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IMMUNOPHARMACOGENETICS OF SCHIZOPHRENIA

IMMUNOPHARMACOGENETICS OF SCHIZOPHRENIA
精神分裂症的免疫药物遗传学
批准号:
3386843
负责人:
EDMOND J YUNIS
金额:
$30.66万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-09-30 至 1995-08-31

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中文摘要
翻译
我们的假设是,MHC标记反映的遗传基础 作为药理学反应的基础(在抗精神病药的情况下, 经典的精神抑制药物和血液学的情况下,氯氮平), 精神分裂症患者 我们的申请提出了一项双臂研究, 精神分裂症免疫遗传机制和药物反应 具体来说,我们将研究MHC标记物之间的关联, 特别是,HLA-A1和精神病患者的抗精神病治疗反应 精神分裂症,因为发现HLA-A1抗原的频率降低 精神分裂症患者中,这些患者对抗精神病药物治疗无效。 中 在以前的研究中,我们报道了HLA-A1的增加和HLA-A2的减少 对精神抑制剂治疗有反应的患者。 在其他实验中,我们 将确定治疗和超治疗精神抑制剂剂量, 来自HLA-A1阳性与阴性患者的淋巴细胞来测试 使用“体外”T细胞活化的神经抑制剂的优先效应 模型 该提案的第二个分支是基于一个协会, 在HLA B38 DR 4 DQw 3单倍型(DRB 1 *0402和DQB 1 *0302)之间发现 等位基因)和易患氯氮平诱导的粒细胞缺乏症 治疗难治性犹太病人的研究 此外,在非犹太人 粒细胞缺乏症患者,HLA-DR 2,DQw 1抗原增加, found.我们将证实MHC易感性单倍型(B38,DR 4, DQw 3)使犹太患者在以下情况下容易发生粒细胞缺乏症 氯氮平治疗。 此外,我们将通过以下方式确定特定的等位基因: 采用PCR-RFLP和PCR-SSO方法检测了参与细胞凋亡的DR 4、Dqw 3和DR 2、Dqw 1基因, 氯氮平诱导的粒细胞缺乏症易感性,以提供一个更 可靠的筛选试验,用于抗精神病药耐药个体, 氯氮平治疗,以尽量减少这种并发症的风险。 很可能是一个常见的MHC II类等位基因负责 粒细胞缺乏症的易感性。 但 第二个基因的可能性,尚未被发现, 与MHC等位基因不平衡,导致粒细胞缺乏症 此时无法消除易感性。
英文摘要
It is our hypothesis that a genetic basis reflected by MHC markers underlies pharmacologic response (both antipsychotic in the case of classical neuroleptic drugs and hematologic in the case of Clozapine) in patients with schizophrenia. Our application proposes a two arm study of immunogenetic mechanisms and pharmacologic response in schizophrenia. Specifically, we will examine the association between MHC markers, in particular, HLA-A1 and neuroleptic treatment response in patients with schizophrenia, since a decrease frequency of the HLA-A1 antigen was found in schizophrenics who were refractory to neuroleptic treatment. In a previous study, we reported an increase in HLA-A1 and a decrease in HLA-A2 in patients responsive to neuroleptic treatment. In other experiments, we will determine the therapeutic and supratherapeutic neuroleptic doses using lymphocytes from HLA-A1 positive versus negative patients to test the preferential effect of neuroleptics using an "in vitro" T cell activation model. The second arm of the proposal is based on an association that was found between the HLA B38 DR4 DQw3 haplotype (DRB1*0402 and DQB1*0302 alleles) and vulnerability to develop Clozapine-induced agranulocytosis among treatment refractory Jewish patients. In addition, among non-Jewish agranulocytosis patients, an increase in HLA-DR2 , DQw1 antigens has been found. We will confirm that the MHC susceptibility haplotype (B38, DR4, DQw3) predisposes Jewish patients to develop agranulocytosis following Clozapine treatment. Also, we will determine the specific alleles by PCR-RFLP and PCR-SSO methods for DR4, Dqw3 and DR2, Dqw1 involved in Clozapine-induced agranulocytosis susceptibility in order to provide a more reliable screening test for neuroleptic resistant individuals undergoing Clozapine treatment in order to minimize the risk of such complication. It is likely that a common MHC class II allele is responsible for agranulocytosis susceptibility between these two groups. However, the possibility of a second gene, yet to be discovered, and in linkage disequilibrium with MHC alleles and responsible for agranulocytosis susceptibility can not be eliminated at this moment.
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HLA CLASS I ON NK CELL SUBSETS, REPERTOIRE AND FUNCTION
  • 批准号:
    6829681
  • 项目类别:
  • 资助金额:
    $36.36万
  • 财政年份:
    2003
  • 负责人:
    EDMOND J YUNIS
  • 依托单位:
STUDIES OF NK AND T CELLS IN RELATION TO THE MAJOR HISTOCOMPATIBILITY COMPLEX
  • 批准号:
    6109676
  • 项目类别:
  • 资助金额:
    $44.31万
  • 财政年份:
    1999
  • 负责人:
    EDMOND J YUNIS
  • 依托单位:
STUDIES OF NK AND T CELLS IN RELATION TO THE MAJOR HISTOCOMPATIBILITY COMPLEX
  • 批准号:
    6272668
  • 项目类别:
  • 资助金额:
    $42.95万
  • 财政年份:
    1998
  • 负责人:
    EDMOND J YUNIS
  • 依托单位:
STUDIES OF NK AND T CELLS IN RELATION TO THE MAJOR HISTOCOMPATIBILITY COMPLEX
  • 批准号:
    6241774
  • 项目类别:
  • 资助金额:
    $41.64万
  • 财政年份:
    1997
  • 负责人:
    EDMOND J YUNIS
  • 依托单位:
海外基金