Nucleic acid amplification testing of hepatitis B virus
Nucleic acid amplification testing of hepatitis B virus
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乙型肝炎病毒核酸扩增检测
DOI：
10.1016/s0140-6736(05)74655-9
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
K. Nishioka
中科院分区：
文献类型：
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作者：
K. Otake;K. Nishioka
SIR-Arif Khwaja和他的同事们(2月26日，第741页)1假设，预烯基化抑制剂可以用于治疗增殖性肾脏疾病。这些研究人员还讨论了普伐他汀在器官移植中减少急性和慢性排斥反应的能力，并认为这些作用“是由于抑制了RAS和Rho的戊烯基化，继而抑制了血管平滑肌的增殖，这是慢性排斥反应的基本组织学特征”。事实上，状态抑制血管平滑肌增殖的能力(在高浓度时)可能有助于其预防慢性排斥反应的特性。此外，他汀类药物和其他预烯基化抑制剂可能通过抑制T细胞的激活和功能来抑制急性和慢性排斥反应。我们已经证明普伐他汀在体外可以抑制T细胞的增殖，这种作用可以通过添加焦磷酸法仑磺酰而不是胆固醇来消除。2这一发现证实了我们的假设，即预烯基化抑制剂通过干扰蛋白质异丙二烯基化来抑制T细胞的激活和功能。我们还表明，紫苏醇，一种自然产生的苯丙基化抑制剂，在大鼠心脏移植模型中抑制急性排斥反应、Th1细胞因子的表达和同种异体抗体的产生。3紫苏醇也干扰T细胞的激活、运动和正常的极性。4紫苏醇优先诱导活化的T细胞凋亡。我们的发现，以及Ras GTP酶在T细胞激活和功能中的作用，证实了我们的假设，即异丙二烯基化抑制剂(RAS抑制剂)是有效的抗排斥药物。
Sir—Arif Khwaja and colleagues (Feb 26, p 741) 1 postulate that prenylation inhibitors could be used to treat proliferative renal diseases. These investigators also discuss pravastatin’s ability to decrease acute and chronic rejection in organ transplantation and suggest that these effects “are due to inhibition of Ras and Rho prenylation with subsequent inhibition of the proliferation of vascular smooth muscle, which is an essential histological feature of chronic rejection”. Indeed, the ability of status to inhibit vascular smooth muscle proliferation (at high concentrations) may contribute to its chronic-rejection prevention properties. Also, statins and other prenylation inhibitors may inhibit acute and chronic rejection by suppressing T-cell activation and function.We have shown that pravastatin inhibits T-cell proliferation in vitro and that this effect is abrogated by addition of farensyl pyrophosphate but not cholesterol. 2 This finding confirms our hypothesis that prenylation inhibitors suppress T-cell activation and function by interfering with protein isoprenylation. We have also shown that perillyl alcohol, a naturally occurring prenylation inhibitor, inhibits acute rejection, Th1 cytokine expression, and alloantibody production in a rat cardiac transplant model. 3 Perillyl alcohol also interfered with T-cell activation, motility, and normal polarity. 4 Furthermore, we showed that perillyl alcohol preferentially induced apoptosis in activated T cells. Our findings, along with the well-documented roles of Ras GTPases in T-cell activation and function confirm our hypothesis that isoprenylation inhibitors (the Ras inhibitors), are effective antirejection agents.