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1.
A. Tchirkov Jacques-Olivier Bay David Pernin Yves-Jean Bignon Pascale Rio Maria Grancho Fabrice Kwiatkowski Michel Giollant Paul Malet Pierre Verrelle 《Human genetics》1997,101(3):312-316
In ataxia-telangiectasia (A-T) patients, mutations in a single gene, ATM, result in an autosomal recessive syndrome that embraces a variety of clinical features and manifests extreme radiosensitivity
and a strong predisposition to malignancy. Heterozygotes for the ATM gene have no clinical expression of A-T but may be cancer prone with a moderate increase in in vitro radiosensitivity. We
performed a blind chromosomal analysis on G2-phase lymphocytes from 7 unrelated A-T patients, 13 obligate A-T heterozygotes (parents of the patients), and 14 normal controls
following X-irradiation with 1 Gy in order to evaluate this cytogenetic method as a tool for detection of ATM carriers. Both A-T homozygotes and heterozygotes showed significantly increased levels of radiation-induced chromatid damage
relative to that of normal controls. These results show that the G2-phase chromosomal radiosensitivity assay can be used for the detection of A-T heterozygotes. In combination with molecular
genetic analyses, this test may be of value in studies of familial and sporadic cancers aimed at determination of the potential
involvement of ATM mutations in tumor risk or development.
Received: 5 May 1997 / Accepted: 26 August 1997 相似文献
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Valérie Mils Stéphanie Bosch Julie Roy Sophie Bel-Vialar Pascale Belenguer Fabienne Pituello Marie-Christine Miquel 《PloS one》2015,10(5)
Mitochondria, long known as the cell powerhouses, also regulate redox signaling and arbitrate cell survival. The organelles are now appreciated to exert additional critical roles in cell state transition from a pluripotent to a differentiated state through balancing glycolytic and respiratory metabolism. These metabolic adaptations were recently shown to be concomitant with mitochondrial morphology changes and are thus possibly regulated by contingencies of mitochondrial dynamics. In this context, we examined, for the first time, mitochondrial network plasticity during the transition from proliferating neural progenitors to post-mitotic differentiating neurons. We found that mitochondria underwent morphological reshaping in the developing neural tube of chick and mouse embryos. In the proliferating population, mitochondria in the mitotic cells lying at the apical side were very small and round, while they appeared thick and short in interphase cells. In differentiating neurons, mitochondria were reorganized into a thin, dense network. This reshaping of the mitochondrial network was not specific of a subtype of progenitors or neurons, suggesting that this is a general event accompanying neurogenesis in the spinal cord. Our data shed new light on the various changes occurring in the mitochondrial network during neurogenesis and suggest that mitochondrial dynamics could play a role in the neurogenic process. 相似文献
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Farzad Pakdel Pascale Le Goff Benita S. Katzenellenbogen 《The Journal of steroid biochemistry and molecular biology》1993,46(6):663-672
The estrogen receptor (ER) is a rapidly turning over protein, with a half-life of ca. 3–4 h in estrogen target cells. Sequence analysis of the human ER reveals a putative PEST sequence, sequences rich in proline (P), glutamic acid (E), serine (S) and threonine (T), in the carboxy-terminal F domain of the protein. Since PEST sequences have been implicated in the rapid turnover of some proteins, we have used site-directed mutagenesis to investigate the role of the F region containing PEST residues in the stability and bioactivity of the receptor. A truncated form of ER lacking the last 41 amino acids of the protein and encompassing the PEST sequences (amino acids 555 to 567) was made by mutagenesis of the ER cDNA. Pulse-chase experiments, involving immunoprecipitation of [35S]methionine/[35]Scysteine labeled receptors or of receptors covalently labeled with tamoxifen aziridine followed by gel electrophoresis, were used to determine the half-life of the wild-type and truncated ERs. These experiments showed that the turnover rate of the receptors expressed in Chinese hamster ovary and monkey kidney (COS-1) cells was 3 to 5 h and that elimination of the PEST residues did not have a significant effect on the degradation rate of the protein. Moreover, deletion of the last 41 amino acids (F domain) of the ER did not affect transactivation ability, ligand binding affinity, or the phosphorylation pattern of the receptor. Therefore, the role of domain F in ER function remains unclear, but it is not a determinant of the relatively rapid rate of ER turnover in cells. 相似文献
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B T Edelson P Cossart E R Unanue 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(8):4087-4090
Listeriolysin O (LLO) is a secreted pore-forming toxin of the facultative intracellular bacterium Listeria monocytogenes. We assessed the ability of a murine anti-LLO mAb to affect the course of infection in mice challenged with Listeria. This mAb was previously shown to be capable of neutralizing LLO-mediated pore formation in vitro, and here we show that the passive administration of this Ab to mice before infection provides increased resistance. Mice treated with the mAb were protected from a lethal challenge with virulent Listeria and showed a significant reduction in Listeria burden during the first hours to days postinfection. These effects of the Ab were independent of host B or T cells, since treatment with the mAb provided enhanced resistance to SCID mice. The titer of anti-LLO Abs during the regular infection of mice with Listeria was found to be low to negative. 相似文献
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Anne Tarrade Delphine Rousseau-Ralliard Marie-Christine Aubrière Nathalie Peynot Michèle Dahirel Justine Bertrand-Michel Tiphaine Aguirre-Lavin Olivier Morel Nathalie Beaujean Véronique Duranthon Pascale Chavatte-Palmer 《PloS one》2013,8(12)
Maternal environment during early developmental stages plays a seminal role in the establishment of adult phenotype. Using a rabbit model, we previously showed that feeding dams with a diet supplemented with 8% fat and 0.2% cholesterol (HH diet) from the prepubertal period and throughout gestation induced metabolic syndrome in adult offspring. Here, we examined the effects of the HH diet on feto-placental phenotype at 28 days post-coïtum (term = 31days) in relation to earlier effects in the blastocyst (Day 6). At 28 days, both male and female HH fetuses were intrauterine growth retarded and dyslipidemic, with males more affected than females. Lipid droplets accumulated in the HH placentas’ trophoblast, consistent with the increased concentrations in cholesteryl esters (3.2-fold), triacylglycerol (2.5-fold) and stored FA (2.12-fold). Stored FA concentrations were significantly higher in female compared to male HH placentas (2.18-fold, p<0.01), whereas triacylglycerol was increased only in HH males. Trophoblastic lipid droplet accumulation was also observed at the blastocyst stage. The expression of numerous genes involved in lipid pathways differed significantly according to diet both in term placenta and at the blastocyst stage. Among them, the expression of LXR-α in HH placentas was reduced in HH males but not females. These data demonstrate that maternal HH diet affects the blastocyst and induces sex-dependent metabolic adaptations in the placenta, which appears to protect female fetuses from developing severe dyslipidemia. 相似文献