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- 저자 : Lupu, Mihaela E (검색결과 8 건)
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Keren-Lee Rozenfeld,Lior Lupu,Ilan Merdler,Samuel Morgan,Shmuel Banai,Yacov Shacham 대한노인병학회 2022 Annals of geriatric medicine and research Vol.26 No.4
Background: Primary percutaneous coronary intervention (PCI) is the preferred treatment strategy for patients with ST-elevation myocardial infarction (STEMI); however, its efficacy remains unclear in very older adult patients with STEMI. Methods: This retrospective single-center observational study included 530 patients aged >75 years admitted to Tel Aviv Sourasky Medical Center with a diagnosis of acute STEMI. Primary PCI was performed for patients with symptoms ≤12 hours in duration, while the other patients were conservatively treated. We evaluated 30-day mortality and complications occurring during hospitalization based on data from patient records. Results: Among the study patients, only 28/530 (5%) were conservatively treated. In-hospital complications, including the use of inotropes or intra-aortic balloon counterpulsation and the need for mechanical ventilation, did not differ significantly between the groups. The only parameter that showed a trend toward significance was the incidence of heart failure during hospitalization (p=0.042). The risk for 30-day mortality was substantially higher in the conservative treatment group than in the invasive treatment group (27% vs. 10%; p = 0.02). Conclusion: Our data suggested that despite concerns regarding the safety of the primary PCI strategy in the older adult STEMI population, this treatment strategy was associated with a survival benefit.
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Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model.
Yang, Kwang Mo,Russell, James,Lupu, Mihaela E,Cho, Hyungjoon,Li, Xiao-Feng,Koutcher, Jason A,Ling, C Clifton Landes Bioscience 2009 Cancer Biology & Therapy Vol.8 No.20
<P>The endothelin-1 antagonist, Atrasentan (ABT-627) was used to modify perfusion in the human tumor xenograft model, HT29, growing in nude mice. Atrasentan produced a significant increase in perfusion, as measured in vivo by Gd-DTPA DCE-MRI. Changes in tumor hypoxia were assessed by comparing the binding of two hypoxia tracers, pimonidazole and EF5 given before and after Atrasentan administration. In vehicle-treated controls, the distribution of EF5 and pimonidazole was very similar. However, Atrasentan treatment was associated with decreased uptake of the second hypoxia tracer (EF5), relative to the first (pimonidazole). Although Atrasentan had no independent effect on the growth of HT29 tumors, Atrasentan combined with 20 Gy radiation led to a modest but significant increase in tumor growth delay compared to radiation alone.</P>
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Cell Cycle-Related Kinase (CCRK) regulates ciliogenesis and Hedgehog signaling in mice
Snouffer, Ashley,Brown, Desmond,Lee, Hankyu,Walsh, Jonathon,Lupu, Floria,Norman, Ryan,Lechtreck, Karl,Ko, Hyuk Wan,Eggenschwiler, Jonathan Public Library of Science 2017 PLoS genetics Vol.13 No.8
<▼1><P>The Hedgehog (Hh) signaling pathway plays a key role in cell fate specification, proliferation, and survival during mammalian development. Cells require a small organelle, the primary cilium, to respond properly to Hh signals and the key regulators of Hh signal transduction exhibit dynamic localization to this organelle when the pathway is activated. Here, we investigate the role of Cell Cycle Related kinase (CCRK) in regulation of cilium-dependent Hh signaling in the mouse. Mice mutant for <I>Ccrk</I> exhibit a variety of developmental defects indicative of inappropriate regulation of this pathway. Cell biological, biochemical and genetic analyses indicate that CCRK is required to control the Hedgehog pathway at the level or downstream of Smoothened and upstream of the Gli transcription factors, Gli2 and Gli3. <I>In vitro</I> experiments indicate that <I>Ccrk</I> mutant cells show a greater deficit in response to signaling over long time periods than over short ones. Similar to <I>Chlamydomonas</I> mutants lacking the CCRK homolog, LF2, mouse <I>Ccrk</I> mutant cells show defective regulation of ciliary length and morphology. <I>Ccrk</I> mutant cells exhibit defects in intraflagellar transport (the transport mechanism used to assemble cilia), as well as slowed kinetics of ciliary enrichment of key Hh pathway regulators. Collectively, the data suggest that CCRK positively regulates the kinetics by which ciliary proteins such as Smoothened and Gli2 are imported into the cilium, and that the efficiency of ciliary recruitment allows for potent responses to Hedgehog signaling over long time periods.