Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype

Histopathology, clinical chemistry, hematology and gene expression data were collected from the rat liver and blood after treatment with eight known hepatotoxins

Standardized ultrasound evaluation of carotid stenosis for clinical trials: University of Washington Ultrasound Reading Center

<p>Abstract</p> <p>Introduction</p> <p>Serial monitoring of patients participating in clinical trials of carotid artery therapy requires noninvasive precision methods that are inexpensive, safe and widely available. Noninvasive ultrasonic duplex Doppler velocimetry provides a precision method that can be used for recruitment qualification, pre-treatment classification and post treatment surveillance for remodeling and restenosis. The University of Washington Ultrasound Reading Center (UWURC) provides a uniform examination protocol and interpretation of duplex Doppler velocity measurements.</p> <p>Methods</p> <p>Doppler waveforms from 6 locations along the common carotid and internal carotid artery path to the brain plus the external carotid and vertebral arteries on each side using a Doppler examination angle of 60 degrees are evaluated. The UWURC verifies all measurements against the images and waveforms for the database, which includes pre-procedure, post-procedure and annual follow-up examinations. Doppler angle alignment errors greater than 3 degrees and Doppler velocity measurement errors greater than 0.05 m/s are corrected.</p> <p>Results</p> <p>Angle adjusted Doppler velocity measurements produce higher values when higher Doppler examination angles are used. The definition of peak systolic velocity varies between examiners when spectral broadening due to turbulence is present. Examples of measurements are shown.</p> <p>Discussion</p> <p>Although ultrasonic duplex Doppler methods are widely used in carotid artery diagnosis, there is disagreement about how the examinations should be performed and how the results should be validated. In clinical trails, a centralized reading center can unify the methods. Because the goals of research examinations are different from those of clinical examinations, screening and diagnostic clinical examinations may require fewer velocity measurements.</p

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Regulates Tumor Necrosis Factor mRNA Stability and Translation Mainly by Altering Tristetraprolin Expression, Stability, and Binding to Adenine/Uridine-Rich Element

The mitogen-activated protein kinase (MAPK) p38/MAPK-activated protein kinase 2 (MK2) signaling pathway plays an important role in the posttranscriptional regulation of tumor necrosis factor (TNF), which is dependent on the adenine/uridine-rich element (ARE) in the 3′ untranslated region of TNF mRNA. After lipopolysaccharide (LPS) stimulation, MK2-deficient macrophages show a 90% reduction in TNF production compared to the wild type. Tristetraprolin (TTP), a protein induced by LPS, binds ARE and destabilizes TNF mRNA. Accordingly, macrophages lacking TTP produce large amounts of TNF. Here, we generated MK2/TTP double knockout mice and show that, after LPS stimulation, bone marrow-derived macrophages produce TNF mRNA and protein levels comparable to those of TTP knockout cells, indicating that in the regulation of TNF biosynthesis TTP is genetically downstream of MK2. In addition, we show that MK2 is essential for the stabilization of TTP mRNA, and phosphorylation by MK2 leads to increased TTP protein stability but reduced ARE affinity. These data suggest that MK2 inhibits the mRNA destabilizing activity of TTP and, in parallel, codegradation of TTP together, with the target mRNA resulting in increased cellular levels of TTP

Hepatic Gene Expression Changes throughout the Day in the Fischer Rat: Implications for Toxicogenomic Experiments

There is increasing use of transcriptional profiling in hepato-toxicity studies in the rat. Understanding hepatic gene expression changes over time is critical, since tissue collection may occur throughout the day. Furthermore, when comparing results from different data sets, times of dosing and tissue collection may vary. Circadian effects on the mouse hepatic transcriptome have been well documented. However, limited reports exist for the rat. In one study approximately 7 % of the hepatic genes showed a diurnal expression pattern in a comparison of rat liver samples collected during the day versus livers collected at night. The results of a second study comparing rat liver samples collected at multiple time points over a circadian day suggest only minimal variation of the hepatic transcriptome. We studied temporal hepatic gene expression in 48 untreated F344/N rats using both approaches employed in these previous studies. Statistical analysis of micro