Biomedical subjects

F Delaunay

Publications and source records attributed to F Delaunay.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of PENELOPE Monte Carlo dose calculations with Fricke dosimeter and ionization chamber measurements in heterogeneous phantoms (18 MeV electron and 12 MV photon beams).

Different measurements of depth-dose curves and dose profiles were performed in heterogeneous phantoms and compared to dose distributions calculated by a Monte Carlo code. These heterogeneous phantoms consisted of lung and/or bone heterogeneities. Irradiations and simulations were carried out for an 18 MeV electron beam and a 12 MV photon beam. Depth-dose curves were measured with Fricke dosimeters and with plane and cylindrical ionization chambers. Dose profiles were measured with a small cylindrical ionization chamber at different depths. The LINAC was modelled using the PENELOPE code and phase space files were used as input data for the calculations of the dose distributions in every simulation. The detectors (Fricke dosimeters and ionization chambers) were not modelled in the geometry. There is generally a good agreement between the measurements and PENELOPE. Some discrepancies exist, near interfaces, between the ionization chamber and PENELOPE due to the attenuation of the lower energy electrons by the wall of the ionization chamber.

Body Burden↗

PubMed2006

[Oropharyngeal ulcers following anaesthesia with the laryngeal tube S].

We report a case of acute tongue and uvula ulcerations consecutive to the use of a laryngeal tube Sonda (LTS) for airway management. The LTS was used during general anaesthesia for hysteroscopy and resection of endometrial hyperplasia. No trouble occurred during LTS insertion and anaesthesia. Symptomatic treatment provided complete resolution within a few days. This event points out the potential risk of more serious lesions.

Adult↗

PubMed2006

N = 14 shell closure in 22O viewed through a neutron sensitive probe.

To investigate the behavior of the N = 14 neutron gap far from stability with a neutron-sensitive probe, proton elastic and 2(1)+ inelastic scattering angular distributions for the neutron-rich nucleus 22O were measured using the MUr à STrip detector array at the Grand Accélérateur National d'Ions Lourds facility. A deformation parameter beta(p,p') = 0.26 +/- 0.04 is obtained for the 2(1)+ state, much lower than in 20O, showing a weak neutron contribution to this state. A microscopic analysis was performed using matter and transition densities generated by continuum Skyrme-Hartree-Fock-Bogoliubov and quasiparticle random phase approximation calculations, respectively. The ratio of neutron to proton contributions to the 2(1)+ state is found close to the N/Z ratio, demonstrating a strong N = 14 shell closure in the vicinity of the neutron drip line.

Journal Article↗

PubMed2005

[Algorithm of determination of circadian gene expression profiles analysed with DNA microarrays].

DNA microarrays allow to simultaneously determine the expression level of thousands of genes. A nycthemeral study must enable to conclude which ones show a circadian rhythm. Two aspects prove this to be quite difficult: firstly, what does "circadian" exactly mean and how to quantify this qualification, and secondly which genes pertain to this definition. Our method, derived from linear optimisation procedures, consists in determining a cost function, depending from magnitudes characterising the notion of circadian rhythm. Given number of genes present on the microarray are known to be expressed rhythmically; their time series are considered as reference series. We have further constructed random series having the same temporal structure as the circadian gene series. We then carried out an optimisation procedure to determine the weighting coefficients in order to obtain a cost function value which orders the time series as follows: the reference series are in the first rows and the random series have low scores. We have tested this method on over 6000 genes expressed in mouse liver. We obtained a circadian gene detection probability of 100% with a false positive rate inferior to 1%.

Algorithms↗

PubMed2004

Expression of the orphan nuclear receptor ERRalpha is under circadian regulation in estrogen-responsive tissues.

Circadian gene expression has been demonstrated in many tissues and involves both positive and negative regulatory loops. The potential interferences of circadian rhythmicity with other well-known biologic rhythms, such as the ovarian cycle, at least in part controlled by estrogens, has not been questioned. The estrogen receptor-related receptor (ERR)alpha is an orphan nuclear receptor that is widely expressed in estrogen-responsive tissues such as liver, uterus and bone. In addition, expression of the ERRalpha gene has been proposed to be transcriptionally controlled by estrogens in the uterus. Here we show that the expression of ERRalpha displays a circadian rhythmicity in liver, bone and uterus. This is in contrast to other uterine estrogen-regulated genes. Analysis of clock/clock mutant mice shows that ERRalpha is an output gene of the circadian clock oscillator. The expression of clock-control genes, such as Bmal1 and Rev-erbalpha, also displays diurnal oscillations in the uterus, but not in bone. In this tissue, however, Per2 displayed a rhythmic expression, altogether suggesting unconventional loops in the regulation of circadian rhythm in bone.

