Heterogeneity within the hemagglutinin genes of canine distemper virus (CDV) strains detected in Ita

OG13 SC正确句子汇总1. In a review of 2,000 studies of human behavior that date back to the 1940s, two Swiss psychologists declared that since most of the studies had failed to control for variables such as social class and family size, none could be taken seriously2. Manufacturers rate batteries in watt-hours; if the higher the watt-hour rating, the longer the battery can be excepted to last.3. Although a surge in retail sales has raised hopes that a recovery is finally under way, many economists say that without a large amount of spending the recovery might not last.4. At the end of 1930s, Duke Ellington was looking for a composer to assisthim-——someone who could not only arrange music for his successful big band, but also mirror his eccentric writing style in order to finish the many pieces he had started but never completed.5. Of all the vast tides of migration that have swept through history, perhaps none was more concentrated than the wave that brought 12 million immigrants onto American shores in little more than three decades.6. Diabetes, together with its serious complications, ranks as the nation's third leading cause of death, surpassed only by heart disease and cancer.7. The intricate structure of the compound insect eye, with its hundreds of miniature eyes called ommatidia, helps explain why scientists have assumed that it evolved independently of the vertebrate eye.8. In late 1997, the chambers inside the pyramid of the Pharaoh Menkaure at Giza were closed to visitors for cleaning and repair because moisture exhaled by tourists had raised the humidity within them to such levels that salt from the stone was crystallizing and fungus was growing on the walls.9. In 1979 lack of rain reduced India's rice production to about 41 million tons, nearly 25 percent less than the 1978 harvest.10. The widely accepted big bang theory holds that the universe began in an explosive instant ten to twenty billion years ago and has been expanding ever since.11. Like the Brontes and Brownings, James Joyce and Virginia Woolf areoften subjected to kind of veneration that blurs the distinction between the artist and human being.12. Carnivorous mammals can endure what would otherwise be lethal levels of body heat because they have a heat-exchange network that keeps the brain from getting too hot.13. There are several ways to build solid walls using just mud or clay, but the most extensively used method has been to form the mud or clay into bricks, and, after some preliminary air drying or sun drying, to lay them in the wall in mud mortar.14. Rising inventories, if not accompanied by corresponding increases in sales, can lead to production cutbacks that would hamper economic growth.15. Many experts regarded the large increase in credit card borrowing in March not as a sign that households were pressed for cash and forced to borrow, but as a sign that households were confident they could safely handle new debt.16. A surge in new home sales and a drop in weekly unemployment claims suggest that the economy might not be as weak as some analysts previously thought.17. Sunspots, vortices of gas associated with strange electromagnetic activity, are visible as dark spots on the surface of the Sun but have never been sighted on the Sun's poles or equator.18. Warning that computers in the United States are not secure, the National Academy of Sciences has urged the nation to revamp computer security procedures, institute new emergency response teams, and create a special nongovernment organization to take charge of computer security planning.19. The exploits of Nellie Bly, a pioneer journalist, included circling the globe faster than Jules Verne's fictional Phileas Fogg.20. Retail sales rose 0.8 of 1 percent in August, intensifying expectations that personal spending in the July-September quarter would more than double the 1.4 percent growth rate in personal spending foe the previous quarter.21. The commission has directed advertisers to restrict the use of the word "natural" to foods that do not contain colour or flavor additives, chemical preservatives, or anything that has been synthesized.22. Plants are more efficient than fungi at acquiring carbon, in the form of carbon dioxide, and converting it to energy-rich sugars.23. The Iroquois were primarily planters, although they supplemented their cultivation of maize, squash, and beans with fishing and hunting.24. Unlike the honeybee, the yellow jacket can sting repeatedly without dying and carries a potent venom that cause intense pain.25. Neuroscientists, having amassed a wealth of knowledge over the past twenty years about the brain and its development from birth to adulthood, are now drawing solid conclusions about how the human brain grows and how babies acquire language.26. Tropical bats play important roles in the rain forest ecosystem, aiding in the dispersal of cashew, date, and fig seeds; pollinating banana, breadfruit, and mango trees; and indirectly helping to produce tequila by pollinating agave plants.27. None of the attempts to specify the causes of crime explains why most of the people exposed to the alleged causes do not commit crimes and, conversely, why so many of those not so exposed do.28. In virtually all types of tissue in every animal species, dioxin induces the production of enzymes that are the organism's attempt to metabolize, or render harmless, the chemical irritant.29. Emily Dickinson's letters to Susan Huntington Dickinson, which were written over a period beginning a few years before Susan's marriage to Emily's brother and ending shortly before Emily's death in 1886, outnumber her letters to anyone else.30. Paleontologists believe that fragments of a primate jawbone unearthed in Burma and estimated to be 40 to 44 million years old provide evidence of a crucial step along the evolutionary path that led to human beings.31. Even though many of her colleagues were convinced that genes were relatively simple and static, Barbara McClintock adhered to her own more complicated ideas about how genes might operate, and in 1983, at age of 81, was awarded a Nobel Prize for her discovery that the genes in corn are capable of moving from one chromosomal site to another.32. Galileo was convinced that natural phenomena, as manifestations of the laws of physics, would appear the same to someone on the deck of a ship moving smoothly and uniformly through the water as to a person standing on land.33. Because an oversupply of computer chips has sent prices plunging, the manufacturer has announced that it will cut production by closing its factories for two days a month.34. Beyond the immediate cash flow crisis that the museum faces, its survival depends on whether it can broaden its membership and leave its cramped quarters for a site where it can store and exhibit its more than 12,000 artifacts.35. By 1940, the pilot Jacqueline Cochran held seventeen official national and international speed records, earned at a time when aviation was still so new that many of the planes she flew were dangerously experimental design.36. Along with the drop in producer prices announced yesterday, the strong retail sales figures released today seem to indicate that the economy, although growing slowly, is not nearing a recession.37. Dressed as a man and using the name Robert Shurtleff, Deborah Sampson, the first woman to draw a soldier's pension, joined the Continental Army in 1782 at the age of 22, was injured three times, and was discharged in 1783 because she had become too ill to serve.38. Bengal-born writer, philosopher, and educated Rabindranath T agore had the greatest admiration for Mohandas K. Gandhi as a person and as a politician, butT agore was also skeptical of Gandhi's form of nationalism and his conservative opinions about India's cultural traditions.39. Although schistosomiasis is not often fatal, it is so debilitating that it has become an economic drain on many developing countries.40. The organization of Petroleum Exporting Countries (OPEC) had long been expected to announce a reduction in output to bolster sagging oil prices, but officials of the organization just recently announced that the group will pare daily production by 1.5 million barrels by the beginning of next year only if non-OPEC nations, including Norway, Mexico, and Russia, trim output by a total of 500,000 barrels a day.41. In 1850, Lucretia Mott published her discourse on Women, a treatise that argued for equal political and legal rights for women and for changes in the married women's property laws.42. T o develop more accurate population forecasts, demographers would have to know a great deal more than they do now about the social and economic determinants of fertility.43. Laos has a land area comparable to that of Great Britain but a population of only four million people, many of whom are members of hill tribes ensconced in the virtually inaccessible mountain valleys of the north.44. The plot of the Bostonians centres on the rivalry that develops between Olive Chancellor, an active feminist, and Basil Ransom, her charming and cynical cousin, when they find themselves drawn to the same radiant young woman whose talent for public speaking has won her ardent following.45. Quasars, at billions of light-years from Earth the most distant observable objects in the universe, are believed to be the cores of galaxies in an early stage of development.46. In ancient Thailand, much of the local artisan's creative energy was expended on the creation of Buddha images and on construction and decoration of the temples in which they were enshrined.47. In 1713, Alexander Pope began his translation of the Iliad, a work that took him seven years to complete and that literacy critic Samuel Johnson, Pope's contemporary, pronounced the greatest translation in any language.48. Though called a sea, the landlocked Caspian is actually the largest lake on Earth, covering more than four times the surface area of its closest rival in size, North America's Lake Superior.49. The automotive conveyor-belt system, which Henry Ford modeled after an seemly-line technique introduced by Ransom Olds, reduced the time required to assemble a Model T from a day and a half to 93 minutes.50. According to some analysts, the gains in the stock market reflect growing confidence that the economy will avoid the recession that many had feared earlier in the year and instead come in for a "soft landing," followed by a gradual increase in business activity.51. A new study suggests that the conversational pace of everyday life may be so brisk that it hampers the ability of some children to distinguish discrete sounds and words and, as a result, to make sense if speech.52. Long before it was fashionable to be an expatriate, Josephine Baker made Paris her home, and she remained in France during the Second World War as a performer and an intelligence agent for the Resistance.53. The nineteenth-century chemist Humphry Davy presented the results of his early experiments in his "Essay on heat and Light," a critique of all chemistry since Robert Boyle as well as a vision of a new chemistry that DAvy hoped to found. 54. The report recommended that the hospital eliminate unneeded beds, consolidate expensive services, and use space in other hospitals.55. Many house builders offer rent-to-buy programs that enable a family with insufficient savings for a conventional down payment to move into new housing and to apply part of the rent to a purchase later.56. Elizabeth Barber, the author of both Prehistoric T extiles, a comprehensive work on cloth in the early cultures of the Mediterranean, and Women's Work, a more general account of early cloth manufacture, is an authority on textiles in ancient societies.57. Many of the earliest known images of Hindu deities in India date from the time of the Kushan Empire and were fashioned either from the spotted sandstone of Mathura or from Gandharan grey schist.58. It can hardly be said that educators are at fault for not anticipating the impact of microcomputer technology: Alvin T offler, one of the most prominent students of the future, did not even mention microcomputers in Future Shock, published in 1970.59. A leading figure in the Scottish Enlightenment, Adam Smith wrote two major books that are to democratic capitalism what Marx's Das Kapital is to socialism.60. The Olympic Games helped to keep pace among the pugnacious states of the Greek world, for a sacred true was proclaimed during the month of the festival.61. While all states face similar industrial waste problems, the predominant industries and the regulatory environment of each state obviously determine the types and amounts of waste produced, as well as the cost of disposal.62. Rivaling the pyramids of Egypt or even the ancient cities if the Maya as an achievement, the army of terra-cotta warriors created to protect Qin Shi Huang, China's first emperor, in his afterlife is more than 2,000 years old and took 700,000 artisans more than 36 years to complete.63. When Congress reconvenes, some newly elected members from rural states will try to establish tighter restrictions on the amount of grain farmers will be allowed to grow and to encourage more aggressive sales of United States farm products overseas.64. Doctors generally agree that such factors as cigarette smoking, eating rich foods high in fats, and alcohol consumption not only do damage by themselves but also aggravate genetic predispositions toward certain diseases.65. Digging in sediments in northern China, scientists have gathered evidence suggesting that complex life-forms emerged much earlier than previous thought.66. In a plan to stop the erosion of East Coast Beaches, the Army Corps of Engineers proposed building parallel to shore a breakwater of rock that would rise six feet above the waterline and act as a buffer, absorbing the energy of crashing waves and protecting the beaches.67. The 32 species that make up dolphin family are closely related to whales and in fact include the animal known as the killer whale which can grow to be 30 feet long and is famous for its aggressive hunting pods.68. Outlining his strategy for nursing the troubled conglomerate back to health, the chief executive announced plans Wednesday to cut the company's huge debt by selling nearly $12 billion in assets over the next 18 months.69. Affording strategic proximity to the Strait of Gibraltar Morocco was also of interest to the French throughout the first half of the twentieth century because they assumed that without it their grip on Algeria would never be secure.70. The first trenches cut into a 500-acre site at T ell Hamoukar, Syria, have yielded strong evidence that centrally administered complex societies in northern regions of Middle East arose simultaneously with but independently of the more celebrated city-states of southern Mesopotamia, in what is now southern Iraq.71. Along the major rivers that traverse the deserts of northeast Africa, the Middle East, and northwest India, the combination of a reliable supply of water and good growing conditions encouraged farming traditions that have, in places, endured for at least 6,000 years.72. His studies of ice-polished rocks in his Alpine homeland, far outside the range of present-day glaciers, led Louis Agassiz in 1837 to propose the concept of an age in which great ice sheets existed in what are temperature areas.73. Unlike the original National Museum of Science and T echnology in Italy, where the models are encased in glass or operated only by staff member, the Virtual Leonardo Project, an online version of the museum, encourages visitors to "touch" each exhibit and thereby active the animated functions of the piece.74. Although it covers the entire planet, Earth's crust is neither seamless nor stationary, but rather fragmented into mobile semirigid plates.75. More and more in recent years, cities are stressing the arts as a means to greater economic development and investing millions of dollars in cultural activities, despite strained municipal budgets and fading federal support.76. Combining enormous physical strength with higher intelligence, the Neanderthals appear to have been equipped to face any obstacle the environment could put in their path, but their relatively sudden disappearance during the Paleolithic era indicates that an inability to adapt to some environmental change led to their extinction.77. A 1972 agreement between Canada and the United States reduced the amount of phosphates that municipalities are allowed to dump into the Great Lakes.78. A proposal has been made to trim the horns from rhinoceroses to discourage poachers; the question is whether tourists will continue to visit game parks to see rhinoceroses once the animals' horn have been trimmed.79. Ryunosuke Akutagawa's knowledge of the literatures of Europe, China, and Japan was instrumental in his development as a writer, informing both his literary style and the content of his fiction.80. The only way for growers to salvage frozen citrus is to have it quickly processed into juice concentrate before warmer weather returns and rots the fruit.81. Fossils of the arm of a sloth, found in Puerto Rico in 1991, have been dated at 34 million years old, making the sloth the earliest known mammal on the Greater Antilles Islands.82.Defense attorneys have occasionally argued that their clients' misconduct stemmed from a reaction to something ingested, but if criminal or delinquent behaviour is attributed to an allergy to some food, the perpetrators are in effect told that they are not responsible for their actions.83. A report by the American Academy for the Advancement of Science has concluded that many of the currently uncontrolled dioxins to which North Americans are exposed come from the incineration of wastes.84. Recently physicians have determined that stomach ulcers are caused not by stress, alcohol, or rich foods, but by a bacterium that dwells in the mucous lining of the stomach.85. According to a recent poll, owning and living in a freestanding house on its own land is still a goal of a majority of young adults, as it was of earlier generations. 