PATHOBIOLOGY OF BONE MARROW SUPPRESSION IN AIDS OR ARC

艾滋病或 ARC 骨髓抑制的病理学

基本信息

  • 批准号:
    3242931
  • 负责人:
  • 金额:
    $ 11.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1989
  • 资助国家:
    美国
  • 起止时间:
    1989-06-01 至 1991-11-30
  • 项目状态:
    已结题

项目摘要

The overall goals of the proposal are to characterize the hematopoietic defects associated with human immunodeficiency virus (HIV) infection in man. These defects have limited the ability to treat the acquired immunodeficiency syndrome (AIDS) with drugs such as azidothymidine (AZT). Specifically, we propose to determine the sensitivity to recombinant human hematopoietic growth factors of marrow progenitor cells obtained from normal subjects, patients who are HIV-antibody-positive but who do not yet have AIDS, and patients with AIDS or AIDS-related complex (ARC). As part of the study, we will establish adherent cell layers from marrow aspirates obtained from the various study groups and determine the ability of these layers to support hematopoiesis in vitro and to respond to inflammatory modulators such as interleukin-1 (IL-1) by the production of specific hematopoietic growth factors. In addition, using in situ hybridization techniques, we will determine if the stromal cells of the adherent marrow cells are infected by HIV. Similarly, we will determine whether hematopoietic progenitor cells are also productively infected by HIV. We will examine the effect of therapeutic drugs such as AZT and related compounds for their effect on hematopoietic progenitor cell growth in an attempt to explain the selectivity of the erythroid suppression exerted by AZT. We also will attempt to reverse the AZT effect through the addition of hematopoietic growth factors in vitro and by adding compounds such as orotic acid to culture to bypass the AZT-imposed cell defect. Finally, we will explore the mechanisms of interaction between AZT and acetominophen, a compound which enhances AZT toxicity. From such studies, we hope to understand the mechanisms underlying marrow suppression in AIDS and how AZT exacerbates marrow failure. Through such understanding may come strategies for reducing the frequency and severity of marrow failure in drug-treated patients.
该提案的总体目标是将造血 与人类免疫缺陷病毒(HIV)感染相关的缺陷 伙计 这些缺陷限制了治疗后天性 免疫缺陷综合征(艾滋病)的药物,如叠氮胸苷(AZT)。 具体而言,我们建议确定对重组人 骨髓祖细胞的造血生长因子, 正常受试者,HIV抗体阳性但尚未 患有艾滋病,以及患有艾滋病或艾滋病相关综合症(ARC)的患者。 一部分 在这项研究中,我们将从骨髓穿刺液中建立贴壁细胞层, 从不同的研究小组获得,并确定这些能力 层以支持体外造血并响应炎症反应, 调节剂,如白细胞介素-1(IL-1),通过产生特异性 造血生长因子 此外,使用原位杂交技术, 技术,我们将确定是否贴壁骨髓的基质细胞 细胞被HIV感染。 同样,我们将确定是否 造血祖细胞也被HIV有效感染。 我们 将检查治疗药物的效果,如AZT和相关的 化合物对造血祖细胞生长的作用, 试图解释红细胞抑制的选择性, AZT 我们还将尝试通过添加 造血生长因子在体外和通过添加化合物, 乳清酸培养绕过AZT强加的细胞缺陷。 最后我们 将探索AZT和对乙酰氨基酚之间相互作用的机制, 一种能增强AZT毒性的化合物 通过这些研究,我们希望 了解艾滋病骨髓抑制的潜在机制以及AZT 加剧骨髓衰竭 通过这种理解, 降低药物治疗患者骨髓衰竭的频率和严重程度 患者

