Question

哪位高手帮忙翻译一下

The risk for neoplasia in the xenotransplantation patient may not be as high as it was in the cited retroviral vector trials (3 of 10 monkeys and 2 of 10 children) where, to achieve transfection, a large number of recipient's target cells were co-cultured, in vitro, with cell-free viral vector and after their transfection were transfused back to the patient. In contrast, in xenotransplantation the endogenous retrovirus (e.g., PERV) is imbedded in the genome of the xenograft cells and will probably not be
released as a free virus in large quantities. Therefore, theoretically, over a given period of time, the probability for an endogenous retrovirus from the xenograft to infect human cells (and trigger an oncogenic event) is smaller than in retroviral gene therapy. Nevertheless, that risk exists and we have to mention that the observed frequency of leukemia-like conditions discussed above (2 of 10 children) exceeded te theoretical probability for oncogenesis as a result of a just random viral integration.
In summary, to date, infectivity studies of PERV have shown that: 1) Porcine cell lines and primary porcine cells (PBMCS and aortic endothelial cells) can release PERV; 2) low-level PERV replication has been detected in some pigs and pig tissues (76, 91); 3) PERV from porcine cell lines and from primary cells can infect human and other mammalian cell lines; 4) PERV from porcine cell lines can also non-productively infect primary human PBMCs; 5) PERV passaged through human cells is no longer susceptible to complement-mediated virolysis (the same would probably be true for PERV from genetically engineered animals whose cells lack a-gal or express human complement-regulatory proteins); and 6) PERV from primary porcine islet cells can infect SCID mice. To date, no infection with PERV has been documented in humans exposed to live porcine cells/ tissues. However, long-lasting porcine cell microchimerism has been found in some patients indicating that the possibility for PERV infection cannot be discounted. The potential for PERV transmission to human cells in a xenotransplantation setting was recently illustrated in a `reverse situation' ± human- to-pig xenotransplantation ± where human hemato- poetic stem cells were transplanted into pig fetuses. This resulted in spontaneous fusion between human and porcine cells. The hybrid cells contained PERV DNA and were able to transmit PERV to an uninfected human cell line in vitro (110)
To ensure that a possible new zoonosis does not spread among humans as a result of xenotransplanation, recipients and their contacts should be routinely screened for zoonotic infectious agents (60).

Answer 1

为在异种器官移植的病人肿瘤的风险可能不高，因为它在引用的逆转录病毒载体试验（3 10猴子和10名儿童2）其中，实现转染，是受援国的靶细胞大量共培养的在体外无细胞病毒载体转染后，被输回病人。相反，在异种器官移植的（例如，PERV）的内源性逆转录病毒是埋藏在基因组和细胞移植可能不会
在释放大量免费的病毒。因此，理论上，在一个给定的时间内，为内源性逆转录病毒在异种感染人体细胞的可能性（和致癌事件触发），比逆转录病毒基因治疗小。然而，这种风险的存在，我们要提及的是，上面讨论白血病般的条件观察到的频率（2 10名儿童）的发生超出作为一个融合的结果只是随机病毒碲理论概率。
总之，迄今为止，对PERV的感染性研究表明：1）猪细胞株和原（单核细胞和血管内皮细胞）猪细胞可释放PERV的; 2）低层次的PERV的复制已经在某些组织中检测猪和猪（76，91）; 3）从猪细胞株和原代细胞PERV的可以感染人类和其他哺乳动物的细胞株; 4）从猪细胞PERV的线也非主要感染人PBMC富有成效5）通过人体细胞PERV的传代不再容易受到补体介导virolysis（同可能能够从转基因动物的细胞缺乏的A -半乳糖苷酶或表达人补体调节蛋白PERV的真实）;和6）从小学猪胰岛细胞PERV的能够感染SCID小鼠。迄今为止，还没有与PERV的感染已被记录在暴露于猪活细胞/组织的人类。然而，持久的猪细胞微嵌合已经发现了一些表明为PERV的感染的可能性也不容忽视病人。为PERV传播的设置在一个异种器官移植的人类细胞的潜力，最近一个'说明了相反的情况下'±人对人类猪异种器官移植造血±其中，诗意的干细胞移植到猪胎儿。这导致了人与猪细胞自发融合。该杂交细胞中PERV的脱氧核糖核酸，并能够传输到未感染的PERV的体外细胞系（110）
为了确保新的人畜共患病可能不会在人与人之间传播作为一种xenotransplanation结果，受助人及其接触者应定期筛查人畜共患（60）传染源。

Answer 2

对于肿瘤的风险在器官移植患者不可能高达是在引用感染向量试验(三10猴子和2个10个孩子,达到转染),大量的接收者的靶细胞被干细胞培养体外,例如,腺病毒载体和之后都回转染术患者。相反,在器官移植的内源性病毒(如变态的人)是镶嵌在基因组中移植细胞的,也许不是
作为一个自由释放大量的病毒。因此,从理论上讲,在给定的时间内,概率为内生逆转录病毒的传染给人类的细胞移植和触发事件)小于突变的基因治疗的感染。然而,这种风险存在,我们不得不提到观测频率的讨论(2种类似白血病的条件下的10个孩子)超过了网球理论的概率为关系的只是随机病毒整合。
综上所述,到目前为止,传染性的研究已经表明,变态的人:(1)猪的细胞,细胞(PBMCS主要猪主动脉内皮细胞),释放变态的人;(2)在低级的变态的人已经在一些复制猪,猪的器官(76,91年);(3)从猪的细胞和变态的人从原始细胞能传染给人类和其它哺乳动物细胞线;4)变态的人从猪的细胞也可以non-productively感染主要人力PBMCS;5)变态的人passaged通过人体细胞是不受complement-mediated virolysis(可能是真正的变态的人从转基因动物的细胞或表达人类complement-regulatory a-gal缺乏蛋白质);6)变态的人从原始猪胰岛细胞能够感染SCID小鼠。到目前为止,没有感染和变态的人已经在猪细胞的人类暴露于生活。/然而,长期猪细胞的微嵌合状态已经发现在一些患者提示可能不会传染变态的人。潜在的变态的人传播给人类的细胞,在一个异种移植设置最近在“扭转局面的人——to-pig±hemato异种移植±人类干细胞移植,诗意,进入猪的胎儿。这导致了人类与自然之间的猪细胞融合。杂交细胞含有脱氧核糖核酸(DNA),并且能够变态的人,一个未受感染的传播行为反常的人对人类细胞系体外(110)。
确保湖北可能成为一种新的并不在人类之间传播的,和他们的联系xenotransplanation应照例检查动物感染(60岁)。