Troglitazone inhibits angiotensin II-induced DNA synthesis and migration in vascular smooth muscle cells

AbstractAngiotensin II (AII) plays a crucial role in controlling the proliferation and migration of vascular smooth muscle cells (VSMCs). The present study was undertaken to determine if troglitazone (Tro) has an effect on the G-protein coupled signaling through AII type I (AT-1) receptors in cultured rat aortic VSMCs. AII-induced MAP kinase activation was inhibited 67.9% by Tro. AII-induced DNA synthesis and migration was completely inhibited by Tro or by the AT-1 receptor blocker irbesartan. The present study demonstrates that troglitazone inhibits AII-induced DNA synthesis, migration and MAP kinase activation in VSMCs which are important molecular events for the development of neointimal hyperplasia and atherosclerosis

A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells

PPARγ ligands have been shown to have antiproliferative effects on many cell types. We herein report that a synthetic dominant-negative (DN) PPARγ mutant functions like a growth factor to promote cell cycle progression and cell proliferation in human coronary artery smooth muscle cells (CASMCs). In quiescent CASMCs, adenovirus-expressed DN-PPARγ promoted G1→S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation. DN-PPARγ expression also markedly enhanced positive regulators of the cell cycle, increasing Rb and CDC2 phosphorylation and the expression of cyclin A, B1, D1, and MCM7. Conversely, overexpression of wild-type (WT) or constitutively-active (CA) PPARγ inhibited cell cycle progression and the activity and expression of positive regulators of the cell cycle. DN-PPARγ expression, however, did not up-regulate positive cell cycle regulators in PPARγ-deficient cells, strongly suggesting that DN-PPARγ effects on cell cycle result from blocking the function of endogenous wild-type PPARγ. DN-PPARγ expression enhanced phosphorylation of ERK MAPKs. Furthermore, the ERK specific-inhibitor PD98059 blocked DN-PPARγ-induced phosphorylation of Rb and expression of cyclin A and MCM7. Our data thus suggest that DN-PPARγ promotes cell cycle progression and cell growth in CASMCs by modulating fundamental cell cycle regulatory proteins and MAPK mitogenic signaling pathways in vascular smooth muscle cells (VSMCs)

Survey of micrometeorological parameters within a forest canopy at Fort Polk, Louisiana, A

CER80-81WZS-FWL-WEM44.Includes bibliographical references (page 44).February 1982.A field investigation of micrometeorological parameters inside and above a forest canopy at Fort Polk, Louisiana, was conducted in conjunction with the Atmospheric Sciences Laboratory Dusty Infrared Test IIIA. The three orthogonal components of the wind, ory- and wet-bulb temperatures and total solar radiation were measured inside this forest canopy by means of an instrumented meteorological tower. In addition, turbulence inside the forest canopy was monitored by means of hot-wire anemometers. Tethersonde balloon sounding above the forest canopy was further performed. The meteorological data was reduced by means of three different statistical methods. Single sample period values, one-minute sample averages and sequential sample values were computed. The latter two methods led to the construction of time series which can readily be used to perform advanced statistical analyses. Totals of 27 h 29 min of meteorological tower data and 2 h 50 min of balloon data were reduced. The results are presented in tabular form in 1422 tables and partially displayed in 1795 figures under separate cover in view of their large volume. Selected samples of the results are, however, presented herein. The results supply a data base for analyses of airflow in a forest canopy. Suggestions for future work of significance for mission-oriented cases and for modeling of airflow in a forest canopy are outlined.Contract DAAG29-76-D-0100 conducted for the U.S. Army Atmospheric Sciences Laboratory, White Sands Missile Range

The Evolutionary Status of SS433

We consider possible evolutionary models for SS 433. We assume that common-envelope evolution is avoided if radiation pressure is able to expel most of a super-Eddington accretion flow from a region smaller than the accretor's Roche lobe. This condition is satisfied, at least initially, for largely radiative donors with masses in the range 4-12 solar masses. For donors more massive than about 5 solar masses, moderate mass ratios q = M_2/M_1 > 1 are indicated, thus tending to favor black-hole accretors. For lower mass donors, evolutionary considerations do not distinguish between a neutron star or black hole accretor. In all cases the mass transfer (and mass loss) rates are much larger than the likely mass-loss rate in the precessing jets. Almost all of the transferred mass is expelled at radii considerably larger than the jet acceleration region, producing the "stationary" H-alpha line, the infrared luminosity, and accounting for the low X-ray luminosity.Comment: 13 pages, Astrophysical Journal Letters, accepte

The ‘Blueprint’ framework for career management skills: a critical exploration

This article examines the Blueprint framework for career management skills as it has been revealed across sequential implementations in the USA, Canada and Australia. It is argued that despite its lack of an empirical basis, the framework forms a useful and innovative means through which career theory, practice and policy can be connected. The framework comprises both core elements (learning areas, learning model and levels) and contextual elements (resources, community of practice, service delivery approach and policy connection). Each of these elements is explored

Report of Seminar on Estate Planning

Reports from the UK/CLE Seminar on Estate Planning held July 19-20, 1974

Taking the Measure of the Universe: Precision Astrometry with SIM PlanetQuest

Precision astrometry at microarcsecond accuracy has application to a wide range of astrophysical problems. This paper is a study of the science questions that can be addressed using an instrument that delivers parallaxes at about 4 microarcsec on targets as faint as V = 20, differential accuracy of 0.6 microarcsec on bright targets, and with flexible scheduling. The science topics are drawn primarily from the Team Key Projects, selected in 2000, for the Space Interferometry Mission PlanetQuest (SIM PlanetQuest). We use the capabilities of this mission to illustrate the importance of the next level of astrometric precision in modern astrophysics. SIM PlanetQuest is currently in the detailed design phase, having completed all of the enabling technologies needed for the flight instrument in 2005. It will be the first space-based long baseline Michelson interferometer designed for precision astrometry. SIM will contribute strongly to many astronomical fields including stellar and galactic astrophysics, planetary systems around nearby stars, and the study of quasar and AGN nuclei. SIM will search for planets with masses as small as an Earth orbiting in the `habitable zone' around the nearest stars using differential astrometry, and could discover many dozen if Earth-like planets are common. It will be the most capable instrument for detecting planets around young stars, thereby providing insights into how planetary systems are born and how they evolve with time. SIM will observe significant numbers of very high- and low-mass stars, providing stellar masses to 1%, the accuracy needed to challenge physical models. Using precision proper motion measurements, SIM will probe the galactic mass distribution and the formation and evolution of the Galactic halo. (abridged)Comment: 54 pages, 28 figures, uses emulateapj. Submitted to PAS

Current Issues in Environmental Law

Materials from the Current Issues in Environmental Law seminar held by UK/CLE in April 1995

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study)

Background. Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. Methods/design. Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. Discussion. The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. Trial registration. Current Controlled Trials ISRCTN46462267