BLOOD SUBSTITUTES--MOLECULAR AND PHYSIOLOGICAL ASPECTS

这个项目的假设是， 通过结构工程适当修饰的血红蛋白将是安全的， 在许多临床情况下有效的治疗，其中红细胞 指出了项目的主要目标是了解 红替代的生理后果和临床潜力 用无细胞的血液替代品来维持血液循环。 在新解决方案的设计、生产和测试方面的专业知识， 在生物化学，生理学， 分子生物学和临床医学将在 该计划项目侧重于大规模的具体问题， 输注无细胞红细胞替代品，同时 利用新兴技术来阐明基本生理学 和生化问题。计划项目的要素反映了 UCSD教师的利益，而不是一个全面的方法， 血液替代品的发展。然而，专业知识广泛， 深入，几乎所有相关领域都将进行研究。核心A将 协调各组成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 正在开发的各类产品，供 各种项目，包括血红蛋白和全氟碳化合物 氧气携带;一些将在计划项目中生产，另一些将在计划项目中生产。 将从其他实验室获得。体外配体结合， 稳定性和毒性将与项目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， 心脏在项目3，肾脏在项目4.在这些数据中获得的 项目1将用于设计新的化学 血红蛋白的修饰或（通过合作）突变衍生物， 项目1中的计算机可视化技术。每个项目将有 UCSD教师的顾问。执行委员会由 每月举行会议的每个项目和核心的主要调查员 去年将形成一个集团的核心，并将继续 分享数据、结果和未来研究计划。内部和外部 将任命由杰出科学家组成的咨询小组， 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.