Примечания книги Эпидемия стерильности. Новый подход к пониманию аллергических и аутоиммунных заболеваний. Автор книги Мойзес Веласкес-Манофф

1

Перевод Николая Пушешникова. Прим. пер.

2

R. Tagore and S. K. Das. The English Writings of Rabindranath Tagore: Poems. New Delhi: Sahitya Akademi, 2004, 45.

3

David E. Elliott and Joel V. Weinstock. “Inflammatory Bowel Disease and the Hygiene Hypothesis: An Argument for the Role of Helminths” // The Hygiene Hypothesis and Darwinian Medicine, ed. Graham Rook.

4

K. H. Safavi et al. “Incidence of Alopecia Areata in Olmsted County, Minnesota, 1975 Through 1989”. Mayo Clinic Proceedings 70, № 7 (1995).

5

Lynn Petukhova et al. “Genome-wide Association Study in Alopecia Areata Implicates Both Innate and Adaptive Immunity”. Nature 466, № 7302 (2010).

6

S. T. Holgate. “The Epidemic of Allergy and Asthma”. Nature 402, № 6760 Suppl. (1999). Статистические данные о заболеваемости астмой взяты с сайта Центра по контролю заболеваемости: www.cdc.gov/vitalsigns/Asthma/index.html (February 15, 2012). Статистические данные о заболеваемости сенной лихорадкой предоставлены Американской академией аллергии, астмы и иммунологии (American Academy of Allergy, Asthma & Immunology).

7

Данные зависят от распространенности аутоиммунного заболевания. В развитых странах от трех до восьми процентов населения страдает от одного или более из восьмидесяти аутоиммунных или воспалительных заболеваний. Pierre Youinou et al. “Geo-epidemiology and Autoimmunity”. Journal of Autoimmunity 34, № 3 (2010).

8

N. A. Molodecky et al. “Increasing Incidence and Prevalence of the Inflammatory Bowel Diseases with Time, Based on Systematic Review”. Gastroenterology 142, № 1 (2012).

9

Edwin A. M. Gale. “The Rise of Childhood Type 1 Diabetes in the 20th Century”. Diabetes 51, № 12 (2002).

10

Alberto Rubio-Tapia et al. “Increased Prevalence and Mortality in Undiagnosed Celiac Disease”. Gastroenterology 137, № 1 (2009).

11

Jean-Francois Bach. “The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases”. New England Journal of Medicine 347, № 12 (2002).

12

“Worldwide Variation in Prevalence of Symptoms of Asthma, Allergic Rhinoconjunctivitis, and Atopic Eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee”. Lancet 351, № 9111 (1998).

13

“Incidence and Trends of Childhood Type 1 Diabetes Worldwide 1990–1999”. Diabetic Medicine 23, № 8 (2006). Christopher C. Patterson и EURODIAB Study Group. “Incidence Trends for Childhood Type 1 Diabetes in Europe during 1989–2003 and Predicted New Cases 2005–2020: A Multicentre Prospective Registration Study”. Lancet 373, № 9680 (2009).

14

G. A. W. Rook. “The Gut, Immunoregulation and Micro-organisms from Man’s Evolutionary Past”. Nutrition Bulletin (2010).

15

Полные статистические данные о распространенности иммуноопосредованных заболеваний в Цимании предоставил сам Майкл Гурвен. По состоянию на 26 октября 2011 года они были такими: восемь случаев аллергического ринита; ни одного случая астмы. Данные о распространенности аутоиммунных заболеваний: 12,3 случая на 10 000 человек. В медицинском обследовании приняли участие 12 116 человек. Некоторые пациенты проходили обследование несколько раз. Общее количество обследований, которые провела команда Гурвена, — 37 000; эти обследования охватили более 95% членов племени цимане.

16

А. Магдалена Уртадо и Ким Хилл на протяжении многих лет изучали племя хиви, обитающее на равнинах Венесуэлы, а также племя аче, которое живет в парагвайской части Амазонии. У членов этих племен нет ни астмы, ни высокого давления, ни диабета. Magdalena Hurtado, Kim Hill, and I. Arenas De Hurtado Selva Rodriguez. “The Evolutionary Context of Chronic Allergic Conditions: The Hiwi of Venezuela”. Human Nature 8, № 1 (1997).

17

Gurven, Michael, et al. “Mortality Experience of Tsimane Amerindians of Bolivia: Regional Variation and Temporal Trends”. American Journal of Human Biology 19, № 3 (2007).

18

Марк Джексон высказывает эту мысль в своей книге «Аллергия: история современного заболевания» (Allergy: The History of a Modern Malady).

19

William Parker. “Reconstituting the Depleted Biome to Prevent Immune Disorders”. Evolution & Medicine Review (2010). http://evmedreview.com/?p=457.

20

Berkley R. Powell, Neil R. M. Buist, and Peter Stenzel. “An X-linked Syndrome of Diarrhea, Polyendocrinopathy, and Fatal Infection in Infancy”. Journal of Pediatrics 100, № 5 (1982).

21

C. L. Bennett et al. “The Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome (IPEX) Is Caused by Mutations of FOXP3”. Nature Genetics 27, № 1 (2001).

22

Речь идет о результатах многих исследований. Более подробную информацию см.: Leonie Taams, Arne N. Akbar, and Marca H. M. Wauben. Regulatory T-cells in Inflammation, Progress in Inflammation Research. Basel and Boston: Birkhäuser, 2005, 3–17.

23

Книга написана в 2012 году. Прим. ред.

24

William McNeill. Plagues and People, 5.

25

R. W. Ashford and W. Crewe. The Parasites of Homo Sapiens: An Annotated Checklist of the Protozoa, Helminths and Arthropods for Which We Are Home. London: Taylor & Francis, 200), IX.

26

George J. Armelagos. “The Paleolithic Disease-scape, the Hygiene Hypothesis, and the Second Epidemiological Transition” // The Hygiene Hypothesis and Darwinian Medicine. Basel and Boston: Birkhäuser, 2009.

27

Все статистические данные взяты из дискуссионного раздела указанной ниже обзорной статьи, в которой основное внимание уделяется племени хадза из Танзании, а также идет речь о племени кунг и других племенах. F. J. Bennett et al. “Helminth and Protozoal Parasites of the Hadza of Tanzania”. Transactions of the Royal Society of Tropical Medicine and Hygiene 64, № 6 (1970).

28

В ходе исследования диких шимпанзе, проведенного в 1976 году в Танзании, было обнаружено шесть разных видов гельминтов и два вида простейших. Из 32 обследованных особей все были заражены минимум одним, а большинство — несколькими паразитами. S. K. File, W. C. McGrew, and C. E. Tutin. “The Intestinal Parasites of a Community of Feral Chimpanzees, Pan Troglodytes Schweinfurthii”. Journal of Parasitology 62, № 2 (1976).

29

R. W. Ashford. “Parasites as Indicators of Human Biology and Evolution”. Journal of Medical Microbiology 49, № 9 (2000).

30

E. P. Hoberg. “Phylogeny of Taenia: Species Definitions and Origins of Human Parasites”. Parasitology International 55 Suppl. (2006).

31

David L. Reed et al. “Pair of Lice Lost or Parasites Regained: The Evolutionary History of Anthropoid Primate Lice”. BMC Biology 5 (2007).

32

Nicholas Wade. “In Lice, Clues to Human Origin and Attire”. The New York Times, March 8, 2007.

33

Robin A. Weiss. “Apes, Lice and Prehistory”. Journal of Biology 8, № 2 (2009).

34

David Reich et al. “Genetic History of an Archaic Hominin Group from Denisova Cave in Siberia”. Nature 468, № 7327 (2010).

35

David L. Reed et al. “Genetic Analysis of Lice Supports Direct Contact between Modern and Archaic Humans”. PLoS Biology 2, № 11 (2004).

36

Odile Loreille, Françoise Bouchet. “Evolution of Ascariasis in Humans and Pigs: A Multi-disciplinary Approach”. Memorias do Instituto Oswaldo Cruz 98, Suppl. 1 (2003).

37

Увлекательное описание жизни в эпоху позднего палеолита: Brigitte M. Holt. “Hunters of the Ice Age: The Biology of Upper Paleolithic People”. American Journal of Physical Anthropology Suppl. 47 (2008).