Animals↗

PubMed2003

[Global analysis of circadian gene expression].

A major goal of chronobiology is to identify clock-controlled genes. The expression of thousands of genes can be monitored simultaneously using DNA microarrays. Application of DNA microarray technology to the field of circadian rhythm has already shown that a number of genes coding for proteins involved in very diverse functions are under the control of the circadian clock.

Animals↗

PubMed2003

A specific and unusual nuclear localization signal in the DNA binding domain of the Rev-erb orphan receptors.

The orphan receptors Rev-erbalpha and Rev-erbbeta are members of the nuclear receptors superfamily and act as transcriptional repressors. Rev-erbalpha is expressed with a robust circadian rhythm and is involved in liver metabolism through repression of the ApoA1 gene, but no role has been yet defined for Rev-erbbeta. To gain better understanding of their function and mode of action, we characterized the proteins encoded by these two genes. Both Rev-erbalpha and Rev-erbbeta proteins were nuclear when transiently transfected in COS-1 cells. The major nuclear location signal (NLS) of Rev-erbalpha is in the amino-terminal region of the protein. Fusion of green fluorescent protein (GFP) to the amino terminus of Rev-erbalpha deletion mutants showed that the NLS is located within a 53 amino acid segment of the DNA binding domain (DBD). The homologous region of Rev-erbbeta fused to GFP also targeted the fusion protein to the nucleus, suggesting that the location of this NLS is conserved among all the Rev-erb group members. Interestingly, members of the phylogenetically closest nuclear orphan receptor group (ROR), which exhibit 58% amino acid identity with Rev-erb in the DBD, do not have their NLS located within the DBD. GFP/DBD. RORalpha or GFP/DBD.RORbeta remained cytoplasmic, in contrast to GFP/DBD. Rev-erb fusion proteins. Alignment of human Rev-erb and ROR DBD amino acid sequences predicted that the two basic residues, K167 and R168, located just upstream from the second zinc finger, could play a critical part in the nuclear localization of Rev-erb proteins. Substitution of these two residues with those found in ROR, in the GFP/DBD. Rev-erb context, resulted in cytoplasmic proteins. In contrast, the reverse mutation of the GFP/DBD. RORalpha towards the Rev-erbalpha residues targeted the fusion protein to the nucleus. Our data demonstrate that Rev-erb proteins contain a functional NLS in the DBD. Its location is unusual within the nuclear receptor superfamily and suggests that Rev-erb orphan receptors control their intracellular localization via a mechanism different from that of other nuclear receptors.

Amino Acid Sequence↗

PubMed2001

Circadian regulation of diverse gene products revealed by mRNA expression profiling of synchronized fibroblasts.

Genes under a 24-h regulation period may represent drug targets relevant to diseases involving circadian dysfunctions. As a testing model of the circadian clock system, we have used synchronized rat fibroblasts that are known to express at least six genes in a circadian fashion. We have determined the expression patterns of 9957 transcripts every 4 h over a total period of 76 h using high density oligonucleotide microarrays. The spectral analysis of our mRNA profiling data indicated that approximately 2% (85 genes) of all expressed genes followed a robust circadian pattern. We have confirmed the circadian expression of previously known clock or clock-driven genes, and we identified 81 novel circadian genes. The majority of the circadian-regulated gene products are known and are involved in diverse cellular functions. We have classified these circadian genes in seven clusters according to their phase of cycling. Our pathway analysis of the mRNA profiling data strongly suggests a direct link between circadian rhythm and cell cycle.

Animals↗

PubMed2001

Comparison of dosimetric standards of Canada and France for photons at 60Co and higher energies.

