BSE - mad cow - scrapie, etc.: Stimulated amyloid degeneration and the toxic fats

by Raymond Peat

BSE -疯牛病-痒病等:刺激淀粉样变性和有毒脂肪

I have written before about the protective effects of carbon dioxide and progesterone, especially for the brain, and how the structure of cell water is affected by adsorbed and dissolved materials, and by metabolic energy. In the high energy (rested) state, cell water behaves as if it were colder than its real temperature, and this affects the behavior of proteins and fats in the cell, allowing “oily” surfaces to remain in contact with the more orderly water. Carbon dioxide spontaneously combines with the amino groups in proteins, stabilizing the normal functional conformation. The loss of carbon dioxide affects the structure of all proteins in the body, and the loss of cellular energy affects the structure of the intracellular proteins and their associated molecules.

我以前写过二氧化碳和黄体酮的保护作用，特别是对大脑的保护作用，以及细胞水的结构是如何被吸附和溶解的物质以及代谢能量所影响的。在高能量(休息)状态下，细胞内的水表现得好像比它的实际温度更低，这影响了细胞内蛋白质和脂肪的行为，使“油性”表面与更有序的水保持接触。二氧化碳自发地与蛋白质中的氨基结合，稳定了正常的功能构象。二氧化碳的损失会影响体内所有蛋白质的结构，而细胞能量的损失则会影响细胞内蛋白质及其相关分子的结构。

In scrapie and many other degenerative diseases (the amyloidoses), proteins condense into fibrils that tend to keep enlarging, with a variety of very harmful effects. The condensation of the “amyloid” proteins is sensitive to temperature, and a slight increase in the disorder of the water can induce functional proteins to change their conformation so that they spontaneously associate into fibrous masses. In the absence of sufficient carbon dioxide, all proteins are susceptible to structural alteration by the addition of sugars and fats and aldehydes, especially under conditions that favor lipid peroxidation.

在痒病和许多其他退行性疾病(淀粉样变)中，蛋白质凝结成纤维，纤维往往不断增大，产生各种非常有害的影响。淀粉样蛋白的缩合对温度很敏感，水的无序程度稍有增加，功能蛋白就会改变其构象，从而自发地结合成纤维团。在缺乏足够的二氧化碳的情况下，所有的蛋白质都易受糖、脂肪和醛的添加的结构变化的影响，特别是在有利于脂质过氧化的条件下。

The amyloidoses affect different tissues in different ways, but when they occur in the brain, they produce progressive loss of function, with the type of protein forming the fibrils determining the nature of the functional loss. The protein which carries thyroid hormone and vitamin A, transthyretin, can produce nerve and brain amyloid disease, but it can also protect against other amyloid brain diseases; in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and the “prion diseases” (scrapie, kuru, CJD, BSE, etc.) amyloid particles are formed by different proteins. The transthyretin protein which is binding small molecules resists condensation into the amyloid fibrils, but without its normal vitamin A and thyroid hormone, it can create toxic fibrils. (Raghu, et al., 2002.)

淀粉样变以不同的方式影响不同的组织，但当它们在大脑中发生时，它们会导致功能的渐进性丧失，而形成原纤维的蛋白质类型决定了功能丧失的性质。含有甲状腺激素和维生素A的蛋白质，能产生神经和脑淀粉样疾病，还能预防其他淀粉样脑疾病;在阿尔茨海默病、帕金森病、亨廷顿病以及“朊病毒病”(痒病、库鲁病、CJD、疯牛病等)中，淀粉样颗粒是由不同的蛋白质形成的。与小分子结合的转甲状腺蛋白能抵抗淀粉样原纤维的凝结，但如果没有正常的维生素A和甲状腺激素，它就会产生有毒的原纤维。(Raghu等人，2002年)。

Around 1970 I read E. J. Field’s suggestion that aging tissues and tissues affected by viral diseases showed some similar structures (“inclusion bodies”) under the electron microscope. In following up those observations, it turned out that old tissues appeared to develop antigens “identical with, or similar to,” scrapie-infected young tissues. The premature aging caused by removal of the thymus gland in newborn animals produced similar results.

大约在1970年，我读到E. J. Field的建议，即老化的组织和受病毒疾病影响的组织在电子显微镜下显示出一些相似的结构(“包涵体”)。在后续观察中，发现旧的组织似乎产生了“与痒病感染的年轻组织相同或相似”的抗原。在新生动物中，由于切除胸腺而导致的过早衰老也产生了类似的结果。

Field’s group and others (e.g., Alpers) were clearly showing that the scrapie infection involved proteins, but not viruses with nucleic acids. In one of Field’s last publications (1978), he even suggested that the infectious process might depend on a structural rearrangement of the host’s molecules, similar to the idea which is now known as the “prion hypothesis.” Field’s suggestion was an important advance in the theory of aging, and the evidence supporting it is now voluminous, but that work has been omitted from the official histories.

菲尔德小组和其他研究人员(如Alpers)清楚地表明，痒病感染涉及蛋白质，而不是含有核酸的病毒。在菲尔德最后发表的一篇论文(1978年)中，他甚至提出，感染过程可能取决于宿主分子的结构重排，类似于现在被称为“朊病毒假说”的观点。菲尔德的建议是衰老理论的一个重要进展，支持它的证据现在是大量的，但这项工作已经从官方历史中被省略了。

Although phenomena of “imprinting” and non-genetic inheritance had been established earlier, the dogmatism of genetics led the scientific establishment to reject everything that challenged the primacy of DNA. When I mentioned to my professors (in 1971) the evidence that scrapie was transmitted without nucleic acid, I could see from their reactions that it would be a very long time before much progress would be made in understanding the degenerative brain diseases. When the exact structure of the “infectious” protein was later worked out, and the 1997 Nobel Prize awarded (to Stanley Prusiner), I was surprised that no one from Field’s group was included. (In 1976, a nobel prize had been awarded to D.C. Gajdusek, for his promotion of the idea of “slow viruses” in general, and particularly for arguing that scrapie, CJD and kuru were caused by slow viruses.)