86. In 2000, a mere two dozen products accounted for half the increase in spending on prescription drugs, a phenomenon that is explained not just by the fact that drugsare becoming more expensive but also by the fact that doctors are writing many more prescriptions for higher-cost drugs.87. According to scientists who monitored its path, an expanding cloud of energized particles ejected from the Sun recently triggered a large storm in the magnetic field that surrounds EArth, brightening the Northern Lights and possibly knocking out a communications satellite.88. Often visible as smog, ozone is formed in the atmosphere when hydrocarbons and nitrogen oxides, two major pollutants emitted by automobiles, react with sunlight.89. Salt deposits and moisture threaten to destroy the Mohenjo-Daro excavation in Pakistan, the site of an ancient civilization that flourished at the same time as the civilizations in the Nile Delta and the river valleys of the Tigris and Euphrates.90. The result of the company's cost-cutting measures are evident in its profits, which have increase 5 percent during the first 3 months of this year after failing over the last two years.91. In an effort to reduce their inventories, Italian vintners have cut prices; their wines are priced to sell, and they do.92.Jazz pianist and composer Thelonious Monk produced a body of work that was rooted in the stride-piano tradition of Willie (The Lion) Smith and Duke Ellington, yet in many ways he stood apart from the mainstream jazz repertory.93. Nobody knows exactly how many languages there are in the world, partly because of the difficulty of distinguishing between a language and the sublanguages or dialects within it, but those who have tried to count typically have found about five thousand.94. Heating-oil price are expected to be higher this year than last because refiners are paying about $5 a barrel more for crude oil than they were last year.95. One of the primary distinctions between our intelligence and that of other pirates may lie not so much in any specific skill as in our ability to extend knowledge gained in one context to new and different ones.96. Even though Clovis points, spear points with longitudinal grooves chipped onto their faces, have been found all over North America, they are named for the New Mexico site where they were fist discovered in 1932.97. Some anthropologists believe that the genetic homogeneity evident in theworld's people is the result of a "population bottleneck"——that at some time in the past our ancestors suffered an event that greatly reduced their numbers and thus our genetic variation.98. Ranked as one of the most important of Europe's young playwrights, Franz Xaver Kroetz has written 40 plays; his works——translated into more than 30 languages——as produced more often than those of any contemporary German dramatist.99. Like the planets, the stars are in motion, some of them at tremendous speed, but they are so faraway from Earth that their apparent positions in the sky do not change enough for their movement to be observed during a single human lifetime.100. Being heavily committed to a course of action, especially one that has worked well in the past, is likely to make an executive miss signs of incipient trouble or misinterpret them when they do appear.101. As rainfall began to decrease in the Southwest about the middle of the twelfth century, most of the the Monument Valley Anasazi abandoned their homes to join other clans whose access to water was less limited.102. Y ellow jackets number among the 900 or so species of the world's social wasps, wasps that live in a highly cooperative and organized society consisting almost entirely of females——the queen and her sterile female workers.103. El Nino, the periodic abnormal warming of the sea surface off Peru, is a phenomenon in which changes in the ocean and atmosphere combine to allow the warm water that has accumulated in the western Pacific to flow back to the east. 104. In her book illustration, which she carefully coordinated with her narratives, Beatrix Potter capitalized on her keen observation and love of the natural world.105. Marconi conceived of the radio as a tool for private conversation that could substitute for the telephone; instead, it has become precisely the opposite, atoll for communicating with a large, public audience.106. Originally developed for detecting air pollutants, a technique calledproton-induced X-ray emission, which can quickly analyze the chemical elects in almost any substance without destroying it, is finding uses in medicine, archaeology, and criminology.107. While the costs of running nuclear plants is about the same as for other types of power plants, the fixed costs that stem from building nuclear plants make the electricity they generate more expensive.108. Authoritative parents are more likely than permissive parents to have children who as adolescents are self-confident,high in self-esteem, and responsibly independent.109. Among the objects found in the excavated temple were small terra-cotta effigies left by supplicants who were either asking the goddess Bona Dea's aid in heating physical and mental ills or thanking her for such help.110. Published in Harlem, The Messenger was owned and edited by two young journalists, A. Philip Randolph, who would later make his reputation as a labor leader, and Chandler Owen.111. A mutual fund having billions of dollars in assets will typically invest that money in hundreds of companies, rarely holding more than one percent of the shares of any particular corporation.112. Construction of the Roman Colosseum, which was officially known as the Flavian Amphitheater, began in A.D. 69, during the reign of Vespasian, and was completed a decade later, during the reign of Titus, who opened the Colosseum with a one-hundred-day cycle of religious pageants, gladiatorial games and spectacles.113. A baby emerges from the darkness of the womb with a rudimentary sense of vision that would be rated about 20/500; an adult with such vision would be deemed legally blind.114. Starfish, with anywhere from five to eight arms, have a strong regenerative ability, and if one arm is lost it is quickly replaced, with the animal sometimes overcompensating and growing an extra one or two.115. Because the new maritime code provides that even tiny islets can be the basis for claims to the fisheries and oil fields of large sea areas, it has already stimulated international disputes over uninhabited islands.116. The original building and loan associations were organized as limited life funds, whose members made monthly payments on their share subscriptions and then took turns drawing on the funds for home mortgages.117. Gall's hypothesis that different mental functions are localized in different parts of the brain is widely accepted today.118.Mauritius was a British colony for almost 200 years, but except in the domains of administration and teaching, the English language was never really spoken on the island.119. George Sand (Aurore Lucile Dupin) was one of the first European writers to consider the rural poor legitimate subjects for literature and to portray them with sympathy and respect in her novels.120. The World Wildlife Fund has declared that global warming, a phenomenon that most scientists agree is caused by human beings' burning of fossil fuels, will create havoc among migratory birds by altering the environment in ways harmful to their habitats.121. New theories propose that catastrophic impacts of asteroids and comets may have caused reversals in the Earth's magnetic field, the onset of ice ages, the splitting apart continents 80 million years ago, and great volcanic eruptions.122. A firm that specializes in the analysis of handwriting claims to be able, from a one-page writing sample, to assess more than 300 personality traits, including enthusiasm, imagination, and ambition.123. Sales of wines declined in the late 1980s, but they began to grow again after the 1991 report that linked moderate consumption of alcohol, and particularly of red wine, with a reduced risk of heart disease.124. Less successful after she emigrated to New Y ork than she had been in her native Germany, photographer Lotte Jacobi nevertheless earned a small group of discerning admirers, and her photographs were eventually exhibited in prestigious galleries across the United States.125. T oday, because of improvements in agricultural technology, the same amount of acreage produces twice as many apples as it did in 1910.126. The use of lie detectors is based on the assumption that lying produces emotional reactions in an individual that, in turn, create unconscious physiological responses.127. Joan of Arc, a young Frenchwoman who claimed to be divinely inspired, turned the tide of English victories in her country by liberating the city of Orleans and persuaded Charles VII of France to claim his throne.128. Australian embryologists have found evidence to suggest that the elephant is descended from an aquatic animal and that its trunk originally evolved as a kind of snorkel.129. Cajuns speak a dialect brought to southern Louisiana by the 4,000 Acadians who migrated there in 1755; their language is basically seventieth-century French to which English, Spanish, and Italian words have been added.130. Over 75 percent of the energy produced in France derives from nuclear power, whereas nuclear power accounts for just over 33 percent of the energy produced in Germany.131. Although the term "psychopath" is popularly applied to an especially brutal criminal, in psychology it refers to someone who is apparently incapable of feeling compassion or the pangs of conscience.132. Although heirloom tomatoes, grown from seeds saved during the previous year, appear less appetizing than most of their round and red supermarket cousins——they are often green and striped, or have plenty of bumps and viruses——heirlooms are more flavourful and thus in increasing demand.133. Last week local shrimpers held a new conference to take some credit for the resurgence of the rare Kemp's ridley turtle, saying that their compliance with laws requiring turtle-excluder devices on shrimp nets is protecting adult sea turtles.134. Recently implemented "shift-work equations" based on studies of the human sleep cycle have reduced sickness, sleeping on the job, and fatigue among shift workers while raising production efficiency in various industries.135. Spanning more than 50 years, Friedrich Muller's career began in an unpromising apprenticeship as a Sanskrit scholar and culminated in virtually every honour that European governments and learned societies could bestow.136. Whereas in mammals the tiny tubes that convey nutrients to bone cells are arrayed in parallel lines, in birds the tubes form a random pattern.137. Joachim Raff and Giacomo Meyerbeer are examples of the kind of composer who receives popular acclaim while living, but whose reputation declines after death and never regains its former status.138. Most efforts to combat such mosquito-borne diseases as malaria and dengue have focused on either vaccinating humans or exterminating.。

医学制药英语词汇(H)医学制药英语词汇(H)医学制药英语词汇(H)h agglutination h 凝集反应h antigen h 抗原habena 系带habenula 系带habit 习惯habit chorea 抽搐habit spasm 抽搐habitual dislocation 习惯性脱位habituation 习性形成hachement 掌缘花hair 毛发hair ball 毛团hair bulb 毛球hair cell 听毛细胞hair follicle 毛囊hair germ 毛基质hair lotion 头发洗剂hair shaft 毛干hair transplantation 毛移植术hairy heart 绒毛心hairy tongue 毛舌half life 半衰期halitosis 口臭hallucination 幻觉hallucinogen 幻觉剂hallucinogenic agent 致幻觉剂hallucinosis 幻觉症halluxhallux valgus 拇指外翻hallux varus 拇指内翻halo 晕halogen 卤素halogenated phenol microbicide 卤化酚系杀微生物药halogenide 卤化物hamartia 错构组织hamartoblastoma 错构胚细胞瘤hamartoma 错构瘤hammer bone 锤骨han yan 颔厌hand 手hand frame 手推车handbarrow 手推车handicap 障碍hanot's cirrhosis 阿诺肝硬变hanot's disease 阿诺肝硬变hansen's disease 麻风haphalgesia 触痛haplodermatitis 单纯性皮肤炎haplopia 单视hapten 半抗原haptics 触觉学haptin 半抗原haptotaxis 钎性hard cancer 硬癌hard chancre 硬性下疳hard fibroma 硬性纤维瘤hard palate 硬腭hard pulse 硬脉hard rays 硬性线hard ulcer 硬性下疳hard water 硬水hare's eye 兔眼harelip 唇裂harpaxophobia 盗贼恐怖harsh breathing 支气管肺胞呼吸hashimoto's disease 桥本病hashish 大麻hashishism 大麻瘾haunch bone 骨hayfever 枯草热hbs antigen 乙型肝炎表面抗原hbsag carrier hbsag 携带者head 头head birth 头位分娩head delivery 头位分娩head nurse 护士长head presentation 头先露headache 头痛headgut 前肠healed tuberculosis 非活动性结核healing 治愈health 健康health care 卫生health carrier 健康带菌者health education 卫生教育health level 健康水平health protection 卫生事业health statistics 卫生统计health status 健康状态health survey 健康甸hearing 听觉hearing aid 助听器hearing test 听力测验heart 心脏heart beat 心搏heart block 心传导阻滞heart burn 胃灼热heart catheter 心导管heart disease cell 心病细胞heart failure 心力衰竭heart failure cell 心病细胞heart hurry 心搏过速heart lung machine 人工心肺机heart meridian 手少阴心经heart murmur 心杂音heart neurosis 心神经机能病heart shadow 心影heart shock 心原性休克heart sound 心音heart stroke 心搏heart transplantation 心移植术heat apoplexy 中暑heat collapse 热虚脱heat cramp 中暑性痉挛heat injury 灼伤heat regulating center 热蝶中枢heat stroke 中暑heated air bath 热气浴heavy chain 重链hebephrenia 青春型精神分裂症hebephrenic schizophrenia 青春型精神分裂症hebetude 兴趣丧失hebiatrics 青年病学hebotomy 耻骨切开术hectic fever 消耗热hedonophobia 欢乐恐怖hedratresia 肛门闭锁hedrocele 直肠突出heel bone 跟骨heel tap reflex 足跟反射heine medin disease 髓灰质炎helcology 溃疡学helcoplasty 溃疡成形术helcosis 溃疡形成heliation 日光疗法helicopodia 螺旋形步态helioencephalitis 日射性脑炎heliopathy 日光病heliophobia 日光恐怖heliosensitivity 光敏性heliosis 日射病heliotherapy 日光疗法helix 耳轮helmet headache 盔形头痛helminth 蠕虫helminth infestation 蠕虫侵袭helminthagogue 抗蠕虫药helminthiasis 蠕虫病helminthic infection 蠕虫感染helminthicide 杀虫剂helminthology 蠕虫学heloma 鸡眼helosis 鸡眼helper cell 协助细胞hemabarometer 血比重计hemacytometer 血细胞计数器hemadynamics 血液动力学hemafecia 便血hemagglutination 血凝反应hemagglutinin 血凝素hemagonium 原血细胞hemanalysis 血液分析hemangiectasia 血管扩张hemangiectasis 血管扩张hemangioblastoma 成血管细胞瘤hemangioendothelioma 血管内皮瘤hemangiofibroma 血管纤维瘤hemangioma 血管瘤hemangiopericytoma 血管外皮细胞瘤hemapheic jaundice 尿胆素性黄疸hemarthrosis 关节血肿hematapostema 血脓疡hemateikon 血像hematemesis 呕血hematencephalon 脑出血hematherapy 血液疗法hematidrosis 血汗hematimeter 血细胞计数器hematinic 补血药hemato encephalic barrier 血脑屏障hematobilia 胆道出血hematocatharsis 清血法hematocele 血肿hematocelia 腹腔积血hematocephalus 头血肿hematochemistry 血液化学hematocrit 血细胞比容hematodinamics 血液动力学hematogenous metastasis 血原性转移hematoglobulin 血红蛋白hematohistology 血液病组织学hematologist 血液学家hematology 血液学hematoma 血肿hematomancy 验血诊断hematometra 子宫积血hematometry 血测定hematomole 血肿性胎块hematomphalocele 血脐疝hematomyelia 脊髓出血hematomyelitis 出血性脊髓炎hematoncometry 血容积测量法hematonic 补血药hematopenia 血液不足hematophage 噬血细胞细胞hematophagocyte 噬血细胞细胞hematoplania 代偿性月经hematopoietic 补血药hematopoietic factor 成血因子hematopoietic tissue 成血组织hematoporphyria 血卟啉病hematoporphyrinuria 血卟啉尿hematoscheocele 阴囊积血hematoscope 血分光镜hematosepsis 败血病hematospectroscopy 血分光镜检查hematosteon 骨髓腔积血hematuria 血尿heme 血红素hemeralopia 昼盲hemiageusia 偏侧味觉缺失hemialgia 偏侧痛hemiamaurosis 偏盲hemianacusia 单侧聋hemianesthesia 偏侧感觉缺失hemianopia 偏盲hemianosmia 偏侧嗅觉缺失hemiapraxia 偏侧失用症hemiasynergia 偏侧协同运动不能hemiataxia 偏身运动失调hemiathetosis 偏侧手足徐动症hemiatrophy 偏侧萎缩hemiballism 偏身颤搐hemic calculus 静脉石hemicephalalgia 偏头痛hemicerebrum 大脑半球hemichorea 偏身舞蹈病hemichromatopsia 偏色盲hemicolectomy 半结肠切除术hemicrania 半无脑hemidysergia 偏身传出性运动失调hemiepilepsy 偏身癫痫hemiglossectomy 半侧舌切除术hemignathia 半下颌畸形hemihypertonia 偏侧肌过度紧张hemihypertrophy 偏身肥大hemihypesthesia 偏身感觉迟钝hemilaminectomy 偏侧椎板切除术hemilaryngectomy 偏侧喉切除术hemimelia 半肢畸形heminephrectomy 半肾切除术hemipagus 胸侧联胎hemiparaplegia 偏侧下身麻痹hemiparesis 轻偏瘫hemiplegia 偏瘫hemisacralization 偏侧腰椎化hemispasm 偏侧痉挛hemisphere 半球hemispherectomy 大脑半球切除术hemivagotony 偏侧迷走神经紧张症hemobarometer 血比重计hemocholecyst 胆囊积血hemocholecystitis 出血胆囊炎hemochromatosis 血色素沉着hemochromometer 血色仪hemoconcentration 血浓缩hemoculture 血培养hemocyte 血细胞hemocytoblast 原血细胞hemocytology 血细胞学hemocytolysis 溶血hemocytometer 血球计hemocytopenia 血细胞减少hemocytozoon 血液寄生物hemodiagnosis 验血诊断hemodialysis 血液肾透析hemodialysis system 血液透析系统hemodilution 血液稀释hemodromograph 血临度描记器hemodromometer 血临度计hemodynamics 血力学hemodynamometer 血压计hemodynamometry 血压测定法hemoglobin 血红蛋白hemoglobinemia 血红蛋白血hemoglobinolysis 血红蛋白分解hemoglobinometry 血红蛋白测定法hemoglobinopathy 血红蛋白病hemoglobinuria 血红蛋白尿hemoglobinuric fever 血红蛋白尿热hemoglobulin 血红蛋白hemogram 血像hemohydraulics 血液水力学hemokoniosis 血尘病hemology 血液病理学hemolymph 血淋巴hemolysin 溶血素hemolysis 溶血hemolytic anemia 溶血性贫血hemolytic chain 溶血链hemolytic jaundice 溶血性黄疸hemolytic poison 溶血毒hemolytic reaction 溶血反应hemolytic uremic syndrome 溶血性尿毒症综合征hemomediastinum 纵隔积血hemometer 血红蛋白计hemonephrosis 肾盂积血hemooncology 血液肿瘤学hemopathology 血液病理学hemopathy 血液病hemoperfusion 血液灌注hemopericardium 心包积血hemoperitoneum 腹腔积血hemopexis 血凝固hemophilia 血友病hemophthalmia 眼球积血hemopleura 血胸hemopneumopericardium 血气心包hemopneumothorax 血气胸hemopoiesis 血生成hemopoietic cell 生血细胞hemopoietic system 生血系统hemoptysis 咯血hemorrhachis 椎管内出血hemorrhage 出血hemorrhagic anemia 出血性贫血hemorrhagic cystitis 出血性膀胱炎hemorrhagic diathesis 出血素质hemorrhagic fever 出血热hemorrhagic infarct 出血性梗塞hemorrhagic pleurisy 出血性胸膜炎hemorrhagic shock 出血性休克hemorrhea 大出血hemorrheology 血液龄学hemorrhoid 痔hemorrhoidectomy 痔切除术hemosiderinuria 含铁血黄素尿症hemosiderosis 含铁血黄素沉着hemospermia 血性精液hemosputum 血痰hemostasis 止血hemostatic 止血药hemostatic method 止血法hemostatic suture 止血缝合hemotherapy 血液疗法hemothorax 血胸hemotympanum 鼓室积血heng ku 横骨henle's