We report the results of a comparison of the dosimetric standards of Canada and France for photon beams at 60Co and a few higher energies. The present primary standard of absorbed dose to water for NRC, Canada is based on measurements made with a sealed water calorimeter. The corresponding standard of the LNHB, France is based on measurements made with a graphite calorimeter at 60Co energy and transferred to absorbed dose to water for 60Co and higher-energy photon beams using both ion chambers and Fricke dosemeters as transfer instruments. To make this comparison, we used three graphite-walled NE2571 Farmer chambers. The absorbed dose to water determined by the LNHB was greater than that determined by NRC by 0.20% at 60Co energy. This difference is not significant given the uncertainties on the standards. In order to do the comparison for higher-energy photons, we interpolated the NRC data set at the beam qualities used at the LNHB. When %dd(10)x is used as the method of specifying beam quality, the determination of absorbed dose to water by the LNHB is about 0.2% greater than that determined by NRC and consistent with the results at 60Co. However, when using TPR20,10 as the beam quality specifier, the LNHB determination is greater than the NRC's determination by 0.8% and 1.2% at 12 and 20 MV respectively. This discrepancy, which systematically increases with increasing energy, eventually exceeds the uncertainties in the ratio of the standards, estimated to be 0.7%. This underscores the importance of selecting the method of specifying beam quality, either %dd(10)x or TPR20,10, at least for the 'soft' beams used by NRC in this comparison. In the case of the air kerma standards, which were also compared at 60Co energy, the LNHB determination was greater than NRC's by 0.14%, which is not significant given the uncertainties on the standards.

Calorimetry↗

PubMed2000

Estrogen receptor beta acts as a dominant regulator of estrogen signaling.

The physiological effects of estrogens are mediated by two intracellular transcription factors, the estrogen receptors (ERs), that regulate transcription of target genes through binding to specific DNA target sequences. Here we describe alterations in cellular responses to different ER agonists and to the anti-estrogenic compound tamoxifen resulting from co-expression of the two ERs in transient co-transfection experiments. Our results demonstrate that ERbeta can act as a negative or positive dominant regulator of ER activity. This is manifested through reduced transcriptional activity at low concentrations of estradiol (E2); increased antagonistic effects of tamoxifen on E2 stimulated activity; and enhanced agonistic action of the phytoestrogenic compound genistein. Furthermore, using chimeric proteins lacking the N-terminal activation function 1 (AF-1), we show that the differential responses of ERalpha and ERbeta to different agonists and antagonists are primarily dictated by inherent differences in the C-terminal ligand-binding domains of the receptors, whereas the magnitude of transcriptional activity is influenced by ERalpha AF-1, but not ERbeta AF-1. The ERalpha AF-1 activity appears to be modulated upon co-expression of both ERs. The alterations in transcriptional activity resulting from co-expression of ERalpha and ERbeta are probably due to the formation of alpha/beta heterodimeric complexes. This study demonstrates that co-localization and subsequent heterodimerization of ERalpha and ERbeta may result in receptor activity distinct from that of ER homodimers.

Cell Line↗

PubMed2000

An inherited functional circadian clock in zebrafish embryos.

Circadian clocks are time-keeping systems found in most organisms. In zebrafish, expression of the clock gene Period3 (Per3) oscillates throughout embryogenesis in the central nervous system and the retina. Per3 rhythmic expression was free-running and was reset by light but not by the developmental delays caused by low temperature. The time of fertilization had no effect on Per3 expression. Per3 messenger RNA accumulates rhythmically in oocytes and persists in embryos. Our results establish that the circadian clock functions during early embryogenesis in zebrafish. Inheritance of maternal clock gene products suggests a mechanism of phase inheritance through ovogenesis.

Amino Acid Sequence↗

PubMed2000

Ligand binding and nuclear receptor evolution.

Nuclear receptors form a superfamily of ligand-activated transcription factors that regulate various physiological functions, from development to homeostasis, in metazoans. The superfamily contains not only receptors for known ligands but also a large number of so-called orphan receptors for which ligands do not exist or have not been identified. The evolution of ligand-binding capacity of nuclear receptors may involve either secondary loss in orphan receptors, or evolutionary acquisition of ligand-binding capacity in liganded receptors. In this review, we present arguments from phylogenetic, functional and structural studies that support the hypothesis that there have been several independent gains of ligand-binding ability of nuclear receptors during metazoan evolution.

