The flail mitral valve: Echocardiographic findings by precordial and transesophageal imaging and doppler color flow mapping

AbstractTo determine the echocardiographic and Doppler characteristics of mitral regurgitation associated with a flail mitral valve, precordial and transesophageal echocardiography with pulsed wave and Doppler color flow mapping was performed in 17 patients with a flail mitral valve leaflet due to ruptured chordae tendineae (Group I) and 22 patients with moderate or severe mitral regurgitation due to other causes (Group II). Echocardiograms were performed before or during cardiac surgery; cardiac catheterization was also performed in 28 patients (72%). Mitral valve disease was confirmed at cardiac surgery in all patients.By echocardiography, the presence of a flail mitral valve leaflet was defined by the presence of abnormal mitral leaflet ccaptation or ruptured chordae. Using these criteria, transesophageal imaging showed a trend toward greater sensitivity and specificity than precordial imaging in the diagnosis of flail mitral valve leaflet. By Doppler color flow mapping, a flail mitral valve leaflet was also characterized by an eccentric, peripheral, circular mitral regurgitant jet that closely adhered to the walls of the left atrium. The direction of flow of the eccentric jet in the left atrium distinguished a flail anterior from a flail posterior leaflet. By transesophageal echocardiography with Doppler color flow mapping, the ratio of mitral regurgitant jet arc length to radius of curvature was significantly higher in Group I than Group II patients (5.0 ± 2.3 versus 0.7 ± 0.6, p < 0.001); all of the Group I patients and none of the Group II patients had a ratio >2.5.Thus, transesophageal imaging with Doppler color flow mapping of mitral regurgitation is complementary to precordial echocardiography in the diagnosis and localization of flail mitral valve leaflet due to ruptured chordae tendineae

Quantum Dots for Tracking Dendritic Cells and Priming an Immune Response In Vitro and In Vivo

Dendritic cells (DCs) play a key role in initiating adaptive immune response by presenting antigen to T cells in lymphoid organs. Here, we investigate the potential of quantum dots (QDs) as fluorescent nanoparticles for in vitro and in vivo imaging of DCs, and as a particle-based antigen-delivery system to enhance DC-mediated immune responses. We used confocal, two-photon, and electron microscopies to visualize QD uptake into DCs and compared CD69 expression, T cell proliferation, and IFN-γ production by DO11.10 and OT-II T cells in vivo in response to free antigen or antigen-conjugated to QDs. CD11c+ DCs avidly and preferentially endocytosed QDs, initially into small vesicles near the plasma membrane by an actin-dependent mechanism. Within 10 min DCs contained vesicles of varying size, motion, and brightness distributed throughout the cytoplasm. At later times, endocytosed QDs were compartmentalized inside lysosomes. LPS-induced maturation of DCs reduced the rate of endocytosis and the proportion of cells taking up QDs. Following subcutaneous injection of QDs in an adjuvant depot, DCs that had endocytosed QDs were visualized up to 400 µm deep within draining lymph nodes. When antigen-conjugated QDs were used, T cells formed stable clusters in contact with DCs. Antigen-conjugated QDs induced CD69 expression, T cell proliferation, and IFN-γ production in vivo with greater efficiency than equivalent amounts of free antigen. These results establish QDs as a versatile platform for immunoimaging of dendritic cells and as an efficient nanoparticle-based antigen delivery system for priming an immune response

The Immunological Synapse: a Dynamic Platform for Local Signaling

The immunological synapse (IS) as a concept has evolved from a static view of the junction between T cells and their antigen-presenting cell partners. The entire process of IS formation and extinction is now known to entail a dynamic reorganization of membrane domains and proteins within and adjacent to those domains. Discussion The entire process is also intricately tied to the motility machinery—both as that machinery directs “scanning” prior to T-cell receptor engagement and as it is appropriated during the ongoing developments at the IS. While the synapse often remains dynamic in order to encourage surveillance of new antigen-presenting surfaces, cytoskeletal forces also regulate the development of signals, likely including the assembly of ion channels. In both neuronal and immunological synapses, localized Ca 2+ signals and accumulation or depletion of ions in microdomains accompany the concentration of signaling molecules in the synapse. Such spatiotemporal signaling in the synapse greatly accelerates kinetics and provides essential checkpoints to validate effective cell–cell communication