38

Erik Trinkaus, Hong Shang. “Anatomical Evidence for the Antiquity of Human Footwear: Tianyuan and Sunghir”. Journal of Archaeological Science 35, № 7 (2008).

39

Mary C. Stiner. “Carnivory, Coevolution, and the Geographic Spread of the Genus Homo”. Journal of Archaeological Research 10, № 1 (2002).

40

Murray P. Cox et al. “Autosomal Resequence Data Reveal Late Stone Age Signals of Population Expansion in Sub-Saharan African Foraging and Farming Populations”. PLoS ONE 4, № 7 (2009).

41

Luisa Pereira et al. “Population Expansion in the North African Late Pleistocene Signalled by Mitochondrial DNA Haplogroup U6”. BMC Evolutionary Biology 10, № 1 (2010).

42

Yali Xue et al. “Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection”. American Journal of Human Genetics 78, № 4 (2006). M. Saleh et al. “Differential Modulation of Endotoxin Responsiveness by Human Caspase-12 Polymorphisms”. Nature 429, № 6987 (2004).

43

Dennis C. Ko et al. “A Genome-wide In Vitro Bacterial-Infection Screen Reveals Human Variation in the Host Response Associated with Inflammatory Disease”. American Journal of Human Genetics 85, № 2 (2009).

44

Хорошую хронику одомашнивания животных можно найти в: M. A. Zeder. “Domestication and Early Agriculture in the Mediterranean Basin: Origins, Diffusion, and Impact”. Proceedings of the National Academy of Sciences 105, № 33 (2008). Brian L. Peasnall et al. “Hallan Çemi, Pig Husbandry, and Post-Pleistocene Adaptations Along the Taurus-Zagros Arc (Turkey)”, Paeléorient 24, № 1 (1998). G. Larson et al. “Patterns of East Asian Pig Domestication, Migration, and Turnover Revealed by Modern and Ancient DNA”. Proceedings of the National Academy of Sciences 107, № 17 (2010). Y. P. Liu et al. “Multiple Maternal Origins of Chickens: Out of the Asian Jungles”. Molecular Phylogenetic Evolution 38, № 1 (2006). A. K. Outram et al. “The Earliest Horse Harnessing and Milking”. Science 323, № 5919 (2009).

45

Carlos A. Driscoll, David W. Macdonald, and Stephen J. Obrien. “From Wild Animals to Domestic Pets, an Evolutionary View of Domestication”. Proceedings of the National Academy of Sciences 106, Suppl. 1 (2009).

46

Shahina Farid. “Çatalhöyük 2009 Archive Report” (catalhoyuk.com).

47

Israel Hershkovitz et al. “Detection and Molecular Characterization of 9,000-Year-Old Mycobacterium Tuberculosis from a Neolithic Settlement in the Eastern Mediterranean”. PLoS ONE 3, № 10 (2008).

48

Vered Eshed et al. “Paleopathology and the Origin of Agriculture in the Levant,” American Journal of Physical Anthropology 143, № 1 (2010).

49

George J. Armelagos. “The Paleolithic Diseasescape, the Hygiene Hypothesis, and the Second Epidemiological Transition” // Rook, The Hygiene Hypothesis.

50

См.: Crawford. Deadly Companions, 65.

51

Пиктограммы с изображением болезней, напоминающих оспу, датируются 3730–1555 годами до н. э. Мумии с оспой появились в период с 1570 по 1085 год до н. э. См.: Crawford. Deadly Companions, 107.

52

J. N. Hays. Epidemics and Pandemics: Their Impacts on Human History. Santa Barbara: ABC–CLIO, 2005.

53

Nikola Koepke, Joerg Baten. “The Biological Standard of Living in Europe during the Last Two Millennia”. European Review of Economic History 9 (2005).

54

См.: Crawford. Deadly Companions, 84, 86.

55

Джаред Даймонд. Ружья, микробы и сталь. История человеческих сообществ. М.: АСТ, 2017. Прим. ред.

56

Насколько узким было человеческое «бутылочное горлышко» и был ли этот эффект обусловлен единственным дискретным событием — это вопрос, вокруг которого до сих пор ведутся жаркие дискуссии. Доводы в пользу этой точки зрения можно найти здесь: The Genographic Project и S. H. Ambrose. “Late Pleistocene Human Population Bottlenecks, Volcanic Winter, and Differentiation of Modern Humans”. Journal of Human Evolution 34, № 6 (1998). Доводы против см.: J. Hawks et al. “Population Bottlenecks and Pleistocene Human Evolution”. Molecular Biology and Evolution 17, № 1 (2000).

57

M. A. Ruffer. “Note on the Presence of ‘Bilharzia Haematobia’ in Egyptian Mummies of the Twentieth Dynasty [1250–1000 B.C.]”. British Medical Journal 1, № 2557 (1910).

58

См. Crawford. Deadly Companions, 69.

59

Matthieu Le Bailly et al. “Diphyllobothrium: Neolithic Parasite?” Journal of Parasitology 91, № 4 (2005).

60

Françoise Bouchet, Stéphanie Harter, Matthieu Le Bailly. “The State of the Art of Paleoparasitological Research in the Old World”. Memórias do instituto Oswaldo Cruz 98, Suppl. 1 (2003).

61

Яйца анкилостомы присутствуют в копролите (окаменелых остатках экскрементов) возрастом 7200 лет, найденном в Бразилии, а также в перуанских мумиях, которым около тысячи лет. И холодный климат не защищает от гельминтов. Останки семилетнего ребенка, похороненного 840 лет назад на острове Адак (Аляска), содержат аскарид и рыбного ленточного червя. F. Bouchet et al. “Identification of Parasitoses in a Child Burial from Adak Island (Central Aleutian Islands, Alaska)”. Comptes Rendus de L’Académie des Sciences Série III, Sciences de la Vie 324, № 2 (2001). Adauto Araujo et al. “Parasites as Probes for Prehistoric Human Migrations?” Trends in Parasitology 24, № 3 (2008).

62

T. Goebel, M. R. Waters, D. H. O’Rourke. “The Late Pleistocene Dispersal of Modern Humans in the Americas”. Science 319, № 5869 (2008).

63

Karl J. Reinhard et al. “Chinese Liver Flukes in Latrine Sediments from Wong Nim’s Property, San Bernardino: Archaeoparasitology of the Caltrans District Headquarters”. Journal of Parasitology 94, № 1 (2008).

64

Charles L. Fisher et al. “Privies and Parasites: The Archaeology of Health Conditions in Albany, New York”. Historical Archaeology 41, № 4 (2007).

65

Из всех возможных вариантов начала промышленной революции я взял представленный здесь: Gavin Weightman. The Industrial Revolutionaries: The Making of the Modern World, 1776–1914. New York: Grove Press, 2007.

66

Многие данные взяты из книги: Martin V. Melosi. Garbage in the Cities.

67

Lewis Mumford. The City in History: Its Origins, Its Transformations, and Its Prospects. New York: Harcourt, 1961, 447.

68

Richard H. Steckel, Roderick Floud. Health and Welfare During Industrialization, National Bureau of Economic Research project report. Chicago: University of Chicago Press, 1997, 93.

69

Kinsgley Davis. “The Urbanization of the Human Population”. Scientific American (September 1965), 41–53.

70

Мальчики из состоятельных семей были также на пятнадцать сантиметров выше своих ровесников из бедных семей. Roderick Floud, Kenneth W. Wachter, Annabel Gregory. Height, Health, and History: Nutritional Status in the United Kingdom, 1750–1980, Cambridge Studies in Population, Economy, and Society in Past Time. Cambridge and New York: Cambridge University Press, 1990, 1.

71

Это наблюдение сделал Томас Кьюбитт. Многие данные взяты из книги: Halliday. The Great Stink of London, 35.

72

См.: Melosi. Garbage in the Cities, 10, и Suellen M. Hoy. Chasing Dirt, 4.

73

Hoy. Chasing Dirt, 4. Melosi. Garbage in the Cities, 10, и Suellen M. Hoy. Chasing Dirt, 8. Вторая цитата принадлежит британскому реформатору сельского хозяйства Уильяму Коббету.

74

Чарльз Диккенс. Холодный дом. М.: Эксмо, 2016.

