SummaryRecent attention has focused on the T helper type 2 (Th2) lymphocyte as a source of interleukin 4 (IL 4) in allergic disease . However, Th2 cells themselves require a pulse of IL-4 to initiate this synthesis. Here we provide immunohistochemical evidence of IL-4 localization to human mast cells of the skin and respiratory tract, and demonstrate that immunoglobulin E-dependent stimulation of purified human lung mast cells leads to the rapid release of IL-4 into the extracellular environment . We propose that mast cell activation in an allergic response provides a rapid and local pulse of IL-4 into the local environment essential for the triggering of T lymphocytes into sustained IL-4 production and to initiate inflammatory cell accumulation and activation.

Naïve and primed pluripotent hESCs bear transcriptional similarity to pre- and post-implantation epiblast and thus constitute a developmental model for understanding the earliest pluripotent stages in human embryo development. To identify new transcription factors that differentially regulate the unique pluripotent stages, we mapped open chromatin using ATAC-Seq and found enrichment of the AP2 transcription factor binding motif at naïve-specific open chromatin. We determined that the AP2 family member TFAP2C is upregulated during primed to naïve reversion and becomes widespread at naïve-specific enhancers. TFAP2C functions to maintain pluripotency and repress neuroectodermal differentiation during the transition from primed to naïve by facilitating the opening of enhancers proximal to pluripotency factors. Additionally, we identify a previously undiscovered naïve-specific POU5F1 (OCT4) enhancer enriched for TFAP2C binding. Taken together, TFAP2C establishes and maintains naïve human pluripotency and regulates OCT4 expression by mechanisms that are distinct from mouse.

Minimally invasive cardiac surgery requires arresting and emptying of the heart, which compromises visualization of the surgical field. In this feasibility study a novel surgical procedure is demonstrated in which real-time MRI is used to guide the placement of a prosthetic aortic valve in the beating heart via direct apical access in eight porcine hearts. A clinical stentless bioprosthetic valve affixed to a platinum stent was compressed onto a balloon-tipped catheter. This was fed through a 15-18-mm delivery port inserted into the left ventricular (LV) apex via a minimally invasive subxyphoid incision. Using interactive real-time MRI, the surgeon implanted the prosthetic valve in the correct location at the aortic annulus within 90 s. In four of the animals immediately after implantation, ventricular function, blood flow through the valve, and myocardial perfusion were evaluated with MRI. MRI-guided beating-heart surgery may provide patients with a less morbid and more durable solution to structural heart disease. Recently there has been a focus on using minimally invasive approaches in cardiac surgery in an effort to reduce trauma and speed recovery for the patient (1-3). In valve surgery, incisions have been shortened and robotics employed to achieve this goal; however, these approaches still require arresting and emptying of the heart to allow visualization. Real-time MRI techniques previously developed for intravascular guidance (4,5) are immediately applicable to provide vision in the surgical field, even in a beating heart with circulating blood, to guide the surgeon.A new generation of short (120 cm), wide-bore (70 cm) 1.5T imaging systems (Magnetom Espree, Siemens Medical Solutions) has recently been introduced. This magnet design gives a clearance of up to 30 cm above the chest of the supine patient, and the short design allows a surgeon to directly manipulate thoracoscopic instruments within the chest with ample "attack angles" and degrees of freedom. The more open bore allows better access to the patient for anesthesia when imaging the heart. While MRguided therapeutic interventions have been pursued extensively (6,7), most MR systems used in these applications to date have not been designed for the highperformance real-time scanning required for guiding cardiac procedures. The imaging gradients and amplifiers of the new systems yield a scanning performance that rivals that of the standard cardiac MR scanners, and therefore high-quality images can be obtained with real-time acquisition speeds. Imaging techniques used for intravascular MR guidance are immediately applicable to minimally invasive surgical procedures. The excellent blood/tissue contrast and the ability to interactively adjust imaging planes to view devices and the beating heart from multiple simultaneous viewpoints makes real-time MR ideal for guiding cardiac surgical interventions.The key to any interventional treatment is achieving the correct balance between risk and benefit. In the surgical treatment of aortic valve disease, the mo...

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