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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:
2079772
负责人:
MADELEINE DUVIC
金额:
$17.51万
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
银屑病和瘙痒性丘疹,包括嗜酸性粒细胞 毛囊炎,可能是人类 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,艾滋病毒的转录产物 通过原位杂交或聚合酶链式反应在皮肤细胞中发现 (聚合酶链式反应),表明艾滋病毒可能通过直接 通过细胞因子或间接影响表皮基因表达 在感染或未感染细胞中的调制。尽管艾滋病毒与 银屑病可能对齐多夫定治疗有暂时反应,许多 患有这两种疾病的患者通常需要紫外线治疗 控制力。然而,最近关于体外感染艾滋病毒的数据 转基因HIV基因的小鼠表明HIV病毒被激活了 通过紫外线(UVL),因此给患者提供光线的安全性是 有问题。另一方面,补骨脂素联合UVA可以灭活HIV 在体外,假设可能是有益的。这项提议将 解决HIV病毒可能通过基因引发银屑病的假设 或通过产生细胞因子来调节或诱导表皮 扩散。患者和对照的活组织检查将被研究 原位定量检测env/pol/gag、Tat或nef的HIV RNA转录本 杂交(ISH),并使用激光扫描共聚焦进行解释 显微镜。将使用聚合酶链式反应-DNA对皮肤损伤中的艾滋病毒进行量化,以及 对组织特异性HIV毒株进行测序。HIV+和HIV+细胞因子的表达 将使用单抗和ISH对艾滋病毒单核细胞进行评估。在……里面 在研究的第二部分,我们将检验UVL给药的假设 激活HIV在皮肤或全身的表达。皮肤活检 如上所述,我们将对灯光前后进行比较。HIV在以下几个子集中 外周血细胞将用流式细胞仪进行定量,使用 荧光原位杂交(FISH)和抗体染色。血样 细胞群、p24抗原和皮肤免疫系统 使用UVL管理随时间测量。紫外线照射对人体免疫缺陷病毒的影响 活体皮肤对HIV+患者的安全至关重要 接受紫外线照射的皮肤病患者,以及所有人的一般健康 艾滋病病毒感染者。
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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