75

См.: J. Komlos. Stature, Living Standards, and Economic Development: Essays in Anthropometric History. Chicago: University of Chicago Press, 1994, 157.

76

См.: Melosi. Garbage in the Cities, 14.

77

S. Smith. The City That Was. New York: Frank Allaben, 1911, 63.

78

Judith Walzer Leavitt, Ronald L. Numbers. Sickness and Health in America: Readings in the History of Medicine and Public Health, 3rd ed. Madison: University of Wisconsin Press, 1997, 442.

79

Marie-Eve Val et al. “The Single-Stranded Genome of Phage CTX Is the Form Used for Integration into the Genome of Vibrio Cholerae”. Molecular Cell 19, № 4 (2005).

80

См.: Christopher Hamlin. Cholera: The Biography, Biographies of Disease. Oxford and New York: Oxford University Press, 2009.

81

См.: Hoy. Chasing Dirt, 64.

82

Президент Закари Тейлор объявил 3 августа 1849 года днем «поста, смирения и молитвы», для того чтобы сдержать волну холеры, захлестывающую страну. Zachary Taylor. “National Fast”. Journal of the American Temperance Union, August 1, 1849.

83

Annabel Ferriman. “BMJ Readers Choose the ‘Sanitary Revolution’ as Greatest Medical Advance Since 1840”. British Medical Journal 334, № 7585 (2007).

84

Показатели ожидаемой продолжительности жизни в Западной Европе взяты из базы данных, собранных в Швеции за один из самых продолжительных периодов. Доступ к этой информации можно получить здесь: John R. Wilmoth, Vladimir Shkolnikov. “The Human Mortality Database”. UC Berkeley, http://demog.berkeley.edu/~bmd/Sweden/LifeTables/e0.1x1. http://demog.berkeley.edu/~bmd/Sweden/Rates/Mx.early.5x1.

85

“World Population Prospects: The 2010 Revision Infant Mortality Rate (Both Sexes Combined) By Major Area, Region and Country, 1950–2100”. United Nations, Department of Economic and Social Affairs, 201.

86

Я сделал этот вывод на основании сравнительного исследования смертности среди охотников и собирателей, которое провел Майкл Гурвен. Michael Gurven, Hillard Kaplan. “Longevity Among Hunter-Gatherers: A Cross-Cultural Examination”. Population and Development Review 33, № 2 (2007).

87

M. B. Emanuel. “Hay Fever, a Post Industrial Revolution Epidemic: A History of Its Growth during the 19th Century”. Clinical & Experimental Allergy 18, № 3 (1988).

88

Наблюдения Блэкли представлены в написанном в 1873 году труде “Experimental Researches on the Causes and Nature of Catarrhus Aestivus” («Экспериментальные исследования природы и причин летнего катара»). K. J. Waite. “Blackley and the Development of Hay Fever as a Disease of Civilization in the Nineteenth Century”. Medical History 39, № 2 (1995).

89

Моррелл Маккензи также обратил внимание на классовый аспект сенной лихорадки. Он обнаружил 61 случай этого заболевания в своей частной практике, но ни одного случая среди пациентов больниц, которые принадлежали к менее состоятельным слоям общества. Gregg Mitman. “Hay Fever Holiday: Health, Leisure, and Place in Gilded-Age America”. Bulletin of the History of Medicine 77, № 3 (2003).

90

Врачом, который заявил о превосходстве англичан в связи с наличием у них такой болезни, как сенная лихорадка, был У. П. Данбар. См.: K. J. Waite. “Blackley and the Development of Hay Fever as a Disease of Civilization in the Nineteenth Century”.

91

См.: A. Maddison. The World Economy: A Millennial Perspective, Vol. 2: Historical Statistics. Academic Foundation, 2007, 264. Эту статью можно найти здесь: theworldeconomy.org.

92

T. Dobzhansky. “Nothing in Biology Makes Sense Except in the Light of Evolution”. American Biology Teacher 35 (1973).

93

Статистические данные по Италии и Сардинии взяты из следующего источника: ISTAT (Istituto Nazionale Di Statistica). http://www.istat.it/en/.

94

Maura Pugliatti et al. “Multiple Sclerosis in Sardinia, Insular Italy: The Highest Burden Worldwide?” European Journal of Neurology 17, Suppl. 3 (2010).

95

M. Songini, C. Lombardo. “The Sardinian Way to Type 1 Diabetes”. Journal of Diabetes Science and Technology 4, № 5 (2010).

96

Paul Reiter. “From Shakespeare to Defoe: Malaria in England in the Little Ice Age”. Emerging Infectious Diseases 6, № 1 (2000).

97

P. W. Hedrick. “Population Genetics of Malaria Resistance in Humans”. Heredity 107, № 4 (2011).

98

A. C. Allison. “Protection Afforded by Sickle-cell Trait Against Subtertian Malarial Infection”. British Medical Journal 1, № 4857 (1954).

99

См. репринтное издание оригинальной работы 1949 года: J. B. S. Haldane. “Disease and Evolution” // Krishna R. Dronamraju and Paolo Arese, eds., Emerging Infectious Diseases of the 21st Century. New York: Springer, 2006.

100

Licinio Contu, Carlo Carcassi, Sandro Orrù. “Malaria e genetica popolazionistica” // Sardegna e Malaria: Un nuovo approccio a un antico malanno, ed. Ugo Carcassi and Ida Mura. Sassari, Sardinia: Carlo Delfino Editore, 2009, 154.

101

На острове Сардиния ландшафт распределяется по категориям по уровню малярийности. Не далее как в 30-х годах малярийность прибрежных районов составляла 80%, а это значит, что почти каждый обитатель этого региона был подвержен воздействию P. falciparum. На высоте 600 метров этот малярийный паразит был распространен на 45% территории. В более гористых районах, достигающих высоты 1000 метров, также был небольшой уровень малярийности — около 10%. Все эти значения выведены на основании данных, представленных в предыдущем источнике: Licinio Contu, Carlo Carcassi, Sandro Orrù. “Malaria e genetica popolazionistica” // Sardegna e Malaria: Un nuovo approccio a un antico malanno, ed. Ugo Carcassi and Ida Mura. Sassari, Sardinia: Carlo Delfino Editore, 2009, 151–152.

102

Stephen L. Dyson, Robert J. Rowland. Archaeolog; History in Sardinia from the Stone Age to the Middle Ages: Shepherds, Sailors, and Conquerors. Philadelphia: University of Pennsylvania Museum of Archaeology and Anthropology, 2007, 22.

103

S. D. Matthews et al. “Evidence for Late Pleistocene Population Expansion of the Malarial Mosquitoes, Anopheles Arabiensis and Anopheles Gambiae in Nigeria”. Medical and Veterinary Entomology 21, № 4 (2007).

104

Weimin Liu et al. “Origin of the Human Malaria Parasite Plasmodium Falciparum in Gorillas”. Nature 467, № 7314 (2010).

105

Crawford. Deadly Companions, 68.

106

A. G. Nerlich et al. “Plasmodium Falciparum in Ancient Egypt”. Emerging Infectious Diseases 14, № 8 (2008).

107

Это затопленное поселение называется сейчас Атлит-Ям. I. Hershkovitz et al. “Possible Congenital Hemolytic Anemia in Prehistoric Coastal Inhabitants of Israel”. American Journal of Physical Anthropology 85, № 1 (1991).

108

См. также S. Sotgiu et al. “Multiple Sclerosis Complexity in Selected Populations: The Challenge of Sardinia, Insular Italy”. European Journal of Neurology 9, № 4 (2002).

109

Eugenia Tognotti. “La lotta alla malaria in Sardegna. Dalle bonifiche al DDT” // Sardegna e Malaria, 69; Eugenia Tognotti. “Program to Eradicate Malaria in Sardinia, 1946–1950”. Emerging Infectious Diseases 15, № 9 (2009).

110

M. Pugliatti et al. “Multiple Sclerosis Epidemiology in Sardinia: Evidence for a True Increasing Risk”. Acta Neurologica Scandinavica 103, № 1 (2001).

111

G. Rosati et al. “Epidemiology of Multiple Sclerosis in Northwestern Sardinia: Further Evidence for Higher Frequency in Sardinians Compared to Other Italians”. Neuroepidemiology 15, № 1 (1996).