虽然“印记”现象和非基因遗传已经建立得更早，遗传学的教条主义导致科学机构拒绝一切挑战DNA的首要地位。当我在1971年向我的教授们提到痒病在没有核酸的情况下传播的证据时，我可以从他们的反应中看出，在了解退行性脑疾病方面要取得很大进展还需要很长一段时间。后来，当“传染性”蛋白质的确切结构被确定下来，1997年诺贝尔奖(授予斯坦利·普鲁西纳)时，我很惊讶，菲尔德的研究小组没有一个人被包括在内。(1976年，华盛顿特区·加达塞克(D.C. Gajdusek)获得了诺贝尔奖，因为他推广了“慢病毒”的概念，特别是他认为痒病、克雅氏病和库鲁病是由慢病毒引起的。)

In reading Prusiner’s autobiographical statements, I was even more surprised to see that he claimed to have been puzzled to find out, around 1983, that the infectious agent was a protein. I had thought that my professors were lethargic authoritarians when they refused to look at the evidence in 1970-72, but Prusiner’s expression of puzzlement so many years later over the absence of nucleic acid in the infectious agent is hard to account for.

在阅读普鲁西纳的自传时，我更惊讶地发现，他声称自己在1983年左右曾困惑地发现，感染源是一种蛋白质。1970年至1972年，当我的教授们拒绝查看证据时，我曾认为他们是无精打采的威权主义者，但这么多年后，普鲁西纳对传染性病原体中缺乏核酸的困惑表现出来，这很难解释。

In my own research in 1971, I was interested in another kind of age-related “inclusion body,”which was variously called lipofuscin, age pigment, and ceroid pigment. This brown (yellow autofluorescent) pigment contained proteins and metals, as well as polyunsaturated lipids, and overlapped in many ways with the amyloid bodies. All of these inclusion bodies were known to be associated with radiation injury, aging, and hormonal-nutritional imbalances. Excess of estrogen, polyunsaturated fatty acids, and oxidative metals were major factors in the development of lipofuscin, and estrogen was also known to cause other types of “inclusion bodies” to develop in cells.

在我1971年的研究中，我对另一种与年龄有关的“包涵体”感兴趣，它被称为脂褐素、年龄色素和蜡样色素。这种棕色(黄色自动荧光)色素含有蛋白质和金属，以及多不饱和脂质，并在许多方面与淀粉体重叠。所有这些包涵体都与辐射损伤、衰老和激素营养失衡有关。过量的雌激素、多不饱和脂肪酸和氧化金属是脂褐素发育的主要因素，雌激素也被认为会导致细胞中其他类型的“包藏体”的发育。

Although very little was known about the composition of the inclusion bodies (they were usually thought to be organelles damaged by free radical activity, or antibodies resulting from autoimmunity), their involvement in aging and degenerative disease was clear, and it was widely known that ionizing radiation accelerated their formation. But it was just at this time that the national research priorities of the U.S. were redirected toward genetic explanations for all major diseases, with for example the “war on cancer” centering on the concepts of the “oncogene” and the cancer virus. Since the “slow virus” of cancer, or the viral oncogene, requires activation by something in the environment, its function is to distract the public’s attention from those environmental causes of disease, viz., radiation and chemical pollution.

尽管对包涵体的组成知之甚少(它们通常被认为是被自由基活动或自身免疫产生的抗体破坏的细胞器)，但它们与衰老和退行性疾病的关系是清楚的，而且人们普遍知道电离辐射加速了它们的形成。但正是在这个时候，美国国家研究的重点转向了所有重大疾病的基因解释，例如“与癌症的战争”围绕着“致癌基因”和癌症病毒的概念。由于癌症的“慢病毒”或病毒致癌基因需要环境中的某些物质的激活，它的功能是转移公众对那些导致疾病的环境因素的注意力，即辐射和化学污染。

The U.S. Public Health Service has historically been one of the branches of the military, and currently has 6000 commissioned officers. It has been intimately involved in all aspects of chemical, biological, and nuclear warfare, and it has participated in many covert projects, including experimentation on people without their knowledge. For decades, information on radiation injury to the public was hidden, classified, altered, or destroyed by the PHS. During the radiation disaster at Three Mile Island, they calmly defended the interests of the nuclear industry.

美国公共卫生服务历来是军队的一个分支，目前有6000名委任军官。它密切参与了化学、生物和核战争的各个方面，并参与了许多秘密项目，包括在人们不知情的情况下进行实验。几十年来，公众对辐射伤害的信息被隐藏、分类、修改或销毁。在三里岛核辐射灾难期间，他们冷静地捍卫了核工业的利益。

After the April, 1986 catastrophe at the reactor in Chernobyl, some of the food being imported into the U.S. was so highly radioactive that the FDA secretly seized it, to prevent the public from being concerned. The first cow found to have BSE in England was in November, 1986, several months after England’s pastures had been heavily contaminated by rainfall carrying radioactive material from Chernobyl, which soaked into the soil and continued to contaminate crops for years (and will continue, for centuries). The number of sick cows increased rapidly to a peak in 1992. Human deaths from the similar disease (“variant CJD”) began a few years later.

1986年4月切尔诺贝利核反应堆发生灾难后，一些进口到美国的食品具有极高的放射性，美国食品和药物管理局(FDA)秘密没收了这些食品，以防止公众担心。1986年11月，在英格兰发现的第一头牛感染了疯牛病，几个月前，英格兰的牧场受到了严重污染，雨水携带了来自切尔诺贝利的放射性物质，渗入土壤，持续污染农作物多年(并将持续几个世纪)。病牛的数量在1992年迅速增加到一个高峰。人类死于类似疾病(“变异型克雅氏病”)是在几年后开始的。

In June, 2000, a wildfire burned across southern Washington, turning the radioactive vegetation on the Hanford Nuclear Site into radioactive smoke, contaminating a wide area, including farms, dairies, and orchards. In 2003, the first cow in the U.S. with BSE was reported, from a dairy a few miles from the Hanford Site.

