CHROMOSOME MUTATION IN THE PATHOGENESIS OF AIDS

艾滋病发病过程中的染色体突变

• 批准号: 3548402
• 负责人: JAMES L GERMAN
• 金额: $ 7.46万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-03-01 至 1987-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3548402
• 关键词: AIDS; B lymphocyte; Kaposi's sarcoma; T lymphocyte; bone marrow; cancer risk; centromere; chromosome aberrations; chromosome deletion; chromosome disorders; chromosome translocation; clone cells; cytogenetics; genetic markers; homosexuals; human tissue; immunosuppression; karyotype; lymph nodes; male; microscopy; molecular pathology

Not only is acquired immunodeficiency syndrome / Kaposi's sarcoma (AIDS/KS) a newly recognized clinical entity, but the persons affected constitute the most recently recognized cancer-prone population. Cytogenetic studies of cancer-prone populations almost always have been illuminating, and such a study is proposed here in the case of the AIDS/KS population. Our decision to undertake this study is consonant with our long-term study of another cancer-prone population, namely, those persons genetically determined to develop cancer who have one of the "chromosome-breakage syndromes." Our interest in the study was engendered especially because of one feature that is prominent in both AIDS/KS and two of the genetic syndromes, ataxia-telangiectasia (AT) and Bloom's syndrome--severe immune deficiency. During the initial phase of the investigation, analyses of cells from persons in the AIDS/KS population will be made using conventional cytogenetic techniques in daily use in our laboratory. To determine whether affected persons present evidence that excessive damage to the genetic material of their somatic cells has occurred, or is occurring, the frequency in their cells of chromatid breaks, gaps, and rearrangements and of sister-chromatid exchanges will be compared with that in persons with AT, BS, and related disorders (these data are in our files already) and that in controls, including a healthy male homosexual population. To determine whether affected persons harbor clones of lymphocytes with mutated chromosome complements in their circulation or lymph nodes, G-banded prometaphase chromosome preparations will be examined for stable chromosome rearrangements. (Such clones are found readily in AT, the condition which in many respects the AIDS patients resemble, and also in a proportion of persons exposed to ionizing radiation and carcinogenic chemicals.) Clones detected will be followed serially, e.g., every two-tree months, to determine their evolution, possibly including evolution into a clone that would be clinically recognizable as cancer. (A strategy using frozen lymphocyte samples from all bona fide patients will be employed that will permit such long-term studies to be made retrospectively in the minority that actually will develop cancer; also cytogenetic analysis will be made of cultured cells, including spontaneously-developing lymphoblastoid cell lines.

获得性免疫缺陷综合征/卡波西肉瘤（AIDS/KS） 新认可的临床实体，但受影响的人构成 最新发现的癌症易感人群。 的细胞遗传学研究 癌症易感人群几乎总是具有启发性的，这样一个 在艾滋病/KS人群的情况下，这里提出了一项研究。 我们的决定 进行这项研究与我们对另一项研究的长期研究是一致的。 癌症易感人群，即那些基因决定 患有"染色体断裂综合征"的人患上癌症。"我们的 人们对这项研究产生了兴趣，特别是因为有一个特点， 在AIDS/KS和两种遗传综合征中都很突出， 共济失调-毛细血管扩张症（AT）和布鲁姆综合征-严重的免疫缺陷。 在研究的初始阶段，对来自 艾滋病/KS人群中的人将使用常规的 我们实验室日常使用的细胞遗传学技术。 以确定 受影响的人是否提出证据，证明过度损害 他们的体细胞的遗传物质已经发生，或正在发生， 染色单体断裂、间隙和重排的频率， 姐妹染色单体交换的比例将与 AT、BS和相关疾病（这些数据已经在我们的文件中）， 包括健康的男性同性恋人群。 到 确定受影响的人是否携带淋巴细胞克隆， 突变的染色体补充在他们的循环或淋巴结， 将检查G显带前中期染色体制备物的稳定性 染色体重排 (Such在AT中容易发现克隆， 在许多方面与艾滋病患者相似的情况， 受电离辐射和致癌物质照射的人口比例 化学品）。 将连续跟踪检测到的克隆，例如，每 两个月的时间，以确定它们的进化，可能包括进化 克隆成一个临床上可以识别的癌症。 （战略 使用来自所有真正患者的冷冻淋巴细胞样本， 这将允许这种长期的研究进行回顾性研究 少数人会患上癌症;细胞遗传学 将对培养的细胞进行分析，包括自发发育的 淋巴母细胞样细胞系。