112

W. McGuire et al. “Severe Malarial Anemia and Cerebral Malaria Are Associated with Different Tumor Necrosis Factor Promoter Alleles”. Journal of Infectious Diseases 179, № 1 (1999).

113

P. P. Bitti et al. “Association Between the Ancestral Haplotype HLA A30B18DR3 and Multiple Sclerosis in Central Sardinia”. Genetic Epidemiology 20, № 2 (2001).

114

Один из вариантов — TNF-376A — присутствовал у 6,5% сицилийцев. В то же время 51% сардинцев оказались носителями этого варианта. Sebastian A. Wirz et al. “High Frequency of TNF Alleles–238A and –376A in Individuals from Northern Sardinia”. Cytokine 26, № 4 (2004).

115

Stefano Sotgiu et al. “Multiple Sclerosis and Anti-Plasmodium Falciparum Innate Immune Response”. Journal of Neuroimmunology 185, № 1 (2007).

116

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Michael Walther et al. “Distinct Roles for FOXP3 and FOXP3 CD4 T-сells in Regulating Cellular Immunity to Uncomplicated and Severe Plasmodium falciparum Malaria”. PLoS Pathogens 5, № 4 (2009).

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Серповидноклеточный признак может проявляться в виде частично толерантного ответа. На протяжении десятков лет ученые вели споры по поводу того, как этот признак защищает его носителей. Он укрепляет защиту красных кровяных клеток, делая их неуязвимыми перед возбудителями инфекции? Он быстрее устраняет паразита? Он помогает очистить пораженные паразитами эритроциты? Многочисленные данные свидетельствуют о том, что ничего из перечисленного выше не соответствует действительности: носители серповидноклеточного признака заражаются малярией так же часто, как и те люди, у которых этого признака нет, а в крови циркулирует много паразитов. Чего им действительно удается избежать, так это церебральной малярии, основного осложнения в результате заражения паразитом P. falciparum. Почему? Они выживают благодаря контролю над многими возбудителями инфекции и толерантности к ним. Tomas N. Williams et al. “An Immune Basis for Malaria Protection by the Sickle Cell Trait”. PLoS Medicine 2, № 5 (2005); M. Cyrklaff et al. “Hemoglobins S and C Interfere with Actin Remodeling in Plasmodium falciparum-infected Erythrocytes”. Science 334, № 6060 (2011).

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Alessandro Mathieu et al. “The Interplay between the Geographic Distribution of HLA-B27 Alleles and Their Role in Infectious and Autoimmune Diseases: A Unifying Hypothesis”. Autoimmunity Reviews 8, № 5 (2009).

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Olivia C. Finney et al. “Homeostatic Regulation of T-Effector to Treg Ratios in an Area of Seasonal Malaria Transmission”. European Journal of Immunology 39, № 5 (2009); Olivia C. Finney, Eleanor M. Riley, Michael Walther. “Regulatory T-cells in Malaria — Friend or Foe?” Trends in Immunology 31, № 2 (2010).

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Marta Barreto et al. “Low Frequency of CD4+CD25+ Treg in SLE Patients: A Heritable Trait Associated with CTLA4 and TGFbeta Gene Variants”. BMC Immunology 10 (2009).

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A. Paolillo et al. “The Effect of Bacille Calmette-Guérin on the Evolution of New Enhancing Lesions to Hypointense T1 Lesions in Relapsing Remitting MS”. Journal of Neurology 250, № 2 (2003).

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Ген, вызывающий предрасположенность к болезни Крона (вариант гена NOD2/CARD15, который кодирует микробный рецептор), был идентифицирован в 2001 году. D. P. Mcgovern et al. “NOD2 (CARD15), the First Susceptibility Gene for Crohn’s Disease”. Gut 49, № 6 (2001). Полное название этого гена — «содержащий нуклеотид-связывающий домен олигомеризации белок 2». Этот ген кодирует рецептор, который помогает обнаруживать различные микроорганизмы, в том числе резидентные бактерии. Наличие одной копии этого гена увеличивает вероятность воспалительных заболеваний кишечника более чем в два раза; наличие двух копий увеличивает эту вероятность в семнадцать раз. Детали того, как работает (или не работает) этот вариант гена, не совсем ясны, но предположительно он влияет на способность иммунной системы отличать друзей от врагов. Shiva Yazdanyar et al. “Penetrance of NOD2/CARD15 Genetic Variants in the General Population”. Canadian Medical Association Journal 182, № 7 (2010).

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Большая часть информации, представленной в главе, взята из: Elliott and Weinstock. “Inflammatory Bowel Disease and the Hygiene Hypothesis: An Argument for the Role of Helminths” // Rook, The Hygiene Hypothesis and Darwinian Medicine.

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В случае более чистых условий жизни в детском возрасте риск воспалительных заболеваний кишечника возрастает в пять раз. A. E. Gent et al. “Inflammatory Bowel Disease and Domestic Hygiene in Infancy”. Lancet 343, № 8900 (1994).

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Joel V. Weinstock et al. “The Possible Link between De-worming and the Emergence of Immunological Disease,” Journal of Laboratory and Clinical Medicine 139, № 6 (2002). D. E. Elliott et al. “Does the Failure to Acquire Helminthic Parasites Predispose to Crohn’s Disease?” FASEB Journal 14, № 12 (2000).

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Большая часть истории о воспалительных заболеваниях кишечника взята из: Joseph B. Kirsner. “The Historical Basis of the Idiopathic Inflammatory Bowel Diseases”. Inflammatory Bowel Diseases, № 1 (1995); S. Wilks. “Morbid Appearances in the Intestine of Miss Bankes”. London Medical Gazette 2 (1859).

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Столл считал, что общий вес самих гельминтов равен весу 442 000 мужчин. «С точки зрения гельминтологии это можно обозначить как тяжелую роль хозяина, которую играют люди в жизни гельминтов», — писал он. N. R. Stoll. “This Wormy World”. Journal of Parasitology 33, № 1 (1947).

145

В начале 70-х годов у трети афроамериканских школьников Нового Орлеана все еще обнаруживали гельминтов, хотя уровень заражения был довольно низким. То же самое можно сказать о Южной Каролине. G. M. Jeffery et al. “Study of Intestinal Helminth Infections in a Coastal South Carolina Area”. Public Health Reports 78 (1963); D. W. Hubbard et al. “Intestinal Parasite Survey of Kindergarten Children in New Orleans”. Pediatric Research 8, № 6 (1974).

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Судя по данным медицинских карт ветеранов, среди солдат из северных штатов было, как правило, больше случаев воспалительных заболеваний кишечника, чем у солдат из южных штатов, а у белых они встречались чаще, чем у афроамериканцев. Более молодые ветераны с разной расовой принадлежностью чаще страдали воспалением кишечника, чем ветераны старшего возраста. Однако этот риск поддавался модификации. Солдаты, которые служили во Вьетнаме и предположительно могли контактировать с тропическими паразитами, болели воспалительными заболеваниями кишечника реже остальных. У бывших военнопленных, которых содержали в грязных условиях, воспаление кишечника встречалось реже, чем у солдат, которым не довелось пережить такие тяжелые испытания. См.: A. Sonnenberg, I. H. Wasserman. “Epidemiology of Inflammatory Bowel Disease Among U.S. Military Veterans”. Gastroenterology 101, № 1 (1991); F. Delcò, A. Sonnenberg. “Military History of Patients with Inflammatory Bowel Disease: An Epidemiological Study Among U.S. Veterans”. American Journal of Gastroenterology 93, № 9 (1998).

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Chris Green et al. “A Population-based Ecologic Study of Inflammatory Bowel Disease: Searching for Etiologic Clues”. American Journal of Epidemiology 164, № 7 (2006).

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R. W. Summers et al. “Trichuris Suis Therapy in Crohn’s Disease”. Gut 54, № 1 (2005); R. W. Summers et al. “Trichuris Suis Therapy for Active Ulcerative Colitis: A Randomized Controlled Trial”. Gastroenterology 128, № 4 (2005).

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G. L. Radford-Smith. “Will Worms Really Cure Crohn’s Disease?”. Gut 54, № 1 (2005).

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Richard L. Kradin et al. “Iatrogenic Trichuris Suis Infection in a Patient with Crohn Disease”. Archives of Pathology & Laboratory Medicine 130, № 5 (2006).

