BLOOD SUBSTITUTES--MOLECULAR AND PHYSIOLOGICAL ASPECTS

该计划项目的基本假设是无细胞 经过结构工程适当修饰的血红蛋白将是安全和 在许多临床情况下的有效治疗，其中红细胞 已注明。该计划项目的主要目标是了解 红色替代的生理后果和临床潜力 血液循环中的血细胞和无细胞血液替代品。 在新解决方案的设计、生产和测试方面具有专业知识， 在生物化学、生理学、 分子生物学和临床医学将在 这项计划计划重点解决大规模的具体问题 输注无细胞红细胞替代品，同时 利用新兴技术为基础生理学提供新的线索 以及生化问题。计划项目的要素反映了 UCSD教职员工的利益，而不是全面的方法 血液替代品的开发。然而，专业知识是广泛的，而且 深入研究，几乎所有相关领域都将得到研究。核心A将 协调组件项目和核心项目的活动，管理预算， 采购、安排会议和研讨会，并提供基本的 秘书支持。核心B将生产或获得代表 正在开发的各种类别的产品，供调查 各种项目，包括基于血红蛋白和基于全氟碳的项目 氧气载体；一些将在计划项目中生产，其他将在计划项目中生产 将从其他实验室获得。体外配基结合， 稳定性和毒性将与工程中的蛋白质结构有关 1，对微循环的影响将在项目2中研究， 项目3中的心脏，项目4中的肾脏。这些数据 项目将在项目1中用于新的化学设计 使用以下方法修饰或(通过协作)突变的血红蛋白衍生物 项目1中的计算机可视化技术。每个项目将有 加州大学圣迭戈分校教职员工的顾问。由以下成员组成的执行委员会 来自每月会面的每个项目和核心的首席调查人员 在过去的一年里将形成一个集团的核心并将继续 共享未来研究的数据、结果和计划。内部和外部 由杰出科学家组成的顾问小组将被任命为 相关领域的专业知识。

The hypothesis underlying this Program Project is that cell free hemoglobin, suitably modified by structural engineering, will be safe and effective therapy in many clinical situations where red blood cells are indicated. The main goal of the Program Project is to understand the physiological consequences and clinical potential of replacement of red blood cells in the circulation with acellular blood substitutes. Expertise in design, production and testing of new solutions, with academic expertise in several key areas of biochemistry, physiology, molecular biology and clinical medicine will be brought together under this Program Project to focus on specific problems of large scale infusions of acellular red cell substitutes, while simultaneously exploiting emerging technology to shed new light on basic physiological and biochemical problems. The elements of the Program Project reflect the interests of the UCSD faculty, rather than a comprehensive approach to development of blood substitutes. However, the expertise is broad and deep, and nearly all relevant areas will be studied. Core A will coordinate activities of the component projects and cores, manage budget, purchasing, scheduling of meetings and seminars, and provide basic secretarial support. Core B will produce or obtain materials representing various classes of products under development for investigation by the various projects, including both hemoglobin- and perflurocarbon-based oxygen carries; some will be produced in the Program Project, and others will be obtained from other laboratories. The in vitro ligand binding, stability and toxicity will be related to protein structure in Project 1, and the effects on the microcirculation will be studied in Project 2, the heart in Project 3, the kidney in Project 4. Data obtained in these projects will be used in Project 1 for the design of new chemically modified or (by collaboration) mutant derivatives of hemoglobin using computer visualization techniques in Project 1. Each project will have advisors from the UCSD faculty. An executive committee made up of the principal investigators from each project and core that has met monthly for the last year will form the nucleus of a group and will continue to share data, results, and plans for future studies. Internal and external advisory groups of outstanding scientists will be appointed to provide expertise in related fields.