Creutzfeldt-Jakob disease

　　克雅氏病

　　Breaking down the barrier

　　攻破屏障

　　A glimmer of hope for a drug that treats diseasecaused by prions

　　藥物治療朊病毒感染疾病的一線希望

　　THE epidemic of mad-cow disease in people that some forecast in the 1990s has not,fortunately, come to pass. But Creutzfeldt-Jakob disease, to give its proper name, is still anasty illness that humanity would be better off without.

　　時至今日，瘋牛病沒有像上世紀90年代的某些預言說的那樣在人群中流行，真是幸運。這種嚴重損害人類性情的疾病的準確名稱叫克雅氏病，治療起來仍然棘手。

　　It is also a strange illness.

　　克雅氏病是一種奇怪的疾病。

　　CJD and a handful of similarneurological conditions are caused by the misfolding of a particular protein that is found inthe membranes of certain nerve cells.

　　該病以及類似的一些神經癥狀是由于某種神經細胞的細胞膜上的一個特殊蛋白發生錯誤折疊所致。

　　The strangeness is that the misfolded protein, known as a prion, somehow catalyses othermolecules of the protein to misfold in the same way.

　　這種錯誤折疊的蛋白稱為朊病毒，令人奇怪的是它可以催化其他蛋白分子發生相同的錯誤折疊，

　　The result is a chain reaction in which more and more protein ends up as prions.

　　這個鏈式反應使越來越多的蛋白質變成朊病毒。

　　Nerve cells containing the prions stop working.

　　含有朊病毒的神經細胞失去正常功能，

　　The sufferer endures memory loss, personality changes and spontaneous, jerky bodilymovements.

　　罹患者出現記憶減退、人格改變和自發的軀體急速抽動等癥狀，

　　Eventually, the disease kills him.

　　最后患者死亡。

　　A drug to treat CJD would therefore be welcome.

　　所以，能夠治療CJD的藥物將大受青睞。

　　And chemicals that seem either to prevent the misfolding, or to help the body clear awaymisfolded molecules, do, indeed, exist.

　　能阻止分子錯誤折疊或幫助機體清除錯誤折疊分子的化學藥品似乎確實存在，

　　The problem is turning at least one of those chemicals into an effective medicine.

　　困難在于如何用至少一種這樣的化學藥品進行有效治療。

　　Adam Renslo of the University of California, San Francisco, and his colleagues have beentrying to do so.

　　舊金山加利福尼亞大學的Adam Renslo與其同事一直在進行將化學藥品用于治療CJD的嘗試，

　　The chemicals they have lighted on are called aminothiazoles.

　　他們感興趣的化學藥品叫做氨噻唑，

　　These are quite effective in reducing the prion levels of cultured nerve cells.

　　它能有效降低體外培養的神經細胞內的朊病毒水平。

　　Testing aminothiazoles in Petri dishes is, however, rather different from testing them on livinganimals.

　　但是，檢驗發現氨噻唑在活動物體內的作用與在體外培養細胞中的作用大不相同。

　　A natural barrier exists between the bloodstream and the brain, to protect it from harmfulchemicals.

　　生理狀態下，血流與腦之間存在著一個屏障，使腦避免接觸有害物質，

　　This barrier interprets many putative drugs, including aminothiazoles, as harmful, and thuskeeps them out.

　　可能有效的許多藥物包括氨噻唑也被這個屏障當作有害物質阻擋在腦外。

　　And if a molecule cannot cross the barrier, it will not make an effective neurologicaltreatment.

　　不能通過屏障進入腦的分子當然就無法完成有效的神經治療。

　　Dr Renslo and his colleagues have therefore been analysing and modifying the chemicalstructure of aminothiazoles to see if this can enable them to cross the blood-brain barrier.

　　為此，Renslo博士與其同事已經在分析并嘗試修飾氨噻唑的分子結構，以使之能通過血腦屏障。

　　As they report in the Journal of Medicinal Chemistry, they think they have now pulled off thetrick.

　　根據他們在藥物化學雜志的報道，他們已經找到了突破口。

　　They did it by removing groups of atoms called hydrogen-bond donors from the originalmolecules and adding a ring of carbon and hydrogen atoms.

　　他們移除氨噻唑分子上一組提供氫鍵的原子，并加上一個碳氫環。修飾后的氨噻唑分子看起來更像膽固醇分子。

　　That made the aminothiazoles look more like cholesterolwhich despite its malign everydayreputation is an important component of brains and routinely crosses the blood-brainbarrier.

　　盡管膽固醇整天被認為是個對人體有害的物質，但它卻是腦的重要成分，是通過血腦屏障的?？汀?/p>

　　It worked.

　　成功了!

　　When Dr Renslo fed mice a diet containing the improved aminothiazoles, he found that themost promising of them accumulated in the brain in concentrations nearly 25 times higherthan those required to clear prions from cultured cells.