2000年6月，一场野火烧毁了华盛顿南部，汉福德核电站的放射性植被变成了放射性烟雾，污染了包括农场、奶牛场和果园在内的大片地区。2003年，美国报道了第一头患有疯牛病的奶牛，它来自汉福德基地几英里外的一个奶牛场。

Beginning in 1946, Bikini Island was used to test atomic bombs. In 1954, they began to test hydrogen bombs in the Pacific; some of the bombs were deliberately designed to vaporize whole islands, so that the effects of radioactive fallout could be studied. In 1954, the first child with kuru was reported in the rainy highlands of New Guinea.

从1946年开始，比基尼岛被用来试验原子弹。1954年，他们开始在太平洋试验氢弹;有些炸弹被故意设计成蒸发整个岛屿，以便研究放射性沉降物的影响。1954年，新几内亚多雨的高地报道了第一个患有库鲁病的儿童。

Within two years, hundreds of people in that area (of the Fore tribe) were dying from kuru, with the mortality highest among the women; in some villages, the majority of the women died from the disease, but by 1957 the mortality was falling rapidly. Between 1957 and 1964, 5% of the population of the Fore tribe died of the disease, according to D.C. Gajdusek, who had been sent by the U.S. Army to investigate the disease. Although Gajdusek graduated in 1946 from Harvard medical school as a pediatrician, in his autobiography he said that when he was drafted in 1951, the army assigned him to work in virology. In 1958, Gajdusek became director of the NIH laboratories for neurological and virological research. This was a remarkable achievement for someone who had supposedly only done some scattered field-work in infectious diseases, and whose purpose in going to New Guinea had been to study child growth and development in primitive cultures. The only published reason I have found that might be a basis for making him head of neurology, was his sending a diseased Fore brain to Fort Detrick in 1957.

两年内，该地区(Fore部落)有数百人死于库鲁病，其中妇女死亡率最高;在一些村庄，大多数妇女死于这种疾病，但到1957年，死亡率迅速下降。据被美国陆军派去调查该疾病的D.C. Gajdusek说，在1957年至1964年间，福尔部落有5%的人口死于该疾病。1946年，他以儿科医生的身份从哈佛大学医学院毕业，但他在自传中说，1951年他应征入伍时，军队派他从事病毒学工作。1958年，Gajdusek成为美国国立卫生研究院神经学和病毒学研究实验室主任。这是一个了不起的成就，因为人们认为他只在传染病方面做了一些零散的实地工作，他去新几内亚的目的是研究“原始文化中的儿童生长和发育”。“我发现的唯一发表的理由可能是他成为神经学领袖的基础，那就是他在1957年把一个患病的福尔大脑送到德特里克堡。

Gajdusek claimed to have seen the Fore people eating dead relatives, but his figures show that the disease was already in rapid decline when he arrived. He took photographs which were widely published in the US, supposedly showing cannibalism, but 30 years later, he said the photographs showed people eating pork, and that he had seen no cannibalism. (At the time Gajdusek was observing kuru in New Guinea, the influence of “cannibalism” on brain function was already in the news, because of the discovery by J.V. McConnell that the behavior of “trained” flatworms could be transmitted to other worms by chopping them up and feeding them to the naive worms.)

Gajdusek声称看到福尔人吃死去的亲人，但他的数据显示，当他到达时，疾病已经在迅速下降。他拍摄的照片在美国被广泛发表，据说照片上的人吃人，但30年后，他说照片上的人吃猪肉，他没有看到同类相食。(当时Gajdusek观察“库鲁”在新几内亚,“同类相食”对大脑功能的影响已经在新闻中,由于发现J.V.麦康奈尔的行为“训练”扁虫可以传送到其他蠕虫通过斩波和喂养他们天真的蠕虫)。

Harvard medical school, in association with the military program centered at Fort Detrick, Fredericksburg, Maryland, was active in biological warfare in the 1940s, and I think it’s more plausible to see Gajdusek as a trouble-shooter for the biological warfare establishment, than as a biological researcher. One of his biographers has written that the idea of associating kuru with scrapie was suggested to him by a veterinarian, and that Gajdusek had responded by claiming to have experiments in progress to test that theory, four years before the experiments were actually made.

In other words, the slow virus theory for which Gajdusek was given the Nobel Prize is scientific junk, which Gajdusek has repeatedly reinterpreted retrospectively, making it seem to have been anticipatory of the prion theory. Whatever actually caused kuru, I think the army was afraid that it was the result of radioactive fallout from one of its bomb tests, and that Gajdusek’s job was to explain it away.

哈佛医学院，与马里兰州弗雷德里克斯堡德特里克堡的军事项目合作，在20世纪40年代活跃于生物战领域，我认为Gajdusek更有可能被视为生物战领域的问题解决者，而不是生物研究者。他的一位传记作者写道，把库鲁病和痒病联系起来的想法是一位兽医向他提出的，而Gajdusek对此的回应是，在实际进行实验的4年前，他声称正在进行实验来验证这一理论。

换句话说，Gajdusek获得诺贝尔奖的慢病毒理论是科学垃圾，Gajdusek反复对其进行回顾性的重新解释，使其看起来似乎是朊病毒理论的预期。不管库鲁病到底是由什么引起的，我认为军方担心这是一次核弹试验的放射性沉降物的结果，而Gajdusek的工作就是为其解释。

I suspect that kuru was the result of an unusual combination of malnutrition (the women were vegetarian) and radiation. In the very short time that Gajdusek spent in New Guinea, he claimed to have done studies to eliminate all of the alternative causes, nutritional, toxic, anthropological, bacterial causes, studies that would normally have required several years of well organized work. I don’t think he mentioned the possibility of radiation poisoning.

我怀疑库鲁病是营养不良(这些妇女是素食者)和辐射不寻常结合的结果。在Gajdusek在新几内亚度过的很短的时间里，他声称已经做了一些研究来消除所有的替代原因，营养的，有毒的，人类学的，细菌的原因，这些研究通常需要几年的精心组织的工作。我想他没有提到辐射中毒的可能性。

In 1998 Congress commissioned a study of the health effects of radiation from bomb testing, and although the study examined the effects of only part of the bomb tests, it concluded that they had killed 15,000 Americans. No one has tried to accurately estimate the numbers killed in other countries.

