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PATHOGENESIS AND TREATMENT OF HIV-ASSOCIATED PSORIASIS

PATHOGENESIS AND TREATMENT OF HIV-ASSOCIATED PSORIASIS
HIV 相关银屑病的发病机制和治疗
批准号:
3160156
负责人:
MADELEINE DUVIC
金额:
$19.12万
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-04-18 至 1996-03-31

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中文摘要
翻译
牛皮癣和湿疹性丘疹,包括嗜酸性粒细胞 毛囊炎,可能是人类的第一个表现, 免疫缺陷病毒(HIV)感染,在这种情况下可能是严重的 而且很难治疗。在这两种疾病中, 通过原位杂交或聚合酶链反应在皮肤细胞中发现 (PCR),这表明艾滋病毒可以直接通过 影响表皮基因表达或间接通过细胞因子 在感染或未感染的细胞中的调节。 虽然艾滋病毒相关 银屑病可能对齐多夫定给药有暂时反应, 患有这两种疾病的患者通常需要紫外线治疗, 控制 然而,最近的数据涉及艾滋病毒的体外转染, 而HIV基因转基因小鼠表明HIV病毒被激活, 紫外线(UVL),所以给病人光照的安全性是 值得怀疑 另一方面,peptide加上UVA可能会使HIV在 体外,并且可以假设是有益的。这项建议会 解决艾滋病毒可能通过基因引发银屑病的假设 调节或通过细胞因子的产生, 增殖 将研究患者和对照组的活检, 通过原位定量检测env/pol/gag、达特或nef的HIV RNA转录物 杂交(ISH),并使用激光扫描共聚焦显微镜进行解释。 显微镜 PCR-DNA将用于定量皮肤病变中的HIV, 对组织特异性HIV病毒株进行测序 HIV+细胞因子表达和 将使用单克隆抗体和ISH评估HIV-单核细胞。 在 研究的第2部分,我们将测试UVL管理的假设, 激活HIV在皮肤或全身的表达。 皮肤活检 如前所述,将比较光之前和之后。 艾滋病病毒在 使用流式细胞术定量外周血细胞, 荧光原位杂交(FISH)和抗体染色。 血液 细胞群,p24抗原和皮肤免疫系统将被 随着时间的推移用UVL施用测量。 紫外线照射对艾滋病病毒感染的影响 体内皮肤对于HIV+患者的安全性至关重要, 皮肤病谁收到紫外线,以及为所有的一般健康 艾滋病毒感染者。
英文摘要
Psoriasis and pruritic papular eruptions, including eosinophilic folliculitis, may be among the first manifestations of human immunodeficiency virus (HIV) infection, and in this setting may be severe and difficult to treat. In both diseases, HIV transcripts have been found in skin cells by in situ hybridization or polymerase chain reaction (PCR), suggesting that HIV could cause these diseases by directly influencing epidermal gene expression or indirectly through cytokine modulation in infected or uninfected cells. Although HIV associated psoriasis may respond temporarily to zidovudine administration, many patients with both conditions often require ultraviolet light therapy for control. However, recent data involving transfections of HIV in vitro and mice transgenic for HIV genes suggest that the HIV virus is activated by ultraviolet light (UVL), so the safety of giving light to patients is questionable. On the other hand psoralen plus UVA may inactivate HIV in vitro, and could hypothetically be beneficial . This proposal will address the hypothesis that HIV virus may trigger psoriasis through gene regulation or through the production of cytokines which induce epidermal proliferation. Biopsies from patients and controls will be studied for HIV RNA transcripts of env/pol/gag, tat, or nef by quantitative in situ hybridization (ISH), and interpreted using the laser scanning confocal microscope. PCR-DNA will be used to quantitate HIV in skin lesions, and to sequence tissue specific HIV strains. Cytokine expression by HIV+ and HIV- monocytes will be assessed using monoclonal antibodies and ISH. In part 2 of the study we will test the hypothesis that UVL administration activates the expression of HIV in skin or systemically. Skin biopsies before and after light will be compared, as above. HIV in subsets of peripheral blood cells will be quantitated with flow cytometry using fluorescent in situ hybridization (FISH) and antibody staining. Blood cell populations, p24 antigen, and cutaneous immune system will be measured over time with UVL administration. The effect of UVL on HIV in skin in vivo is of utmost importance for the safety of HIV+ patients with skin disease who receive UVL, as well as for the general health of all HIV infected individuals.
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