loop 享勒襻hens' egg 鸡蛋hepaptosis 肝下垂heparinization 肝素化heparinocyte 肝素细胞hepatalgia 肝痛hepatargia 肝衰竭hepatatrophia 肝萎缩hepatectomy 肝切除术hepatic amebiasis 肝阿米巴病hepatic bile 肝胆汁hepatic cell 肝细胞hepatic cirrhosis 肝硬变hepatic coma 肝性昏迷hepatic cords 肝细胞索hepatic echography 肝回波描记术hepatic failure 肝衰竭hepatic fetor 肝病性口臭hepatic insufficiency 肝衰竭hepatic lobule 肝小叶hepatic tumor 肝瘤hepatico duodenostomy 肝十二指肠吻合术hepatico enterostomy 肝小肠吻合术hepatico gastrostomy 肝管胃吻合术hepatico jejunostomy 肝管空肠吻合术hepaticotomy 肝管切开术hepatitis 肝炎hepatitis virus 肝炎病毒hepatization 肝样变hepatoblastoma 肝胚细胞瘤hepatocarcinoma 肝癌hepatocele 肝突出hepatocellular carcinoma 肝细胞癌hepatocellular jaundice 肝细胞性黄疸hepatocerebral syndrome 肝脑综合征hepatocholangioduodenostomy 肝管十二指肠吻合术hepatocholangioenterostomy 肝管肠吻合术hepatocholangiogastrostomy 肝管胃吻合术hepatocholangiostomy 胆管造口术hepatocirrhosis 肝硬变hepatocyte 肝细胞hepatodynia 肝痛hepatogenous diabetes 肝原性糖尿病hepatogram 肝搏动图hepatography 肝x 线照相术hepatolenticular degeneration 肝豆状核变性hepatolith 肝石hepatolithectomy 肝石切除术hepatolithiasis 肝石病hepatology 肝脏病学hepatoma 肝细胞瘤hepatomegalia 肝大hepatomegaly 肝大hepatomelanosis 肝黑变病hepatomphalocele 脐部肝突出hepatomphalos 脐部肝突出hepatonephritis 肝肾炎hepatopexy 肝固定术hepatorenal syndrome 肝肾综合征hepatorrhagia 肝出血hepatorrhaphy 肝缝术hepatorrhea 肝液溢hepatorrhexis 肝破裂hepatoscintigram 肝闪烁图hepatoscopy 肝检查hepatosis 肝机能障碍hepatosplenography 肝脾x 线照相术hepatosplenomegaly 肝脾大hepatotherapy 肝剂疗法hepatotomy 肝切开术hepatotoxemia 肝性毒血病hepatotoxicity 肝毒性herb tea 药茶herbicide 除莠剂hereditary 遗传的hereditary character 遗传性状hereditary hemorrhagic telangiectasia 遗传性出血性毛细管扩张hereditary spherocytosis 遗传性球形红细胞症heredity 遗传heredoimmunity 遗传免疫heredopathia 遗传性疾病heredosyphilology 遗传梅毒学heritability 遗传力heritable variation 遗传性变异hermaphroditism 两性畸形hernia 疝hernial sac 疝囊herniation 疝形成herniology 疝病学hernioplasty 疝根治术herniorrhaphy 疝缝术herniotomy 疝切开术heroinism 海洛因瘾herpangina 疱疹性咽峡炎herpes 疱疹herpes simplex 单纯性疱疹herpes zoster 带状疱疹herpetic keratitis 角膜疱疹herpetiform 疱疹样的heteroautoplasty 自身异位移植heterochromia 虹彩异色性heterochrony heterochronia 异时现象heterodymus 非对称联胎heterogeneity 异种性heteroinfection 外源性传染heterointoxication 外源性中毒heterokaryon 异核体heterokeratoplasty 异种角膜成形术heteromeral cells 连合细胞heterometropia 屈光参差heteromorphosis 异形再生heteropagus 非对称联胎heterophoria 隐斜眼heterophthalmia 两眼异色heteroplasia 发育异常heteroplasty 异种组织移植术heteroploidy 异倍体性heteropsia 双眼不等视heterorexia 味觉异常heteroserotherapy 异种血清疗法heterosexuality 异性性欲heterosis 杂种优势heterotaxia 内脏异位heterotaxy 内脏异位heterotonia 张力变异heterotopia 异位heterotopic pain 异位痛heterotopic transplantation 异位移植heterotransplantation 异种移植heterotrichosis 毛异色heterotropia 斜眼heterotropic chromosome 异型染色体heterovaccine 异种疫苗heterozygosity 杂合性heterozygote 杂合子hexamethonium 六烃季铵hexenal 环已巴比妥hexenmilch 新生儿乳hexobarbital 环已巴比妥hibernation 冬眠hibernoma 蛰伏脂瘤hiccough 打呃hiccup 打呃hidradenitis 汗腺炎hidradenoma 汗腺腺瘤hidrocystoma 汗腺囊瘤hidropoiesis 汗生成hidroschesis 止汗hieralgia 骨痛high calorie diet 高卡饮食high pelvic position 特伦德伦伯格卧位high protein diet 高蛋白饮食hillock 小丘hilus 门himantosis 悬雍垂延长hind kidney 后肾hindbrain 菱脑hindgut 后肠hip bone 骨hippocamp 海马hippocampal gyrus 海马回hippuric acid 马尿酸hippus 虹膜震颤hirci 腋毛hircismus 腋窝臭hirsutism 多毛hirudin 水蛭素hirudiniasis 水蛭病histamine release test 组胺试验histiocytoma 组织细胞瘤histiocytosis 组织细胞增多病histiocytosis x 组织细胞增多病x histioid tumor 组织瘤histoanatomy 组织解剖学histochemistry 组织化学histocompatibility 组织相容性histocompatibility antigen 组织相容性抗原histocyte 组织细胞histodiagnosis 组织学诊断histofluorescence 组织荧光histogenesis 组织发生histogeny 组织发生histoincompatibility 组织不相容的histologic anatomy 组织学histology 组织学histolysis 组织分解histoma 组织瘤histone 组蛋白histoneurology 神经组织学histopathology 病理组织学histoplasmosis 组织胞浆菌病historadiography 自体放射照相法history 历史histotherapy 组织疗法hla antigen hla 抗原ho ku 合谷ho liaoho liao te 22ho yang 合阳hoarse voice 嘶哑hoarseness 嘶哑hobnail liver 鞋钉状肝hodgkin's disease 何杰金氏病holandric gene 全雄基因holarthritis 多关节炎hollow back 脊柱前凸hollow foot 凹足holoacardius 无心寄生胎畸胎holocrine gland 全分泌腺holoprosencephaly 前脑无裂畸形holotherapy 全息医疗home care 家庭护理homeopath 顺势医疗者homeopathic remedy 顺式治疗药homeopathist 顺势医疗者homeopathy 顺势疗法homeostasis 体内平衡homergy 正常代谢homesickness 怀乡病homicide 杀人homicidomania 杀人狂homoeroticism 同性恋homogamete 同型配子homogametic 同型配子的homogeneity 均质性homogenesis 同型生殖homogenization 均化homogenizer 均质器homogeny 同型生殖homologous chromosome 同源染色体homology 同种性homosexualism 同性恋homosexuality 同性恋homotopic transplantation 正位移植homozygote 纯合子honeycomb lung 蜂窝肺honeycomb tetter 黄癣hookworm 钩虫hookworm disease 钩虫病hordeolum 睑腺炎horismascope 尿蛋白测定仪horizocardia 水平心horizontal transmission 水平传播hormone 激素hormone dependent tumor 激素依赖性瘤hormonology 内分泌学hormonoprivia 激素缺乏hormonotherapy 激素疗法horn 角horny layer 角质层hospital 医院hospital care 住院治疗hospital gangrene 医院坏疽hospital infection 院内感染hospital mortality 医院死亡率hospitalization 住院host 宿主hot compress 温敷布hou hsi 后溪hou ting 后顶hourglass stomach 葫芦胃hourglass tumor 哑铃瘤house fly 家蝇hsia hsi 侠溪hsia kuan 下关hsia liaohsia lien 下廉hsia pai 侠白hsia wan 下脘hsiao chang shu 小肠俞hsiao hai 小海hsiao lo 消泺hsien ku 陷谷hsin hui 囟会hsin shu 心俞hsing chien 行间hsiung hsiang 胸乡ht 1 极泉ht 2 青灵ht 3 少海ht 4 灵道ht 5 通里ht 6 阴郄ht 7 神门ht 8 少府ht 9 少冲ht 手少阴心经hua jou men 滑肉门hua kai 华盖huang men 肓门huang shu 肓俞huant t'iao 环跳hueo yin 会阴huge fetus 巨大胎hui yang 会阳human ecology 人类生态学human genetics 人类遗传学humectant 湿剂humectation 增湿humic acid 腐植酸humid gangrene 湿性坏疽humid tetter 湿性湿疹humidification 增湿humidifier 增湿器humidity 湿度humor 体液humoral immunity 体液免疫humoral pathology 体液病理学humpback 脊柱后凸hun men 魂门hunger edema 饥饿水肿hunger sensation 饥饿感hunger therapy 饥饿疗法huo chung 或中huoi tsung 会宗hutchinson's teeth 哈钦森牙hyaline 透檬hyaline cast 玻璃样圆柱hyaline membrane disease 透盲病hyaline thrombus 玻璃样血栓hyalinosis 透娩性hyaloplasm 透檬hybaroxia 高压充氧hybrid 杂种hybridation 杂交hydatid 包虫hydatid disease 包虫病hydatid mole 葡萄胎hydatid pregnancy 葡萄胎妊娠hydatidoma 包虫囊肿hydatidosis 包虫病hydatidostomy 棘球囊切引刘hydramnion 羊水过多hydramnios 羊水过多hydranencephaly 积水性无脑hydrargyria 汞中毒hydrargyris 汞中毒hydrargyrism 汞中毒hydrarthrosis 关节水肿hydremia 血水分过多hydriatrics 水疗法hydride 氢化物hydroappendix 阑尾积水hydrocalycosis 肾盏积水hydrocardia 心包积水hydrocele 水囊肿hydrocephalus 脑积水hydrocholecystis 胆囊积水hydrocolpocele 阴道积液hydrocolpos 阴道积液hydrocyanism 氢氰酸中毒hydrocyst 水囊肿hydrocystoma 水囊肿hydrodipsomania 剧渴性癫狂hydrodiuresis 低渗尿hydrogen 氢hydrogymnastics 水中运动疗法hydrokinesitherapy 水中运动疗法hydrolability 水分不稳定性hydrolysate 水解物hydrolysis 水解hydroma 水囊瘤hydromassage 水按摩hydromeningitis 浆液性脑膜炎hydromeningocele 积水性脑膜突出hydrometrocolpos 子宫阴道积水hydronephrosis 肾盂积水hydropenia 缺水hydropericarditis 积水性心包炎hydropericardium 心包积水hydroperitoneum 腹水hydrophobe 恐水病的hydrophobia 狂犬病hydrophobic 恐水病的hydrophobic base 疏水性基质hydropic degeneration 水肿性变性hydropneumopericardium 水气心包hydropneumoperitoneum 水气腹hydropneumothorax 水气胸hydrops 积水hydropsy 积水hydrorrhea 液溢hydrosalpinx 输卵管积水hydrosarca 全身水肿hydrosarcocele 睾丸积水肉样肿hydroscheocele 积水性阴囊疝hydrosis 多汗hydrospirometer 水柱肺活量计hydrosyringomyelia 脊髓积水空洞症hydrotherapy 水疗法hydrothorax 胸膜积水hydrotubation 输卵管通水hydroureter 输尿管积水hydruria 稀尿症hygienesanitary science 卫生hygienics 卫生hygiology 卫生学hygroma 水囊瘤hylophobia 森林恐怖hymen 处女膜hymenitis 处女膜炎hymenolepiasis 膜壳绦虫病hymenotomy 处女膜切开术hyoid 舌骨形的hyoid arch 舌骨弓hyoid bone 舌骨hypalgesia 痛觉减退hypalgia 痛觉减退hypamnion 羊水过少hypengyophobia 责任恐怖hyperacanthosis 棘皮层增殖hyperacidity 酸过多hyperacusis 听觉过敏hyperadenosis 淋巴腺增大hyperadiposis 肥胖过度hyperadiposity 肥胖过度hyperadrenalemia 血肾上腺素过多hyperadrenocorticism 肾上腺皮质机能亢进hyperaldosteronism 醛甾酮过多症hyperalgesia 痛觉过敏hyperalgia 痛觉过敏hyperalimentation 饮食过量hyperammonemia 血氨过多hyperanakinesia 运动过多病hyperaphia 触觉过敏hyperbaric oxygenation 高压氧合疗法hyperbarism 高气压病hyperbilirubinemia 血胆红素过多hypercalcemia 血钙过多hypercalcinuria 高钙尿hypercalciuria 高钙尿hypercapnia 碳酸过多hypercarbia 碳酸过多hypercementosis 牙骨质增生hyperchlorhydria 胃酸过多hypercholesteremia 血胆甾醇过多hypercholesterolemia 血胆甾醇过多hypercholia 胆汁过多hyperchromatism 着色过度hyperchromia 着色过度hypercinesia 运动机能亢进hypercoagulability 凝固性过高hypercorticalism 皮质机能亢进hypercorticoidism 皮质机能亢进hypercrinia 内分泌过多hypercryalgesia 冷觉过敏hypercryesthesia 冷觉过敏hyperemesis 剧吐hyperemesis gravidarum 妊娠剧吐hyperemia 充血hyperemization 人工充血法hyperergasia 活动力过强hyperergy 超反应性hyperesthesia 感觉过敏hyperextension 伸展过度hyperfibrinogenemia 高纤维蛋白原血hyperfunction 机能亢进hypergalactia 乳汁过多hypergalactosis 乳汁过多hypergammaglobulinemia 血丙种球蛋白过多hypergasia 机能减退hypergenesis 发育过度hypergenitalism 生殖脾育过度hypergeusia 味觉过敏hyperglobulinemia 血球蛋白过多hyperglobulism 红细胞增多hyperglycemia 高血糖hyperglycorrhachia 脑脊液糖分过多hypergonadism 生殖脾育过度hyperidrosis 多汗hyperimmunoglobulinemia 高免疫球蛋白血症hyperinsulinemia 血胰岛素过多hyperinvolution 复旧过度hyperkalemia 高钾血hyperkeratosis 皮肤角化病hyperkinesia 运动过多病hyperkinesis 运动机能亢进hyperleukocytosis 白细胞增多hyperlipemia 血脂过多hyperlipoidemia 血脂过多hyperlipoproteinemia 血脂蛋白过多hypermagnesemia 血镁过多hypermastia 乳腺肥大hypermelanosis 色素沉着过多hypermenorrhea 月经过多hypermetabolism 代谢增进hypermimia 表情过分hypermnesia 记忆过旺hypermotility 运动过强hypermyotonia 肌张力过度hypernatremia 血钠过多hyperneocytosis 幼稚白细胞增多hypernephroma 肾上腺样瘤hypernutrition 营养过度hyperonychia 甲肥大hyperonychosis 甲肥大hyperopia 远视hyperopic astigmatism 远视散光hyperorchidism 睾丸机能亢进hyperosmia 嗅觉过敏hyperospheresia 嗅觉过敏hyperovaria 卵巢机能亢进hyperovarism 卵巢机能亢进hyperoxaluria 高草酸盐尿hyperoxemia 血酸过多hyperoxia 氧过多hyperpancreatism 胰液分泌机能亢进hyperparasitism 重寄生hyperparathyroidism 甲状旁腺机能亢进hyperparotidism 腮腺机能亢进hyperpepsia 消化酶分泌过多hyperpepsinia 胃蛋白酶过多hyperperistalsis 蠕动过强hyperphoria 上隐斜视hyperphrenia 精神兴奋过度hyperpigmentation 色素沉着过多hyperpituitarism 垂体机能亢进hyperplasia 增生hyperpnea 呼吸过度hyperprochoresis 蠕动过强hyperproteinemia 血蛋白过多hyperpyrexia 高热hyperreflexia 反射亢进hypersalivation 多涎hypersarcosinemia 高肌氨酸血症hypersecretion 分泌过多hypersensitiveness 敏感过度hypersensitivity 敏感过度hypersialosis 多涎hyperskeocytosis 幼稚白细胞增多hypersomnia 睡眠过度hypersplenism 脾机能亢进hypersteatosis 皮脂分泌过多hypersthenia 体力过盛hypersthenuria 高比重尿hypersusceptibility 感受性过强hypertelorism 距离过远hypertension 高血压hypertensive encephalopathy 高血压性脑病hypertensive heart disease 高血压性心病hypertensor 加压剂hyperthelia 多乳头hyperthermia 高热疗法hyperthermy 高热疗法hyperthrombinemia 血凝血酶过多hyperthymia 情感增盛hyperthymism 胸腺机能亢进hyperthymization 胸腺机能亢进hyperthyroid heart disease 甲状腺机能亢进心病hyperthyroidism 甲状腺机能亢进hypertoxicity 剧毒性hypertrophic cardiomyopathy 肥大型心肌病hypertrophic gastritis 肥大性胃炎hypertrophy 肥大hypertropia 上斜视hypertyrosinemia 血酪氨酸过多hyperuricemia 血尿酸过多hyperuricuria 尿尿酸过多hypervaccination 超接种hyperventilation 换气过度hyperventilation syndrome 过度换气综合征hyperviscosity 粘滞性过高hypervitaminosis 维生素过多hypervolemia 血容量过多hypesthesia 感觉减退hyphedonia 快感减少hyphema 眼前房出血hyphidrosis 少汗症hypnagogic 催眠的hypnagogic hallucination 入睡前幻觉hypnagogue 安眠药hypnalgia 睡眠疼痛hypnesthesia 嗜眠hypnogenesis 催眠hypnolepsy 发自睡病hypnologist 催眠术者hypnonarcosis 催眠麻醉法hypnophobia 睡眠恐怖hypnosis 催眠术hypnotherapy 催眠疗法hypnotic 安眠药hypnotic state 催眠状态hypnotization 诱导催眠hypnotizer 催眠术者hypoacidity 酸过少hypoacusis 听觉减退hypoadenia 腺机能减退hypoadrenalism 肾上腺机能减退hypoadrenia 肾上腺机能减退hypoalbuminemia 血白蛋白减少hypoalimentation 营养不足hypobaropathy 低气压病hypobulia 意志薄弱hypocalcemia 血钙过少hypocapnia 碳酸过少hypochloremia 血氯过少hypochlorhydria 胃酸过少hypocholia 胆汁过少hypochondria 疑病hypochondriasis 疑病hypochondrium 季肋部hypochromasia 血红蛋白过少hypochromatosis 细胞核消失hypochromia 血红蛋白过少hypochylia 胃液过少hypocinesia 运动减少hypocorticalism 肾上腺皮质机能减退hypocorticoidism 肾上腺皮质机能减退hypocrinism 内分泌过少hypocystotomy 经会阴膀胱切开术hypoderm 皮下组织hypodermic tablet 皮下注射片hypodermoclysis 皮下输液hypoesthesia 感觉减退hypoexophoria 下外隐斜眼hypofunction 机能减退hypogalactia 乳汁减少hypogammaglobulinemia 血丙种球蛋白过少hypogastrium 腹下部hypogastropagus 下腹联胎hypogenesis 发育不全hypogenitalism 性腺机能减退hypogeusia 味觉减退hypoglossal nerve 舌下神经hypoglycemia 低血糖hypoglycemic agent 血糖下降药hypoglycorrhachia 脑脊液糖分过少hypogonadism 性腺机能减退hypogranulocytosis 粒细胞过少症hypohemia 贫血hypohepatia 肝衰竭hypohydration 水分过少hypohydrochloria 胃酸过少hypokalemia 血钾过少hypokinemia 心输出血量不足hypokinesia 运动减少hypokinesis 运动减少hypoleydigism 莱迪希间介细胞机能减退hypolipidemia 血脂过少hypolymphemia 淋巴细胞减少hypomastia 乳腺过小hypomenorrhea 月经过少hypometabolism 代谢减退hypometria 伸展不足hypomineralization 矿质过少hypomnesia 记忆减退hypomnesis 记忆减退hypomotility 运动减弱hypomyotonia 肌张力减低hypomyxia 粘液减退hyponatremia 血钠过少hyponutrition 营养不良hyponychium 甲床hypopancreatism 胰腺机能减退hypoparathyroidism 甲状旁腺机能减退hypopepsia 消化不良hypoperistalsis 蠕动退缓hypophonia 发声过弱hypophoria 下隐斜视hypophosphatasia 磷酸酯酶过少hypophosphatemia 血磷酸盐过少hypophrenia 智力薄弱hypophyseal cachexia 垂体性恶病质hypophyseal infantilism 垂体性幼稚型hypophyseal syndrome 垂体综合征hypophysectomy 垂体切除hypophysis 垂体hypophysoma 垂体瘤hypopituitarism 垂体机能减退hypoplasia 形成不全hypoplasty 形成不全hypoplasy 形成不全hypoporosis 骨痂形成不全hypopotassemia 血钾过少hypoproteinemia 血蛋白过少hypoprothrombinemia 低凝血酶原血hyposecretion 分泌减少hyposensitivity 感受性hyposensitization therapy 脱敏疗法hyposialadenitis 颌下腺炎hyposmia 嗅觉减退hypospadia 尿道下裂hypostasis 坠积hypostatic pneumonia 坠积性肺炎hyposthenuria 低渗尿hypostosis 骨发育不全hyposynergia 协同不足hypotaxia 控制力减弱hypotension 低血压hypotensive agent 抗高血压剂hypotensive anesthesia 低血压麻醉hypothalamus 丘脑下部hypothenar 小指球hypothermal medicine 低温医学hypothermia 体温降低hypothermy 体温降低hypothesis 假说hypothymism 胸腺机能减退hypothyroid infantilism 甲状腺机能减退性幼稚型hypothyroidism 甲状腺机能减退hypotonia 张力减退hypotonic solution 低张液hypotonus 张力减退hypotony 张力减退hypotrichosis 稀毛hypotrophy 营养不足hypotropia 下斜视hypovaria 卵巢机能减退hypovarionism 卵巢机能减退hypoventilation 肺换气不足hypovitaminosis 维生素缺少hypoxemia 血氧过少hypoxia 氧过少hypoxidosis 氧过少hypurgia 护理hysteralgia 子宫痛hysterectomy 子宫切除术hysteria 癔病hysteric pregnancy 精神性假妊娠hysterical aphonia 癔病性失声hysterical blindness 癔病盲hysterical chorea 癔病性舞蹈病hysterical personality 歇斯底里人格hysterical state 癔病状态hystericism 癔病素质hysterics 癔病发作hysteritis 子宫炎hysterocele 子宫疝hysterocervicotomy 子宫颈切开hysterocleisis 子宫口闭合术hysterodynia 子宫痛hysterogram 子宫收缩描记图hysterology 子宫学hysteromyoma 子宫肌瘤hysteromyomectomy 子宫肌瘤切除术hysteropexy 子宫固定术hysterophore 子宫托hysteroplasty 子宫成形术hysteroptosia 子宫下垂hysteroptosis 子宫下垂hysterorrhaphy 子宫缝术hysterorrhexis 子宫破裂hysterosalpingography 子宫输卵管照相术。

Available online at Astrocyte heterogeneity:an underappreciated topic in neurobiologyYe Zhang and Ben A BarresAstrocytes,one of the most numerous types of cells in the central nervous system,are crucial for potassium homeostasis,neurotransmitter uptake,synapse formation,regulation of blood –brain-barrier,and the development of the nervous system.Historically,astrocytes have been studied as a homogeneous group of cells.However,evidence hasaccumulated that suggests heterogeneity of astrocytes across brain regions as well as within the same brain regions.Astrocytes differ in their morphology,developmental origin,gene expression profile,physiological properties,function,and response to injury and disease.A better understanding of the heterogeneity of astrocytes will greatly aid investigation of the function of astrocytes in normal brain as well as the roles of astrocytes in neurological disorders.Address299Campus Dr.West.Department of Neurobiology Stanford University,Stanford,CA 94305-5125,United StatesCorresponding author:Zhang,Ye (zhangye@ )Current Opinion in Neurobiology 2010,20:588–594This review comes from a themed issue on Neuronal and glial cell biologyEdited by Michael Ehlers and Franck Polleux Available online 23rd July 20100959-4388/$–see front matter#2010Elsevier Ltd.All rights reserved.DOI 10.1016/j.conb.2010.06.005Astrocytes,or astroglia,are named with the Greek root word ‘astro’,which means star.They are named so because of the ‘stars in the night sky’appearance on Golgi stained sample.In the late nineteenth century and the early twentieth century Camillo Golgi and Ramon y Cajal had already noticed that although astrocytes share the stellate feature,their morphology is extremely diverse (Figure 1,[1]),perhaps as diverse as the morphology of different types of neurons.Modern scientists have con-firmed the morphological diversity of astrocytes in vitro and in vivo [2–4].Since Cajal’s time,neurobiology has developed in a way that the understanding of glia lags a long way behind the understanding of neurons.We now have learned much about the function of neurons and also the functional diversity of neurons with different morphology.Forexample,pyramidal shaped neurons project long axons and transmit information over a long distance.Inter-neurons of various shapes modulate local circuits and each morphologically distinct class (e.g.basket cells,chandelier cells)has a distinct physiological and func-tional signature.Though the heterogeneity of astrocytes was documented over a century ago,we are only begin-ning to understand the function of astrocytes in the past two decades.In addition to the long recognized role of astrocytes in regulating extracellular concentrations of potassium ion and neurotransmitters,astrocytes also promote synapse formation,regulate blood –brain-barrier,respond to neuronal activation,communicate with neurons by releasing gliotransmitters,and function as neural stem cells (reviewed in [5]).Whether these func-tions are shared by all astrocytes or just specific subsets is less clear.In this review,we will summarize recent progress on the heterogeneity of astrocytes from different brain regions as well as the heterogeneity of astrocytes within the same brain region.We argue that knowledge of the functional heterogeneity of astrocytes is urgently needed.This knowledge would greatly facilitate investigations of neuron –glia interactions and might generate novel approaches of treating neurological disorders as astrocytes are involved in almost every disease of the nervous system.Readers are directed to a few more detailed reviews to obtain a more complete view of the field [6–8].Developmental heterogeneityDifferent types of neurons originate from distinct pro-genitors.For example,cortical projection neurons originate from progenitors in the embryonic ventricular zone and they migrate radially to their final location.By contrast,cortical GABAergic interneurons arise from pro-genitors in the embryonic subpallium region and migrate tangentially to the cortex [9].Astrocytes are found throughout the central nervous system.Do they arise from the same pool of progenitors or distinct groups of progenitors?The latter is true,at least in the spinal cord.Rowitch and colleagues demonstrated a domain specific requirement of the transcription factor scl for astrocyte production in the p2domain of the