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Robert W. Summers, David E. Elliott, Joel V. Weinstock. “Why Trichuris Suis Should Prove Safe for Use in Inflammatory Bowel Diseases”. Inflammatory Bowel Diseases 11, № 8 (2005).

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События происходят в 2010 году. Прим. ред.

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Elizabeth Cohen. “Man Finds Extreme Healing Eating Parasitic Worms”. CNN. http://www.cnn.Com/2010/HEALTH/12/09/worms.health/index.html.

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H. G. Desai, P. A. Gupte. “Increasing Incidence of Crohn’s Disease in India: Is It Related to Improved Sanitation?”. Indian Journal of Gastroenterology 24, № 1 (2005).

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J. Kabeerdoss et al. “Exposure to Hookworms in Patients with Crohn’s Disease: A Case-Control Study”. Alimentary Pharmacology & Therapeutics 34, № 10 (2011).

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Vivekanandhan Aravindhan et al. “Decreased Prevalence of Lymphatic Filariasis Among Subjects with Type-1 Diabetes”. American Journal of Tropical Medicine and Hygiene 83, № 6 (2010).

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D. I. Pritchard, A. Brown. “Is Necator americanus Approaching a Mutualistic Symbiotic Relationship with Humans?” Trends in Parasitology 17, № 4 (2001).

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Более подробную информацию о том, как гельминты могут сдерживать иммунный ответ на малярию, см.: Mathieu Nacher. “Interactions Between Worm Infections and Malaria”. Clinical Reviews in Allergy & Immunology 26, № 2 (2004).

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H. Yemaneberhan et al. “Prevalence of Wheeze and Asthma and Relation to Atopy in Urban and Rural Ethiopia”. Lancet 350, № 9071 (1997).

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Мария Язданбакхш не первая, кто проводил эксперименты такого рода. Нил Линч из Института биомедицины при Центральном университете Венесуэлы в Каракасе предпринял первое интервенционное исследование для изучения аллергии в группе участников эксперимента, зараженных паразитами. К тому времени он уже обратил внимание на то, что распространенность аллергии существенно отличается в разных социально-экономических группах столицы Венесуэлы Каракаса: чем беднее группа, тем меньше в ней аллергических заболеваний. Показатель распространенности гельминтов среди бедных жителей Каракаса был относительно высоким. Кроме того, уровень IgE был у них в десять раз выше, чем у представителей состоятельных слоев населения, в большей степени подверженных аллергии. Подобно Дэвиду Причарду, Линч пришел к выводу о том, что заражение гельминтами защищает от аллергии, а люди, которые наиболее эффективно изгоняют гельминтов, с большей вероятностью страдают аллергией в случае их отсутствия. Работая в бедном районе Каракаса Баррио Лос Эрасос, где заражение гельминтами было повсеместным, Линч лечил 107 детей посредством двухлетнего курса дегельминтизации. В конце исследования он измерил аллергическую реактивность кожи и сравнил полученные данные с показателями в самом начале исследования, а также с показателями группы детей, не проходивших процедуру дегельминтизации. После изгнания гельминтов уровень аллергической реактивности существенно повышался. Другими словами, освободив детей от гельминтов, Линч сделал их более подверженными аллергии. У этого исследования были свои недостатки. Исследователи знали, кто проходит лечение, а в контрольную группу были включены дети, которые отказались принимать дегельминтизационные препараты. Кроме того, в конце 80-х — начале 90-х годов Венесуэлу охватили политические и экономические беспорядки, которые ухудшили ситуацию в трущобах. В итоге за период исследования члены контрольной группы получили еще больше гельминтов, что затрудняло сопоставление данных. Тем не менее это первое интервенционное исследование показало, что гельминты оказывают непосредственное и постоянное воздействие на иммунную систему человека. После исчезновения гельминтов аллергическая реакция стремительно росла. Линч объяснял власть гельминтов над аллергической реакцией одной из версий гипотезы о насыщении мастоцитов: множество бесполезных антител IgE заполняют мастоциты, снижая чувствительность к любому специфическому аллергену. N. R. Lynch et al. “Effect of Anthelmintic Treatment on the Allergic Reactivity of Children in a Tropical Slum”. Journal of Allergy and Clinical Immunology 92, № 3 (1993); N. R. Lynch et al. “Allergic Reactivity and Socio-economic Level in a Tropical Environment”. Clinical Allergy 17, № 3 (1987).

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Mark S. Wilson et al. “Suppression of Allergic Airway Inflammation by Helminth-Induced Regulatory T-Cells”. Journal of Experimental Medicine 202, № 9 (2005). Mark S. Wilson, Rick M. Maizels. “Regulatory T-cells Induced by Parasites and the Modulation of Allergic Responses”. Chemical Immunology and Allergy 90 (2006).

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181

Льюис Кэрролл называл шахматные фигуры красными, поскольку в шахматных наборах тех лет именно таким был цвет темных фигур. Сегодня принято переводить Red Queen как «Черная Королева» с учетом цвета шахматных фигур, распространенного в наше время. Прим. пер.

182

Описание работы Курта Лайвли, посвященной улиткам, можно найти на сайте Университета штата Индиана: http://www.indiana.edu/~curtweb/Research/cost%20of%20males.html. Большая часть материала взята из: Zuk. Riddled with Life.

183

Michael P. Muehlenbein, David P. Watts. “The Costs of Dominance: Testosterone, Cortisol and Intestinal Parasites in Wild Male Chimpanzees”. Biopsychosocial Medicine 4 (2010).

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J. Hopkin. “Immune and Genetic Aspects of Asthma, Allergy and Parasitic Worm Infections: Evolutionary Links”. Parasite Immunology 31, № 5 (2009).

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Matteo Fumagalli et al. “Parasites Represent a Major Selective Force for Interleukin Genes and Shape the Genetic Predisposition to Autoimmune Conditions”. Journal of Experimental Medicine 206, № 6 (2009); Matteo Fumagalli et al. “The Landscape of Human Genes Involved in the Immune Response to Parasitic Worms”. BMC Evolutionary Biology 10 (2010).

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Matteo Fumagalli et al. “Signatures of Environmental Genetic Adaptation Pinpoint Pathogens as the Main Selective Pressure through Human Evolution”. PLoS Genetics 7, № 11 (2011); Gopalakrishnan Netuveli et al. “Ethnic Variations in UK Asthma Frequency, Morbidity, and Health-Service Use: A Systematic Review and Meta-analysis”. Lancet 365, № 9456 (2005).

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John A. Jenkins, Heimo Breiteneder, E. N. Clare Mills. “Evolutionary Distance from Human Homologs Reflects Allergenicity of Animal Food Proteins”. Journal of Allergy and Clinical Immunology 120, № 6 (2007).

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История Эрики фон Мутиус основана на интервью. См. также: Rob Hyde. “Erika von Mutius: Reshaping the Landscape of Asthma Research”. Lancet 372, № 9643 (2008).

196

Подобно Дэвиду Стрэкану, фон Мутиус пришла к выводу, что старшие сестры и братья защищают младших от аллергии. T. Nicolai, E. von Mutius. “Respiratory Hypersensitivity and Environmental Factors: East and West Germany”. Toxicology Letters 86, nos. 2–3 (1996); E. von Mutius et al. “Prevalence of Asthma and Allergic Disorders Among Children in United Germany: A Descriptive Comparison”. British Medical Journal (Clinical Research Ed.) 305, № 6866 (1992).

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P. M. Matricardi et al. “Sibship Size, Birth Order, and Atopy in 11,371 Italian Young Men”. Journal of Allergy and Clinical Immunology 101, № 4, pt. 1 (1998); P. M. Matricardi et al. “Exposure to Foodborne and Orofecal Microbes versus Airborne Viruses in Relation to Atopy and Allergic Asthma: Epidemiological Study”. British Medical Journal (Clinical Research Ed.) 320, № 7232 (2000).

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Paolo Maria Matricardi et al. “Hay Fever and Asthma in Relation to Markers of Infection in the United States”. Journal of Allergy and Clinical Immunology 110, № 3 (2002).

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C. Braun-Fahrländer et al. “Prevalence of Hay Fever and Allergic Sensitization in Farmers’ Children and Their Peers Living in the Same Rural Community”. Clinical and Experimental Allergy 29, № 1 (1999).