1998年，国会委托进行了一项关于核弹试验辐射对健康影响的研究，尽管这项研究只检查了部分核弹试验的影响，但它得出的结论是，这些试验造成1.5万美国人死亡。没有人试图准确估计其他国家的死亡人数。

Even very low doses of ionizing radiation create an inflammatory reaction (Vickers, et al., 1991), and there is evidence that the inflammatory state can persist as long as the individual lives; in Japan, the “acute phase” proteins are still elevated in the people who were exposed to radiation from the atomic bombs. The acute phase proteins that are increased by malnutrition and radiation increase the tendency to form amyloid deposits. Strong radiation can even cause, after a delay of more than a year, the development of vacuoles, which are the most obvious feature of the “prion” brain diseases. The persistent inflammatory reaction eventually produces cellular changes, but these were originally overlooked because of the theory that radiation is harmful only when it produces immediate changes in the DNA.

即使是极低剂量的电离辐射也会产生炎症反应(Vickers, et al.， 1991)，而且有证据表明，炎症状态可以持续到个体的生命周期;在日本，那些受到原子弹辐射的人体内的“急性期”蛋白质水平仍然很高。由于营养不良和辐射而增加的急性期蛋白质增加了淀粉样沉积的倾向。强辐射甚至可以在延迟一年以上后导致空泡的发育，这是“朊病毒”脑疾病最明显的特征。持续的炎症反应最终会产生细胞变化，但这些变化最初被忽视了，因为有理论认为，辐射只有在DNA立即发生变化时才有害。

Radiation damage to the brain is most visible early in life, and in old age. In 1955, Alice Stewart showed that prenatal x-rays increase the incidence of brain cancer, leukemia, and other cancers. In 1967, a study in Japanese bomb survivors found that prenatal exposure to radiation had reduced their head size and brain size. In 1979, Sternglass and Bell showed extremely close correspondence between scores on the SAT and prenatal exposure to radiation.

辐射对大脑的损害在生命早期和老年时最为明显。1955年，Alice Stewart指出产前x光会增加脑癌、白血病和其他癌症的发病率。1967年，一项针对日本原子弹幸存者的研究发现，产前暴露在辐射下会使他们的头部和大脑变小。1979年，斯特恩格拉斯和贝尔在SAT分数和产前辐射暴露之间发现了极其密切的对应关系。

Serum amyloid A, which can increase 1000-fold under the influence of proinflammatory cytokines, resulting from irradiation, stress, trauma, or infection, is an activator of phospholipase A2 (PLA2), which releases fatty acids. Some of the neurodegenerative states, including amyloid-prion diseases, involve activated PLA2, as well as increases in the toxic breakdown products of the polyunsaturated fatty acids, such as 4-hydroxynonenal. The quantity of PUFA in the tissues strongly determines the susceptibility of the tissue to injury by radiation and other stresses. But a diet rich in PUFA will produce brain damage even without exceptional stressors, when there aren’t enough antioxidants, such as vitamin E and selenium, in the diet.

血清淀粉样蛋白A是磷脂酶A2 (PLA2)的激活物，它能释放脂肪酸，在辐射、应激、创伤或感染等促炎细胞因子的影响下可增加1000倍。一些神经退行性状态，包括淀粉样朊病毒疾病，涉及激活的PLA2，以及多不饱和脂肪酸(如4-羟基壬烯醛)的毒性分解产物的增加。组织中多聚不饱和脂肪酸的含量强烈地决定了组织对辐射和其他应力损伤的敏感性。但是，当饮食中没有足够的抗氧化剂(如维生素E和硒)时，即使没有异常的压力源，富含不饱和脂肪酸的饮食也会造成脑损伤。

Amyloidosis has traditionally been thought of as a condition involving deposits mainly in blood vessels, kidneys, joints and skin and in extracellular spaces in the brain, and the fact that the “amyloid” stained in a certain way led to the idea that it was a single protein. But as more proteins–currently about 20–were identified in amyloid deposits, it was gradually realized that the deposits can be identified inside cells of many different tissues, before the larger, very visible, extracellular deposits are formed.

淀粉样变传统上被认为是一种主要沉积在血管、肾脏、关节、皮肤和大脑细胞外空间的疾病，而以某种方式染色的“淀粉样蛋白”使人们认为它是一种单一的蛋白质。但随着越来越多的蛋白质(目前约有20种)在淀粉样蛋白沉积物中被识别出来，人们逐渐意识到，在更大的、非常可见的细胞外沉积物形成之前，淀粉样蛋白沉积物可以在许多不同组织的细胞内被识别出来。

There is evidence of a steady increase in the death rate from amyloidosis. It kills women at a younger age than men, often at the age of 50 or 60.

有证据表明淀粉样变性的死亡率在稳步上升。女性的死亡年龄比男性要小，通常在50或60岁。

Serum amyloid P is called “the female protein” in hamsters, because of its association with estrogen; castrated (or estrogen treated) males also produce large amounts of it, and its excess is associated with the deposition of amyloid (Coe and Ross, 1985). It can bind other amyloid proteins together, accelerating the formation of fibrils, but this function is probably just a variation of a normal function in immunity, tissue repair, and development.

血清淀粉样蛋白P在仓鼠中被称为“雌性蛋白”，因为它与雌激素有关;被阉割(或雌激素治疗)的男性也会产生大量的淀粉样蛋白，过量的淀粉样蛋白与淀粉样蛋白的沉积有关(Coe和Ross, 1985)。它可以结合其他淀粉样蛋白，加速原纤维的形成，但这种功能可能只是免疫、组织修复和发育中正常功能的变体。

Estrogen increases the inflammation-associated substances such as IL-6, C-reactive protein, and amyloid, and liberates fatty acids, especially the unstable polyunsaturated fatty acids. It also increases fibrinogen and decreases albumin, increasing the leakiness of capillaries. The decrease of albumin increases the concentration of free fatty acids and tryptophan, which would normally be bound to albumin.