spinal cord [10].Anderson and colleagues identified three positionally distinct groups of white matter astrocytes in the spinal cord that derive from distinct progenitor domains [11 ].Similarly,in Drosophila several different types of glia cells,including astrocyte-like cells,are found to arise from different precursors and the development of sometypes of these glia cells require the transcription factor,gcm,whereas other types do not [12,13 ].Astrocytes differ in their proliferation potential.Subsets of astrocytes in the adult subventricular zone (SVZ)in the walls of the lateral ventricals and the subgranular zone (SGZ)in the dentate gyrus of hippocampus are neural stem cells whereas most astrocytes in other parts of the adult brain do not normally proliferate (reviewed in [14]).Intriguingly,the electrophysiological properties of astro-cytes that function as neural stem cells are similar to those of other astrocytes in the brain [15].Thus,there is hidden heterogeneity in the seemingly homogeneous population of astrocytes that sometimes can only be revealed by very careful investigation.Reprogramming differentiated cells in the adult brain to become stem cells is bringing hope to treating neurological disorders,for example,Parkinson’s disease.Astrocytes in the adult brain can be repro-grammed to become radial glial cells that give rise to new neurons.But only a subset of astrocytes has that potential [16].The molecular mechanism that differen-tiates astrocyte subtypes in their proliferation potential isstill elusive.Astrocytomas,one of the most common types of brain tumors,typically occur in specific brain regions.One possible reason for the regional difference in tumor susceptibility is the regional difference in the ability of astrocytes to proliferate.Indeed,a tumor suppressor gene was reported to be differentially expressed by astrocytes from different brain regions [17 ].Astrocytes are crucial at every step of neural develop-ment.They function as neural stem cells and generate neurons [14];they stimulate neurite outgrowth [18];they guide axon projections [19];they promote synapse for-mation [20–22],and they maintain neuronal survival [18].The field of neural development would progress more rapidly if we have a better understanding of how different subtypes of astrocytes develop.Gene expression heterogeneityExtensive evidence showed that astrocytes are highly heterogeneous with regard to their gene expression pro-fiing a novel translational profiling approach called translating ribosome affinity purification (TRAP),HeintzAstrocyte heterogeneity:an underappreciated topic in neurobiology Zhang and Barres 589Figure1Morphological heterogeneity of astrocytes.Golgi staining of astrocytes in the human cerebellum by Ramon y Cajal.b,Bergmann glia.s,smooth protoplasmic astrocytes.v,velate astrocytes.f,fibrous astrocytes.M,molecular layer.P,Purkinje cell layer.G,granule cell layer.W,whitematter.Modified from [8].Reproduced with kind permission from Springer Science+Business Media:Astrocytes in (patho)physiology of the nervous system,astrocyte heterogeneity or homogeneity?2009,page 3,Harold Kimelberg,figure 1-1.and colleagues compared translated mRNAs in cortical astrocytes,cerebellar astrocytes,and cerebellar Bergman glia,and reported substantial differences in gene expres-sion between astrocytes from different brain regions [23 ].A recent microarray analysis of cultured astrocytes from four different brain regions also revealed major gene expression differences[17 ].In addition to the above mentioned genome wide gene expression studies,numer-ous other studies identified a large number of genes that are differentially expressed by subsets of astrocytes in vivo or in vitro.These genes encode proteins including surface glycoproteins[24],neuropeptides[25,26],sodium channels[27],potassium channels[28–31],metabotropic glutamate receptors[32],NMDA receptors[33],dopa-mine receptors[34],opioid receptors[35],adrenergic receptors[36,37],oxytocin receptors[38],erbB receptors [39],adenosine receptors[40,37],glutamate transporters [41,42],glycine transporters[43],nitric oxide synthase [44],monoamine oxidase(which breaks down dopamine and serotonin),and g-aminobutyric acid(GABA)trans-aminase(which breaks down GABA)[45].Even glial fibrillary acidic protein(GFAP),an intermediatefillament protein once thought to be the‘pan-astrocyte’marker,is heterogeneously expressed by different types of astro-cytes.GFAP is highly expressed in white matter astro-cytes(fibrous astrocytes)and expressed at very low levels in grey matter astrocytes(protoplasmic astrocytes)[46]. So far the most widely and homogeneously expressed astrocyte specific protein is Aldh1L1[46].The heterogeneity of gene expression in astrocytes implies functional diversity of astrocytes.For example, differences in surface glycoprotein expression suggest differences in astrocyte–neuron interactions or astro-cyte–astrocyte interactions;differences in neuropeptide expression suggest differences in peptidergic signaling activity;and differences in the expression of enzymes that break down dopamine,serotonin,and GABA suggest differences in their role in neurotransmitter metabolism. To date,the functional implications of gene expression heterogeneity of astrocytes are largely unexplored exper-imentally.Gene expression heterogeneity provides an excellent entry point to investigate the functional hetero-geneity of astrocytes.Physiological heterogeneityAstrocytes have been traditionally described as a uniform group of cells with negative resting membrane potential, low input resistance,and extensive gap junction coupling.Recent studies indicate that astrocytes are highly diverse in their electrophysiological properties, calcium dynamics,and gap junction coupling.The resting membrane potential of astrocytes varies widely,ranging from aboutÀ85toÀ25mV in acute hippocampal slices[47]and isolated optic nerves[48]. The distribution of resting membrane potentials seems to be bimodal,suggesting the existence of distinct types of astrocytes[47].Astrocytes differ in current profiles.This has been reported for astrocytes from different brain regions[49]as well as astrocytes within the same brain region[50–53].Electrophysiologically‘complex astro-cytes’and‘passive astrocytes’have been described [54–57].‘Complex astrocytes’have voltage-dependent currents,express AMPA-type glutamate receptors but not glutamate transporters,and are not coupled by gap junctions.‘Passive astrocytes’show linear voltage–current relationships,express glutamate transporters but not glu-tamate receptors,and are coupled by gap junctions. Recent studies showed that‘complex astrocytes’include immature astrocytes and NG2cells[58].NG2cells make synaptic contacts with neurons and respond to neuronal release of glutamate and GABA(reviewed in[59]).They are now considered a separate type of glia instead of ‘complex astrocytes’.Recent in vivo fate mapping studies have found that NG2 cells generate oligodendrocytes and are therefore referred to as oligodendrocyte precursor cells[60–63].Some of these studies,however,found that astrocytes and neurons can also be generated by NG2cells.Because these studies used different cre transgenic lines(under the control of the regulatory sequences of PDGFa,NG2,Olig2,or PLP genes)to label NG2cells,which might actually label different populations of cells,this discrepancy suggests the possibility of an unexpected heterogeneity within the NG2/oligodendrocyte precursor cell population.Ca2+concentration in astrocytes undergoes transient elevation either spontaneously or in response to synaptic activity.Sometimes Ca2+transient propagates to neighbor-ing astrocytes over a long distance as Ca2+waves.Different groups of astrocytes exhibit distinct features of spon-taneous Ca2+activity.Cortical layer1astrocytes showed frequent asynchronous Ca2+activity whereas layer2/3 astrocytes showed infrequent synchronous Ca2+activity [64 ].Behavior evoked Ca2+activities also differ between astrocyte subpopulations.A subpopulation of astrocytes, but not all astrocytes,in the somatosensory cortex showed Ca2+transients correlated to locomotion behavior in awake mobile mice[65].Cerebellar Bergman glia showed spread-ing Ca2+transients different from patterns of Ca2+activities in neocortical protoplasmic astrocytes[66 ].Astrocytes are extensively coupled by gap junctions. However,instead of a homogenous syncytium,the extent of coupling differs widely in astrocytes from different brain regions[67,68]and the connectivity of astrocytic networks is highly specific[69 ,70].Functional heterogeneityAstrocytes carry out a number of important functions including regulating extracellular concentrations of pot-assium ion and neurotransmitters,promoting synapse590Neuronal and glial cell biologyformation,regulating blood–brain-barrier,promoting neuronal survival and growth,producing neurons,and perhaps modulating synaptic transmission and plasticity. The effects of astrocytes on synaptic transmission are highly controversial.A number of studies employing a variety of pharmacological,optical,and genetic methods suggest that astrocytes regulate synaptic transmission and plasticity in a calcium dependent manner[71–79].Recent reports,however,that manipulate calcium signaling in astrocytes in vivo did not observe changes in synaptic transmission or plasticity[80–82].Much more work is needed to clarify the function of astrocytes in synaptic transmission and plasticity.Astrocytes are an extremely diverse group of cells in their gene expression profiles and physiological properties.They are widely distributed throughout the central nervous system and they are components of neural circuits with different metabolic needs.It is highly probable that astrocytes are a function-ally heterogeneous population of cells,although exper-imental evidence for the functional heterogeneity of astrocytes is still scarce.Here are a few examples. Cultured astrocytes from different brain regions have different capacities in stimulating neurite growth and branching[83,84].They also differ in their permissivity to neuronal migration.Precursors of olfactory bulb inter-neurons migrate through a narrow corridor called the rostral migratory stream(RMS)and the adjacent cortical tissue is non-permissive to neuronal migration.Neuro-blasts migrate faster on cultured astrocytes from RMS than on cultured astrocytes from adjacent cortical region [85].If these in vitro results reflect in vivo functional heterogeneity of astrocytes,the heterogeneity of astro-cytes might define neurite length and branching patterns in different brain regions,and the migratory routes of neurons,and thus help define the three dimensional organization of the brain.Glutamate uptake is a well-characterized function of astrocytes.However,different populations of astrocytes differ in their ability to take up extracellular glutamate [86,87].A group of astrocytes from the hypothalamus lacks glutamate uptake current[87]. Heterogeneous response to injury and diseaseAstrocytes respond to various injuries,infections,and diseases by reactive astrogliosis,which has both detri-mental effects,for example,scar formation that prevents regrowth of injured axon and beneficial effects,for example,sealing the blood brain barrier.Astrocytes in epileptic brain both promote and oppose seizure devel-opment through a variety of mechanisms.Astrocytes play a key role in the pathogenesis of hepatic encephalopathy. Damage to astrocytes is seen in neurodegenerative dis-eases including Parkinson’s disease,Huntington’s dis-ease,amyotrophic lateral sclerosis(ALS),and prion disease.And these damages are important contributors to disease progression.For example,reducing mutant SOD in astrocytes slows the progression of ALS.Given the crucial roles of astrocytes in brain development, metabolism,and function,it is not surprising that astro-cytes are involved in almost every disease of the central nervous system.Being a highly diverse group of cells,astrocytes respond to disease and injury in different manners.Reactive astrocytes appear in different brain regions at different time points after diffuse traumatic brain injury.And these reactive astrocytes in different brain regions differ dramatically in their morphology and gene expression patterns[88].The functional implications of these differ-ences are yet to be studied.Different astrocytes also respond differently to ischemic brain injury.Two groups reported different sensitivities of grey matter astrocytes (protoplasmic astrocytes)and white matter astrocytes (fibrous astrocytes)to ischemia,although the two studies came to opposite conclusions with their different exper-imental paradigms[89,90].Viral or bacterial infections induce reactive astrogliosis and production of cytokines and chemokines.Astrocytes cultured from different brain regions are heterogeneous in their expression of immuno-reactive surface markers and in chemokine and cytokine production[91,92].A better understanding of astrocyte heterogeneity is urgently needed if we were to under-stand the exact roles astrocytes play in diseases of the nervous system and to develop treatment that targets specific groups of astrocytes that are either exacerbating the disease or protecting neurons from damages. ConclusionsAstrocytes are a far more heterogeneous group of cells than was previously appreciated.Different subtypes of astrocytes differ in morphology,development,metab-olism,physiology,and pathology.However,our current understanding of astrocyte heterogeneity,in particular the functional heterogeneity of astrocytes is still rudi-mentary.A large number of studies mentioned above are based on observations from cultured astrocytes in vitro. Improved culture methods that faithfully maintain in vivo gene expression profiles of astrocytes would be great tools for studying astrocyte heterogeneity.Ultimately in vivo study of astrocyte heterogeneity will be needed.To this end,developing molecular tools that allow selective labeling and manipulation of specific subsets of astrocytes is the key.We predict that future work that better characterizes the heterogeneity of astrocytes will greatly illuminate how the nervous system develops,how neuronal circuits function,and how neurological disorders can be treated.AcknowledgementsThe authors apologize to colleagues whose work was not included because of the space restrictions.Astrocyte heterogeneity:an underappreciated topic in neurobiology Zhang and Barres591References and recommended readingPapers of particular interest,published within the period of review, have been highlighted as:of special interestof outstanding interest1.Kettenmann H,Ransom B:Neuroglia.edn2.New York:OxfordUniversity Press;2005.2.Raff MC,Abney ER,Cohen J,Lindsay R,Noble M:Two types ofastrocytes in cultures of developing rat white matter:differences in morphology,surface gangliosides,and growth characteristics.J Neurosci1983,3:1289-1300.3.Yong VW,Yong FP,Olivier A,Robitaille Y,Antel JP:Morphologicheterogeneity of human adult astrocytes in culture:correlation with HLA-DR expression.J Neurosci Res1990,27:678-688.4.Bailey MS,Shipley MT:Astrocyte subtypes in the rat olfactorybulb:morphological heterogeneity and differential laminardistribution.J Comp Neurol1993,328:501-526.5.Barres BA:The mystery and magic of glia:a perspective ontheir roles in health and disease.Neuron2008,60:430-440. 6.Hewett JA:Determinants of regional and local diversity withinthe astroglial lineage of the normal central nervous system.J Neurochem2009,110:1717-1736.7.Matyash V,Kettenmann H:Heterogeneity in astrocytemorphology and physiology.Brain Res Rev2009.8.Kimelberg H:Astrocyte heterogeneity or homogeneity.InAstrocytes in(Patho)Physiology of the Nervous System.Edited by Parpura,Haydon.Springer;2009.9.Marin O,Rubenstein JL:Cell migration in the forebrain.AnnuRev Neurosci2003,26:441-483.10.Muroyama Y,Fujiwara Y,Orkin SH,Rowitch DH:Specification ofastrocytes by bHLH protein SCL in a restricted region of the neural tube.Nature2005,438:360-363.11. 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1株H3N2亚型猪流感病毒的分离鉴定齐海涛;闫军霞;粟硕;黄震;曹楠;谭力凯;孔维立;张桂红【摘要】为了解广东猪流感病毒(SIV)的流行变异情况,2010年11月从广东某规模猪场采集流感症状的猪鼻拭子60份,接种10日龄SPF鸡胚,分离到1株猪流感病毒,通过流感分型RT-PCR和HI试验鉴定为H3N2亚型SIV,命名为A/swine/Guangdong/L22/2010(H3N2),进行全基因序列测定及相似性分析发现,该分离株有低致病性流感分子特征,该毒株的8个基因片段连同最近广东猪群流行的流感毒株与2000年前后H3N2人流感病毒有较高的同源性.系统遗传演化显示,该病毒分离株可能是由1999年人源H3N2流感病毒A/Moscow/10/99(H3N2)进化而来.【期刊名称】《中国兽医杂志》【年(卷),期】2012(048)012【总页数】4页(P24-27)【关键词】H3N2;猪流感病毒;分离鉴定【作者】齐海涛;闫军霞;粟硕;黄震;曹楠;谭力凯;孔维立;张桂红【作者单位】华南农业大学兽医学院,广东广州 510642;华南农业大学兽医学院,广东广州 510642;华南农业大学兽医学院,广东广州 510642;华南农业大学兽医学院,广东广州 510642;华南农业大学兽医学院,广东广州 510642;华南农业大学兽医学院,广东广州 510642;华南农业大学兽医学院,广东广州 510642;华南农业大学兽医学院,广东广州 510642【正文语种】中文【中图分类】S855.3猪流感（SI）是由A型流感病毒引起的猪的一种急性、传染性呼吸道疾病，以发热、流鼻液、咳嗽、食欲减退等症状为特征，病猪可在短期内康复，但会降低饲料报酬，延迟上市时间。

目前猪群中的SIV主要有H1N1、H1N2和H3N2 3种亚型。

我国猪群中普遍存在H3和H1亚型感染。

更为重要的是，猪可以被禽流感病毒和人流感病毒同时感染，猪被认为是流感病毒的“混合器”，在“禽－猪－人”的传播链中具有独特的地位［1－2］，SI具有重要的公共卫生意义。