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O. S. von Ehrenstein et al. “Reduced Risk of Hay Fever and Asthma Among Children of Farmers”. Clinical and Experimental Allergy 30, № 2 (2000).

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Charlotte Braun-Fahrländer. “Environmental Exposure to Endotoxin and Other Microbial Products and the Decreased Risk of Childhood Atopy: Evaluating Developments since April 2002”. Current Opinion in Allergy and Clinical Immunology 3, № 5 (2003); F. Horak et al. “Parental Farming Protects Children Against Atopy: Longitudinal Evidence Involving Skin Prick Tests”. Clinical and Experimental Allergy 32, № 8 (2002).

209

Даже в тех случаях, когда ведение сельского хозяйства не обеспечивало защиту от аллергии, причины были весьма познавательными. На Крите фермеры, занимавшиеся животноводством, страдали аллергией в той же степени, что и другие люди, жившие в непосредственной близости. В обеих группах астма отмечалась в два раза реже, чем у городских жителей Крита. Однако в средиземноморском климате животные целый год оставались на улице, что ограничивало непосредственные контакты с ними, характерные для сараев и коровников в умеренном климате Швейцарии и Германии. В Новой Зеландии ведение животноводческого хозяйства не только не защищало, но и немного повышало риск развития аллергии. Однако новозеландские фермеры чаще всего разводили овец. Какими бы ни были причины, овцы не защищали от аллергии; при этом они также оставались на улице круглый год. Тесные контакты с овцами были ограничены. Тем не менее даже в Новой Зеландии потребление йогурта и непастеризованного молока (а также непосредственные контакты с животными, дающими молоко) сокращало вероятность развития аллергии на две трети. K. Wickens et al. “Farm Residence and Exposures and the Risk of Allergic Diseases in New Zealand Children”. Allergy 57, № 12 (2002); M. Barnes et al. “Crete: Does Farming Explain Urban and Rural Differences in Atopy?” Clinical and Experimental Allergy 31, № 12 (2001).

210

U. Gehring et al. “Exposure to Endotoxin Decreases the Risk of Atopic Eczema in Infancy: A Cohort Study”. Journal of Allergy and Clinical Immunology 108, № 5 (2001).

211

Roger P. Lauener et al. “Expression of CD14 and Toll-like Receptor 2 in Farmers’ and Non-Farmers’ Children”. Lancet 360, № 9331 (2002).

212

Charlotte Braun-Fahrländer et al., “Environmental Exposure to Endotoxin and Its Relation to Asthma in School-Age Children,” New England Journal of Medicine 347, no. 12 (2002).

213

Matthew S. Perzanowski et al. “Endotoxin in Inner-City Homes: Associations with Wheeze and Eczema in Early Childhood”. Journal of Allergy and Clinical Immunology 117, № 5 (2006).

214

Benjamin J. Song, Andrew H. Liu. “Metropolitan Endotoxin Exposure, Allergy and Asthma”. Current Opinion in Allergy and Clinical Immunology 3, № 5 (2003); J. E. Gereda et al. “Metropolitan Home Living Conditions Associated with Indoor Endotoxin Levels”. Journal of Allergy and Clinical Immunology 107, № 5 (2001).

215

M. K. Tulic, P. G. Holt, P. D. Sly. “Modification of Acute and Late-phase Allergic Responses to Ovalbumin with Lipopolysaccharide”. International Archives of Allergy Immunology 129, № 2 (2002).

216

Steve M. Lee et al. “Regulatory T-Cells Contribute to Allergen Tolerance Induced by Daily Airway Immunostimulant Exposures”. American Journal of Respiratory Cell and Molecular Biology 44, № 3 (2011).

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Meri K. Tulic et al. “Role of Toll-like Receptor 4 in Protection by Bacterial Lipopolysaccharide in the Nasal Mucosa of Atopic Children but Not Adults”. Lancet 363, № 9422 (2004).

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O. L. Frick et al. “Allergen Immunotherapy with Heat-Killed Listeria monocytogenes Alleviates Peanut and Food-induced Anaphylaxis in Dogs”. Allergy 60, № 2 (2005).

219

F. Estelle Simons et al. “Selective Immune Redirection in Humans with Ragweed Allergy by Injecting Amb a 1 Linked to Immunostimulatory DNA”. Journal of Allergy and Clinical Immunology 113, № 6 (2004).

220

Peter S. Creticos et al. “Immunotherapy with a Ragweed-toll-like Receptor 9 Agonist Vaccine for Allergic Rhinitis”. New England Journal of Medicine 355, № 14 (2006).

221

Gail M. Gauvreau et al. “Immunostimulatory Sequences Regulate Interferon-Inducible Genes but Not Allergic Airway Responses”. American Journal of Respiratory and Critical Care Medicine 174, № 1 (2006).

222

T. Shirakawa et al. “The Inverse Association between Tuberculin Responses and Atopic Disorder”. Science 275, № 5296 (1997); T. Annus et al. “Atopic Disorders among Estonian Schoolchildren in Relation to Tuberculin Reactivity and the Age at BCG Vaccination”. Allergy 59; 10 (2004); C. C. Obihara et al. “Inverse Association between Mycobacterium tuberculosis Infection and Atopic Rhinitis in Children”. Allergy 60, № 9 (2005); Graham A. W. Rook, Eckard Hamelmann, L. Rosa Brunet. “Mycobacteria and Allergies”. Immunobiology 212, № 6 (2007).

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S. L. Young et al. “Environmental Strains of Mycobacterium avium Interfere with Immune Responses Associated with Mycobacterium bovis BCG Vaccination”. Infection and Immunity 75, № 6 (2007).

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Джессика Снайдер Сакс. Микробы хорошие и плохие. Наше здоровье и выживание в мире бактерий. М.: АСТ, 2015.

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P. D. Arkwright, T. J. David. “Effect of Mycobacterium vaccae on Atopic Dermatitis in Children of Different Ages”. British Journal of Dermatology 149, № 5 (2003).

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Claudia Zuany-Amorim et al. “Suppression of Airway Eosinophilia by Killed Mycobacterium vaccae-induced Allergen-Specific Regulatory T-cells”. Nature Medicine 8, № 6 (2002); J. R. F. Hunt et al. “Intragastric Administration of Mycobacterium vaccae Inhibits Severe Pulmonary Allergic Inflammation in a Mouse Model”. Clinical and Experimental Allergy 35, № 5 (2005).

227

Информацию об исследованиях, в ходе которых были подтверждены защитные свойства неочищенной воды, см.: Carsten Flohr et al. “Poor Sanitation and Helminth Infection Protect against Skin Sensitization in Vietnamese Children: A Cross-sectional Study”. Journal of Allergy and Clinical Immunology 118, № 6 (2006).

228

T. Laatikainen et al. “Allergy Gap between Finnish and Russian Karelia on Increase”. Allergy 66, № 7 (2011); Anita Kondrashova et al. “A Six-fold Gradient in the Incidence of Type 1 Diabetes at the Eastern Border of Finland”. Annals of Medicine 37, № 1 (2005); Anita Kondrashova et al. “Lower Economic Status and Inferior Hygienic Environment May Protect Against Celiac Disease”. Annals of Medicine 40, № 3 (2008).

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Hanna Viskari et al. “Circulating Vitamin D Concentrations in Two Neighboring Populations with Markedly Different Incidence of Type 1 Diabetes”. Diabetes Care 29, № 6 (2006).

230

Erkki Vartiainen et al. “Allergic Diseases, Skin Prick Test Responses, and IgE Levels in North Karelia, Finland, and the Republic of Karelia, Russia”. Journal of Allergy and Clinical Immunology 109, № 4 (2002).

231

Leena C. von Hertzen et al. “Infectious Burden as a Determinant of Atopy: A Comparison Between Adults in Finnish and Russian Karelia”. International Archives of Allergy and Immunology 140, № 2 (2006).

232

L. von Hertzen et al. “Microbial Content of Drinking Water in Finnish and Russian Karelia: Implications for Atopy Prevalence”. Allergy 62, № 3 (2007).

233

L. von Hertzen et al. “Risk of Atopy Associated with Microbial Components in House Dust”. Annals of Allergy, Asthma & Immunology 104, № 3 (2010).

