Biomedical subjects

V Grandjean

Publications and source records attributed to V Grandjean.

10 recordsLinked to original sources

PubMed2002

Nutritional intake of French soccer players at the clairefontaine training center.

Young, French male athletes undergoing intensive elite sports training at the National Training Centre in Clairefontaine served as the subjects (N = 180; age range: 13 to 16 years) in a 3-year dietary survey aimed at characterizing their nutritional intake in terms of energy, macronutrients, calcium, and iron. Each year, the subjects were grouped by level into 3 promotions so that 9 groups could be studied. Dietary intake data were collected each year for each subject in the 9 groups, using a 5-day food record. The results showed that their total energy intake (TEI) was insufficient for athletes (ranging from 2352 454 to 3395 396 kcal/d as opposed to the recommended range of between 3819 and 5185 kcal/d). Furthermore, their diet was unbalanced, with too great an emphasis upon fatty foods (29.1 2.8 to 34.1 3.1% TEI vs. the 20% recommended), to the detriment of carbohydrates (48.5 4.3 to 56.6 3.1% TEI vs. the 55 to 60% recommended). The calcium intake was too low in 5 of the 9 groups while, in contrast, the iron intake was satisfactory in all groups. Furthermore, during this 3-year period at the Clairefontaine Centre, the subjects significantly (p <.05) improved their calcium and iron intakes (1021 197 and 12 2 mg/d in 1996, 1299 155 and 16 2 mg/d in 1997, and 1252 184 and 17 2 mg/d in 1998). This rise in micronutrient intakes may have been due to a physiological adaptation to growth or to the positive effects of courses on nutrition given during their stay at the Centre.

Adaptation, Physiological↗

PubMed2001

Genomic imprinting and cancer; new paradigms in the genetics of neoplasia.

The role of epigenetic modification of gene expression is becoming increasingly important in how we understand the loss of tumour suppressor gene function in a variety of tumours and tumour predisposing syndromes. This review explores the importance of epimutation in Beckwith-Wiedemann syndrome and Wilms' tumour and focuses on genomic methylation in both imprinted and non-imprinted genes as a key mechanism in the development of cancer.

Aging↗

PubMed2001

Relationship between DNA methylation, histone H4 acetylation and gene expression in the mouse imprinted Igf2-H19 domain.

DNA methylation and histone H4 acetylation play a role in gene regulation by modulating the structure of the chromatin. Recently, these two epigenetic modifications have dynamically and physically been linked. Evidence suggests that both modifications are involved in regulating imprinted genes - a subset of genes whose expression depends on their parental origin. Using immunoprecipitation assays, we investigate the relationship between DNA methylation, histone H4 acetylation and gene expression in the well-characterised imprinted Igf2-H19 domain on mouse chromosome 7. A systematic regional analysis of the acetylation status of the domain shows that parental-specific differences in acetylation of the core histone H4 are present in the promoter regions of both Igf2 and H19 genes, with the expressed alleles being more acetylated than the silent alleles. A correlation between DNA methylation, histone hypoacetylation and gene repression is evident only at the promoter region of the H19 gene. Treatment with trichostatin A, a specific inhibitor of histone deacetylase, reduces the expression of the active maternal H19 allele and this can be correlated with regional changes in acetylation within the upstream regulatory domain. The data suggest that histone H4 acetylation and DNA methylation have distinct functions on the maternal and paternal Igf2-H19 domains.

Acetylation↗

PubMed2001

Balanced translocations for the analysis of imprinted regions of the mouse genome.

Experimental studies that investigate the functional and mechanistic properties of an imprinted locus require material in which the two parental chromosome homologs can be easily distinguished. The use of animals with uniparental duplications and deficiencies of imprinted regions of interest is one powerful approach. This material not only allows the successful analysis of the monoallelic expression and genome modifications associated with imprinting, but also is useful for studying the developmental roles of imprinted genes through the analysis of conceptuses in which the dosage of imprinted genes has been perturbed (1-3).

Animals↗

PubMed2000

Increased IGF-II protein affects p57kip2 expression in vivo and in vitro: implications for Beckwith-Wiedemann syndrome.