Leading EdgeReview Hallmarks of Cancer:The Next GenerationDouglas Hanahan1,2,*and Robert A.Weinberg3,*1The Swiss Institute for Experimental Cancer Research(ISREC),School of Life Sciences,EPFL,Lausanne CH-1015,Switzerland2The Department of Biochemistry&Biophysics,UCSF,San Francisco,CA94158,USA3Whitehead Institute for Biomedical Research,Ludwig/MIT Center for Molecular Oncology,and MIT Department of Biology,Cambridge, MA02142,USA*Correspondence:dh@epfl.ch(D.H.),weinberg@(R.A.W.)DOI10.1016/j.cell.2011.02.013The hallmarks of cancer comprise six biological capabilities acquired during the multistep develop-ment of human tumors.The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease.They include sustaining proliferative signaling,evading growth suppressors,resisting cell death,enabling replicative immortality,inducing angiogenesis,and acti-vating invasion and metastasis.Underlying these hallmarks are genome instability,which generates the genetic diversity that expedites their acquisition,and inflammation,which fosters multiple hall-mark functions.Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list—reprogramming of energy metabolism and evading immune destruction.In addition to cancer cells,tumors exhibit another dimension of complexity:they contain a repertoire of recruited,ostensibly normal cells that contribute to the acquisition of hall-mark traits by creating the‘‘tumor microenvironment.’’Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.INTRODUCTIONWe have proposed that six hallmarks of cancer together consti-tute an organizing principle that provides a logical framework for understanding the remarkable diversity of neoplastic diseases (Hanahan and Weinberg,2000).Implicit in our discussion was the notion that as normal cells evolve progressively to a neoplastic state,they acquire a succession of these hallmark capabilities,and that the multistep process of human tumor pathogenesis could be rationalized by the need of incipient cancer cells to acquire the traits that enable them to become tumorigenic and ultimately malignant.We noted as an ancillary proposition that tumors are more than insular masses of proliferating cancer cells.Instead,they are complex tissues composed of multiple distinct cell types that participate in heterotypic interactions with one another.We de-picted the recruited normal cells,which form tumor-associated stroma,as active participants in tumorigenesis rather than passive bystanders;as such,these stromal cells contribute to the development and expression of certain hallmark capabilities. During the ensuing decade this notion has been solidified and extended,revealing that the biology of tumors can no longer be understood simply by enumerating the traits of the cancer cells but instead must encompass the contributions of the ‘‘tumor microenvironment’’to tumorigenesis.In the course of remarkable progress in cancer research subsequent to this publication,new observations have served both to clarify and to modify the original formulation of the hall-mark capabilities.In addition,yet other observations have raised questions and highlighted mechanistic concepts that were not integral to our original elaboration of the hallmark traits.Moti-vated by these developments,we now revisit the original hall-marks,consider new ones that might be included in this roster, and expand upon the functional roles and contributions made by recruited stromal cells to tumor biology.HALLMARK CAPABILITIES—CONCEPTUAL PROGRESSThe six hallmarks of cancer—distinctive and complementary capabilities that enable tumor growth and metastatic dissemina-tion—continue to provide a solid foundation for understanding the biology of cancer(Figure1;see the Supplemental Informa-tion for downloadable versions of thefigures for presentations). In thefirst section of this Review,we summarize the essence of each hallmark as described in the original presentation in 2000,followed by selected illustrations(demarcated by sub-headings in italics)of the conceptual progress made over the past decade in understanding their mechanistic underpinnings. In subsequent sections we address new developments that broaden the scope of the conceptualization,describing in turn two enabling characteristics crucial to the acquisition of the six hallmark capabilities,two new emerging hallmark capabilities, the constitution and signaling interactions of the tumor microen-vironment crucial to cancer phenotypes,and wefinally discuss the new frontier of therapeutic application of these concepts.Sustaining Proliferative SignalingArguably the most fundamental trait of cancer cells involves their ability to sustain chronic proliferation.Normal tissues carefully control the production and release of growth-promoting signals that instruct entry into and progression through the cell growth-and-division cycle,thereby ensuring a homeostasis of cell646Cell144,March4,2011ª2011Elsevier Inc.32.401number and thus maintenance of normal tissue architecture and function.Cancer cells,by deregulating these signals,become masters of their own destinies.The enabling signals are conveyed in large part by growth factors that bind cell-surface receptors,typically containing intracellular tyrosine kinase domains.The latter proceed to emit signals via branched intra-cellular signaling pathways that regulate progression through the cell cycle as well as cell growth (that is,increases in cell size);often these signals influence yet other cell-biological prop-erties,such as cell survival and energy metabolism.Remarkably,the precise identities and sources of the prolifer-ative signals operating within normal tissues were poorly under-stood a decade ago and in general remain so.Moreover,we still know relatively little about the mechanisms controlling the release of these mitogenic signals.In part,the understanding of these mechanisms is complicated by the fact that the growth factor signals controlling cell number and position within tissues are thought to be transmitted in a temporally and spatially regu-lated fashion from one cell to its neighbors;such paracrine signaling is difficult to access experimentally.In addition,the bioavailability of growth factors is regulated by sequestration in the pericellular space and extracellular matrix,and by the actions of a complex network of proteases,sulfatases,and possibly other enzymes that liberate and activate them,apparently in a highly specific and localized fashion.The mitogenic signaling in cancer cells is,in contrast,better understood (Lemmon and Schlessinger,2010;Witsch et al.,2010;Hynes and MacDonald,2009;Perona,2006).Cancer cells can acquire the capability to sustain proliferative signaling in a number of alternative ways:They may produce growth factor ligands themselves,to which they can respond via the expres-sion of cognate receptors,resulting in autocrine proliferative stimulation.Alternatively,cancer cells may send signals to stim-ulate normal cells within the supporting tumor-associated stroma,which reciprocate by supplying the cancer cells with various growth factors (Cheng et al.,2008;Bhowmick et al.,2004).Receptor signaling can also be deregulated by elevating the levels of receptor proteins displayed at the cancercellFigure 1.The Hallmarks of CancerThis illustration encompasses the six hallmark capabilities originally proposed in our 2000per-spective.The past decade has witnessed remarkable progress toward understanding the mechanistic underpinnings of each hallmark.surface,rendering such cells hyperre-sponsive to otherwise-limiting amounts of growth factor ligand;the same outcome can result from structural alter-ations in the receptor molecules that facilitate ligand-independent firing.Growth factor independence may also derive from the constitutive activation of components of signaling pathways oper-ating downstream of these receptors,obviating the need to stimulate these pathways by ligand-mediated receptoractivation.Given that a number of distinct downstream signaling pathways radiate from a ligand-stimulated receptor,the activa-tion of one or another of these downstream pathways,for example,the one responding to the Ras signal transducer,may only recapitulate a subset of the regulatory instructions transmitted by an activated receptor.Somatic Mutations Activate Additional Downstream PathwaysHigh-throughput DNA sequencing analyses of cancer cell genomes have revealed somatic mutations in certain human tumors that predict constitutive activation of signaling circuits usually triggered by activated growth factor receptors.Thus,we now know that 40%of human melanomas contain activating mutations affecting the structure of the B-Raf protein,resulting in constitutive signaling through the Raf to mitogen-activated protein (MAP)-kinase pathway (Davies and Samuels 2010).Similarly,mutations in the catalytic subunit of phosphoi-nositide 3-kinase (PI3-kinase)isoforms are being detected in an array of tumor types,which serve to hyperactivate the PI3-kinase signaling circuitry,including its key Akt/PKB signal transducer (Jiang and Liu,2009;Yuan and Cantley,2008).The advantages to tumor cells of activating upstream (receptor)versus downstream (transducer)signaling remain obscure,as does the functional impact of crosstalk between the multiple pathways radiating from growth factor receptors.Disruptions of Negative-Feedback Mechanisms that Attenuate Proliferative SignalingRecent results have highlighted the importance of negative-feedback loops that normally operate to dampen various types of signaling and thereby ensure homeostatic regulation of the flux of signals coursing through the intracellular circuitry (Wertz and Dixit,2010;Cabrita and Christofori,2008;Amit et al.,2007;Mosesson et al.,2008).Defects in these feedback mech-anisms are capable of enhancing proliferative signaling.The prototype of this type of regulation involves the Ras oncoprotein:the oncogenic effects of Ras do not result from a hyperactivation of its signaling powers;instead,the oncogenic mutations affecting ras genes compromise Ras GTPase activity,whichCell 144,March 4,2011ª2011Elsevier Inc.647operates as an intrinsic negative-feedback mechanism that nor-mally ensures that active signal transmission is transitory. Analogous negative-feedback mechanisms operate at multiple nodes within the proliferative signaling circuitry.A prom-inent example involves the PTEN phosphatase,which counter-acts PI3-kinase by degrading its product,phosphatidylinositol (3,4,5)trisphosphate(PIP3).Loss-of-function mutations in PTEN amplify PI3K signaling and promote tumorigenesis in a variety of experimental models of cancer;in human tumors,PTEN expression is often lost by promoter methylation(Jiang and Liu,2009;Yuan and Cantley,2008).Yet another example involves the mTOR kinase,a coordinator of cell growth and metabolism that lies both upstream and down-stream of the PI3K pathway.In the circuitry of some cancer cells, mTOR activation results,via negative feedback,in the inhibition of PI3K signaling.Thus,when mTOR is pharmacologically inhibited in such cancer cells(such as by the drug rapamycin), the associated loss of negative feedback results in increased activity of PI3K and its effector Akt/PKB,thereby blunting the antiproliferative effects of mTOR inhibition(Sudarsanam and Johnson,2010;O’Reilly et al.,2006).It is likely that compromised negative-feedback loops in this and other signaling pathways will prove to be widespread among human cancer cells and serve as an important means by which these cells can achieve proliferative independence.Moreover,disruption of such self-attenuating signaling may contribute to the development of adaptive resistance toward drugs targeting mitogenic signaling. Excessive Proliferative Signaling Can Trigger Cell SenescenceEarly studies of oncogene action encouraged the notion that ever-increasing expression of such genes and the signals mani-fested in their protein products would result in correspondingly increased cancer cell proliferation and thus tumor growth.More recent research has undermined this notion,in that excessively elevated signaling by oncoproteins such as RAS,MYC,and RAF can provoke counteracting responses from cells,specifi-cally induction of cell senescence and/or apoptosis(Collado and Serrano,2010;Evan and d’Adda di Fagagna,2009;Lowe et al.,2004).For example,cultured cells expressing high levels of the Ras oncoprotein may enter into the nonproliferative but viable state called senescence;in contrast,cells expressing lower levels of this protein may avoid senescence and proliferate. Cells with morphological features of senescence,including enlarged cytoplasm,the absence of proliferation markers,and expression of the senescence-induced b-galactosidase enzyme,are abundant in the tissues of mice engineered to over-express certain oncogenes(Collado and Serrano,2010;Evan and d’Adda di Fagagna,2009)and are prevalent in some cases of human melanoma(Mooi and Peeper,2006).These ostensibly paradoxical responses seem to reflect intrinsic cellular defense mechanisms designed to eliminate cells experiencing excessive levels of certain types of signaling.Accordingly,the relative intensity of oncogenic signaling in cancer cells may represent compromises between maximal mitogenic stimulation and avoidance of these antiproliferative defenses.Alternatively, some cancer cells may adapt to high levels of oncogenic signaling by disabling their senescence-or apoptosis-inducing circuitry.Evading Growth SuppressorsIn addition to the hallmark capability of inducing and sustaining positively acting growth-stimulatory signals,cancer cells must also circumvent powerful programs that negatively regulate cell proliferation;many of these programs depend on the actions of tumor suppressor genes.Dozens of tumor suppressors that operate in various ways to limit cell growth and proliferation have been discovered through their characteristic inactivation in one or another form of animal or human cancer;many of these genes have been validated as bonafide tumor suppressors through gain-or loss-of-function experiments in mice.The two prototypical tumor suppressors encode the RB(retinoblas-toma-associated)and TP53proteins;they operate as central control nodes within two key complementary cellular regulatory circuits that govern the decisions of cells to proliferate or,alter-natively,activate senescence and apoptotic programs.The RB protein integrates signals from diverse extracellular and intracellular sources and,in response,decides whether or not a cell should proceed through its growth-and-division cycle (Burkhart and Sage,2008;Deshpande et al.,2005;Sherr and McCormick,2002).Cancer cells with defects in RB pathway function are thus missing the services of a critical gatekeeper of cell-cycle progression whose absence permits persistent cell proliferation.Whereas RB transduces growth-inhibitory signals that originate largely outside of the cell,TP53receives inputs from stress and abnormality sensors that function within the cell’s intracellular operating systems:if the degree of damage to the genome is excessive,or if the levels of nucleotide pools,growth-promoting signals,glucose,or oxygenation are suboptimal,TP53can call a halt to further cell-cycle progression until these conditions have been normalized.Alternatively,in the face of alarm signals indicating overwhelming or irreparable damage to such cellular subsystems,TP53can trigger apoptosis.Notably,the various effects of activated TP53are complex and highly context dependent,varying by cell type as well as by the severity and persistence of conditions of cell stress and genomic damage.Although the two canonical suppressors of proliferation—TP53and RB—have preeminent importance in regulating cell proliferation,various lines of evidence indicate that each oper-ates as part of a larger network that is wired for functional redun-dancy.For example,chimeric mice populated throughout their bodies with individual cells lacking a functional Rb gene are surprisingly free of proliferative abnormalities,despite the expec-tation that loss of RB function would allow continuousfiring of the cell division cycle in these cells and their lineal descendants; some of the resulting clusters of Rb null cells should,by all rights, progress to neoplasia.Instead,the Rb null cells in such chimeric mice have been found to participate in relatively normal tissue morphogenesis throughout the body;the only neoplasia observed was in the development of pituitary tumors late in life (Lipinski and Jacks,1999).Similarly,TP53null mice develop nor-mally,show largely proper cell and tissue homeostasis,and again develop abnormalities later in life,in the form of leukemias and sarcomas(Ghebranious and Donehower,1998).Both exam-ples must reflect the operations of redundantly acting mecha-nisms that serve to constrain inappropriate replication of cells lacking these key proliferation suppressors.648Cell144,March4,2011ª2011Elsevier Inc.Mechanisms of Contact Inhibition and Its EvasionFour decades of research have demonstrated that the cell-to-cell contacts formed by dense populations of normal cells prop-agated in two-dimensional culture operate to suppress further cell proliferation,yielding confluent cell monolayers.Importantly, such‘‘contact inhibition’’is abolished in various types of cancer cells in culture,suggesting that contact inhibition is an in vitro surrogate of a mechanism that operates in vivo to ensure normal tissue homeostasis,one that is abrogated during the course of tumorigenesis.Until recently,the mechanistic basis for this mode of growth control remained obscure.Now,however, mechanisms of contact inhibition are beginning to emerge. One mechanism involves the product of the NF2gene,long implicated as a tumor suppressor because its loss triggers a form of human neurofibromatosis.Merlin,the cytoplasmic NF2gene product,orchestrates contact inhibition via coupling cell-surface adhesion molecules(e.g.,E-cadherin)to transmem-brane receptor tyrosine kinases(e.g.,the EGF receptor).In so doing,Merlin strengthens the adhesivity of cadherin-mediated cell-to-cell attachments.Additionally,by sequestering growth factor receptors,Merlin limits their ability to efficiently emit mito-genic signals(Curto et al.,2007;Okada et al.,2005).A second mechanism of contact inhibition involves the LKB1 epithelial polarity protein,which organizes epithelial structure and helps maintain tissue integrity.LKB1can,for