Rappaport Faculty of Medicine

About: Rappaport Faculty of Medicine is a based out in . It is known for research contribution in the topics: Population & Heparanase. The organization has 3205 authors who have published 3915 publications receiving 114533 citations.

Accuracy and reproducibility of left ventricular outflow tract diameter measurement using transthoracic when compared with transesophageal echocardiography in systole and diastole

Abstract: Aims Accurate measurement of left ventricular outflow tract diameter (LVOTd) is essential for reliable estimation of aortic valve area (AVA) using the continuity equation. Transesophageal echocardiography (TEE) can accurately delineate the LVOT. The aim of this study was to assess the accuracy and reproducibility of LVOTd measurement using transthoracic echocardiography (TTE) with harmonic imaging when compared with TEE, in both systole and diastole. Methods and results We prospectively studied 50 patients [20 with aortic stenosis (AS) and 30 without AS]. LVOTd was measured offline in a blinded fashion in both systole and diastole by two experienced observers using TTE in the parasternal long axis view and TEE in the mid-oesophageal aortic view (∼130°). There was strong correlation between TTE and TEE ( r = 0.91). LVOTd was slightly smaller by TTE when compared with TEE (2.11 ± 0.21 vs. 2.16 ± 0.22 cm, mean difference −0.05 ± 0.09 cm, P = 0.0003). Compared with TEE, 95% (2SD) of LVOTd measurements by TTE were within +0.14 and −0.24 cm. Inter- and intra-observer variability for LVOTd was 4.8 ± 4.1 and 2.8 ± 1.9% for TTE and 4.2 ± 3.1 and 2.5 ± 1.6% for TEE ( P = 0.4 and 0.6). In patients with AS, estimated AVA was 0.93 ± 0.22 cm2 using TTE and 0.96 ± 0.24 cm2 using TEE, P = 0.08. Diastolic LVOTd by TEE was slightly smaller compared with systolic LVOTd by TEE (−0.03 ± 0.07 cm, P = 0.0005), and there was strong correlation between the two ( r = 0.95). Conclusion We present the data regarding accuracy and reproducibility of LVOTd measurements by TTE when compared with TEE. LVOTd measurements at end-diastole may be helpful when systolic images are suboptimal.

Retention of Oxidized LDL by Extracellular Matrix Proteoglycans Leads to Its Uptake by Macrophages An Alternative Approach to Study Lipoproteins Cellular Uptake

Abstract: Interaction between arterial macrophages and oxidized LDL (Ox-LDL) leads to foam cell formation, a critical step during early atherogenesis. Until now, cellular uptake of lipoproteins was studied through incubation of the media-soluble lipoprotein with cultured macrophages. However, as lipoproteins in the arterial wall are bound to subendothelial matrix, we questioned whether the retention (binding) of Ox-LDL to a macrophage-derived extracellular matrix (ECM) could lead to enhanced uptake by macrophages. The uptake of ECM-bound Ox-LDL by activated macrophages (by phorbol myristate acetate) was lipoprotein dose dependent, time dependent and higher (by 1.5-fold) than the uptake of ECM-bound native LDL. Preincubation of the ECM with lipoprotein lipase before the addition of Ox-LDL was essential for the uptake of ECM-bound Ox-LDL by the macrophages. After radiolabeling of the ECM glycosaminoglycans (GAGs), we found that ECM-bound Ox-LDL is taken up by the macrophages together with the ECM-GAG. Finally, these results were further confirmed through the use of ECM obtained from mouse peritoneal macrophages (MPMs), derived from atherosclerotic, apoE-deficient mice. In 24-week-old mice with developed atherosclerosis, the GAG content of their MPM-derived ECM increased by 52%, the ability of their MPM-derived ECM to bind Ox-LDL increased by 57%, and macrophage uptake of Ox-LDL that was retained by the MPM-derived ECM increased by 86%. In conclusion, the present study demonstrated that ECM-bound Ox-LDL is taken up by activated macrophages. This may represent a physiopathological phenomenon that leads to cholesterol and oxysterol accumulation in arterial macrophages, the hallmark of early atherosclerosis.

Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-α secretion

Abstract: Monocytes/macrophages in ischemic tissues are involved in inflammation and suppression of adaptive immunity via secretion of proinflammatory cytokines and reduced ability to trigger T cells, respectively. We subjected human mononuclear cells and mouse macrophages to hypoxia and reoxygenation, the main constituents of ischemia and reperfusion, and added lipopolysaccharide (LPS) to simulate bacterial translocation, which frequently accompanies ischemia. We monitored the secretion of tumor necrosis factor alpha (TNF-alpha) and the surface expression of human leukocyte antigen-DR and the costimulatory molecules CD80 and CD86 on monocytes/macrophages. Hypoxia selectively reduced the surface expression of CD80 (P<0.01), and synergistically with LPS, it enhanced TNF-alpha secretion (P<0.003). Reoxygenation reversed both phenomena. In the mouse macrophage cell line RAW 264.7, hypoxia reduced the surface expression of CD80 and increased its concentrations in the supernatants (P<0.01). Down-regulation of the mRNA coding for the membrane-anchored CD80 was observed, suggesting that hypoxia triggers alternative splicing to generate soluble CD80. Cumulatively, these results suggest that hypoxia simultaneously affects monocytes/macrophages to enhance inflammation and reduce their ability to initiate adaptive-immunity responses associated with ischemic injury.