Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the early and late results of mitral valve replacement and reconstruction for mitral insufficiency due to ruptured chordae tendineae respectively, 74 consecutive cases were analyzed. Fifty-five (74.3%) of the patients were men, and the mean age was 48 +/- 12 years old (range 16 to 76). The causes of the mitral disease were idiopathic in 50 (67.6%), rheumatic in 7 (9.4%) and infective endocarditis in 11 (14.9%) patients. In idiopathic 50 cases, 24 had mitral valve prolapse and 16 had both mitral valve prolapse and hypertension. Forty-one (55.4%) of the patients were in NYHA functional class III or IV preoperatively. Thirty (40.5%) cases underwent surgery within one year after their initial symptoms of heart failure onsets including six emergency operation cases due to uncontrollable acute lung edema. Chordae to anterior mitral leaflet were ruptured in 31 (a5, m16, p10)[41%] patients, to the posterior mitral leaflet in 45 (a4, m23, p18)[59%], and to both leaflets in one patient. Mitral valve replacement was performed in 68 patients (91.9%) and 6 patients (8.1%) underwent mitral valve repairs. Twenty cases underwent associated procedures that included tricuspid valve annuloplasty in 8, aortic valve replacement in 5 and myocardial revascularization in 4 cases. There were two operative deaths (2.4%); both occurred after replacement, left ventricular rupture in one and DIC in one. Mean follow-up period was 4.5 years (range 1 to 17) in 67 cases. There were four late deaths; all occurred after replacement. However five patients sustained mild mitral insufficiency after mitral valve repair including one that became worse of regurgitation three years after isolated Kay's annuloplasty, there were no cases that had needed reoperation and no late death after reconstruction. Left ventricular function and pulmonary arterial pressure were almost normalized in more than 90% cases postoperatively. Our data indicated that mitral valve reconstruction (McGoon's plus Kay's method as standardized maneuver) was the procedure of choice for selected patients with mitral insufficiency owing to ruptured chordae tendineae to the posterior mitral leaflet, including more limited patients with ruptured chordae to the anterior mitral leaflet.
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PMID:[Mitral insufficiency due to ruptured chordae tendineae--clinical features, early and late results of valve replacement and repair]. 273 33

Vascular permeability is a hallmark of several disease states including acute lung injury (ALI). Endocytosis of VE-cadherin, away from the interendothelial junction (IEJ), causes acute endothelial barrier permeability. A novel protein, p18, anchors to the endosome membrane and plays a role in late endosomal signaling via MAPK and mammalian target of rapamycin. However, the fate of the VE-cadherin-positive endosome has yet to be elucidated. We sought to elucidate a role for p18 in VE-cadherin trafficking and thus endothelial barrier function, in settings of ALI. Endothelial cell (EC) resistance, whole-cell ELISA, and filtration coefficient were studied in mice or lung ECs overexpressing wild-type or nonendosomal-binding mutant p18, using green fluorescent protein as a control. We demonstrate a protective role for the endocytic protein p18 in endothelial barrier function in settings of ALI in vitro and in vivo, through enhanced recycling of VE-cadherin-positive early endosomes to the IEJ. In settings of LPS-induced ALI, we show that Src tethered to the endosome tyrosine phosphorylates p18 concomitantly with VE-cadherin internalization and pulmonary edema formation. We conclude that p18 regulates pulmonary endothelial barrier function in vitro and in vivo, by enhancing recycling of VE-cadherin-positive endosomes to the IEJ.
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PMID:p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling of VE-cadherin. 2540 10

Pulmonary edema occurs in settings of acute lung injury, in diseases, such as pneumonia, and in acute respiratory distress syndrome. The lung interendothelial junctions are maintained in part by vascular endothelial (VE)-cadherin, an adherens junction protein, and its surface expression is regulated by endocytic trafficking. The Rab family of small GTPases are regulators of endocytic trafficking. The key trafficking pathways are regulated by Rab4, -7, and -9. Rab4 regulates the recycling of endosomes to the cell surface through a rapid-shuttle process, whereas Rab7 and -9 regulate trafficking to the late endosome/lysosome for degradation or from the trans-Golgi network to the late endosome, respectively. We recently demonstrated a role for the endosomal adaptor protein, p18, in regulation of the pulmonary endothelium through enhanced recycling of VE-cadherin to adherens junction. Thus, we hypothesized that Rab4, -7, and -9 regulate pulmonary endothelial barrier function through modulating trafficking of VE-cadherin-positive endosomes. We used Rab mutants with varying activities and associations to the endosome to study endothelial barrier function in vitro and in vivo. Our study demonstrates a key role for Rab4 activation and Rab9 inhibition in regulation of vascular permeability through enhanced VE-cadherin expression at the interendothelial junction. We further showed that endothelial barrier function mediated through Rab4 is dependent on extracellular signal-regulated kinase phosphorylation and activity. Thus, we demonstrate that Rab4 and -9 regulate VE-cadherin levels at the cell surface to modulate the pulmonary endothelium through extracellular signal-regulated kinase-dependent and -independent pathways, respectively. We propose that regulating select Rab GTPases represents novel therapeutic strategies for patients suffering with acute respiratory distress syndrome.
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PMID:Select Rab GTPases Regulate the Pulmonary Endothelium via Endosomal Trafficking of Vascular Endothelial-Cadherin. 2655 Oct 54