example, overrule the mitogenic effects of the powerful Myc oncogene when the latter is upregulated in organized,quiescent epithelial structures;in contrast,when LKB1expression is suppressed, epithelial integrity is destabilized,and epithelial cells become susceptible to Myc-induced transformation(Partanen et al., 2009;Hezel and Bardeesy,2008).LKB1has also been identified as a tumor suppressor gene that is lost in certain human malig-nancies(Shaw,2009),possibly reflecting its normal function as a suppressor of inappropriate proliferation.It remains to be seen how frequently these two mechanisms of contact-medi-ated growth suppression are compromised in human cancers; no doubt yet other contact-induced proliferative barriers are yet to be discovered.Clearly mechanisms like these that enable cells to construct and maintain architecturally complex tissues represent important means of suppressing and counterbalanc-ing inappropriate proliferative signals.Corruption of the TGF-b Pathway Promotes Malignancy TGF-b is best known for its antiproliferative effects,and evasion by cancer cells of these effects is now appreciated to be far more elaborate than simple shutdown of its signaling circuitry(Ikush-ima and Miyazono,2010;Massague´,2008;Bierie and Moses, 2006).In many late-stage tumors,TGF-b signaling is redirected away from suppressing cell proliferation and is found instead to activate a cellular program,termed the epithelial-to-mesen-chymal transition(EMT),that confers on cancer cells traits asso-ciated with high-grade malignancy,as discussed in further detail below.Resisting Cell DeathThe concept that programmed cell death by apoptosis serves as a natural barrier to cancer development has been established by compelling functional studies conducted over the last two decades(Adams and Cory,2007;Lowe et al.,2004:Evan and Littlewood,1998).Elucidation of the signaling circuitry governing the apoptotic program has revealed how apoptosis is triggered in response to various physiologic stresses that cancer cells experience during the course of tumorigenesis or as a result of anticancer therapy.Notable among the apoptosis-inducing stresses are signaling imbalances resulting from elevated levels of oncogene signaling,as mentioned earlier,and DNA damage associated with hyperproliferation.Yet other research has re-vealed how apoptosis is attenuated in those tumors that succeed in progressing to states of high-grade malignancy and resistance to therapy(Adams and Cory,2007;Lowe et al.,2004). The apoptotic machinery is composed of both upstream regu-lators and downstream effector components(Adams and Cory, 2007).The regulators,in turn,are divided into two major circuits, one receiving and processing extracellular death-inducing signals(the extrinsic apoptotic program,involving for example the Fas ligand/Fas receptor),and the other sensing and inte-grating a variety of signals of intracellular origin(the intrinsic program).Each culminates in activation of a normally latent protease(caspases8and9,respectively),which proceeds to initiate a cascade of proteolysis involving effector caspases responsible for the execution phase of apoptosis,in which the cell is progressively disassembled and then consumed,both by its neighbors and by professional phagocytic cells.Currently, the intrinsic apoptotic program is more widely implicated as a barrier to cancer pathogenesis.The‘‘apoptotic trigger’’that conveys signals between the regu-lators and effectors is controlled by counterbalancing pro-and antiapoptotic members of the Bcl-2family of regulatory proteins (Adams and Cory,2007).The archetype,Bcl-2,along with its closest relatives(Bcl-x L,Bcl-w,Mcl-1,A1)are inhibitors of apoptosis,acting in large part by binding to and thereby suppress-ing two proapoptotic triggering proteins(Bax and Bak);the latter are embedded in the mitochondrial outer membrane.When relieved of inhibition by their antiapoptotic relatives,Bax and Bak disrupt the integrity of the outer mitochondrial membrane, causing the release of proapoptotic signaling proteins,the most important of which is cytochrome c.The released cytochrome c activates,in turn,a cascade of caspases that act via their proteo-lytic activities to induce the multiple cellular changes associated with the apoptotic program.Bax and Bak share protein-protein interaction domains,termed BH3motifs,with the antiapoptotic Bcl-2-like proteins that mediate their various physical interac-tions.The activities of a subfamily of related proteins,each of which contains a single such BH3motif,are coupled to a variety of sensors of cellular abnormality;these‘‘BH3-only’’proteins act either by interfering with antiapoptotic Bcl-2proteins or by directly stimulating the proapoptotic members of this family (Adams and Cory,2007;Willis and Adams,2005).Although the cellular conditions that trigger apoptosis remain to be fully enumerated,several abnormality sensors that play key roles in tumor development have been identified(Adams and Cory,2007;Lowe et al.,2004).Most notable is a DNA-damage sensor that functions via the TP53tumor suppressor (Junttila and Evan,2009);TP53induces apoptosis by upregulat-ing expression of the Noxa and Puma BH3-only proteins,doing so in response to substantial levels of DNA breaks and other chromosomal abnormalities.Alternatively,insufficient survivalCell144,March4,2011ª2011Elsevier Inc.649factor signaling(for instance inadequate levels of interleukin-3in lymphocytes or of insulin-like growth factor1/2[Igf1/2]in epithe-lial cells)can elicit apoptosis through a BH3-only protein called Bim.Yet another condition leading to cell death involves hyper-active signaling by certain oncoproteins,such as Myc,which triggers apoptosis(in part via Bim and other BH3-only proteins) unless counterbalanced by antiapoptotic factors(Junttila and Evan,2009;Lowe et al.,2004).Tumor cells evolve a variety of strategies to limit or circumvent apoptosis.Most common is the loss of TP53tumor suppressor function,which eliminates this critical damage sensor from the apoptosis-inducing circuitry.Alternatively,tumors may achieve similar ends by increasing expression of antiapoptotic regulators (Bcl-2,Bcl-x L)or of survival signals(Igf1/2),by downregulating proapoptotic factors(Bax,Bim,Puma),or by short-circuiting the extrinsic ligand-induced death pathway.The multiplicity of apoptosis-avoiding mechanisms presumably reflects the diver-sity of apoptosis-inducing signals that cancer cell populations encounter during their evolution to the malignant state.The structure of the apoptotic machinery and program,and the strategies used by cancer cells to evade its actions,were widely appreciated by the beginning of the last decade.The most notable conceptual advances since then have involved other forms of cell death that broaden the scope of‘‘pro-grammed cell death’’as a barrier to cancer.Autophagy Mediates Both Tumor Cell Survival and Death Autophagy represents an important cell-physiologic response that,like apoptosis,normally operates at low,basal levels in cells but can be strongly induced in certain states of cellular stress, the most obvious of which is nutrient deficiency(Levine and Kroemer,2008;Mizushima,2007).The autophagic program enables cells to break down cellular organelles,such as ribo-somes and mitochondria,allowing the resulting catabolites to be recycled and thus used for biosynthesis and energy metabo-lism.As part of this program,intracellular vesicles termed auto-phagosomes envelope intracellular organelles and then fuse with lysosomes wherein degradation occurs.In this fashion,low-molecular-weight metabolites are generated that support survival in the stressed,nutrient-limited environments experi-enced by many cancer cells.Like apoptosis,the autophagy machinery has both regulatory and effector components(Levine and Kroemer,2008;Mizush-ima,2007).Among the latter are proteins that mediate autopha-gosome formation and delivery to lysosomes.Of note,recent research has revealed intersections between the regulatory circuits governing autophagy,apoptosis,and cellular homeo-stasis.For example,the signaling pathway involving the PI3-kinase,AKT,and mTOR kinases,which is stimulated by survival signals to block apoptosis,similarly inhibits autophagy;when survival signals are insufficient,the PI3K signaling pathway is downregulated,with the result that autophagy and/or apoptosis may be induced(Levine and Kroemer,2008;Sinha and Levine, 2008;Mathew et al.,2007).Another interconnection between these two programs resides in the Beclin-1protein,which has been shown by genetic studies to be necessary for induction of autophagy(Levine and Kroemer, 2008;Sinha and Levine,2008;Mizushima,2007).Beclin-1is a member of the BH3-only subfamily of apoptotic regulatory proteins,and its BH3domain allows it to bind the Bcl-2/Bcl-x L proteins.Stress-sensor-coupled BH3proteins can displace Be-clin-1from its association with Bcl-2/Bcl-x L,enabling the liber-ated Beclin-1to trigger autophagy,much as they can release proapoptotic Bax and Bak to trigger apoptosis.Hence,stress-transducing BH3proteins(e.g.,Bid,Bad,Puma,et al.)can induce apoptosis and/or autophagy depending on the physio-logic state of the cell.Mice bearing inactivated alleles of the Beclin-1gene or of certain other components of the autophagy machinery exhibit increased susceptibility to cancer(White and DiPaola,2009: Levine and Kroemer,2008).These results suggest that induction of autophagy can serve as a barrier to tumorigenesis that may operate independently of or in concert with apoptosis.Accord-ingly,autophagy appears to represent yet another barrier that needs to be circumvented during tumor development(White and DiPaola,2009).Perhaps paradoxically,nutrient starvation,radiotherapy,and certain cytotoxic drugs can induce elevated levels of autophagy that are apparently cytoprotective for cancer cells,impairing rather than accentuating the killing actions of these stress-inducing situations(White and DiPaola,2009;Apel et al.,2009; Amaravadi and Thompson,2007;Mathew et al.,2007).More-over,severely stressed cancer cells have been shown to shrink via autophagy to a state of reversible dormancy(White and DiPaola,2009;Lu et al.,2008).This survival response may enable the persistence and eventual regrowth of some late-stage tumors following treatment with potent anticancer agents. Thus,in analogy to TGF-b signaling,which can be tumor sup-pressing at early stages of tumorigenesis and tumor promoting later on,autophagy seems to have conflicting effects on tumor cells and thus tumor progression(Apel et al.,2009;White and DiPaola,2009).An important agenda for future research will involve clarifying the genetic and cell-physiologic conditions that dictate when and how autophagy enables cancer cells to survive or causes them to die.Necrosis Has Proinflammatory and Tumor-Promoting PotentialIn contrast to apoptosis,in which a dying cell contracts into an almost-invisible corpse that is soon consumed by neighbors, necrotic cells become bloated and explode,releasing their contents into the local tissue microenvironment.Although necrosis has historically been viewed much like organismic death,as a form of system-wide exhaustion and breakdown, the conceptual landscape is changing:cell death by necrosis is clearly under genetic control in some circumstances,rather than being a random and undirected process(Galluzzi and Kroemer,2008;Zong and Thompson,2006).Perhaps more important,necrotic cell death releases proin-flammatory signals into the surrounding tissue microenviron-ment,in contrast to apoptosis and autophagy,which do not. As a consequence,necrotic cells can recruit inflammatory cells of the immune system(Grivennikov et al.,2010;White et al., 2010;Galluzzi and Kroemer,2008),whose dedicated function is to survey the extent of tissue damage and remove associated necrotic debris.In the context of neoplasia,however,multiple lines of evidence indicate that immune inflammatory cells can be actively tumor promoting,given that such cells are capable650Cell144,March4,2011ª2011Elsevier Inc.。

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蚯蚓血红蛋白hemidesmosome 半桥粒hemikaryon 单倍核hemiketal 半缩酮hemimethylated 半甲基化的hemimethylation 半甲基化hemin 氯高铁血红素，氯高铁原卟啉hemiterpene 半萜hemizygote 半合子hemizygous gene 半合基因hemochromoprotein 血色蛋白hemocyanin 血蓝蛋白hemocytometer 血细胞计hemoflavoprotein 血红素黄素蛋白hemoglobinopathy 血红蛋白病hemolysin 溶血素hemolysis 溶血（作用）hemopexin 血色素结合蛋白hemophilia 血友病hemophilus 嗜血杆菌属hemophilus influenzae 流感嗜血杆菌hemopoiesis 血细胞生成hemopoietin 血细胞生成素hemoporphyrin 血卟啉hemoprotein 血红素蛋白hemorheology 血液流变学hemorrhage 出血hemorrhagic fever 出血热hemosiderin 血铁黄素蛋白hemostasis 止血hepadnavirus 嗜肝dna病毒heparan 类肝素，乙酰肝素heparin 肝素hepatoalbumin 肝白蛋白，肝清蛋白hepatocrinin 促肝泌素hepatocyte 肝细胞hepatoglobulin 肝球蛋白hepatoma 肝癌hepatotoxin 肝脏毒素hepatovirus 肝病毒属[模式成员是甲型肝炎病毒] heptoglobin 七珠蛋白heptose 庚糖herbicidin 除莠菌素herbimycin 除莠霉素herpesvirus 疱疹病毒heteroallel 异点等位基因heterobifunctional agent 异（基）双功能试剂，双异官能团试剂heterobrachial inversion 异臂倒位heterochain polymer 杂链聚合物heterochromatin 异染色体heterochromatinization 异染色质化heterochromosome 异染色体heterocyst 异形（囊）胞heterocytotropic antibody 嗜异种细胞抗体heterodimer 异（源）二聚体，异源双体heteroduplex 异源双链（体）heteroecism 转主寄生（现象）heterofermentation 异型发酵heterogamete 异形配子heterogamy 异配生殖heterogeneity 不均一性heterograft 异种移植物heterokaryon 异核体heterokaryosis 异核现象，异核性heterokinesis 异化分裂heterologous 异源性heterology 异源性heterolysis 异裂heteromorphism 异态性，异形性；多晶现象heterophylly 异形叶性heterophyte 异养生物heteroplasmy 异质性[如指线粒体dna长度的可变性]heteroploid 异倍体heteroploidy 异倍性heteropolyacid 杂多酸heteropolybase 杂多碱heteropolymer 杂聚物heteropolysaccharide 杂多糖heteropyknosis 异固缩heterosis 杂种优势heterospore 异形孢子heterospory 孢子异型heterostyly 花柱异长heterothallic yeast 异宗配合酵母（菌）heterothallism 异宗配合heterotrimer 异（源）三聚体，异源三体heterotristyle 三式花柱式heteroxeny 转主寄生（现象）heterozygosis 杂合（现象）heterozygote 杂合子，异形合子hexagonal closs packing 六方密堆积hexonmer 六邻粒[见于腺病毒]hexosaminidase 氨基己糖苷酶hill plotting 希尔作图法[如用于酶动力反应]hirudin 水蛭素hisactophilin 富组亲动蛋白[富含组氨酸的膜周边蛋白，可促进肌动蛋白的聚合]histaminase 组（织）胺酶histamine 组（织）胺histidinal 组氨醛histidinol 组氨醇histocompatibility 组织相容性histocyte 组织细胞，间质细胞histogen 组织原[用于植物]histone 组蛋白histopine 章鱼组氨酸，组氨章鱼碱histoplasmin 组织胞质菌素histotope 组（织）位[抗原呈递中，ii类主要组织相容性复合体与t细胞抗原受体相互作用的部位]histotroph 组织营养素holandric ingeritance 限雄遗传holliday structure 霍利迪结构[重组时两个dna双链体以四股dna在连结点交换配对而在电镜下所呈现的十字形结构]holocrine 全（质分）泌holoenzyme 全酶hologynic ingeritance 限雌遗传holomycin 全霉素holoprotein 全蛋白holozygote 全合子homeobox 同源（异型）框[最初发现于果蝇、爪蟾形态发生调节蛋白的一种dna结合区]homeodomain 同源（异型）域homeoprotein 同源异型蛋白（质）homeostasis （体内）稳态homoacetogenic bacteria 同型（产）乙酸（细）菌[在厌氧条件下可从1mol六碳糖产生3mol乙酸]homoallele 同点等位基因homoarginine 高精氨酸homochromatography 同系层析homocitrate 高柠檬酸homocopolymer 同型共聚物homocysteine 高半胱氨酸homocystine 高胱氨酸homocytotropic antibody 嗜同种细胞抗体homodimer 同（源）二聚体，同源双体homoduplex 同源双链（体）homofermentation 同型发酵homogametic sex 同配性别homogamy 同配生殖；雌雄（蕊）同熟homogenate 匀浆（物），匀浆（液）homogeneous eia 均相酶免疫测定homogony 花蕊同长homograft 同种移植homoiothermy 温血，恒温homoisoleucine 高异亮氨酸homokaryon 同核体homolog 同系物homologous 同源的homology 同源性homolysis 均裂homomorph 全型[真菌中包括有性、无性孢子的生活史各阶段都已知类型]homomultimeric protein 同（聚）多亚基蛋白homophilic adhesion 同嗜性粘着[同种细胞（或分子）间的粘着] homoploid 同倍体homopolymer 同聚物，同聚体homopolymeric tailing 同聚物加尾（反应）homopolymerization 同聚（反应），均聚（反应）homopolypeptide 同聚多肽homopolysaccharide 同多糖homoserine 高丝氨酸homoserinelactone 高丝氨酸内酯homostyle 花柱同长homothallic yeast 同宗配合酵母homothallism 同宗配合homotopic 等位的[在分子整体中，碳原子上完全等同的原子、基团或面]homotrimer 同（源）三聚体，同源三体homotropic effect 同促效应homotype 同型homozygote 纯合子homozygote typing cell 纯合子分型细胞homozygous sex 纯合性别honeycomb support 蜂窝状载体hopping library 跳查文库hordein 大麦醇溶蛋白hordeivirus 大麦病毒[一组植物病毒，模式成员是大麦条纹花叶病毒]horizontal transmission 水平传递[通过质粒、转座子而进行遗传物质传递]；水平传播[病原体在宿主不同个体间的传播]hormesis 刺激作用hormogonian [蓝细菌]连锁体horseradish peroxidase 辣根过氧化物酶hot phenol method 热酚法[提取细胞总rna的一种方法]hot spot 热点[基因或蛋白质中突变率特别高的位点]hu protein 细菌组蛋白hughes press hughes压碎器[一种利用冷冻挤压原理制成的高压匀浆器]human chorionic gonadotropin 人绒毛膜促性腺素humanization 人源化humanized antibody 人源化抗体humics 腐殖质humulone 葎草酮humus 腐殖土、腐殖质hyaloplasm 透明质hyaluronidase 透明质酸酶hybond membrane hybond膜，杂交膜[amersham公司的商标] hybrid depletion method 杂交体耗竭法[用于cdna克隆]hybridoma 杂交瘤hydantoin 乙内酰脲hydathode 排水器[见于植物]hydratase 水合酶hydrazide 酰肼hydrazine 肼hydrazone 腙hydrocortisone 氢化可的松，皮质醇hydrogel 水凝胶hydrogenase 氢化酶hydrogenogen 产氢菌hydrogenolysis 氢解hydrolase 水解酶hydrolysate 水解（产）物，水解液hydrolysis 水解（作用），水解（反应）hydropathy 亲水性hydropathy profile 亲水性分布图hydroperoxide 氢过氧化物hydrophily 水媒hydrophobic collapse 疏水折拢[由疏水作用而引起肽链的折叠] hydrophobic labeling 疏水标记[例如通过非极性相互作用对蛋白质的内核进行光标记]hydrophobicity 疏水性hydrophobin 疏水蛋白[见于真菌孢子的疏水鞘]hydrophyte 水生植物hydroponics 水培hydroquinone 氢醌hydrosol 水溶胶hydrotaxis 趋水性hydrotropism 向水性hydroxocobalamin 羟钴胺素hydroxyacetylneuraminic acid 羟乙酰神经氨酸hydroxyalkylation 羟烷基化hydroxyallysine 羟赖氨醛hydroxyallysine aldol 羟赖氨醇hydroxyapatite 羟（基）磷灰石hydroxybenzotriazole 羟基苯并三唑hydroxycholecalciferol 羟胆钙化（固）醇hydroxycorticosteroid 羟（基）皮质醇hydroxylation 羟化hydroxylysine 羟赖氨酸hydroxymethylcytosine 羟甲基胞嘧啶hydroxynervonic acid 羟神经酸，2-羟基-顺-15二十四碳单烯酸hydroxyproline 羟脯氨酸hydroxyquinoline 羟基喹啉hydroxysuccinimide eater 羟基琥珀酰亚胺酯hydroxytryptamine 羟色胺hydroxytryptophan 羟色氨酸hydroxyurea 羟（基）脲hygromycin 潮霉素hylambatin 援木蛙肽hymenium 子实层[见于真菌]hymenophore 子实层体hyoscytamine 天仙子胺hypercholesterolemia 高胆固醇血症hyperchromic effect 增色效应hyperchromicity 增色性hyperchromism 增色性hyperdiploid 超二倍体hyperfiltration 超滤hyperfunction 技能亢进hyperimmunization 超免疫hypermutation 高变，超变hypermutator state 超增变状态hyperploid 超倍体hyperploidy 超倍性hyperpolarization 超极化hyperreiterated dna 高度重复dnahypersensitive site 超敏（感）位点，高敏位点[类似热点或高变区中的位点]hypersensitivity 超敏（反应），过敏性hypertrophy 过度生长hypervariable 高变的，变异度高的hypha [真菌]菌丝hypholytic action 菌溶丝作用hypnospore 休眠孢子hypo 海波hypochromicity 减色性hypochromism 减色性hypocotyl 下胚轴hypodermics 皮下组织hypofunction 机能减退hypophase 低相，下相hypophasic 低相性的[趋向于留存于低相的] hypophysin 垂体后叶激素hypoploid 亚倍体hypoploidy 亚倍性hypostatic gene 下位基因hypothalamus 下丘脑hypoxanthine 次黄嘌呤hypoxanthine riboside 次黄（嘌呤核）苷hysteresis 滞后（现象）。