雌激素增加炎症相关物质如IL-6、c反应蛋白、淀粉样蛋白，释放脂肪酸，特别是不稳定的多不饱和脂肪酸。它也增加纤维蛋白原和减少白蛋白，增加毛细血管的渗漏。白蛋白的减少增加了游离脂肪酸和色氨酸的浓度，而这些脂肪酸和色氨酸通常会与白蛋白结合。

In the U.S. and Europe, livestock are fed large amounts of high-protein feeds, and currently these typically contain fish meal and soybeans. The estrogenic materials in soybeans increase the animals’ tendency toward inflammation (with increased serum amyloid).

在美国和欧洲，牲畜被喂食大量高蛋白饲料，目前这些饲料通常含有鱼粉和大豆。大豆中的雌激素物质增加了动物的炎症倾向(增加了血清淀粉样蛋白)。

Officially, BSE appeared because cows were fed slaughter-house waste containing tissues of sheep that had died of scrapie. Scrapie was a nerve disease of sheep, first reported in Iceland in the 18th century. When I was studying the digestive system and nutrition of horses, I learned that it was common for horses in Norway to be fed dried fish during the winter. This abundant food was probably used for sheep, as well as for horses. The extra protein provided by fish meal is still important for sheep in areas where pastures are limited, but it has now become common to use it to increase productivity and growth throughout the lamb, beef, and dairy industries, as well as in most lab chows fed to experimental animals, such as the hamsters used for testing the infectivity of the diseased tissues.

官方称，疯牛病的出现是因为牛被喂食含有死于痒病的羊组织的屠宰场垃圾。痒病是羊的一种神经疾病，最早于18世纪在冰岛报道。当我在研究马的消化系统和营养时，我了解到在挪威，马在冬天吃鱼干是很常见的。这种丰富的食物很可能是用来喂养羊和马的。在牧场有限的地区，鱼粉提供的额外蛋白质对绵羊来说仍然很重要，但现在已经普遍使用它来提高羊肉、牛肉和奶制品行业的生产率和生长，以及在大多数喂养实验动物的实验室中，比如用来测试患病组织传染性的仓鼠。

Increased dietary polyunsaturated fatty acids (PUFA) suppress the activity of the ruminal bacteria which are responsible for the hydrogenation-detoxication of PUFA in the animal’s diet. This allows the unstable fats, 98% of which are normally destroyed, to pass into the animals’ tissues and milk.

增加饲粮多不饱和脂肪酸(PUFA)会抑制瘤胃细菌的活性，而这些细菌负责动物饲粮中多不饱和脂肪酸的氢化-解毒作用。正常情况下，98%的不稳定脂肪都已被破坏，这样就可以进入动物的组织和牛奶中。

The polyunsaturated fats in fish are very unstable, and when they get past the bacterial saturases (biohydrogenases) in the rumen that normally protect ruminants from lipid peroxidation, they are likely to cause their toxic effects more quickly than in humans, whose antioxidant systems are highly developed. The toxic effects of polyunsaturated fats involve altered (immunogenic) protein structure, decreased energy metabolism, and many inflammatory effects produced by the prostaglandin-like substances. Marine fish are now so generally polluted with dioxin, that in Japan there is a clear association between the amount of fish in a person’s diet (their body content of EPA and DHA) and the amount of dioxin in their body.

鱼类中的多不饱和脂肪非常不稳定，当它们通过瘤胃中通常保护反刍动物免受脂质过氧化的细菌饱和酶(生物氢化酶)时，它们很可能比抗氧化系统高度发达的人类更快地产生毒性作用。多不饱和脂肪的毒性作用包括改变(免疫原性)蛋白质结构，降低能量代谢，以及前列腺素类物质产生的许多炎症效应。现在海洋鱼类普遍受到二恶英污染，以至于在日本，人们饮食中的鱼类数量(他们体内的EPA和DHA含量)和他们体内的二恶英数量之间有明显的联系。

Radiation and many kinds of poisoning cause early peroxidation of those highly unsaturated fats, and the breakdown products accelerate the changes in the folding and chelating behavior of proteins. The accumulation of altered proteins is associated with the degenerative diseases. The role of toxic metals in brain inflammation is well established (e.g., aluminum, lead, mercury: Campbell, et al., 2004; Dave, et al., 1994; Ronnback and Hansson, 1992).

辐射和多种中毒导致这些高不饱和脂肪的早期过氧化，分解产物加速蛋白质折叠和螯合行为的变化。改变蛋白的积累与退行性疾病有关。有毒金属在脑炎症中的作用已经得到证实(例如，铝、铅、汞:Campbell等，2004;戴夫等人，1994;Ronnback和Hansson, 1992)。

The “prion hypothesis” has the value of weakening the fanaticism of the DNA-genetics doctrine, but it has some problems. There are now several examples in which other degenerative diseases have been transmitted by procedures similar to those used to test the scrapie agent. (e.g., Goudsmit, et al., 1980; Xing, et al., 2001; Cui, et al., 2002.) Experimental controls haven’t been adequate to distinguish between the pure prion and its associated impurities. Gajdusek burned a sample of the infective hamster brain to ash, and found that it still retained “infectivity.” He argued that there was a mineral template that transmitted the toxic conformation to normal proteins. Others have demonstrated that the active structure of the infective agent is maintained by a carbohydrate scaffolding, or that the infectivity is destroyed by the frequency of ultraviolet light that destroys the active lipid of bacterial endotoxin, lipopolysaccharide.