234

Harri Alenius et al. “Contrasting Immunological Effects of Two Disparate Dusts: Preliminary Observations”. International Archives of Allergy and Immunology 149, № 1 (2009).

235

Markus Johannes Ege et al. “Not All Farming Environments Protect Against the Development of Asthma and Wheeze in Children”. Journal of Allergy and Clinical Immunology 119, № 5 (2007).

236

Leonid Gorelik et al. “Modulation of Dendritic Cell Function by Cowshed Dust Extract”. Innate Immunity 14, № 6 (2008); M. Peters et al. “Inhalation of Stable Dust Extract Prevents Allergen Induced Airway Inflammation and Hyperresponsiveness”. Torax 61, № 2 (2006).

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Marcus Peters et al. “Arabinogalactan Isolated from Cowshed Dust Extract Protects Mice from Allergic Airway Inflammation and Sensitization”. Journal of Allergy and Clinical Immunology 126, № 3 (2010).

238

Markus J. Ege et al. “Exposure to Environmental Microorganisms and Childhood Asthma”. New England Journal of Medicine 364, № 8 (2011); Robert Teodoor van Strien et al. “Microbial Exposure of Rural School Children, as Assessed by Levels of N-acetyl-muramic Acid in Mattress Dust, and Its Association with Respiratory Health”. Journal of Allergy and Clinical Immunology 113, № 5 (2004).

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Caroline Roduit et al. “Prenatal Animal Contact and Gene Expression of Innate Immunity Receptors at Birth Are Associated with Atopic Dermatitis”. Journal of Allergy and Clinical Immunology 127, № 1 (2011).

240

Exposure to environmental microorganisms and childhood asthma. Ege M. J., Mayer M., Normand A. C., Genuneit J., Cookson W. O., Braun-Fahrländer C., Heederik D., Piarroux R., von Mutius E.; Gabriela Transregio 22 Study Group. N. Engl. J. Med. 2011 Feb 24; 364 (8): 701–709. DOI: 10.1056/NEJMoa1007302. Прим. науч. ред.

241

В ходе этого исследования было выполнено также сравнение Польши со Швецией и Эстонией. Чувствительность к аллергенам имела место у каждого шестого поляка. L. Bråbäck et al. “Risk Factors for Respiratory Symptoms and Atopic Sensitisation in the Baltic Area”. Archives of Disease in Childhood 72, № 6 (1995).

242

B. Björkstén et al. “The Intestinal Microflora in Allergic Estonian and Swedish 2-Year-Old Children”. Clinical and Experimental Allergy 29, № 3 (1999); E. Sepp et al. “Intestinal Microflora of Estonian and Swedish Infants”. Acta Paediatrica 86, № 9 (1997).

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R. Bennet et al. “Intestinal Bacteria of Newborn Ethiopian Infants in Relation to Antibiotic Treatment and Colonisation by Potentially Pathogenic Gram-Negative Bacteria”. Scandinavian Journal of Infectious Diseases 23, № 1 (1991); I. Adlerberth et al. “Intestinal Colonization with Enterobacteriaceae in Pakistani and Swedish Hospital-delivered Infants”. Acta Paediatrica Scandinavica 80, nos. 6–7 (1991).

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B. Björkstén et al. “Allergy Development and the Intestinal Microflora During the First Year of Life”. Journal of Allergy and Clinical Immunology 108, № 4 (2001).

245

M. Kalliomaki et al. “Distinct Patterns of Neonatal Gut Microflora in Infants in Whom Atopy Was and Was Not Developing”. Journal of Allergy and Clinical Immunology 107, № 1 (2001).

246

M. M. Grönlund et al. “Importance of Intestinal Colonisation in the Maturation of Humoral Immunity in Early Infancy: A Prospective Follow-up Study of Healthy Infants Aged 0–6 Months”. Archives of Disease in Childhood: Fetal and Neonatal Edition 83, № 3 (2000); A. E. Wold. “The Hygiene Hypothesis Revised: Is the Rising Frequency of Allergy Due to Changes in the Intestinal Flora?” Allergy 53, № 46 Suppl. (1998).

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M. F. Böttcher et al. “Endotoxin Levels in Estonian and Swedish House Dust and Atopy in Infancy”. Clinical and Experimental Allergy 33, № 3 (2003).

248

Более подробное описание этой концепции см.: I. Adlerberth, A. E. Wold. “Establishment of the Gut Microbiota in Western Infants”. Acta Paediatrica 98, № 2 (2009).

249

K. Julge, M. Vasar, B. Björkstén. “Development of Allergy and IgE Antibodies during the First Five Years of Life in Estonian Children”. Clinical and Experimental Allergy 31, № 12 (2001).

250

M. F. Böttcher et al. “Cytokine Responses to Allergens during the First 2 Years of Life in Estonian and Swedish Children”. Clinical and Experimental Allergy 36, № 5 (2006).

251

Sara Tomicić et al. “Breast Milk Cytokine and IgA Composition Differ in Estonian and Swedish Mothers: Relationship to Microbial Pressure and Infant Allergy”. Pediatric Research 68, № 4 (2010).

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M. F. Böttcher et al. “Low Breast Milk TGF-beta2 Is Induced by Lactobacillus reuteri Supplementation and Associates with Reduced Risk of Sensitization During Infancy”. Pediatric Allergy and Immunology 19, № 6 (2008).

253

Vibeke Rosenfeldt et al. “Effect of Probiotic Lactobacillus Strains in Children with Atopic Dermatitis”. Journal of Allergy and Clinical Immunology 111, № 2 (2003).

254

Marko Kalliomäki et al. “Probiotics during the First 7 Years of Life: A Cumulative Risk Reduction of Eczema in a Randomized, Placebo-controlled Trial”. Journal of Allergy and Clinical Immunology 119, № 4 (2007).

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Matthias Volkmar Kopp et al. “Randomized, Doubleblind, Placebo-controlled Trial of Probiotics for Primary Prevention: No Clinical Effects of Lactobacillus GG Supplementation”. Pediatrics 121, № 4 (2008).

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Angie L. Taylor, Janet A. Dunstan, Susan L. Prescott. “Probiotic Supplementation for the First 6 Months of Life Fails to Reduce the Risk of Atopic Dermatitis and Increases the Risk of Allergen Sensitization in High-Risk Children: A Randomized Controlled Trial”. Journal of Allergy and Clinical Immunology 119, № 1 (2007).

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Mei Wang et al. “Reduced Diversity in the Early Fecal Microbiota of Infants with Atopic Eczema”. Journal of Allergy and Clinical Immunology 121, № 1 (2008); Y. M. Sjögren et al. “Altered Early Infant Gut Microbiota in Children Developing Allergy Up to 5 Years of Age”. Clinical and Experimental Allergy 39, № 4 (2009).

258

Anna Sandin et al. “High Salivary Secretory IgA Antibody Levels Are Associated with Less Late-onset Wheezing in IgE-sensitized Infants”. Pediatric Allergy and Immunology (2011).

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L. A. M. Smit et al. “Atopy and New-onset Asthma in Young Danish Farmers and CD14, TLR2, and TLR4 Genetic Polymorphisms: A Nested Case-control Study”. Clinical and Experimental Allergy 37, № 11 (2007).

260

Adnan Custovic et al. “Effect of Day Care Attendance on Sensitization and Atopic Wheezing Differs by Toll-like Receptor 2 Genotype in 2 Population-Based Birth Cohort Studies”. Journal of Allergy and Clinical Immunology 127, № 2 (2011).

261

April Zambelli-Weiner et al. “Evaluation of the CD14/-260 Polymorphism and House Dust Endotoxin Exposure in the Barbados Asthma Genetics Study”. Journal of Allergy and Clinical Immunology 115, № 6 (2005).

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Цитата Дэвида Баркера и большая часть информации о нем взяты из статьи: Stephen S. Hall. “Small and Tin”. New Yorker, November 19, 2007.

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Оценку гипотезы Баркера см.: Alexander Vaiserman. “Early-life Origin of Adult Disease: Evidence from Natural Experiments”. Experimental Gerontology 46, nos. 2–3 (2011).