生物专业英语课程考试试卷A+答案一、单词翻译（中英文互译，共10小题，每小题1分，共10分）1.zygote\homology mortality\natality3.chlorophyll\ribulose biphosphate4.meiosis\mitosis5.allele\homologous pair6.光合作用、核糖体7.二倍体、单倍体8.显性、隐性9.腺嘌呤、胞嘧啶10.物种、再生二.判断题（每题1分，共10分，正确打√，错误打?）1.Ribosomes are derived from the nucleoli.2.Light-independent reactions take place in the thylakoid membrane.3.All daughter cells are haploid.4.Sexual organisms cannot be cloned.5.Mendel's second law states that characters are inherited dependently.6.The sequence of bases on the DNh molecule carries the genetic information.7.Fungal mitosis，unlike mitosis in all other organism，occurs within the nucleus，8.Parthenogenesis produces only females.9.Subspecies are genetically inferior to full species.petition and predation are examples of density-independent factors.三、阅读理解（共20小题，每小题2分，共40分）（1）Most animals use more than one species as food.Therefore，the term“food meb”is a hetter description of food relationships than“food chain".A food web is a complex feeding system that contains several food chains. For example, mice, rabbits, and deer eat plants. owls eat mice and rabbits. Mountain lions eat rabhits and deer.These five species are parts of food chains that together form a food web.The first link in a food chain is always a green plant. Only organisms with chlorophy11, such as green plants can make food. for example, the first link aquatic food chains is algae. Most algae are microscopic green plants that produce food by photosynthesis. In photosynthesis, energy from sunlight converts carbon dioxide and water to sugar. Tiny fish in lakes, streams and oceans eat algae. In turn, these tiny fish are eaten by larger fish. The larger fish are eaten by still larger fish. The food supply for fish is made by algae. This food is then passed through the food chains as one animal eats another.Organisms may be divided into three groups based on how they obtain food. These groups are producers, decomposer and consumer. Organisms containing chlorophyll are producers. thus, green plants are producers. Animals that eat other animals and plants as consumers. Microbes, one-celled organisms that cause the decay of dead plants and animals are decomposers. Since decomposers cannot make their owm food, they are also consumers.1. The main purpose of the passage is to .A. determine which food chain is the most efficientB. describe the food network among plants and animalsC. explain the process of photosynthesis in green plantsD. appeal to conservationists to protect endangered plant specics2. According to the author, what is a "food web?A.A complicated system of several food chainsB.A society that distributes foodC. The relationship of one ereen plants to anotherD. The device that spiders use to catch food3. Which of the following would most likely be the first link in a food chain?A. TermitesB. FishC. LionsD. Grass4. The author divides organisms according to , A. how they use up energy B. how they obtain foodC. how much energy they require in order to moveD. whether they live on the land or in the sea5. Which of the following organism could not be a consumer as described in the passage?A.a microbeB.a rabbitC.a treeD.a fish(2) Lichens can be spectacular for anyone who cares to look, but few people take the trouble. Often modestly colored and seemingly two-dimensional as they cling to whatever surface they find, they grow in the background: as though designed to be ignored. Yet they hold a special fascination for botanists, partly because they present mysteries still to be solved and partly because they do so many things so well.No casual observer of a lichen would ever suspect that it was a composite of interacting life forms. The seemingly uncomplicated lichen is actually composed of afungus and a colony of algae(or blue-green algae, which some scientists now consider to be bacteria).A few species even include all three of these diverse forms of life.A complete lichen is strikingly different from its separated partners in both appearance and biochemistry; many produce unique compounds which cannot be made by the component organisms alone.Lichens grow in almost every natural habitat imaginable, from deserts to tropical rain forests-even on the back of certain beetles in New Guinca and inside rocks(along with algae) in the otherwise barren dry valleys of Antarctica.Many species can not tolerate extreme heat, cold or dryness. Very few, however, can survive heavy air pollution, and many live only where the air is very clean. The disappearance of lichens from an area gives warning of a threatened environment.1. Which of the following would be the best title for the passage?A. The versatility and complexity of the lowly lichenB. The hidden characteristics of algae coloniesC. The disappcarance of the lichen speciesD. The habitats of spectacular fungi2. The author states that lichens grow "as though designed to be ignored"because they are A. not totally understood by botanists B. troublesome to collect for the purposes of study C. uncomplicated in their intemal structure D. not easily noticed by observers3. According to the author, most people are unaware that lichen is a.A. lcafy plantB. class of simple bacteriaC. two-dimensional life formD. Combination of organisms4. The"unique"compounds mentioned in the second paragraph are produced A. through the cooperative efforts of the lichen's parts B. only under laboratory conditions C. through one of the three possible processes D. once in the lichen's life cycle5. The author implies that lichens might be used to.A. find water sourcesB. destroy unwanted plant lifeC. test for air purityD. provide food in remote areas(3) Insects' lives are very short and they have many enemies, but they must survive long enough to breed and perpetuate their kind.The less insect like they look, the better their chance of survival.To look "inedible"by resembling or imitating plants, is a deception widely practiced by insects. Mamals rarely use this type of camouflage, but many fishes and invertebrates do.The stick caterpillar is well named. It is hardly distinguishable from a bromn or green twig. This caterpillar is quite common and can be found almost anywhere in North America. It is also called "measuring worm"of "inchworm". It walks by arching its body, then stretching out and grasping the branch withits front feet, then looping its body again to bring the hind feet forward. When danger threatens, the stick caterpillar stretchesits body away from the branch at an angle and resains rigid and still, like a twig, until the danger has passed.Walkingsticks, or stick insects, do not have to assume a rigid, twiglike pose to find protection, they look like inedible twigs in anyposition. There are many kinds of walkingsticks, ranging in sizefrom the few inches of the North American variety to some tropicalspecies that may be over a foot long. Then at rest their front legs are stretched out. Some of the tropical species are adorned with spines or ridges, imitating the thorny bushes or trees in which they live.leaves also seem to be a favorite object for insects to imitate. Many butter flies can suddenly disappear from viem by folding their wings and sitting quietly among the foliage that they resemble.6. What is the main subject of the passage?E. Catepillars that live in treesF. The feeding habits of insectsG. How some insects camouflage themselvesH. Insects that are threatened with extinction7. In lines 1, the word "enemies"refers to E. other creatures competing for space F. extreme weather conditionsG. creatures that eat insects H. inedible insects8. According to the passage, how does the stick caterpillar make itself look like a twig?E. By holding its body stiff and motionlessF. By looping itself around a stickG. By changing the color of its skinH. By laying its body flat against a branch9. Which of the following is true of stick insects?E. They resemble their surroundings all the time.F. They make themselves look like other insects.G. They are camouflaged only when walking.H. They change color to make themselves invisible.10. Which of the following are not mentioned in the passage as ob jects that are imitated as a means of protection?A. ThornsB. FlowersC. leavesD. Sticks6. In which paragraph does the author describe the way in which stick caterpillars move?A. Paragraph oneB. Paragraph twoC. Paragraph threeD. Paragraph four(4) Wide-ranging research on tooth decay has recently produced some surprising findings, one indicates that cheddar may actually inhibit the tooth-decay process. It seems to have decay-slowing effect on human teeth if it is eaten immediately after sugar. Thy cheese should have such an effect is unknown. It is speculated that the food might interfere with the acidthat decays teeth or with bacteria that produce the acid. If so, it would be the first common food found to have this useful property. The other suprprising research finding was that heavily sweetened cereals proved ahout equally potent in causing decay whether they contained eight percent,sugar or almost eight times that much.1.According to the passage，how many of the test results were unexpected？A.OneB.TroC.ThreeD.Eight2.According to the passage，what effect does cheddar cheese seem to have？E.It interferes with the function of teeth.F.It makes sugar taste sueeter.G.It decreases the rate at which teeth decay.H.It helps in the digestion of food.3.It can be inferred from the passage that the research on the relationship between cheese and tooth A.has been discredited B.will be slowed considerablyC.has been found to be conclusiveD.will be continued4.Researchers discovered that sweetened cereals were A.important nutritionally B.all surprisingly heavy in sugar C.more expensive than cheese D.all equally harmful to teeth.四、短文翻译（第1题英文短句翻译成中文，每小题2分，共20分，第2题中文翻译成英文，20分，共40分）1.英文短句翻译成中文（1）A1l eukaryotic cells contain most of the various kinds of organelles，and each organelle performs a specialized function in the cell.（2）Photosynthesis occurs only in the chlorophyl1-containing cells of green plants，algae，and certain protists and bacteria.（3）A pictorial display of an organisms chromosomes in thecoiled，condensed state is knon as a karyotype.Karyotype reveal that in most cells all but sex chromosomes are present as two copies，referred to as homologous pairs.（4）An organism that inherits identical alleles for a trait from each parent is said to be homozygous for that traits:if different alleles for a trait are inherited，the organism is heterozygous for that trait.（5）The leading strand is synthesized continuously，while the lagging strand is synthesized in short stretches known as Okazaki fragments.（6）Taxonomy reveals a great deal about the evolutionary relationshipsamong organisms.A clade is a taxonomic unit whose mesbers are derived from a common ancestor.（7）A11 fungi carry out extracellular digestion:they secrete enzymes that digest organic matter，and then they absorb the resulting nutrients.（8）The organs and tissues of the embryo arise during organogenesis，as cells inside the embryo and on its surface become specialized.（9）Populations of a species that are spread out over a broad geographical range are often arrayed in a cline-a gradual change in one or more characteristics as each population evolves adaptations to its own local environment.（10）Just as competition，predation，and other elements interact todetermine the size of a population within a comsunity，population distribution is the result of many interrelated factors.2.短文翻译（中译英）蛋白质很难说明蛋白质在生命系统中有多么重要。

Intratumor Heterogeneity and Branched Evolution Revealedby Multiregion SequencingMarco Gerlinger, M.D., Andrew J. Rowan, B.Sc., Stuart Horswell, M.Math., James Larkin, M.D., Ph.D., David Endesfelder, Dip.Math., Eva Gronroos, Ph.D., Pierre Martinez, Ph.D., Nicholas Matthews, B.Sc.,Aengus Stewart, M.Sc., Patrick Tarpey, Ph.D., Ignacio Varela, Ph.D., Benjamin Phillimore, B.Sc., Sharmin Begum, M.Sc.,Neil Q. McDonald, Ph.D., Adam Butler, B.Sc., David Jones, M.Sc., Keiran Raine, M.Sc., Calli Latimer, B.Sc., Claudio R. Santos, Ph.D., Mahrokh Nohadani, H.N.C., Aron C. Eklund, Ph.D., Bradley Spencer-Dene, Ph.D.,Graham Clark, B.Sc., Lisa Pickering, M.D., Ph.D., Gordon Stamp, M.D., Martin Gore, M.D., Ph.D., Zoltan Szallasi, M.D.,Julian Downward, Ph.D., P. Andrew Futreal, Ph.D., and Charles Swanton, M.D., Ph.D.Abstr actFrom the Cancer Research UK London Research Institute (M. Gerlinger, A.J.R., S.H., D.E., E.G., P.M., N.M., A.S., B.P., S.B., N.Q.M., C.R.S., B.S.-D., G.C., G.S., J.D., C.S.), Royal Marsden Hospital De-partment of Medicine (J.L., M.N., L.P., G.S., M. Gore), Wellcome Trust Sanger Institute (P.T., I.V., A.B., D.J., K.R., C.L., P.A.F.), Barts Cancer Institute at the Barts and the London School of Medicine and Dentistry (M. Gerlinger), and the Uni-versity College London Cancer Institute (C.S.) — all in London; the Technical Uni-versity of Denmark, Lyngby (A.C.E., Z.S.); and Harvard Medical School, Boston (Z.S.). Address reprint requests to Dr. Swanton at the Cancer Research UK London Research Institute, Translational Cancer Therapeu-tics Laboratory, 44 Lincoln’s Inn Fields, London WC2A 3LY, United Kingdom, or at charles.swanton@.Drs. Gerlinger, Larkin, Gronroos, Martinez, and Swanton and Mr. Rowan, Mr. Hors-well, Mr. Endesfelder, Mr. Matthews, and Mr. Stewart contributed equally to this article.N Engl J Med 2012;366:883-92.Copyright © 2012 Massachusetts Medical Society.BackgroundIntratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.Methodstained from primary renal carcinomas and associated metastatic sites. We character-ized the consequences of intratumor heterogeneity using immunohistochemical analy-sis, mutation functional analysis, and profiling of messenger RNA expression.ResultsPhylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple dis-tinct and spatially separated inactivating mutations within a single tumor, suggesting ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tu-Conclusionsciated with heterogeneous protein function, may foster tumor adaptation and thera-peutic failure through Darwinian selection. (Funded by the Medical Research Council and others.)T h e ne w engl a nd jour na l o f medicineL arge-scale sequencing analyses of solid cancers have identified extensive hetero-geneity between individual tumors.1-6 Genet-ic intratumor heterogeneity has also been shown7-15portant consequences for personalized-medicine approaches that commonly rely on single tumor-biopsy samples to portray tumor mutational land-scapes. Studies comparing mutational profiles of primary tumors and associated metastatic le-sions16,17 or local recurrences18 have provided evi-dence of intratumor heterogeneity at nucleotide mary tumors and associated metastatic sites has not been systematically characterized by next-gen-eration sequencing. We applied exome sequenc-ing, chromosome aberration analysis, and DNA ploidy profiling to study multiple spatially sepa-rated biopsy samples from primary renal-cell car-cinomas and associated metastatic sites. We in-vestigated the phenotypic consequences of genetic intratumor heterogeneity and the representation of the tumor genomic landscape by a single tumor-biopsy sample, the current basis for most bio-marker discovery and personalized-medicine ap-proaches.MethodsWe evaluated tumor-biopsy samples from four con-secutive patients with metastatic renal-cell carci-noma who were enrolled in the Personalized RNA Interference to Enhance the Delivery of Individu-alized Cytotoxic and Targeted Therapeutics clinical trial of everolimus (E-PREDICT; EudraCT number, 2009-013381-54) before and after cytoreductive ne-the initiation of 6 weeks of treatment with evero-limus. After a 1-week washout period in which patients did not receive everolimus, a nephrectomy was performed. Everolimus treatment was contin-ued after recovery from surgery until tumor pro-timelines.We performed whole-exome multiregion spatial sequencing on DNA that was extracted from fresh-frozen samples obtained from Patients 1 and 2, as described previously,19ysis on Illumina Omni2.5 and messenger RNA (mRNA) expression profiling on Affymetrix Gene 1.0 arrays.All four patients provided written informed consent. Details regarding materials and meth-ods are provided in the Supplementary Appen-dix, available with the full text of this article at . The study protocol is also available at .R esultsPatientsPatient 1 had a clear-cell carcinoma, pulmonary metastases, and a chest-wall metastasis. Sequenc-VHL mutational inactivation, which is characteristic of clear-cell carcinoma. After 6 weeks of everolimus treatment and a 1-week washout period, a nephrec-tomy was performed. The patient restarted evero-limus for 6 weeks and after another 1-week wash-out period proceeded to surgery of the chest-wall Fig. 1). Computed tomography (CT) did not reveal any change in the dimensions of the primary tumor or chest-wall metastasis during everolimus treatment.MutationsFor Patient 1, we performed exon-capture multire-wall metastasis (PreM), nine primary-tumor re-gions of the nephrectomy specimen (R1 to R9), a metastasis in the perinephric fat of the nephrecto-my specimen (M1), two regions of the excised chest-wall metastasis (M2a and M2b), and germline DNA19Fig. 2Amentary Appendix). Nonsynonymous somatic point mutations and insertions and deletions (in-dels) that change the protein amino acid sequence were filtered and manually reviewed to remove se-quencing and alignment errors and to determine the regional distribution of mutations. Regions R6 and R7 were excluded from analyses since only one nonsynonymous variant passed filtering. We identified 101 nonsynonymous point mutations and 32 indels (Table 2 in the Supplementary Ap-Fig. 2B). Sanger sequencing wasIntratumor Heterogeneity Revealed by multiregion SequencingFig. 