Animals↗

PubMed2000

Functional differences between the amino-terminal domains of estrogen receptors alpha and beta.

Human estrogen receptors alpha (ERalpha) and beta (ERbeta) are ligand-inducible transcription factors that are highly homologous in their central DNA-binding and carboxyl-terminal ligand-binding domains. In contrast, there is very little conservation between ERalpha and ERbeta in the amino-terminal domain. Using different human cell lines, we show that wild-type ERbeta transcriptional activity is lower or similar to that of ERalpha, depending on the cell type. Deletion of the amino-terminal domain in both ER subtypes resulted in no or a lower decrease of transcriptional activity of ERbeta compared with ERalpha, suggesting that the ERbeta amino-terminal domain contains a weaker transcriptional activation function-1. Using ERalpha and ERbeta deletion mutants, we showed that the amino-terminal transcriptional activity of ERbeta maps to amino acids 1-31. Interestingly, this domain contains a six amino-acid motif (amino acids 5-10 in human ERbeta) that is part of the ERalpha-activation function-1 region (amino acids 49-54 in human ERalpha) and highly conserved among all mammalian ERalpha amino-terminal domains. Despite this similarity between the two ER subtypes, no autonomous and ligand-independent activity of the ERbeta-amino-terminal domain was observed in yeast and mammalian cells in contrast to ERalpha. This study provides a molecular basis for the difference in transcriptional activity between ERalpha and ERbeta and establishes that ERbeta contains a structurally and functionally restricted amino-terminal transcriptional activity.

Cells, Cultured↗

PubMed2000

Circadian and glucocorticoid regulation of Rev-erbalpha expression in liver.

Rev-erbalpha [NR1D1], a member of the nuclear receptor superfamily, is an orphan receptor that constitutively represses gene transcription. Rev-erbalpha has been shown to play a role in myocyte differentiation and to be induced during adipogenesis. Furthermore, Rev-erbalpha is a regulator of lipoprotein metabolism. It was recently shown that Rev-erbalpha messenger RNA (mRNA) levels oscillate diurnally in rat liver. Here, we report that the circadian rhythm of Rev-erbalpha in liver is maintained in primary cultures of rat hepatocytes. Because glucocorticoids have been shown to regulate other transcription factors with circadian expression, it was furthermore examined whether hepatic Rev-erbalpha expression is also regulated by glucocorticoids. Treatment of rats with dexamethasone resulted in a decrease of Rev-erbalpha mRNA levels by 70% after 6 h. Furthermore, dexamethasone decreased Rev-erbalpha expression in rat primary hepatocytes in a dose-dependent fashion. This effect was mediated by the glucocorticoid receptor because simultaneous addition of the glucocorticoid antagonist RU486 prevented the decrease in Rev-erbalpha mRNA levels by dexamethasone. Protein synthesis inhibition with cycloheximide markedly induced Rev-erbalpha mRNA levels; however, this induction was reduced by dexamethasone supplementation in both rat and human primary hepatocytes. Treatment with actinomycin D blocked the repression of Rev-erbalpha expression by dexamethasone in rat hepatocytes, suggesting that glucocorticoids regulate Rev-erbalpha expression at the transcriptional level. Transient transfection experiments further indicated that Rev-erbalpha promoter activity is repressed by dexamethasone in the presence of cotransfected glucocorticoid receptor. Taken together, these data demonstrate that Rev-erbalpha expression is under the control of both the circadian clock and glucocorticoids in the liver.

Animals↗

PubMed1997

Pancreatic beta cells are important targets for the diabetogenic effects of glucocorticoids.

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired beta cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. To evaluate that possible role of glucocorticoids in beta cell function independent of their other effects, transgenic mice with an increased glucocorticoid sensitivity restricted to their beta cells were generated by overexpressing the glucocorticoid receptor (GR) under the control of the insulin promoter. Intravenous glucose tolerance tests showed that the GR transgenic mice had normal fasting and postabsorptive blood glucose levels but exhibited a reduced glucose tolerance compared with their control littermates. Measurement of plasma insulin levels 5 min after intravenous glucose load demonstrated a dramatic decrease in acute insulin response in the GR transgenic mice. These results show that glucocorticoids directly inhibit insulin release in vivo and identify the pancreatic beta cell as an important target for the diabetogenic action of glucocorticoids.

