Core--cell, tissue and animal facility

核心——细胞、组织和动物设施

• 批准号: 6659341
• 负责人: Howard E Gendelman
• 金额: $ 26.66万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6659341
• 关键词: AIDS dementia complex; animal colony; biomedical facility; clinical research; human immunodeficiency virus 1; human tissue; laboratory mouse; tissue /cell culture; tissue resource /registry

DESCRIPTION: (Provided by applicant): The purpose of this core is to assist in the design of adjunctive therapeutic strategies for treatment and/or prevention of neurologic disease following human immunodeficiency virus type-one (HIV-1) infection. In this regard, purified human monocyte-derived macrophages (MDM) and MDM conditioned media (MCM) will be supplied, following HIV-1 infection and/or immune activation, to all investigators on request, within the Rochester Cooperative NeuroAIDS Drug Discovery Group (RCNDDG). In addition, promising anti-inflammatory and/or neuroprotective drugs, developed in laboratory assays or proposed, will be tested for therapeutic efficacy in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). Brain tissue and/or sera will be made available for measuring drug levels and pathology in the HIVE mice. Such works will support translational (bench to bedside) research efforts and directly effect the performance of subsequent clinical trials. The works, in toto, are based on the concept that HIV-1 associated dementia (HAD) is, in part, a reversible metabolic encephalopathy caused by defective immunity of virus-infected mononuclear phagocytes [(MP), microglia, perivascular and parenchymal macrophages]. These MPs serve both as reservoirs for productive HIV-1 infection and principal sources of neurotoxic activities within the central nervous system (CNS). The development of ways to inhibit toxic inflammatory activities in brain may serve to both ameliorate and prevent complications of persistent viral replication in brain serving as critical adjunctive therapies to ongoing potent anti-retroviral regimens, the principal goals of the RCNDDG.

描述：（由申请人提供）：该核心的目的是协助 治疗和/或辅助治疗策略的设计 预防人类免疫缺陷病毒引起的神经系统疾病 一型 (HIV-1) 感染。在这方面，纯化的人单核细胞来源 将提供巨噬细胞 (MDM) 和 MDM 条件培养基 (MCM)，如下 HIV-1 感染和/或免疫激活，根据要求向所有研究人员提供， 隶属于罗彻斯特神经艾滋病药物研发合作小组 (RCNDDG)。在 此外，还开发了有前途的抗炎和/或神经保护药物 在实验室测定或提议中，将测试治疗效果 HIV-1脑炎的严重联合免疫缺陷（SCID）小鼠模型 （蜂巢）。脑组织和/或血清将可用于测量药物 HIVE小鼠的水平和病理学。此类作品将支持翻译 （从工作台到临床）研究工作的努力并直接影响绩效 随后的临床试验。这些作品总体上基于以下概念： HIV-1 相关痴呆 (HAD) 部分是一种可逆代谢性疾病 病毒感染的单核细胞免疫缺陷引起的脑病 吞噬细胞[(MP)、小胶质细胞、血管周围和实质巨噬细胞]。这些 国会议员既是生产性 HIV-1 感染的储存库，又是主要的 中枢神经系统（CNS）内神经毒性活动的来源。这 开发抑制大脑毒性炎症活动的方法可能 有助于改善和预防持续性病毒的并发症 大脑中的复制作为持续治疗的关键辅助疗法 有效的抗逆转录病毒治疗方案是 RCNDDG 的主要目标。