Search

Summary Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels, and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic state. Mice with EC deletion of BMPR2 develop hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic littermates, does not reverse upon reoxygenation and is associated with reduced PA microvessels and lung EC p53, PGC1α and TFAM, regulators of mitochondrial biogenesis, and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during reoxygenation represses p53, PGC1α, NRF2, TFAM, mitochondrial membrane potential, and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing PAEC BMPR2 in normoxia increases p53, PGC1α, TFAM, mitochondrial membrane potential, ATP production, and glycolysis, and induces mitochondrial fission and a pro-inflammatory state. These features are recapitulated in PAECs from PAH patients with mutant BMPR2. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To evaluate the detectability of urinary calculi on material decomposition (MD) images generated from spectral computed tomography (CT) and identify the influencing factors. Materials and Methods: Forty-six patients were examined with true nonenhanced (TNE) CT and spectral CT urography in the excretory phase. The contrast medium was removed from excretory phase images using water-based (WB) and calcium-based (CaB) MD analysis. The sensitivity for detection on WB and CaB images was evaluated using TNE results as the reference standard. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) on MD images were evaluated. Using logistic regression, the influences of image noise, attenuation, stone size, and patient's body mass index (BMI) were assessed. Threshold values with maximal sensitivity and specificity were calculated by means of receiver operating characteristic analyses. Results: One hundred thirty-six calculi were detected on TNE images; 98 calculi were identified on WB images (sensitivity, 72.06%) and 101 calculi on CaB images (sensitivity, 74.26%). Sensitivities were 76.92% for the 3–5-mm stones and 84.51% for the 5-mm or larger stones on both WB and CaB images but reduced to 46.15% on WB images and 53.85% on CaB images for small calculi (<3 mm). Compared to WB images, CaB images showed lower image noise, higher SNR but similar CNR. Larger stone sizes (both >2.71 mm on WB and CaB) and greater CT attenuation (>280 Hounsfield units [HU] on WB, >215 HU on CaB) of the urinary stones were significantly associated with higher stone visibility rates on WB and CaB images (P ≤ .003). Image noise and BMI showed no impact on the stone detection. Conclusions: MD images generated from spectral CT showed good reliability for the detection of large (>2.71 mm) and hyperattenuating (>280 HU on WB, >215 HU on CaB) urinary calculi. [Copyright &y& Elsevier]