40 research outputs found

    The Role of the CD4 Receptor versus HIV Coreceptors in Envelope-Mediated Apoptosis in Peripheral Blood Mononuclear Cells

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    AbstractWe examined the role of CD4, CXCR4, and CCR5 in HIV envelope-mediated apoptosis by measuring the response of activated PBMCs to recombinant envelope proteins derived from CXCR4- and CCR5-utilizing viruses. Apoptosis of T cells was assessed by annexin-V staining and TdT-mediated dUTP-biotin nick-end labeling. Treatment of CCR5Δ32 homozygote PBMCs with a CCR5-specific envelope induced apoptosis in T cells, demonstrating that envelope–CD4 interactions are sufficient to induce apoptosis. However, a CXCR4-specific envelope induced higher levels of apoptosis than a CCR5-specific envelope, suggesting that envelope-mediated apoptosis can be enhanced by envelope–CXCR4 interactions. We conclude that envelope can induce apoptosis in T cells independently of the coreceptor specificity of a given envelope, or the expression profile of CXCR4 or CCR5 on a target cell. However, envelope–coreceptor interactions, and in particular, envelope–CXCR4 interactions, can contribute to this process

    Exploring Physician Perceptions of the 2018 United States Heart Transplant Allocation System

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    BACKGROUND: After the implementation of the 2018 US heart transplant allocation system, the experience and perceptions of heart transplant clinicians have not been well-cataloged. METHODS AND RESULTS: This web-based survey of both heart failure cardiologists and surgeons examined physician perspectives about the policy changes and whether the system is meeting its intended goals. The majority of participants (94%, n = 113) responded that the 2018 heart allocation system requires modification. Eighty-four percent reported using more temporary mechanical circulatory support to achieve higher status and 86% were concerned about the change in physician behavior and practices under the new system. CONCLUSIONS: Suggestions for possible improvement included higher status for patients on durable left ventricular assist device support, changes to criteria for status 2, modification of status exceptions, and advocacy for a heart allocation score

    Priorities for Cardiovascular Outcomes Research: A Report of the National Heart, Lung, and Blood Institute\u27s Centers for Cardiovascular Outcomes Research Working Group

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    The Centers for Cardiovascular Outcomes Research (CCORs) held a meeting to review how cardiovascular outcomes research had evolved in the decade since the National Heart, Lung, and Blood Institute 2004 working group report and to consider future directions. The conference involved representatives from governmental agencies, outcomes research thought leaders, and public and private healthcare partners. The main purposes of this meeting were to (1) advance collaborative high-yield, high-impact outcomes research; (2) identify priorities and barriers to important cardiovascular outcomes research; and (3) define future needs for the field. This report highlights the key topics covered during the meeting, including an examination of the recent history of outcomes research, an evaluation of the current academic climate, and a vision for the future of cardiovascular outcomes research
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