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The biology of hematopoietic growth factors: studies in vitro under serum-deprived conditions.
造血生长因子的生物学:血清剥夺条件下的体外研究。
  • DOI:
  • 发表时间:
    1990
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Migliaccio,G;Migliaccio,AR;Adamson,JW
  • 通讯作者:
    Adamson,JW
GATA-1-independent regulation of the expression of the erythropoietin receptor (EPO-R) gene in a human EPO-dependent cell line, UT-7 EPO.
在人类 EPO 依赖性细胞系 UT-7 EPO 中,促红细胞生成素受体 (EPO-R) 基因表达的 GATA-1 独立调节。
  • DOI:
    10.1111/j.1749-6632.1994.tb55740.x
  • 发表时间:
    1994
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Migliaccio,AR;Jiang,Y;Migliaccio,G;Nicolis,S;Crotta,S;Ronchi,A;Ottolenghi,S;Adamson,JW
  • 通讯作者:
    Adamson,JW
Transcriptional and posttranscriptional regulation of the expression of the erythropoietin receptor gene in human erythropoietin-responsive cell lines.
  • DOI:
    10.1182/blood.v82.12.3760.3760
  • 发表时间:
    1993-12
  • 期刊:
  • 影响因子:
    20.3
  • 作者:
    A. Migliaccio;Y. Jiang;Giovanni Migliaccio;S. Nicolis;Stefania Crotta;A. Ronchi;S. Ottolenghi;John W. Adamson
  • 通讯作者:
    A. Migliaccio;Y. Jiang;Giovanni Migliaccio;S. Nicolis;Stefania Crotta;A. Ronchi;S. Ottolenghi;John W. Adamson
Comparative analysis of hematopoietic growth factors released by stromal cells from normal donors or transplanted patients.
  • DOI:
    10.1182/blood.v75.1.305.305
  • 发表时间:
    1990
  • 期刊:
  • 影响因子:
    20.3
  • 作者:
    A. Migliaccio;G. Migliaccio;G. Johnson;J. Adamson;B. Torok-Storb
  • 通讯作者:
    A. Migliaccio;G. Migliaccio;G. Johnson;J. Adamson;B. Torok-Storb
Expansion of human neonatal progenitor cells in vitro under serum-deprived conditions.
在血清剥夺条件下体外扩增人类新生儿祖细胞。
  • DOI:
  • 发表时间:
    1994
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Migliaccio,AR;Migliaccio,G;Adamson,JW
  • 通讯作者:
    Adamson,JW
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JOHN W ADAMSON其他文献

JOHN W ADAMSON的其他文献

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{{ truncateString('JOHN W ADAMSON', 18)}}的其他基金

SMALL INSTRUMENTATION GRANT
小型仪器补助金
  • 批准号:
    2231695
  • 财政年份:
    1994
  • 资助金额:
    $ 11.2万
  • 项目类别:
PROLIFERATION AND DIFFERENTIATION OF ISOLATED STEM CELLS
分离的干细胞的增殖和分化
  • 批准号:
    3365640
  • 财政年份:
    1991
  • 资助金额:
    $ 11.2万
  • 项目类别:
PROLIFERATION AND DIFFERENTIATION OF ISOLATED STEM CELLS
分离的干细胞的增殖和分化
  • 批准号:
    3365642
  • 财政年份:
    1991
  • 资助金额:
    $ 11.2万
  • 项目类别:
PROLIFERATION AND DIFFERENTIATION OF ISOLATED STEM CELLS
分离的干细胞的增殖和分化
  • 批准号:
    3365641
  • 财政年份:
    1991
  • 资助金额:
    $ 11.2万
  • 项目类别:
PROLIFERATION AND DIFFERENTIATION OF ISOLATED STEM CELLS
分离的干细胞的增殖和分化
  • 批准号:
    2223012
  • 财政年份:
    1991
  • 资助金额:
    $ 11.2万
  • 项目类别:
PATHOBIOLOGY OF BONE MARROW SUPPRESSION IN AIDS OR ARC
艾滋病或 ARC 骨髓抑制的病理学
  • 批准号:
    3242929
  • 财政年份:
    1989
  • 资助金额:
    $ 11.2万
  • 项目类别:
PATHOBIOLOGY OF BONE MARROW SUPPRESSION IN AIDS OR ARC
艾滋病或 ARC 骨髓抑制的病理学
  • 批准号:
    3242930
  • 财政年份:
    1989
  • 资助金额:
    $ 11.2万
  • 项目类别:
PATHOBIOLOGY OF BONE MARROW SUPPRESSION IN AIDS OR ARC
艾滋病或 ARC 骨髓抑制的病理学
  • 批准号:
    3242932
  • 财政年份:
    1989
  • 资助金额:
    $ 11.2万
  • 项目类别:
MARROW FAILURE: VIRUS-INDUCED DISEASE
骨髓衰竭:病毒引起的疾病
  • 批准号:
    3343026
  • 财政年份:
    1983
  • 资助金额:
    $ 11.2万
  • 项目类别:
GROWTH FACTORS IN NORMAL AND NEOPLASTIC HEMATOPOIESIS
正常和肿瘤造血中的生长因子
  • 批准号:
    3169705
  • 财政年份:
    1982
  • 资助金额:
    $ 11.2万
  • 项目类别:
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