“朊病毒假说”具有削弱dna遗传学学说狂热的价值，但它也存在一些问题。现在有几个例子表明，其他退行性疾病是通过类似于瘙痒剂测试的程序传播的。(例如，Goudsmit等人，1980;邢等，2001;崔等，2002。实验控制还不足以区分纯朊病毒及其相关杂质。Gajdusek将感染仓鼠的大脑样本烧成灰烬，发现它仍然保留着“传染性”。他认为有一种矿物模板可以将有毒的构象传递给正常的蛋白质。其他人已经证明，感染源的活性结构是由碳水化合物支架维持的，或者是传染性被紫外线的频率破坏，紫外线破坏细菌内毒素的活性脂质，脂多糖。

But simply injuring the brain or other organ (by injecting anything) will sometimes activate a series of reactions similar to those seen in aging and the amyloidoses. When a slight trauma leads to a prolonged or expanding disturbance of structure and function, the process isn’t essentially different from transmitting a condition to another individual. The problem is being “transmitted” from the initial injury, recruiting new cells, and passing the disturbed state on to daughter cells in a disturbed form of regeneration. Keloids, hypertrophic scars, are analogous to the dementias in their overgrowth of connective tissue cells: In the aging or injured brain, the glial cells (mainly astrocytes) proliferate, in reparative processes that sometimes become exaggerated and harmful.

但仅仅是损伤大脑或其他器官(通过注射任何东西)有时会激活一系列类似于衰老和淀粉样变的反应。当轻微的创伤导致长期或扩大的结构和功能紊乱时，这一过程与将疾病传染给另一个人并无本质区别。问题是从最初的损伤“传递”，招募新的细胞，并以一种紊乱的再生形式将紊乱状态传递给子细胞。瘢痕疙瘩，即增生性瘢痕，在结缔组织细胞过度生长方面类似于痴呆:在衰老或受伤的大脑中，胶质细胞(主要是星形胶质细胞)增殖，在修复过程中，有时变得夸张和有害。

When tissue phospholipids contain large amounts of polyunsaturated fatty acids, large amounts of prostaglandins are immediately formed by any injury, including low doses of ionizing radiation. The liberated free fatty acids have many other effects, including the formation of highly reactive aldehydes, which modify DNA, proteins, and other cell components.

当组织磷脂含有大量的多不饱和脂肪酸时，任何损伤，包括低剂量的电离辐射，都会立即形成大量的前列腺素。释放出来的游离脂肪酸有许多其他作用，包括形成高度活性的醛，它可以修饰DNA、蛋白质和其他细胞成分。

Animals which are “deficient” in the polyunsaturated fatty acids have a great resistance to a variety of inflammatory challenges. Their tissues appear to be poor allergens or antigens, since they can be easily grafted onto other animals without rejection. Something related to this can probably be seen in the data of human liver transplants. Women’s livers are subjected to more lipid peroxidation than men’s, because of the effects of estrogen (increasing growth hormone and free fatty acids, and selectively mobilizing the polyunsaturated fatty acids and increasing their oxidation). Liver transplants from middle-aged female donors fail much more often (40 to 45%) than livers from male donors (22 to 25%), and other organs show the same effect. The autoimmune diseases are several times as common in women as in men, suggesting that some tissues become relatively incompatible with their own body, after prolonged exposure to the unstable fatty acids. If we consider the healthy function of the immune system to be the removal or correction of injured tissue, it’s reasonable to view the random interactions of oxidized fats with proteins as exactly the sort of thing our immune system takes care of.

多不饱和脂肪酸“缺乏”的动物对各种炎症挑战有很强的抵抗力。它们的组织似乎不是很好的过敏原或抗原，因为它们可以很容易地移植到其他动物身上而不会产生排斥反应。在人类肝脏移植的数据中，可能可以看到一些与此相关的东西。由于雌激素的作用(增加生长激素和游离脂肪酸，选择性地调动多不饱和脂肪酸并增加其氧化)，女性的肝脏比男性遭受更多的脂质过氧化。来自中年女性的肝脏移植比来自男性的肝脏移植更容易失败(40 - 45%)，其他器官也表现出同样的效果。自身免疫性疾病在女性中的发病率是男性的几倍，这表明在长期接触不稳定脂肪酸后，一些组织与自身的身体相对不相容。如果我们认为免疫系统的健康功能是去除或纠正受损组织，那么将氧化脂肪与蛋白质的随机相互作用视为我们的免疫系统所负责的事情是合理的。

The serum amyloids A and P and the closely related lipoproteins are considered to be important parts of our “innate immunity,” operating in a more general way than the familiar system of specific acquired immunities.

血清淀粉样蛋白A和P以及密切相关的脂蛋白被认为是我们“先天免疫”的重要组成部分，其运作方式比我们熟悉的特异性获得性免疫系统更为普遍。

The amyloids and lipoproteins are powerfully responsive to bacterial endotoxin, LPS, and their structural feature that binds it, the “pleated sheet” structure, appears to also be what allows the amyloids to form amorphous deposits and fibrils under some circumstances. Our innate immune system is perfectly competent for handling our normal stress-induced exposures to bacterial endotoxin, but as we accumulate the unstable fats, each exposure to endotoxin creates additional inflammatory stress by liberating stored fats. The brain has a very high concentration of complex fats, and is highly susceptible to the effects of lipid peroxidative stress, which become progressively worse as the unstable fats accumulate during aging.

淀粉样蛋白和脂蛋白对细菌内毒素(LPS)有强烈的反应，它们与之结合的结构特征，即“折叠片”结构，似乎也是在某些情况下允许淀粉样蛋白形成无定形沉积物和原纤维的原因。我们的先天免疫系统完全有能力处理由压力引起的细菌内毒素暴露，但当我们积累不稳定脂肪时，每次暴露于内毒素会释放储存的脂肪，从而产生额外的炎症压力。大脑中有非常高浓度的复合脂肪，而且极易受到脂质过氧化应激的影响，随着不稳定的脂肪在衰老过程中积累，脂质过氧化应激变得越来越严重。

More than 60 years ago, a vitamin E deficiency was known to cause a brain disease, sometimes associated with sterility and muscular dystrophy. The symptoms of the brain disease were similar to those of “mad cow disease,” and the condition is now usually called “crazy chick disease.” Veterinarians are usually taught that it is caused by a selenium deficiency, but it is actually the result of an excess of PUFA in the diet, and is exacerbated by increased iron or other oxidants, and prevented by increased vitamin E, selenium, or substitution of saturated fats for the unsaturated.