</P></▼1><▼2><P><B>Author summary</B></P><P>The importance of cilia in development and disease has become broadly appreciated in recent years due in part to their roles in signal transduction. Despite this attention, crucial aspects of ciliary assembly and function, such as the mechanisms controlling ciliary assembly and the signal transduction events occurring in cilia, remain unclear. Cilia play a central role in sensing and transducing Hedgehog signals in the context of mammalian embryogenesis and in a variety of cancers. Here, we investigate the functions of Cell Cycle Related Kinase (CCRK), which plays an evolutionarily conserved function in the assembly of cilia and flagella. We find that mouse CCRK positively and negatively regulates ciliary length. We show that CCRK controls multiple aspects of Hedgehog signaling <I>in vivo</I> and <I>in vitro</I> by regulating the processing and activities of the Gli transcription factors. Our data suggest that CCRK controls Hedgehog signaling by promoting the efficient ciliary import of core signaling components.</P></▼2>
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The influence of foreign vs. North American emissions on surface ozone in the US
Reidmiller, D. R.,Fiore, A. M.,Jaffe, D. A.,Bergmann, D.,Cuvelier, C.,Dentener, F. J.,Duncan, B. N.,Folberth, G.,Gauss, M.,Gong, S.,Hess, P.,Jonson, J. E.,Keating, T.,Lupu, A.,Marmer, E.,Park, R.,Schu Copernicus GmbH 2009 Atmospheric Chemistry and Physics Vol.9 No.14
<P>Abstract. As part of the Hemispheric Transport of Air Pollution (HTAP; http:// www.htap.org) project, we analyze results from 15 global and 1 hemispheric chemical transport models and compare these to Clean Air Status and Trends Network (CASTNet) observations in the United States (US) for 2001. Using the policy-relevant maximum daily 8-h average ozone (MDA8 O3) statistic, the multi-model ensemble represents the observations well (mean r2=0.57, ensemble bias = +4.1 ppbv for all US regions and all seasons) despite a wide range in the individual model results. Correlations are strongest in the northeastern US during spring and fall (r2=0.68); and weakest in the midwestern US in summer (r2=0.46). However, large positive mean biases exist during summer for all eastern US regions, ranging from 10-20 ppbv, and a smaller negative bias is present in the western US during spring (~3 ppbv). In nearly all other regions and seasons, the biases of the model ensemble simulations are ≤5 ppbv. Sensitivity simulations in which anthropogenic O3-precursor emissions (NOx + NMVOC + CO + aerosols) were decreased by 20% in four source regions: East Asia (EA), South Asia (SA), Europe (EU) and North America (NA) show that the greatest response of MDA8 O3 to the summed foreign emissions reductions occurs during spring in the West (0.9 ppbv reduction due to 20% emissions reductions from EA + SA + EU). East Asia is the largest contributor to MDA8 O3 at all ranges of the O3 distribution for most regions (typically ~0.45 ppbv) followed closely by Europe. The exception is in the northeastern US where emissions reductions in EU had a slightly greater influence than EA emissions, particularly in the middle of the MDA8 O3 distribution (response of ~0.35 ppbv between 35-55 ppbv). EA and EU influences are both far greater (about 4x) than that from SA in all regions and seasons. In all regions and seasons O3-precursor emissions reductions of 20% in the NA source region decrease MDA8 O3 the most - by a factor of 2 to nearly 10 relative to foreign emissions reductions. The O3 response to anthropogenic NA emissions is greatest in the eastern US during summer at the high end of the O3 distribution (5-6 ppbv for 20% reductions). While the impact of foreign emissions on surface O3 in the US is not negligible - and is of increasing concern given the recent growth in Asian emissions - domestic emissions reductions remain a far more effective means of decreasing MDA8 O3 values, particularly those above 75 ppb (the current US standard). </P>
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