BEHAVIORAL DISORDERS AND TNF CHANNELS IN AIDS

行为、认知和运动障碍是临床表现。 艾滋病痴呆综合征(ADC)。ADC很可能是中介的，至少在 部分，由细胞因子肿瘤坏死因子-α(TNF-α)和 淋巴毒素(LT)。肿瘤坏死因子和肿瘤坏死因子是由 巨噬细胞和淋巴细胞。肿瘤坏死因子和肿瘤坏死因子具有广泛的 激素和细胞毒作用，但肿瘤坏死因子和细胞毒的作用机制 这是未知的。我们实验室最近发现，肿瘤坏死因子和 它可以在平面类脂薄膜中形成离子渗透通道，我们有 提出经络的形成可能解释了一些生理效应 肿瘤细胞杀伤和肌肉去极化等肿瘤坏死因子 细胞。有几条证据表明肿瘤坏死因子与病理生理学有关 包括艾滋病患者体内肿瘤坏死因子水平升高的事实 患者中，肿瘤坏死因子可引起恶病质，肿瘤坏死因子可增加艾滋病毒复制，以及 肿瘤坏死因子可以杀死感染艾滋病毒的淋巴细胞。肿瘤坏死因子可以增加艾滋病毒的复制， 而肿瘤坏死因子可以杀死感染艾滋病毒的淋巴细胞。肿瘤坏死因子也在 艾滋病患者脑脊液及其去极化细胞和 脱髓鞘神经纤维可能与艾滋病痴呆综合征有关 (ADC)。这项研究的广泛目标是了解 并在这些途径中寻找艾滋病的病理生理学途径 修饰肿瘤坏死因子和肿瘤坏死因子在艾滋病中的破坏性作用。肿瘤坏死因子和肿瘤坏死因子 通道将使用电生理学技术在 脂质双层和全细胞(膜片钳)。

Behavioral, cognitive, and motor disorders are clinical manifestations of AIDs Dementia Complex (ADC). ADC is likely mediated, at least in part, by the cytokines tumor necrosis factor alpha (TNF-alpha) and lymphotoxin (LT). TNF and LT are pleiotropic cytokines secreted by macrophages and lymphocytes. TNF and LT possess a broad range of hormonal and cytotoxic actions, but the mechanism of action of TNF and LT is unknown. Our laboratory has made the recent discovery that TNF and LT can form ion-permeable channels in planar lipid membranes, and we have proposed that channel formation may explain some physiologic effects of TNF such as the killing of tumor cells and the depolarization of muscle cells. Several lines of evidence implicate TNF in the pathophysiology of AIDS including the facts that TNF levels are elevated in AIDS patients, TNF can cause cachexia, TNF can increase HIV replication, and TNF can kill HIV-infected lymphocytes. TNF can increase HIV replication, and TNF can kill HIV-infected lymphocytes. TNF has also been found in the CSF of AIDS patients and its ability to depolarize cells and demyelinate nerve fibers may contribute to the dementia complex of AIDS (ADC). The broad goal of this research is to understand the role of these channels in the pathophysiology of AIDS and to search for ways to modify the destructive actions of TNF and LT in AIDS. TNF and LT channels will be characterized using electrophysiologic techniques in lipid bilayer and whole cells (patch clamp).