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The presence of checkpoint mechanisms which are able to recognize damaged
chromatin and thereafter to prevent exit from metaphase I has been
investigated in giant mouse oocytes produced by fusion of a normal
metaphase I oocyte with an equivalent oocyte with damaged chromatin. The
presence of damaged chromatin did not prevent the onset of anaphase I in
both sets of chromatin in the fused cells. Interestingly, fused or unfused
cells containing only damaged chromatin failed to enter anaphase and
persisted instead in a metaphase-like state. These results demonstrate the
fragility of checkpoint controls in mammalian female germ cells.
相似文献
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Serena Xodo Gabriele Saccone Ewoud Schuit Isis Amer-Wåhlin 《The journal of maternal-fetal & neonatal medicine》2017,30(19):2306-2308
Recently, a meta-analysis, including 26?526 laboring vertex singletons at term, summarized all available level-1 data from six high-quality randomized clinical trials (RCTs) on the use of ST analysis (STAN) during labor as an adjunct to conventional intrapartum fetal heart rate monitoring. The meta-analysis showed that STAN did not improve perinatal outcomes or decrease cesarean deliveries. Nonetheless, there are still reasons to believe STAN may have a role in the future research on intrapartum fetal monitoring. Out of six trials included in the meta-analysis, two included all cephalic singletons in labor, and four enrolled only high-risk pregnant women. This combination of both low- and high-risk populations may have distorted the potential impact of STAN. The test for heterogeneity between both subgroups was found to be statistically significant, indicating that the effect of STAN was different in high-risk women compared to a combination of both low- and high-risk women. Furthermore, the classifications of the fetal heart rate patterns used in the included randomized trials were different. Last but not least, despite?>26?000 women with singleton gestations were included in the meta-analysis, the evidence still suffers from a lack of power, especially for subgroup analyses. In summary, while the level-1 data so far indicate overall no perinatal benefit of adding STAN to conventional intrapartum fetal heart rate monitoring for the outcomes most of interest, several issues point to the fact that more research is needed before the STAN technology can be deemed of no value for fetal monitoring in labor. 相似文献
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Rice JP Hartz SM Agrawal A Almasy L Bennett S Breslau N Bucholz KK Doheny KF Edenberg HJ Goate AM Hesselbrock V Howells WB Johnson EO Kramer J Krueger RF Kuperman S Laurie C Manolio TA Neuman RJ Nurnberger JI Porjesz B Pugh E Ramos EM Saccone N Saccone S Schuckit M Bierut LJ;the GENEVA Consortium 《Addiction (Abingdon, England)》2012,107(11):2019-2028
AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerstr?m Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β?=?-0.08, P?=?0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci. 相似文献
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BackgroundPain management of many pancreatic diseases remains a major clinical concern. This problem reflects our poor understanding of pain signaling from the pancreas.ObjectivesThis review provides an overview of our current knowledge, with emphasis on current pain management strategies and recent experimental findings.MethodsA systematic search of the scientific literature was carried out using EMBASE, PubMed/MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965–2011 to obtain access to all publications, especially randomized controlled trials, systematic reviews, and meta-analyses exploring pain and its management in disease states such as acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic cancer (PC).ResultsOver the last decade, numerous molecular mediators such as nerve growth factor and the transient receptor potential (TRP) cation channel family have been implicated in afferent nerve signaling. More recent animal studies have indicated the location of the receptive fields for the afferent nerves in the pancreas and shown that these are activated by agents including cholecystokinin octapeptide, 5-hydroxytryptamine and bradykinin. Studies with PC specimens have shown that neuro-immune interactions occur and numerous agents including TRP cation channel V1, artemin and fractalkine have been implicated. Experimental studies in the clinical setting have demonstrated impairment of inhibitory pain modulation from supraspinal structures and implicated neuropathic pain mechanisms.ConclusionsOur knowledge in this area remains incomplete. Characterization of the mediators and receptors/ion channels on the sensory nerve terminals are required in order to facilitate the development of new pharmaceutical treatments for AP and CP. 相似文献
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Headache is regarded by patients as a disturbing (or unpleasant) symptom. It can be produced by either organic diseases or functional head abnormalities. Twenty-five years ago headache was supposed to be a psychosomatic angiospastic algia. Certain unusual forms were thought to be caused by triggers like anger, cough, exertion, and sexual activity. Experimental research explored the role of circulating serotonin, prostaglandin, estrogen levels, and platelet abnormalities. As computed tomography, helical computed tomography, and scanning or magnetic resonance imaging evolved, new data became available. None of the newer reports have demonstrated liver involvement as a cause of headache. This minireview intends to cover the spectrum of brain alteration in liver disease. It describes some of the pathophysiological characteristics of hepatic encephalopathy and, also, the relationship among migraine, constipation, and liver disease. 相似文献
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Thrombopoietin (Tpo), the ligand for the c-Mpl receptor, is a major regulator of megakaryopoiesis. Treatment of mice with Tpo raises the platelet count fourfold within a few days. Conversely, c-mpl knock-out mice have platelet counts that are 15% that of normal. The subunit structure of the c-Mpl receptor is not fully understood. Some cytokines that stimulate megakaryopoiesis (IL-6, IL-11, leukemia inhibitory factor, and oncostatin M) bind to receptors that use gp130 as a signal transduction subunit. For these reasons, we determined whether gp130 function was required for Tpo-induced signal transduction. Murine marrow cells were cultured in semi-solid media in the presence of Tpo or IL-3, with or without a neutralizing anti-gp130 monoclonal antibody (RX187) or a soluble form of c-Mpl receptor (soluble Mpl) that blocks Tpo bioactivity, and the numbers of colony-forming unit-megakaryocyte (CFU-Meg) colonies were counted on day 5. Murine marrow cells were also cultured in suspension under serum-free conditions for 5 days, and megakaryocyte DNA content was measured by flow cytometry, as an index of nuclear maturation. The addition of RX187 did not block Tpo-induced CFU-Meg colony growth nor CFU-Meg nuclear maturation in suspension culture. However, IL-3-induced CFU-Meg colony growth and megakaryocyte nuclear maturation decreased in the presence of RX187. Soluble Mpl completely ablated Tpo-induced CFU-Meg growth, and partially blocked IL- 3-stimulated CFU-Meg growth. Thus the effects of Tpo on megakaryopoiesis in vitro do not depend on cytokines that signal through gp130. Furthermore, it is unlikely that gp 130 serves as a beta chain for the c-Mpl receptor, as Tpo signalling is unimpaired in the presence of RX187. In contrast, the effects of IL-3 on CFU-Meg growth are mediated in part through Tpo and through gp130-signalling cytokines. 相似文献