The North American tree-ring fire-scar network

Fire regimes in North American forests are diverse and modern fire records are often too short to capture important patterns, trends, feedbacks, and drivers of variability. Tree-ring fire scars provide valuable perspectives on fire regimes, including centuries-long records of fire year, season, frequency, severity, and size. Here, we introduce the newly compiled North American tree-ring fire-scar network (NAFSN), which contains 2562 sites, >37,000 fire-scarred trees, and covers large parts of North America. We investigate the NAFSN in terms of geography, sample depth, vegetation, topography, climate, and human land use. Fire scars are found in most ecoregions, from boreal forests in northern Alaska and Canada to subtropical forests in southern Florida and Mexico. The network includes 91 tree species, but is dominated by gymnosperms in the genus Pinus. Fire scars are found from sea level to >4000-m elevation and across a range of topographic settings that vary by ecoregion. Multiple regions are densely sampled (e.g., >1000 fire-scarred trees), enabling new spatial analyses such as reconstructions of area burned. To demonstrate the potential of the network, we compared the climate space of the NAFSN to those of modern fires and forests; the NAFSN spans a climate space largely representative of the forested areas in North America, with notable gaps in warmer tropical climates. Modern fires are burning in similar climate spaces as historical fires, but disproportionately in warmer regions compared to the historical record, possibly related to under-sampling of warm subtropical forests or supporting observations of changing fire regimes. The historical influence of Indigenous and non-Indigenous human land use on fire regimes varies in space and time. A 20th century fire deficit associated with human activities is evident in many regions, yet fire regimes characterized by frequent surface fires are still active in some areas (e.g., Mexico and the southeastern United States). These analyses provide a foundation and framework for future studies using the hundreds of thousands of annually- to sub-annually-resolved tree-ring records of fire spanning centuries, which will further advance our understanding of the interactions among fire, climate, topography, vegetation, and humans across North America

Imaging Effector Memory T cells in the Ear After Induction of Adoptive DTH

Delayed type hypersensitivity (DTH) is an immune reaction in which the main players are CCR7- effector / memory T lymphocytes. Here, we demonstrate a method for inducing and recording the progress of a DTH reaction in the rat ear. This is followed by a demonstration of the preparation of rat ear tissue for two-photon imaging of the CCR7- effector / memory T cell response

Response of the interatrial septum to transatrial pressure gradients and its potential for predicting pulmonary capillary wedge pressure: An intraoperative study using transesophageal echocardiography in patients during mechanical ventilation

AbstractObjectives. We hypothesized that the directional movement of the interatrial septum and its curvature may reflect the pressure relations between the left and right atria.Background. Interventricular septal shape is primarily dependent on the pressure gradient between the left and the right ventricle. No analogous study has carefully evaluated the determinants of interatrial septum shape and motion.Methods. Patients (n = 52) undergoing cardiac or vascular surgery were studied intraoperatively at multiple intervals with transesophageal echocardiography and simultaneous measurement of central venous pressure, pulmonary capillary wedge pressure and airway pressure.Results. Overall interatrial septum shape, which usually curved toward the right atrium, changed concordantly with the interatrial pressure gradient (pulmonary capillary wedge pressure-central venous pressure difference). The degree of interatrial septum curvature was also primarily dependent on the interatrial pressure gradient and, to a lesser extent, was affected by changes in left atrial size (F = 130.4 vs. F = 14.1). During passive mechanical expiration, the interatrial pressure gradient, usually positive, often reverses transiently and the interatrial septum momentarily bows toward the left atrium. Midsystolic reversal was seen in 64 of 72 episodes when the pulmonary capillary wedge pressure was ≤15 mm Hg but in only 2 of 40 episodes when it was >15 mm Hg (sensitivity = 0.89, specificity = 0.95, positive predictive value = 0.97).Conclusions. These findings suggest that overall interatrial septum shape depends on the pressure gradient between the left and right atria. Midsystolic reversal of the interatrial septum, which probably reflects the increased venous return in the right relative to the left atrium during mechanical expiration, may be a useful indicator of the pulmonary capillary wedge pressure