503,903 research outputs found

    A higher Angiogenin expression is associated with a non-nuclear Maspin location in laryngeal carcinoma

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    Objectives. In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC). Methods. Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes. Results. On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression 655.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression 655.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041). Conclusion. Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC

    Transient receptor potential melastatin 7 cation channel kinase new player in angiotensin II–induced hypertension

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    Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein comprising a magnesium (Mg2+)/cation channel and a kinase domain. We previously demonstrated that vasoactive agents regulate vascular TRPM7. Whether TRPM7 plays a role in the pathophysiology of hypertension and associated cardiovascular dysfunction is unknown. We studied TRPM7 kinase–deficient mice (TRPM7Δkinase; heterozygous for TRPM7 kinase) and wild-type (WT) mice infused with angiotensin II (Ang II; 400 ng/kg per minute, 4 weeks). TRPM7 kinase expression was lower in heart and aorta from TRPM7Δkinase versus WT mice, effects that were further reduced by Ang II infusion. Plasma Mg2+ was lower in TRPM7Δkinase versus WT mice in basal and stimulated conditions. Ang II increased blood pressure in both strains with exaggerated responses in TRPM7Δkinase versus WT groups (P&lt;0.05). Acetylcholine-induced vasorelaxation was reduced in Ang II–infused TRPM7Δkinase mice, an effect associated with Akt and endothelial nitric oxide synthase downregulation. Vascular cell adhesion molecule–1 expression was increased in Ang II–infused TRPM7 kinase–deficient mice. TRPM7 kinase targets, calpain, and annexin-1, were activated by Ang II in WT but not in TRPM7Δkinase mice. Echocardiographic and histopathologic analysis demonstrated cardiac hypertrophy and left ventricular dysfunction in Ang II–treated groups. In TRPM7 kinase–deficient mice, Ang II–induced cardiac functional and structural effects were amplified compared with WT counterparts. Our data demonstrate that in TRPM7Δkinase mice, Ang II–induced hypertension is exaggerated, cardiac remodeling and left ventricular dysfunction are amplified, and endothelial function is impaired. These processes are associated with hypomagnesemia, blunted TRPM7 kinase expression/signaling, endothelial nitric oxide synthase downregulation, and proinflammatory vascular responses. Our findings identify TRPM7 kinase as a novel player in Ang II–induced hypertension and associated vascular and target organ damage

    Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodeling

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    The renin angiotensin system (RAS) is integral to cardiovascular physiology, however, dysregulation of this system largely contributes to the pathophysiology of cardiovascular disease (CVD). It is well established that angiotensin II (Ang II), the main effector of the RAS, engages the angiotensin type 1 receptor and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodeling of the heart and vasculature, ultimately leading to the development and progression of various CVDs including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centered on the actions of angiotensin converting enzyme 2 (ACE2) and the resultant production of angiotensin-(1-7) (Ang-(1-7) from Ang II, antagonizes the actions of Ang II via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1-9), has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. This review will discuss the role of the counter-regulatory RAS peptides, Ang-(1-7) and Ang-(1-9) in the cardiovascular system, with a focus on their effects in remodeling of the heart and vasculature

    Study of the three-dimensional shape and dynamics of coronal loops observed by Hinode/EIS

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    We study plasma flows along selected coronal loops in NOAA Active Region 10926, observed on 3 December 2006 with Hinode's EUV Imaging Spectrograph (EIS). From the shape of the loops traced on intensity images and the Doppler shifts measured along their length we compute their three-dimensional (3D) shape and plasma flow velocity using a simple geometrical model. This calculation was performed for loops visible in the Fe VIII 185 Ang., Fe X 184 Ang., Fe XII 195 Ang., Fe XIII 202 Ang., and Fe XV 284 Ang. spectral lines. In most cases the flow is unidirectional from one footpoint to the other but there are also cases of draining motions from the top of the loops to their footpoints. Our results indicate that the same loop may show different flow patterns when observed in different spectral lines, suggesting a dynamically complex rather than a monolithic structure. We have also carried out magnetic extrapolations in the linear force-free field approximation using SOHO/MDI magnetograms, aiming toward a first-order identification of extrapolated magnetic field lines corresponding to the reconstructed loops. In all cases, the best-fit extrapolated lines exhibit left-handed twist (alpha < 0), in agreement with the dominant twist of the region.Comment: 17 pages, 6 figure

    GAIA Spectroscopy and Radial Velocities

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    GAIA spectroscopic and radial velocity performancies are reviewed on the base of ground-based test observations and simulations. The prospects for accurate analysis of stellar atmospheres (temperature, gravity, chemical abundances, rotation, peculiarities) and precise radial velocities (single stars, binaries, pulsating stars) are colorful provided the spectral dispersion is high enough. A higher dispersions also favors a given precision of radial velocities to be reached at fainter magnitudes: for example, with current parameters for GAIA spectrograph, a 1 km/sec accuracy on epoch RVs of a K0 star is reached at V~13.0 mag with 0.25 Ang/pix dispersion spectra, at V~10.3 mag for 0.5 Ang/pix, and V~6.7 mag for 1 Ang/pix. GAIA radial velocities for single stars can match the ~0.5 km/sec mean accuracy of tangential motions at V=15 mag, provided the observations are performed at a dispersion not less than 0.5 Ang/pix.Comment: proceedings of Les Houches 2001 summer school "GAIA, an European Space Project", published by Editions De Physique, 14 page

    Gran Telescopio Canarias OSIRIS Transiting Exoplanet Atmospheric Survey: Detection of potassium in XO-2b from narrowband spectrophotometry

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    We present Gran Telescopio Canarias (GTC) optical transit narrow-band photometry of the hot-Jupiter exoplanet XO-2b using the OSIRIS instrument. This unique instrument has the capabilities to deliver high cadence narrow-band photometric lightcurves, allowing us to probe the atmospheric composition of hot Jupiters from the ground. The observations were taken during three transit events which cover four wavelengths at spectral resolutions near 500, necessary for observing atmospheric features, and have near-photon limited sub-mmag precisions. Precision narrow-band photometry on a large aperture telescope allows for atmospheric transmission spectral features to be observed for exoplanets around much fainter stars than those of the well studied targets HD209458b and HD189733b, providing access to the majority of known transiting planets. For XO-2b, we measure planet-to-star radius contrasts of R_pl/R_star=0.10508+/-0.00052 at 6792 Ang, 0.10640+/-0.00058 at 7582 Ang, and 0.10686+/-0.00060 at 7664.9 Ang, and 0.10362+/-0.00051 at 8839 Ang. These measurements reveal significant spectral features at two wavelengths, with an absorption level of 0.067+/-0.016% at 7664.9 Ang due to atmospheric potassium in the line core (a 4.1-sigma significance level), and an absorption level of 0.058+/-0.016% at 7582 Ang, (a 3.6-sigma significance level). When comparing our measurements to hot-Jupiter atmospheric models, we find good agreement with models which are dominated in the optical by alkali metals. This is the first evidence for potassium in an extrasolar planet, an element that has long been theorized along with sodium to be a dominant source of opacity at optical wavelengths for hot Jupiters.Comment: 11 pages, 6 figures, accepted in A&A, minor changes to wording, primarily section 4.2, and the title has also been slightly modifie

    Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.

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    The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration
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