Biomedical subjects

Michel Roger

Publications and source records attributed to Michel Roger.

22 records · Page 2Linked to original sources

PubMed2002

Allele frequency of three functionally active polymorphisms of the MDR-1 gene in high-risk HIV-negative and HIV-positive Caucasians.

Recent data suggest that MDR-1 expression may affect HIV-1 infectivity by modulating the immune response and its cellular permissiveness. We investigated whether three functional MDR-1 polymorphims (T-129C, G2677T/A, C3435T) were associated with the risk of infection in 137 Caucasians highly exposed to HIV (70 infected and 67 uninfected). There was no difference in allelic frequencies for each MDR-1 polymorphic site among both groups. This finding suggests that P-glycoprotein expression does not influence HIV-1 infection per se.

Gene Frequency↗

PubMed2002

Timing and plasticity of specification of CaM-Kinase II alpha expression by neocortical neurons.

In this work, the differential expression of a chemical marker, the alpha-isoform of the calcium/calmodulin-dependent protein kinase II (CaM-Kinase II alpha) and the development of the spinal cord projection were used to determine in vivo the embryonic stages at which different aspects of the phenotype of neocortical cells are specified. We first performed a quantitative, immunocytochemical study on the levels of CaM-Kinase II alpha expression in the frontal, parietal and occipital cortical areas of control adult rats. We found that the levels of expression of CaM-Kinase II alpha were larger in the frontal and parietal areas than in the occipital areas. In addition, all layer V neurons identified as projecting to the spinal cord were CaM-Kinase II alpha immunopositive. We then grafted embryonic day (E) 12 or 14 cells from the presumptive frontal or occipital cortex of donor fetuses into the frontal or occipital cortex of newborn hosts. Cortical cells grafted at E12 differentiate neurons with molecular (CaM-Kinase II alpha) and connectivity (spinal cord projection) phenotypes appropriate to the cortical area where they complete their development whereas cells taken at E14 differentiate neurons with molecular and connectivity phenotypes appropriate to their cortical locus of origin. These findings suggest that E12 progenitors destined to generate layer V neurons are multipotent. The final phenotype of their progeny depends on regionalizing signals expressed in the environment. Later in corticogenesis, committed progenitors become unable to respond to regionalizing signals and generate neurons whose phenotype is appropriate to the initial cortical position of the precursor.

Animals↗

PubMed2002

Cortical diffusible factors increase MAP-2 immunoreactive neuronal population in thalamic cultures.

Previous experiments have established that grafts of embryonic day (E) 16 frontal cortex placed into the occipital cortex of postnatal day (P) 0-P1 rats selectively attract axons from the ventrolateral and ventromedial (VL/VM) thalamic nuclei (Frappé et al., Exp. Neurol. 169 (2001) 264). The present study was therefore undertaken to identify any possible maturation-promoting activity of the cortex on VL/VM thalamic cells. In a first step, a primary culture of VL/VM thalamic cells taken from P0-P1 rats was developed. Neurons, glial cells and a few immature, nestin immunoreactive cells were identified in the culture. In a second step, VL/VM thalamic cells that had been maintained in vitro for 4-5 days were cultured for 7 additional days in isolation (control condition) or with an E16 or P5 explant of frontal or occipital cortex placed on a microporous membrane. In control conditions, the total cell population and the percentage of MAP-2 immunoreactive neurons were not modified with time. In contrast, the percentage of MAP-2 immunoreactive neurons was increased in E16 cortex co-cultures whereas the total cell population was unchanged and the proliferative activity remained very low. Also, the mean number of neurites per neuron was increased but no effect was found on neuritic length. Similar effects on neuronal maturation were found with E16 frontal or occipital cortex explants, indicating a lack of areal specificity. P5 cortex also produced, but to a lesser extent, an increase in percentage of MAP-2 immunoreactive neurons. Further, P5 cortex had no effect on mean number of neurites per neuron but substantially promoted elongation of neuronal processes. We propose that in addition to their well-established survival promoting effect, diffusible molecules released by embryonic and early postnatal cortex can promote in vitro the maturation of thalamic neurons.

Animals↗

PubMed2002

HLA-G exhibits low level of polymorphism in indigenous East Africans.

Human leukocyte antigen G (HLA-G) is a nonclassical HLA class I antigen that is predominantly expressed on invasive cytotrophoblastic cells, and is postulated to be a mediator of maternal-fetal tolerance. Almost all studies in Caucasian and Asian populations have consistently reported that HLA-G exhibits low levels of allelic polymorphism unlike the classical class I genes. However, the concept that HLA-G is nonpolymorphic has recently been challenged in a single study of African-American subjects. We have examined the DNA sequences of the first seven HLA-G exons by single-strand conformational polymorphism (SSCP) and DNA direct sequencing procedures in 45 healthy individuals from an indigenous African population. Overall, we detected 14 sequence variations: 3 in the signal peptide (exon 1); 2 in the alpha-1 domain (exon 2); 5 in the alpha-2 domain (exon 3); 2 in alpha-3 domain (exon 4); 2 in transmembrane domain (exon 5); and none in the cytoplasmic tail (exons 6 and 7). Of these variants, only three result in amino acid substitutions at the protein level. Of particular interest, we identified a novel nucleotide substitution (C727T), 56 bp before the HLA-G gene transcription start site, located in the putative binding site for polyomavirus enhancer-binding protein 2 (PEBP2) transcriptor factor. These data confirm previous reports describing HLA-G exhibiting limited allelic polymorphism. Further studies are needed to determine the impact of the C727T polymorphism on the level or developmental regulation of HLA-G expression.

Africa, Eastern↗