　　Renslo博士給小鼠喂食含有改進后的氨噻唑的飲食后，發現這些最有希望的分子在小鼠的腦內聚集，其濃度達到清除體外培養細胞內朊病毒所需濃度的25倍。

　　The molecular changes did not, though, seem to change the aminothiazoles prion-killingattributes.

　　氨噻唑分子的改變似乎并沒有改變其殺滅朊病毒的特性。

　　When tested in Petri dishes, the new molecules were as good as their precursors.

　　在培養皿實驗中，修飾后的分子與其前體一樣有效。

　　More importantly, preliminary results suggest they are effective at extending the lives ofprion-infected mice.

　　更重要的是，初步的實驗結果提示這些分子能有效延長朊病毒感染小鼠的壽命，

　　Such mice lived for 100 days longer when treated with the new molecules than they didwhen untreated.

　　用這些新分子治療的小鼠比不治療的小鼠多存活100天。

　　That is a significant fraction of the two to three years a healthy laboratory mouse might beexpected to survive if it is not experimented on.

　　考慮到實驗室中未受試的健康小鼠的預期壽命是2到3年，染毒小鼠獲得延長的這部分存活期顯得很顯著了。

　　Trials in mice are, of course, just the beginning. But breaching the blood-brain barrier in thisway is a crucial step, and one that might be generalised to potential treatments for otherbrain diseasesAlzheimer s, for example.

　　當然，用小鼠進行的試驗只是個開始。但藥物以這種方式突破血腦屏障確實是個關鍵步驟，在此基礎上，人們還可能找到治療阿爾茨海默爾病這樣的其他腦部疾病的良方。

　　If that came to pass, this small step on the journey of drug discovery might come to be seen,in retrospect, as a giant leap.

　　在達到那些目標之后，回過頭來看，實現藥物通過屏障的這一小步將被視為一個巨大的跨步。

　　詞語解釋

　　1.disease n.疾病

　　The disease is still in its primary stage.

　　這疾病仍然在初發階段。

　　2.forecast n.預測;預報

　　Share prices plunged as a result of the gloomyeconomic forecast.

　　關于經濟前景暗淡的預測導致股票價格大跌。

　　3.humanity n.人類;人性

　　Such a man is a stain to humanity.

　　這種人是人類的恥辱。

　　4.membrane n.薄膜;膜狀物

　　A plastic membrane serves as selective diffusion barrier.

　　一層塑料薄膜起著選擇性滲透屏障的作用。

　　5.protein n.蛋白質

　　You need more protein to build you up.

　　你需要增加蛋白質以增強體質。

　　Creutzfeldt-Jakob disease

　　克雅氏病

　　Breaking down the barrier

　　攻破屏障

　　A glimmer of hope for a drug that treats diseasecaused by prions

　　藥物治療朊病毒感染疾病的一線希望

　　THE epidemic of mad-cow disease in people that some forecast in the 1990s has not,fortunately, come to pass. But Creutzfeldt-Jakob disease, to give its proper name, is still anasty illness that humanity would be better off without.

　　時至今日，瘋牛病沒有像上世紀90年代的某些預言說的那樣在人群中流行，真是幸運。這種嚴重損害人類性情的疾病的準確名稱叫克雅氏病，治療起來仍然棘手。

　　It is also a strange illness.

　　克雅氏病是一種奇怪的疾病。

　　CJD and a handful of similarneurological conditions are caused by the misfolding of a particular protein that is found inthe membranes of certain nerve cells.

　　該病以及類似的一些神經癥狀是由于某種神經細胞的細胞膜上的一個特殊蛋白發生錯誤折疊所致。

　　The strangeness is that the misfolded protein, known as a prion, somehow catalyses othermolecules of the protein to misfold in the same way.

　　這種錯誤折疊的蛋白稱為朊病毒，令人奇怪的是它可以催化其他蛋白分子發生相同的錯誤折疊，

　　The result is a chain reaction in which more and more protein ends up as prions.

　　這個鏈式反應使越來越多的蛋白質變成朊病毒。

　　Nerve cells containing the prions stop working.

　　含有朊病毒的神經細胞失去正常功能，

　　The sufferer endures memory loss, personality changes and spontaneous, jerky bodilymovements.

　　罹患者出現記憶減退、人格改變和自發的軀體急速抽動等癥狀，

　　Eventually, the disease kills him.

　　最后患者死亡。

　　A drug to treat CJD would therefore be welcome.

　　所以，能夠治療CJD的藥物將大受青睞。

　　And chemicals that seem either to prevent the misfolding, or to help the body clear awaymisfolded molecules, do, indeed, exist.

　　能阻止分子錯誤折疊或幫助機體清除錯誤折疊分子的化學藥品似乎確實存在，

　　The problem is turning at least one of those chemicals into an effective medicine.

　　困難在于如何用至少一種這樣的化學藥品進行有效治療。

　　Adam Renslo of the University of California, San Francisco, and his colleagues have beentrying to do so.