2B Fig. 1ing genetic intratumor heterogeneity.A low false negative mutation call rate is re-quired to avoid overestimation of intratumor het-R4 or R9 could be detected by increasing the se-quencing depth (i.e., the median number of se-mutations (in ITGB3 and AKAP8, both in R4) pres-the Supplementary Appendix).Somatic Mutational Heterogeneity and Clonal Ordering40 ubiquitous mutations, 59 mutations shared by several but not all regions, and 29 mutations that subdivided shared mutations into 31 mutations shared by most of the primary tumor regions of the nephrectomy specimen (R1 to R3, R5, and R8 to R9), pretreatment biopsy samples of the primary tumor, and 28 mutations shared by most of the metastatic regions. The detection of private muta-We inferred ancestral relationships and con-20 (Fig. 2C ), which revealed branching rather than linear tumor evolution. One branch evolved into the clones present in metastatic sites, and the other diversified into primary tumor regions. R4 shared some, but not all, primary-tumor and meta-static mutations, which suggested the presence of at least two clonal populations in this region that arose from progenitor cells of the metastases and of other primary tumor sites. Variant frequencies in the R4 ultradeep-sequencing data revealed that mutations shared with metastatic sites were de-tected at higher frequencies than were mutations shared with other primary-tumor regions, furthersupporting the presence of two subclones in R4 (Fig. 2 in the Supplementary Appendix). (For an exploratory phylogenetic analysis of the synony-mous mutations, see Fig. 3 in the Supplementary Appendix.)tations detected in this tumor. Only 34% of all mutations that were detected by multiregion se-quencing in the nephrectomy specimen were pres-ent in all regions (31% if pretreatment and me-tastasectomy samples were included), indicating that a single biopsy was not representative of the mutational landscape of the entire tumor bulk.To address whether everolimus exposure may contribute to intratumor heterogeneity, we com-pared the phylogenetic relationships of pretreat-ment samples with those obtained after treatment Fig. 2C ent in post-treatment primary-tumor regions, and 64 of 66 mutations in the chest-wall metastases were present in post-treatment metastatic regions, of the mutations in pretreatment samples of theT h e ne w engl a nd jour na l o f medicine primary tumor and chest-wall metastases were notshared by both biopsy samples. Clones in R4 areunlikely to have evolved from pretreatment sam-ples of the primary tumor or chest-wall metastasesduring therapy, since such evolution would haverequired the reversion of a large number of so-matic mutations to wild-type, further supportingthe presence of intratumor heterogeneity before6 and 12 weeks of everolimus exposure had simi-Fig. 4in the Supplementary Appendix). Thus, everolimusdoes not appear to increase the mutational load,and the main phylogenetic branches were presentin the tumor before treatment, indicating that in-tratumor heterogeneity was not a consequence ofeverolimus treatment.Ploidy profiling21 revealed a diploid profile for themajority of primary regions, whereas region m2bsubtetraploid populations (Fig. 2Dmost resembling the metastatic sites throughclonal-ordering analysis, had a tetraploid profile,which suggests that the subtetraploid populationin the chest-wall metastasis may have developedfrom a tetraploid intermediate in R4. Tumor re-gions were subjected to SNP-array–based allelic-imbalance detection to identify chromosomal aber-rations. Pretreatment samples of the primary tumorand metastasis were excluded because of insuffi-cient DNA, and R1, R3, and R5 failed quality con-trol. Sections of allelic imbalance on chromosomein the Supplementary Appendix). Taken together with the corresponding reduced array signal in-erozygosity through single deletion events in these 3p sections encoding VHL and the histone H3K36 methyltransferase SETD2. No tumor regions shared identical allelic-imbalance profiles, and heteroge-neity of allelic imbalance within metastases, which is probably driven by aneuploidy, indicates that chromosomal aberrations contribute to genetic intratumor heterogeneity.Intratumor Genetic Heterogeneityand Convergent Tumor EvolutionA comparison of genes that were mutated in this tumor with genes recurrently mutated in clear-cell carcinoma4,22 identified VHL, KDM5C, SETD2, and MTOR Fig. 2B VHL was mutated ubiquitously in all analyzed regions. In contrast, SETD2 harbored three distinct muta-Fig. 2C the metastases shared a missense mutation, R4 car-ried a splice-site mutation, and all other regions shared a 2-bp frameshift deletion, which was also detected in R4. Since SETD2 trimethylates H3K36, we stained several tumor regions with an antibody for trimethylated H3K36 to identify the conse-quences of mutational intratumor heterogeneity on protein function. Trimethylated H3K36 was re-duced in cancer cells but positive in most stromal cells and in a SETD2 wild-type control clear-cell carcinoma (Fig. 6 in the Supplementary Appendix). These data support phenotypic convergent evolu-Intratumor Heterogeneity Revealed by multiregion Sequencingtion through loss of SETD2 methyltransferase func-tion driven by three distinct, regionally separated mutations on a background of ubiquitous loss of the other SETD2 allele on chromosome 3p.Convergent evolution was observed for the X-chromosome–encoded histone H3K4 demeth-ylase KDM5C, harboring disruptive mutations in R1 through R3, R5, and R8 through R9 (missenseand frameshift deletion) and a splice-site mutation Fig. 2B and 2C ).m The mammalian target of rapamycin (mTOR) ki-nase carried a kinase-domain missense mutation (L2431P) in all primary tumor regions except R4.All tumor regions harboring mTOR (L2431P) hadB Regional Distribution of MutationsC Phylogenetic Relationships of Tumor RegionsD Ploidy ProfilingA Biopsy SitesR2R4DI=1.43DI=1.81M2bR9TetraploidR4bR9R8R5R4aR1R3R2M1M2b M2aVHLKDM5C (missense and frameshift)mTOR (missense)SETD2 (missense)KDM5C (splice site)SETD2 (splice site) ?SETD2 (frameshift)PreP PreMNormal tissuePrePPreM R1R2R3R5R8R9R4M1M2a M2b C 2o r f 85W D R 7S U P T 6H C D H 19L A M A 3D I X D C 1H P S 5N R A P K I A A 1524S E T D 2P L C L 1B C L 11A I F N A R 1A D A M T S 10 C 3K I A A 1267K R T 4C D 44A N K R D 26T M 7S F 4S L C 2A 1D A C H 2M M A B Z N F 521H M G 20A D N M T 3A R L F M A M L D 1M A P 3K 6H D A C 6P H F 21B F A M 129B R P S 8C I B 2R A B 27A S L C 2A 12D U S P 12A D A M T S L 4N A P 1L 3U S P 51K D M 5C S B F 1T O M 1M Y H 8W D R 24I T I H 5A K A P 9F B X O 1L I A S T N I K S E T D 2C 3o r f 20M R 1P I A S 3D I O 1E R C C 5K L A L K B H 8D A P K 1D D X 58S P A T A 21Z N F 493N G E F D I R A S 3L A T S 2 I T G B 3F L N A S A T L 1K D M 5C K D M 5C R B F O X 2N P H S 1S O X 9C E N P N P S M D 7R I M B P 2G A L N T 11A B H D 11U G T 2A 1M T O R P P P 6R 2Z N F 780A W S C D 2C D K N 1B P P F I A 1T H S S N A 1C A S P 2P L R G 1S E T D 2C C B L 2S E S N 2M A G E B 16N L R P 7I G L O N 5K L K 4W D R 62K I A A 0355C Y P 4F 3A K A P 8Z N F 519D D X 52Z C 3H 18T C F 12N U S A P 1T O X 4K D M 2B M R P L 51C 11o r f 68A N O 5E I F 4G 2M S R B 2R A L G D S E X T 1Z C 3H C 1P T P R Z 1I N T S 1C C R 6D O P E Y 1A T X N 1W H S C 1C L C N 2S S R 3K L H L 18S G O L 1V H L C 2o r f 21A L S 2C R 12P L B 1F C A M R I F I 16B C A S 2I L 12R B 2PrivateUbiquitousShared primaryShared metastasisPrivate UbiquitousLung metastasesChest-wall metastasis Perinephric metastasisM110 cmR7 (G4)R5 (G4)R9R3 (G4)R1 (G3)R2 (G3)R4 (G1)R6 (G1)H i l u mR8 (G4)Primary tumorShared primaryShared metastasis M2bM2aPropidium Iodide StainingN o . o f C e l l sT h e ne w engl a nd jour na l o f medicineincreased staining of the downstream mTOR path-way targets phospho-S6 and phospho-4EBP. Re-gions harboring wild-type mTOR had absent phospho-S6 and phospho-4EBP staining in tumor Fig. 3A). It is unlikely that everolimus would imens, which were acquired 7 days after drug dis-continuation (drug half-life, 30 hours).23 Transfec-tion of complementary DNA encoding mTOR (L2431P) into a clear-cell carcinoma line enhanced phospho-S6 staining after serum starvation, indi-cating that L2431P promotes constitutive mTOR Fig. 3Bnal-cell carcinoma lines with the mutant mTOR construct did not affect everolimus sensitivity in vitro (data not shown). The mTOR sequence was aligned with the structurally related phosphati-dylinositol 3 (PI3) kinase beta (Fig. 7 in the Supple-from this alignment suggests that L2431 maps to a hydrophobic pocket within an autoinhibitory do-main adjacent to the activation loop. The substi-tution of L2431 by proline may affect the confor-mation of the mTOR activation loop. These data associated with functional heterogeneity of kinase activity.SignatureWe determined the intratumoral expression of a 110-gene signature shown to classify clear-cell car-cinoma into two molecular subgroups: clear-cellA (associated with a good prognosis) and clear-cellB (associated with a poor prognosis).24 Consistent with the phylogenetic analysis, metastatic sites and the primary-tumor site R4 segregated together, en-riched for genes in the clear-cell A subgroup, in contrast to the remaining tumor regions that were enriched for the clear-cell B subgroup (Fig. 3C). Thus, prognostic gene-expression signatures may not correctly predict outcomes if they are assessed from a single region of a heterogeneous tumor.Intratumor Genetic Heterogeneity in Three Consecutive TumorsTo determine whether intratumor heterogeneity was present in consecutive clear-cell carcinomas from the E-PREDICT trial, we performed multire-gion exome sequencing on the primary tumor and a metastasis from Patient 2 and ploidy and allelic-imbalance profiling on primary tumors from Pa-tients 2, 3, and 4. CT imaging showed no change in tumor dimensions during 6 weeks of everolimus treatment.Patient 2 had a metastatic tumor with a 1-bp deletion in VHL. Pretreatment core biopsy samples contained less than 5% tumor cells and were ex-cluded. Primary-tumor regions from R1 through R9 were harvested from the nephrectomy speci-men. After 5 months of participation in the trial with no objective tumor response, a core biopsy metastasis. We performed exon-capture sequenc-coverage, 61 reads) (Table 1 in the Supplementaryindicating high stromal contamination. A total of 119 somatic mutations were detected and their regional distribution mapped (Fig. 4A, and Table 4 sequencing to validate somatic mutations in the tumor-suppressor genes VHL, PBRM1, and TP53, in 2 independent and spatially separated mutations in SETD2 (missense and frameshift mutations) and PTEN (splice-site and missense mutations), and inSomatic Mutational Heterogeneity Phylogenetic analysis of tumor from Patient 2 re-Fig. 4B), which was consistent with the findings from primary tumor and metastases obtained from Patient 1. Only 37% of the somatic mutations that were identified in the nephrectomy specimen were ubiquitously de-tectable in all regions (31% if the metastasis, which was biopsied at the time of progression, was in-sociated with an increase in the number of non-synonymous mutations in the liver metastasis, as compared with the nephrectomy-biopsy specimens indicating that everolimus does not increase the mutational load.excluded because of insufficient DNA) identified multiple heterogeneous chromosomal aberrationsIntratumor Heterogeneity Revealed by multiregion SequencingTrimethylated H3K36 staining was absent SETD2 frame-shift or missense mutations (Fig. 12 in the Sup-tions together with a 3p deletion confer convergent loss of function. Regions with either a splice-site mutation or a missense mutation in PTEN, a negative regulator of the PI3 kinase–Akt pathway located on chromosome 10, showed phospho-Akt staining, as compared with PTEN and convergent phenotypic evolution.samples from four patients had identical allelic-imbalance profiles (tumor from Patient 3 in R1, R3, R4, and R9). Chromosome 3p aberrations oc-curred ubiquitously in all regions from all tumors, and allelic imbalances of 10q (in tumor from Pa-tient 2) and in 5q and 6q (in tumor from Patient 4)C Prognostic Signature GenesA Phospho-S6S6GFP-mTOR ActinPhospho-S6Phospho-4EBPR4R4R5R5mTOR (wild type)mTOR (wild type)mTOR (L2431P)mTOR (L2431P)M2a M2b R4R8R5T h e ne w engl a nd jour na l o f medicinewere ubiquitously present in one case each. These early ubiquitous events were outnumbered by non-ubiquitous aberrations, indicating that the majority of chromosomal events occurred after tumors diverged, providing further evidence of branching evolution. profiling detected intratumor the Supplementary and se-quencing of SETD2intratumor heterogeneity in Patient 4: seven re-gions of tumor sharing a SETD2 frameshift muta-tion harbored absent trimethylated H3K36 stain-ing, whereas a single region with wild-type SETD2 but mutant VHL harbored strong tumor-cell tri-DiscussionMultiregion genetic analysis of four consecutive tu-mors provided evidence of intratumor heterogene-geneous somatic mutations and chromosomal imbalances leading to phenotypic intratumor diver-sity (activating mutation in MTOR) and uniformity (loss-of-function mutation in SETD2 and PTEN Of all somatic mutations found on multiregion se-two tumors. Therefore, we found that a single tumor-biopsy specimen reveals a minority of ge-balance, and ploidy) that are present in an entire tumor.Pretreatment tumor-biopsy specimens from Pa-tient 1 had branched mutational profiles that were almost identical to those detected after everolimus exposure. Everolimus is not known to be muta-genic, and the number of nonsynonymous muta-tions did not increase after the administration of everolimus. Intratumor heterogeneity is unlikely to be confounded by clonal selection, since no tumorIntratumor Heterogeneity Revealed by multiregion Sequencingresponses were observed during the brief preopera-tive treatment period. Since intratumor heteroge-neity preceded therapy, it is unlikely that treatment biased the interpretation of these analyses.An unexpected finding was the detection of spatially separated distinct somatic mutations affecting the histone H3K36 methyltransferase SETD2, the histone H3K4 demethylase KDM5C, and the negative regulator of the PI3 kinase–Akt tumor progression, phenotypic convergent evolu-tion occurs, indicating a high degree of mutational diversity, a substrate for Darwinian selection, and evolutionary adaptation.The heterogeneous MTOR mutation renders the kinase constitutively active, increasing S6 phos-phorylation, a potential biomarker of response to mTOR inhibitors in clear-cell carcinoma.25 Such spatially separated somatic mutations altering pathway activity suggest that multiregional anal-yses may be required to predict the therapeutic outcome. Further studies will assess whether acti-vating mutations in MTOR depend on this pathway, which may result in higher responsiveness to mTOR inhibition.Intratumor heterogeneity was evident at the RNA-expression level, with expression signatures of good or poor prognosis detected in different regions of the same tumor. Although the 7-day washout period minimized a direct influence of everolimus on prognostic signature expression, we cannot exclude the possibility that potential unknown and persistent effects of everolimus pretreatment on the tumor–stroma composition might alter mRNA expression. The prognostic signature was described to be independent of metastatic stage,24consistent with the occur-rence of the good prognostic signature in metas-tases.Branched tumor evolution underscores the im-portance of targeting ubiquitous alterations in the trunk of the phylogenetic tree. Such ubiquitous allelic-imbalance events were seen on chromosome 3p (encoding VHL, PBRM1, and SETD2), 5q, 6q, and 10q. Larger multiregional series will probably iden-tify genes that can be targeted in the trunks of the phylogenetic tree for clear-cell carcinoma. Intratumor heterogeneity within the primary tu-mor may account for the benefits associated with cytoreductive nephrectomy26-28 by eliminating an evolutionary reservoir of phenotypic tumor-cell diversity.Genomics analyses from single tumor-biopsy specimens may underestimate the mutational bur-geneity may explain the difficulties encountered in sampling bias,29tion of preexisting drug-resistant clones,12,30 and predict therapeutic resistance.13 Reconstructing tumor clonal architectures and the identification of common mutations located in the trunk of the phylogenetic tree may contribute to more robust biomarkers and therapeutic approaches. Supported by grants from the Medical Research Council, Cancer Research UK, the Royal Marsden Hospital Renal Re-search Fund, Novartis, EU Framework 7 Personalized RNA In-terference to Enhance the Delivery of Individualized Cytotoxic and Targeted Therapeutics (PREDICT), and the Wellcome Trust (to Dr. Futreal).Disclosure forms provided by the authors are available with the full text of this article at .We thank the patients; Nasir Khan, Isobelle Coombes, Kim Edmonds, Amy Thomas, Jade Griffiths, Phil Clarke, Maggie James, and Peter Campbell; and the U.K. National Institute for Health Research.This article is dedicated to Tim Christmas.References1. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321:1807-12.2. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancre-atic cancers revealed by global genomic analyses. Science 2008;321:1801-6.3. Sjöblom T, Jones S, Wood LD, et al. 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