In both human and mouse, the Igf2 gene, localized on chromosomes 11 and 7, respectively, is expressed from the paternally inherited chromosome in the majority of tissues. Insulin-like growth factor-II (IGF-II) plays an important role in embryonic growth, and aberrant IGF2 expression has been documented in several human pathologies, such as Beckwith-Wiedemann syndrome (BWS), and a wide variety of tumors. Human and mouse genetic data strongly implicate another gene, CDKN1C (p57(kip2)), located in the same imprinted gene cluster on human chromosome II, in BWS. p57(KIP2) is a cyclin-dependent kinase inhibitor and is required for normal mouse embryonic development. Mutations in CDKN1C (p57(kip2)) have been identified in a small proportion of patients with BWS, and removal of the gene from mice by targeted mutagenesis produces a phenotype with elements in common with this overgrowth syndrome. Patients with BWS with biallelic expression of IGF2 or with a CDKN1C (p57(kip2)) mutation, as well as overlapping phenotypes observed in two types of mutant mice, the p57(kip2) knockout and IGF-II-overexpressing mice, strongly suggest that the genes may act in a common pathway of growth control in situations where Igf2 expression is abnormal. Herein, we show that p57(kip2) expression is reduced on IGF-II treatment of primary embryo fibroblasts in a dose-dependent manner. In addition, p57(kip2) expression is down-regulated in mice with high serum levels of IGF-II. These data suggest that the effects of increased IGF-II in BWS may, in part, be mediated through a decrease in p57(kip2) gene expression.

3T3 Cells↗

PubMed1997

Stage-specific signals in germ line differentiation: control of Sertoli cell phagocytic activity by spermatogenic cells.

Differentiation of male germ cells requires a continuous cross-talk with their somatic support, the Sertoli cell. An in vitro model of Sertoli cells was recently provided by established cell lines which maintain Sertoli-specific characteristics, among which is a regulated phagocytic capacity. In vivo, Sertoli cells take up the residual cytoplasm expelled from the maturing sperm, a process restricted to a limited period of germinal maturation, and they also eliminate abnormally differentiated germ cells in case of hormonal deficiency. Cells of the Sertoli line efficiently take up latex beads, as well as dead cells in the cultures. A semiquantitative assay of phagocytosis was developed, based on the uptake of fluorescent latex beads. 15P-1 cultures were found to contain a minor fraction of active phagocytes. After addition of a defined fraction of germ cells, however, all the cells internalized beads as efficiently as macrophages. The inducing cell was identified as the pachytene spermatocyte, a cell type which, in vivo, is associated with Sertoli cells when they express their phagocytic potential. These inducing meiotic cells were not internalized themselves. Rather, they interacted with Sertoli cells via a surface signal that was resistant to formaldehyde fixation. The whole induction process does not involve changes in Sertoli gene expression, since it occurs even in the presence of high doses of cycloheximide. After the required initial contact, further maintenance of the activity was dependent on factor(s) secreted in the medium of the activated culture. Phagocytosis was, on the other hand, abrogated in the presence of factor(s) secreted by a distinct fraction of germ cells, enriched in the late stages (second division) of meiosis.

Animals↗

PubMed1997

Antimicrobial protection of the mouse testis: synthesis of defensins of the cryptdin family.

We report the synthesis by mouse testicular cells of antibiotic peptides related to the defensins secreted by the Paneth cells of the intestinal epithelium. A Sertoli cell-derived line (15P-1), Sertoli cells in primary cultures, and explanted testicular tissue in culture medium were observed to release protease-sensitive material with a broad-spectrum antibacterial activity. The activity of 15P-1 culture medium was increased 10- to 50-fold in the presence of fractions enriched in round spermatids and of nerve growth factor. Two series of results suggest that this activity may correspond to the release by testicular cells of defensin peptides, and specifically, of peptides of the cryptdin family first identified in the Paneth cells of intestinal crypts. First, a characteristic nucleotide sequence corresponding to the conserved first exon of the mouse cryptdin and cryptdin-related (CRS) genes was evidenced in the RNA of 15P-1 cells and of the testis. Second, immunohistochemical analysis demonstrated the presence of cryptdins of the cryp-1, -2, -3, -6 group in 15P-1 cells, and identified two distinct localizations in the testis. Inside the seminiferous tubule, these cryptdins were found accumulated in Sertoli cells at stages corresponding to the maturation of spermatids. In the interstitial space, Leydig cells also contained immunoreactive cryptdins.