60多年前，已知维生素E缺乏会导致一种脑部疾病，有时与不育和肌肉营养不良有关。这种脑部疾病的症状与“疯牛病”类似，现在通常被称为“疯鸡病”。兽医们通常被告知，这是由缺乏硒引起的，但实际上是饮食中过多的不饱和脂肪酸的结果，增加铁或其他氧化剂会加剧不饱和脂肪酸，增加维生素E、硒或用饱和脂肪替代不饱和脂肪可以预防不饱和脂肪酸。

Terminology, established by tradition and thoughtless memorization, obscures many of the commonalities in the various brain diseases. Brain inflammation (Betmouni and Perry, 1999; Perry, et al., 1998), myelination disorders, edema, overgrowth of the astroglia, and circulatory changes are common occurrences in most of the degenerative encephalopathies, but traditional textbook descriptions have created the impression that each disease is pathologically very distinct from the others. The current classification of “the prion diseases”is reifying a group of symptoms that aren’t specific to any specific known cause. And standard laboratory procedures for preparing brain sections for microscopic examination may cause brain cells to shrink to 5% of their original volume (Hillman and Jarman, Atlas of the cellular structure of the human nervous system, 1991), so the objectivity of pathological studies shouldn’t be over-estimated.

术语，建立在传统和轻率的记忆，模糊了许多共同之处，在各种脑疾病。脑炎症(贝特穆尼和佩里，1999;Perry等人，1998)，髓鞘形成障碍，水肿，星形胶质细胞过度生长和循环变化是大多数退行性脑病的常见症状，但传统教科书的描述给人的印象是每一种疾病在病理上都非常不同。目前对“朊病毒疾病”的分类是将一组症状具体化，这些症状不是针对任何已知的特定原因。而为显微镜检查准备脑切片的标准实验室程序可能会导致脑细胞缩小到原来体积的5% (Hillman And Jarman, Atlas of the cell structure of the human nervous system, 1991)，所以病理学研究的客观性不应被过高估计。

According to a 1989 study (Laura Manuelidis, neuropathology department at Yale), 13% of the people who had died from “Alzheimer’s disease” actually had CJD. Between 1979 and 2000, the number of people dying annually from Alzheimer’s disease increased 50-fold. Very competent neuropathologists differ radically in their descriptions of the dementia epidemic.

根据1989年的一项研究(Laura Manuelidis，耶鲁大学神经病理科)，13%死于“阿尔茨海默病”的人实际上患有CJD。从1979年到2000年，每年死于阿尔茨海默病的人数增加了50倍。非常能干的神经病理学家对痴呆症流行的描述大相径庭。

By some tests, the “prion” resembles the LPS endotoxin. One of the interesting developments of the prion theory is that a particular structure that appears when the prion becomes toxic, the “beta pleated sheet,” is also a feature of most of the normal proteins that can form amyloid, and that this structure is directly related to binding and eliminating the bacterial LPS. If the prion theory is correct about the conversion of a normal protein into the pleated sheet, it isn’t necessarily correct about the incurability of the condition. The innate immune system should be able to inactivate the prion just as it does the bacterial endotoxin, if we remove the conditions that cause the innate immune reaction to amplify the inflammation beyond control.

通过一些测试发现-“朊病毒”类似于LPS内毒素。朊病毒的一个有趣的发展理论是一个特定的结构。当朊病毒变得有毒-β折叠片,“也是一个特性的最正常的蛋白质-可以形成淀粉样蛋白,这种结构是直接关系到绑定和消除细菌有限合伙人。如果朊病毒理论关于正常蛋白质转化成褶皱的理论是正确的，那么关于这种情况的不可治愈性就不一定是正确的。先天免疫系统应该能够灭活朊病毒，就像它灭活细菌内毒素一样，如果我们消除导致先天免疫反应的条件，使炎症扩大到无法控制的程度。

In the prion diseases, the severely damaged brain appears to have a “pathological overactivity” of the serotonergic systems (Fraser, et al., 2003). This is an interesting parallel to Alzheimer’s disease, since it has been known for several years that the blood platelets have an increased tendency to release serotonin in that more common form of dementia. Serotonin itself is toxic to nerves, and is part of the adaptive system that gets out of control during prolonged inflammation. Serotonin is an important activator of the phospholipases.

在朊病毒疾病中，严重受损的大脑似乎具有5 -羟色胺能系统的“病理过度活跃”(Fraser, et al.， 2003)。这与阿尔茨海默病有一个有趣的相似之处，因为多年来人们已经知道，在更常见的痴呆症中，血小板释放血清素的趋势增加。血清素本身对神经是有毒的，它是适应系统的一部分，在长时间的炎症反应中会失控。血清素是磷脂酶的重要激活剂。

The modification of proteins’ structure by glycosylation is involved in the development of the toxic form of the “prionic” protein, as well as in all the degenerative processes of aging. Until the ability to use sugar is impaired, cells produce enough carbon dioxide to protect proteins against random glycation, but with each exposure to free polyunsaturated fatty acids, the ability to use glucose is damaged. In the dementias, the brain has a greatly reduced ability to use glucose.

糖基化对蛋白质结构的修饰涉及朊蛋白毒性形式的发展，以及衰老的所有退行性过程。在利用糖的能力受损之前，细胞会产生足够的二氧化碳来保护蛋白质不受随机糖化的影响，但每次接触游离多不饱和脂肪酸，利用葡萄糖的能力就会受损。在痴呆症中，大脑使用葡萄糖的能力大大降低。

One of estrogen’s central effects is to shift metabolism away from the oxidation of glucose, decreasing carbon dioxide production. There is a much higher incidence of Alzheimer’s disease in women, and estrogen exposure exacerbates all of the changes that lead to it, such as shifts in nerve transmitters, increased vascular leakiness, and the increased production of the acute phase proteins.