　　舊金山加利福尼亞大學的Adam Renslo與其同事一直在進行將化學藥品用于治療CJD的嘗試，

　　The chemicals they have lighted on are called aminothiazoles.

　　他們感興趣的化學藥品叫做氨噻唑，

　　These are quite effective in reducing the prion levels of cultured nerve cells.

　　它能有效降低體外培養的神經細胞內的朊病毒水平。

　　Testing aminothiazoles in Petri dishes is, however, rather different from testing them on livinganimals.

　　但是，檢驗發現氨噻唑在活動物體內的作用與在體外培養細胞中的作用大不相同。

　　A natural barrier exists between the bloodstream and the brain, to protect it from harmfulchemicals.

　　生理狀態下，血流與腦之間存在著一個屏障，使腦避免接觸有害物質，

　　This barrier interprets many putative drugs, including aminothiazoles, as harmful, and thuskeeps them out.

　　可能有效的許多藥物包括氨噻唑也被這個屏障當作有害物質阻擋在腦外。

　　And if a molecule cannot cross the barrier, it will not make an effective neurologicaltreatment.

　　不能通過屏障進入腦的分子當然就無法完成有效的神經治療。

　　Dr Renslo and his colleagues have therefore been analysing and modifying the chemicalstructure of aminothiazoles to see if this can enable them to cross the blood-brain barrier.

　　為此，Renslo博士與其同事已經在分析并嘗試修飾氨噻唑的分子結構，以使之能通過血腦屏障。

　　As they report in the Journal of Medicinal Chemistry, they think they have now pulled off thetrick.

　　根據他們在藥物化學雜志的報道，他們已經找到了突破口。

　　They did it by removing groups of atoms called hydrogen-bond donors from the originalmolecules and adding a ring of carbon and hydrogen atoms.

　　他們移除氨噻唑分子上一組提供氫鍵的原子，并加上一個碳氫環。修飾后的氨噻唑分子看起來更像膽固醇分子。

　　That made the aminothiazoles look more like cholesterolwhich despite its malign everydayreputation is an important component of brains and routinely crosses the blood-brainbarrier.

　　盡管膽固醇整天被認為是個對人體有害的物質，但它卻是腦的重要成分，是通過血腦屏障的?？?。

　　It worked.

　　成功了!

　　When Dr Renslo fed mice a diet containing the improved aminothiazoles, he found that themost promising of them accumulated in the brain in concentrations nearly 25 times higherthan those required to clear prions from cultured cells.

　　Renslo博士給小鼠喂食含有改進后的氨噻唑的飲食后，發現這些最有希望的分子在小鼠的腦內聚集，其濃度達到清除體外培養細胞內朊病毒所需濃度的25倍。

　　The molecular changes did not, though, seem to change the aminothiazoles prion-killingattributes.

　　氨噻唑分子的改變似乎并沒有改變其殺滅朊病毒的特性。

　　When tested in Petri dishes, the new molecules were as good as their precursors.

　　在培養皿實驗中，修飾后的分子與其前體一樣有效。

　　More importantly, preliminary results suggest they are effective at extending the lives ofprion-infected mice.

　　更重要的是，初步的實驗結果提示這些分子能有效延長朊病毒感染小鼠的壽命，

　　Such mice lived for 100 days longer when treated with the new molecules than they didwhen untreated.

　　用這些新分子治療的小鼠比不治療的小鼠多存活100天。

　　That is a significant fraction of the two to three years a healthy laboratory mouse might beexpected to survive if it is not experimented on.

　　考慮到實驗室中未受試的健康小鼠的預期壽命是2到3年，染毒小鼠獲得延長的這部分存活期顯得很顯著了。

　　Trials in mice are, of course, just the beginning. But breaching the blood-brain barrier in thisway is a crucial step, and one that might be generalised to potential treatments for otherbrain diseasesAlzheimer s, for example.

　　當然，用小鼠進行的試驗只是個開始。但藥物以這種方式突破血腦屏障確實是個關鍵步驟，在此基礎上，人們還可能找到治療阿爾茨海默爾病這樣的其他腦部疾病的良方。

　　If that came to pass, this small step on the journey of drug discovery might come to be seen,in retrospect, as a giant leap.

　　在達到那些目標之后，回過頭來看，實現藥物通過屏障的這一小步將被視為一個巨大的跨步。

　　詞語解釋

　　1.disease n.疾病

　　The disease is still in its primary stage.

　　這疾病仍然在初發階段。

　　2.forecast n.預測;預報

　　Share prices plunged as a result of the gloomyeconomic forecast.

　　關于經濟前景暗淡的預測導致股票價格大跌。

　　3.humanity n.人類;人性

　　Such a man is a stain to humanity.

　　這種人是人類的恥辱。

　　4.membrane n.薄膜;膜狀物

　　A plastic membrane serves as selective diffusion barrier.

　　一層塑料薄膜起著選擇性滲透屏障的作用。

　　5.protein n.蛋白質

　　You need more protein to build you up.

　　你需要增加蛋白質以增強體質。