite stage, but the promastigotes. The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent protein (GFP) or the luciferase, opened up new possibilities for the development of drug screening tests. In this review we will focus on available methodologies for direct drug screening purposes against the mammalian stage of the parasite, with emphasis on the future developments that could improve sensitivity, reliability, versatility and the throughput of the intracellular model screening.

Animals↗
PubMed2006

Looking for putative functions of the Leishmania cytosolic SIR2 deacetylase.

During the past few years, the silent information regulator SIR2 protein family has attracted great interest due to its implication in an organism's life span extension. They bear diverse subcellular localization and play a role in transcriptional silencing and DNA repair. The biochemical reaction catalysed by these enzymes (nicotinamide adenine dinucleotide-dependant deacetylase/adenosine diphosphate-ribosyl transferase) is supposed to be linked to metabolism. Members of this protein family were described in parasitic organisms, but little information is available on potential functions of such enzymes in these organisms. In this article, we review recent information on structure and peculiar functions of SIR2s in eukaryotes, with emphasis on parasitic protozoa, particularly the Trypanosomatidae. Through the enzyme localization and the diverse substrates and by-products of the enzymatic reactions, we approach the potential pathways in which the Leishmania cytosolic SIR2 protein can be involved.

Amino Acid Sequence↗
PubMed2005

Differential infectivity and immunopathology in murine experimental infections by two natural clones belonging to the Trypanosoma cruzi I lineage.

Immunopathology of Chagas' disease in Balb/c mice infected with 2 Trypanosoma cruzi clones, belonging to the T. cruzi I lineage and presenting different in vitro virulence (P/209 cl1 > SO34 c14) was compared. In the acute phase, evading mechanisms such as parasite-induced lymphocyte polyclonal activation and T cell immunosuppression were higher in mice infected with the clone giving a higher parasitaemia (P/209 cl1). A similar increase of non-specific isotypes was observed in both infections with IgG2a prevalence. Interestingly, CD8+ cell hypercellularity and lymphocyte immunosuppression were observed during the chronic phase (245 days post-infection) in mice infected by the most virulent clone. In the same way, the parasite-specific antibody response was more intense in P/209 cl1-infected mice over the acute phase. During the chronic phase this response remarkably dropped down in SO34 cl4-infected mice exclusively. Finally, P/209 cl1-infected mice presented a more severe inflammation and tissue damage in heart and quadriceps than SO34 cl4-infected mice. This comparative study showed differences between the two clones: a higher virulence in vivo being clearly associated with a greater ability to induce evasion mechanisms and severe tissue damage.

Animals↗
PubMed1998

Non-stoichiometric reduced complexity probes for cDNA arrays.

A method is presented in which the reduced complexity and non-stoichiometric amplification intrinsic to RNA arbitrarily primed PCR fingerprinting (RAP-PCR) is used to advantage to generate probes for differential screening of cDNA arrays. RAP-PCR fingerprints were converted to probes for human cDNA clones arrayed as Escherichia coli colonies on nylon membranes. Each array contained 18 432 cDNA clones from the IMAGE consortium. Hybridization to approximately 1000 cDNA clones was detected using each RAP-PCR probe. Different RAP-PCR fingerprints gave hybridization patterns having very little overlap (<3%) with each other or with hybridization patterns from total cDNA probes. Consequently, repeated application of RAP-PCR probes allows a greater fraction of the message population to be screened on this type of array than can be achieved with a radiolabeled total cDNA probe. This method was applied to RNA from HaCaT keratinocytes treated with epidermal growth factor. Two RAP-PCR probes detected hybridization to 2000 clones, from which 22 candidate differentially expressed genes were observed. Differential expression was tested for 15 of these clones using RT-PCR and 13 were confirmed. The use of this cDNA array to analyze RAP-PCR fingerprints allowed for an increase in detection of 10-20-fold over the conventional denaturing polyacrylamide gel approach to RAP-PCR or differential display. Throughput is vastly improved by the reduction in cloning and sequencing afforded by the use of arrays. Also, repeated cloning and sequencing of the same gene or of genes already known to be regulated in the system of interest is minimized. The procedure we describe uses inexpensive arrays of plasmid clones spotted as E.coli colonies to detect differential expression, but these reduced complexity probes should also prove useful on arrays of PCR-amplified fragments and on oligonucleotide chips. Genesobserved in this manuscript: H11520, U35048, R48633, H28735, M13918, H12999, H05639, X79781, M31627, H23972, AB000712, R75916, U66894, AF067817.

DNA, Complementary↗
PubMed1995

RNA fingerprinting and differential display using arbitrarily primed PCR.

RNA fingerprinting by arbitrarily primed PCR can be used to detect and clone transcripts that are differentially expressed between cells that have been subject to different environments or developmental programs. The method also allows an estimate of the number of genes that are differentially expressed under various circumstances. When many experimental treatments are compared in parallel, intersecting regulatory pathways are reflected in genes that are perturbed by more than one treatment.

Animals↗
PubMed1994

Identification of Trypanosoma brucei gambiense group I by a specific kinetoplast DNA probe.

A set of 26 Trypanosoma brucei stocks from various African countries, previously characterized by multilocus enzyme electrophoresis (MLEE) for 18 polymorphic loci, have been selected to be representative of the three T. brucei classic subspecies. The kinetoplast DNA minicircle variable regions from these stocks have been amplified using the polymerase chain reaction (PCR) technique, and hybridized with the amplified variable regions of three T. brucei reference stocks, previously identified as T. brucei brucei, T. brucei gambiense, and T. brucei rhodesiense, respectively. Both T. b. brucei and T. b. rhodesiense probes hybridized only with their own stocks, but the T. b. gambiense probe specifically hybridized with a group of 12 stocks that represented most of the human stocks from West and Central Africa in our sample. These stocks, which appeared as a clearly separable cluster based on previous MLEE analysis, probably correspond to T. brucei gambiense group I. No other stock hybridized with this amplified fragment. Since the T. b. gambiense probe obtained is specific for many isolates that are pathogenic for humans in Central and West Africa, it appears to be a promising tool for epidemiologic and medical surveys.

Africa↗