Animals↗

PubMed1996

Noncomplementing diploids from Bacillus subtilis protoplast fusion: relationship between maintenance of chromosomal inactivation and segregation capacity.

Fusions of Bacillus subtilis protoplasts from two genetically marked strains produce noncomplementing heterodiploid bacteria. These noncomplementing diploids (Ncds) carry both parental chromosomes, but only one is expressed. Fusion products of strains polymorphic for NotI restriction sites provide new physical evidence to support the conclusion that Ncds are not an artifact of cross feeding or cell adhesion. We show that reversible chromosomal inactivation can only account for the biparental trait of unstable Ncds. Two types of cells were recovered from the late progeny of unstable Ncds: Ncds with irreversible chromosome silencing (stable Ncds) and secondary recombinants that displayed a genomic mosaic NotI profile. Segregants from an unstable Ncd population gave rise to two viable haploid cell types. By contrast, stable Ncds segregated into a population of viable and inviable haploid cells. We propose that the latter are derived from irreversible chromosome silencing. Our results indicate that clonal populations of stable Ncds are heterogenous and suggest that segregation and inactivation are independent parameters.

Bacillus subtilis↗

PubMed1993

Establishment of a new replicon generated from an integrational plasmid and a cryptic pUB110 origin-like region in Bacillus subtilis.

A Bacillus subtilis integrational plasmid pVG4 (7.3 kb) was constructed. It was composed of a part of pBR322 (Ap, OriC), a part of pUB110 (Nm), and a part of the spoOA gene. The origin region of pUB110 had been deleted over 1.4 kb. Surprisingly, the replicative plasmids (8 kb) were generated by transformation of B. subtilis BG83 with pVG4 on selection with Nm. Analysis of the total DNA indicated the presence of repeated DNA and that pVG4 did not appear to integrate at the spoOA locus. The new replicon termed pYV exhibited a quite different restriction pattern from pVG4 due to dramatic DNA rearrangements. Although some components initially present in pVG4 were either present in pYV (Ap, oriC, and Nm) or lost (spoOA), other ones were newly gained such as a chromosomal fragment and a pUB110-type origin-like region. The latter was identified by restriction sites mapping and limited sequence analyses. By PCR amplification, the origin region of pYV was shown to be present as a cryptic sequence in the chromosome of strain BG83. The chromosomal fragment integrated into pYV was at least 0.25 kb long and located in a 19-kb SfiI fragment mapping at 106 degrees. We propose that the establishment of the new replicon pYV is the result of a genetic recombination between the pUB110 part present in the integrational plasmid pVG4 and the cryptic origin region of pUB110 harbored in the chromosome of the recipient strain BG83 in relation with a particular role of neomycin selection.

Bacillus subtilis↗

PubMedDate not supplied

Chromosomal inactivation of Bacillus subtilis exfusants: a prokaryotic model of epigenetic regulation.

Epigenetic mechanisms are not exclusively reserved to eukaryotic organisms. They are also observed in prokaryotes. As described first by Hotchkiss and Gabor, protoplast fusion between strains of Bacillus subtilis produces heterodiploid cells. Heterodiploidy is associated with the inactivation of one of the chromosomes. To study the physical structure of the fusion product and the molecular mechanisms of inactivation, we constructed heterodiploid clones containing two chromosomes labeled by a NotI restriction fragment length polymorphism. In the progeny, we identified haploid recombinant clones that contain a chromosome carrying large regions of inactivated DNA. Studies of both recombinants of the latter kind and heterodiploid cells indicated that chromosomal inactivation was not determined by alteration of the inactivated nucleotide sequence, but was probably due to a modification in the structure of the bacterial chromatin.

Bacillus subtilis↗