Animals↗

PubMed1997

A new function for the C-terminal zinc finger of the glucocorticoid receptor. Repression of RelA transactivation.

Glucocorticoids inhibit NF-kappaB signaling by interfering with the NF-kappaB transcription factor RelA. Previous studies have identified the DNA-binding domain (DBD) in the glucocorticoid receptor (GR) as the major region responsible for this repressive activity. Using GR mutants with chimeric DBDs the repressive function was found to be located in the C-terminal zinc finger. As predicted from these results the mineralocorticoid receptor that contains a C-terminal zinc finger identical to that of the GR was also able to repress RelA-dependent transcription. Mutation of a conserved arginine or a lysine in the second zinc finger of the GR DBD (Arg-488 or Lys-490 in the rat GR) abolished the ability of GR to inhibit RelA activity. In contrast, C-terminal zinc finger GR mutants with mutations in the dimerization box or mutations necessary for full transcriptional GR activity were still able to repress RelA-dependent transcription. In addition, we found that the steroid analog ZK98299 known to induce GR transrepression of AP-1 had no inhibitory effect on RelA activity. In summary, these results demonstrate that the inhibition of NF-kappaB by glucocorticoids involves two critical amino acids in the C-terminal zinc finger of the GR. Furthermore, the results from the use of mineralocorticoid receptor and anti-glucocorticoids suggest that the mechanisms for GR-mediated repression of NF-kappaB and AP-1 are different.

Amino Acid Sequence↗

PubMed1997

Comparison of graphite-to-water absorbed-dose transfers for 60Co photon beams using ionometry and Fricke dosimetry.

To derive the absorbed dose to water from a standard of absorbed dose to graphite, the metrology laboratories which apply such a method usually make use of cavity ionization chambers as transfer instruments. In addition, the BNM-LPRI has tested, as such instruments, two types of Fricke dosimeter in its cobalt-60 beam. The two procedures are compared and their results are found to be in good agreement (the difference is less than 0.1%). Both procedures are then taken into account for the calculation of the reference value of absorbed dose to water.

Cobalt Radioisotopes↗

PubMed1996

Glucocorticoid receptor lacking the tau 1 transactivation domain is a gene-specific regulator of the wild-type glucocorticoid-receptor activity.

The glucocorticoid receptor (GR) contains a major transactivation function (tau 1), located in the N-terminal domain. tau 1 contributes to about 80% of the ligand-inducible transcriptional activity of GR. In this study, we show that GR devoid of tau 1 (symbol: see text] GR) can inhibit activation of gene expression by wild-type GR but this does not occur for all target genes. Activation of the mouse mammary tumor virus promoter by wild-type GR in transiently transfected chinese hamster ovary (CHO) cells lacking endogenous GR was repressed by cotransfecting [symbol: see text] GR. This effect was proportional to the amount of transfected [symbol: see text] GR and was not due to squelching. A moderate expression level of stably transfected [symbol: see text] GR mutant was also shown to repress the transcriptional activity of endogenous GR present in rat skeletal myoblast L8 cells. Glucocorticoid mediated down regulation of endogenous GR gene expression can be blocked by the [symbol: see text] GR mutant in stably transfected L8 cells. In contrast, no inhibition was observed on glucocorticoid induction of the endogenous glutamine synthetase gene in L8 cells. However, glucocorticoid induction of a reporter gene driven by the chicken glutamine synthetase promoter was inhibited by [symbol: see text] GR in L8 cells. Stable expression of wild-type GR in CHO cells rendered the cells glucocorticoid responsive with regard to glutamine synthetase induction but coexpression of [symbol: see text] GR did not repress induction of the endogenous glutamine synthetase gene expression by wild-type GR. Expression of [symbol: see text] GR alone in CHO cells did not render the glutamine synthetase gene glucocorticoid responsive, indicating that [symbol: see text] GR has no transcriptional activity on the glutamine synthetase gene. We conclude from these results that the structure of glucocorticoid-response elements within target genes may be very critical for the ability of the mutant receptor to exhibit a dominant negative effect.

Animals↗