雌激素的主要作用之一是使新陈代谢远离葡萄糖的氧化，减少二氧化碳的产生。女性阿尔茨海默病的发病率要高得多，雌激素暴露加剧了所有导致这一疾病的变化，如神经递质的变化，血管渗漏的增加，以及急性期蛋白质的增加。

Everything that is known about the “always fatal” prionic diseases, the diseases of disturbed protein folding, suggests that they can be avoided and even reversed by systematically reversing the processes that amplify inflammation.

关于“总是促挂的”朊病毒疾病，即蛋白质折叠紊乱的疾病，我们所知道的一切表明，它们可以通过系统地逆转放大炎症的过程来避免，甚至逆转。

People who take aspirin, drink coffee, and use tobacco, have a much lower incidence of Alzheimer’s disease than people who don’t use those things. Caffeine inhibits brain phospholipase, making it neuroprotective in a wide spectrum of conditions. In recent tests, aspirin has been found to prevent the misfolding of the prion protein, and even to reverse the misfolded beta sheet conformation, restoring it to the harmless normal conformation. Nicotine might have a similar effect, preventing deposition of amyloid fibrils and disrupting those already formed (Ono, et al., 2002). Vitamin E, aspirin, progesterone, and nicotine also inhibit phospholipase, which contributes to their antiinflammatory action. Each of the amyloid-forming proteins probably has molecules that interfere with its toxic accumulation.

服用阿司匹林、喝咖啡和吸烟的人患阿尔茨海默病的几率要比不服用这些东西的人低得多。咖啡因抑制大脑磷脂酶，使其在广泛的条件下具有神经保护作用。在最近的测试中，人们发现阿司匹林可以防止朊病毒蛋白的错误折叠，甚至可以逆转错误折叠的β板构象，使其恢复到无害的正常构象。尼古丁可能有类似的效果，可以防止淀粉样原纤维的沉积，并扰乱已经形成的淀粉样原纤维(Ono等，2002年)。维生素E、阿司匹林、孕酮和尼古丁也能抑制磷脂酶，这有助于它们的抗炎作用。每一种淀粉样蛋白可能都有干扰其毒性积累的分子。

Thyroid hormone, vitamins A and E, niacinamide (to inhibit systemic lipolysis), magnesium, calcium, progesterone, sugar, saturated fats, and gelatin all contribute in basic ways to prevention of the inflammatory states that eventually lead to the amyloid diseases. The scarcity of degenerative brain disease in high altitude populations is consistent with a protective role for carbon dioxide.

甲状腺激素、维生素A和E、烟酰胺(抑制全身脂肪分解)、镁、钙、黄体酮、糖、饱和脂肪和明胶都有助于预防最终导致淀粉样疾病的炎症状态。在高海拔人群中，退化性脑疾病的缺乏与二氧化碳的保护作用是一致的。

The relatively sudden acceptability of the idea of non-genetic transmission doesn't mean that Lamarck has been rehabilitated by the scientific establishment; it could just be that it's the most politically acceptable way to explain the outbreaks of deadly disease caused by the industrialization of foods and the exposure of the population to dangerous levels of radiation.

非基因传播这一观点的相对突然被接受并不意味着拉马克已经被科学机构恢复了名誉;这可能只是一种政治上最容易接受的方式来解释由食品工业化引起的致命疾病的爆发以及民众暴露在危险水平的辐射中。

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Arterioscler Thromb Vasc Biol. 2003 Dec 29. Effect of Lower Dosage of Oral Conjugated Equine Estrogen on Inflammatory Markers and Endothelial Function in Healthy Postmenopausal Women. Wakatsuki A, Ikenoue N, Shinohara K, Watanabe K, Fukaya T. {Oral estrogen) “… increases plasma C-reactive protein (CRP) and interleukin-6 (IL-6) concentration. The proinflammatory effect of oral ERT may explain the increased risk of coronary heart disease (CHD) associated with this treatment.”

Am J Pathol. 1997 Jun; 150(6): 2181-95. Free fatty acids stimulate the polymerization of tau and amyloid beta peptides.In vitro evidence for a common effector of pathogenesis in Alzheimer's disease. Wilson DM, Binder LI. “We have discovered that free fatty acids (FFAs) stimulate the assembly of both amyloid and tau filaments in vitro.” “Utilizing fluorescence spectroscopy, unsaturated FFAs were also demonstrated to induce beta-amyloid assembly.” [These results] “…suggest that cortical elevations of FFAs may constitute a unifying stimulatory event driving the formation of two of the obvious pathogenetic lesions in Alzheimer's disease.”

Lab Invest. 2001 Apr; 81(4): 493-9. Transmission of mouse senile amyloidosis. Xing Y, Nakamura A, Chiba T, Kogishi K, Matsushita T, Li F, Guo Z, Hosokawa M, Mori M, Higuchi K. “In mouse senile amyloidosis, apolipoprotein A-II polymerizes into amyloid fibrils (AApoAII) and deposits systemically. Peripheral injection of AApoAII fibrils into young mice induces systemic amyloidosis….” “We isolated AApoAII amyloid fibrils from the livers of old R1.P1-Apoa2© mice and injected them with feeding needles into the stomachs of young R1.P1-Apoa2© mice for 5 consecutive days. After 2 months, all mice had AApoAII deposits in the lamina propria of the small intestine. Amyloid deposition extended to the tongue, stomach, heart, and liver at 3 and 4 months after feeding. AApoAII suspended in drinking water also induced amyloidosis.” “Amyloid deposition was induced in young mice reared in the same cage for 3 months with old mice who had severe amyloidosis. Detection of AApoAII in feces of old mice and induction of amyloidosis by the injection of an amyloid fraction of feces suggested the propagation of amyloidosis by eating feces. Here, we substantiate the transmissibility of AApoAII amyloidosis and present a possible pathogenesis of amyloidosis, ie, oral transmission of amyloid fibril conformation, where we assert that exogenous amyloid fibrils act as templates and change the conformation of endogenous amyloid protein to polymerize into amyloid fibrils.”

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