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Bianca Schaub et al. “Neonatal Immune Responses to TLR2 Stimulation: Influence of Maternal Atopy on FOXP3 and IL-10 Expression”. Respiratory Research 7 (2006); Bianca Schaub et al. “Impairment of T-regulatory Cells in Cord Blood of Atopic Mothers”. Journal of Allergy and Clinical Immunology 121, № 6 (2008).

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Michael Brown et al. “Helminth Infection Is Not Associated with Faster Progression of HIV Disease in Coinfected Adults in Uganda”. Journal of Infectious Diseases 190, № 10 (2004).

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Harriet Mpairwe et al. “Anthelminthic Treatment during Pregnancy Is Associated with Increased Risk of Infantile Eczema: Randomised-controlled Trial Results”. Pediatric Allergy and Immunology 22, № 3 (2011).

284

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Если астмой страдает отец, у детей в возрасте до пяти лет риск бронхиальной обструкции увеличивается в 1,6 раза, если же астмой страдает мать, риск возрастает в пять раз. A. A. Litonjua et al. “Parental History and the Risk for Childhood Asthma: Does Mother Confer More Risk than Father?” American Journal of Respiratory and Critical Care Medicine 158, № 1 (1998).

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290

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291

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292

Miranda Smith et al. “Children with Egg Allergy Have Evidence of Reduced Neonatal CD4(+)CD25(+)CD127(lo/—) Regulatory T-cell Function”. Journal of Allergy and Clinical Immunology 121, № 6 (2008).

293

Pia Reece et al. “Maternal Allergy Modulates Cord Blood Hematopoietic Progenitor Toll-like Receptor Expression and Function”. Journal of Allergy and Clinical Immunology 127, № 2 (2011).

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Meri K. Tulic et al. “Differences in Innate Immune Function Between Allergic and Nonallergic Children: New Insights into Immune Ontogeny”. Journal of Allergy and Clinical Immunology 127, № 2 (2011).

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Кататония — нервно-психическое расстройство с преобладанием двигательных нарушений (ступор или возбуждение). Впервые было описано немецким психиатром Кальбаумом в 1868 году, который и предложил этот термин. Прим. ред.

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J. M. Harris et al. “New Pregnancies and Loss of Allergy”. Clinical and Experimental Allergy 34, № 3 (2004); S. Upchurch, J. M. Harris, P. Cullinan. “Temporal Changes in UK Birth Order and the Prevalence of Atopy”. Allergy 65, № 8 (2010).

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EpiPen — aвтоинъектор эпинефрина, медицинское устройство для инъекции измеренной дозы или доз адреналина. Чаще всего используется для лечения анафилактического шока. Прим. ред.

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Эта мысль позаимствована у Мартина Блейзера и Стэнли Фолкоу.

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От греч. eremites — «затворник, отшельник». Уилсон использует этот термин в разных трудах. Прим. пер.

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316

Mohammed M. Khalifa, Radwa R. Sharaf, Ramy K. Aziz. “Helicobacter pylori: A Poor Man’s Gut Pathogen?” Gut Pathogens 2, № 1 (2010).

317

Например, в 90-х годах носителями H. pylori были три четверти граждан Южной Кореи, но эта бактерия не заражала всех корейцев в равной мере. H. pylori обнаруживали более чем у 40% детей из бедных корейских семей и только у 12% детей из семей со средним и высоким уровнем доходов. В США имела место такая же закономерность, но она распространялась на расовые и этнические группы. В Хьюстоне афроамериканцы и иммигранты из числа латиноамериканцев в два раза чаще становились носителями H. pylori, чем белые. См.: H. M. Malaty et al. “Prevalence of Helicobacter pylori Infection in Korean Children: Inverse Relation to Socioeconomic Status despite a Uniformly High Prevalence in Adults”. American Journal of Epidemiology 143, № 3 (1996); D. Y. Graham et al. “Epidemiology of Helicobacter pylori in an Asymptomatic Population in the United States. Effect of Age, Race, and Socioeconomic Status”. Gastroenterology 100, № 6 (1991).

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J. E. Tomas et al. “Early Helicobacter pylori Colonisation: The Association with Growth Faltering in the Gambia”. Archives of Disease in Childhood 89, № 12 (2004).

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M. J. Blaser. “The Bacteria Behind Ulcers”. Scientific American 274, № 2 (1996).

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Sam M. Mbulaiteye, Michie Hisada, Emad M. El-Omar. “Helicobacter pylori Associated Global Gastric Cancer Burden”. Frontiers in Bioscience 14 (2009).

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См.: Ondek Biologic Delivery Systems. http://www.ondek.com/.

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M. J. Blaser et al. “Infection with Helicobacter pylori Strains Possessing CagA Is Associated with an Increased Risk of Developing Adenocarcinoma of the Stomach”. Cancer Research 55, № 10 (1995).

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J. E. Richter, G. W. Falk, M. F. Vaezi. “Helicobacter pylori and Gastroesophageal Reflux Disease: The Bug May Not Be All Bad”. American Journal of Gastroenterology 93, № 10 (1998).

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J. J. Vicari et al. “The Seroprevalence of CagA-positive Helicobacter pylori Strains in the Spectrum of Gastroesophageal Reflux Disease”. Gastroenterology 115, № 1 (1998).

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Chandrabali Ghose et al. “East Asian Genotypes of Helicobacter pylori Strains in Amerindians Provide Evidence for Its Ancient Human Carriage”. Proceedings of the National Academy of Sciences 99, № 23 (2002).

328

Daniel Falush et al. “Traces of Human Migrations in Helicobacter pylori Populations”. Science 299, № 5612 (2003).

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Maria-Gloria Dominguez-Bello, Martin J. Blaser. “The Human Microbiota as a Marker for Migrations of Individuals and Populations”. Annual Review of Anthropology 40 (2011).

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Bodo Linz et al. “An African Origin for the Intimate Association between Humans and Helicobacter pylori”. Nature 445, № 7130 (2007).

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Yu Chen, Martin J. Blaser. “Inverse Associations of Helicobacter pylori with Asthma and Allergy”. Archives of Internal Medicine 167, № 8 (2007); J. Reibman et al. “Asthma Is Inversely Associated with Helicobacter pylori Status in an Urban Population”. PLoS ONE 3, № 12 (2008); Yu Chen, Martin J. Blaser. “Helicobacter pylori Colonization Is Inversely Associated with Childhood Asthma”. Journal of Infectious Diseases 198, № 4 (2008).

332

T. U. Kosunen et al. “Increase of Allergen-specific Immunoglobulin E Antibodies from 1973 to 1994 in a Finnish Population and a Possible Relationship to Helicobacter pylori Infections”. Clinical and Experimental Allergy 32, № 3 (2002).

333

Anne McCune et al. “Reduced Risk of Atopic Disorders in Adults with Helicobacter pylori Infection”. European Journal of Gastroenterology & Hepatology 15, № 6 (2003); Olf Herbarth et al. “Helicobacter pylori Colonisation and Eczema”. Journal of Epidemiology & Community Health 61, № 7 (2007); Shigeyoshi Imamura et al. “Inverse Association between Helicobacter pylori Infection and Allergic Rhinitis in Young Japanese”. Journal of Gastroenterology and Hepatology 25, № 7 (2010).

334

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S. M. Raj et al. “Evidence Against Helicobacter pylori Being Related to Childhood Asthma”. Journal of Infectious Diseases 199, № 6 (2009).

336

K. Robinson et al. “Helicobacter pylori-induced Peptic Ulcer Disease Is Associated with Inadequate Regulatory T-cell Responses”. Gut 57, № 10 (2008).

337

Эта работа не опубликована, а представлена в форме доклада. D. P. Letley et al. “Helicobacter pylori-induced Protection from Allergy Is Associated with Peripheral Blood Regulatory Cells” // Regulatory T-cells in Inflammatory and Infectious Diseases: New Horizons for Old Friends. Kennedy Lecture Theater, UCL Institute of Child Health, London, 2010.

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C. Holcombe. “Helicobacter pylori: The African Enigma”. Gut 33, № 4 (1992).

341

Более подробную информацию о специфике иммунного ответа на H. pylori в развивающихся странах см.: Sam M. Mbulaiteye et al. “H. pylori-infection and Antibody Immune Response in a Rural Tanzanian Population”. Infectious Agents and Cancer 1 (2006); H. M. Mitchell et al. “Major Differences in the IgG Subclass Response to Helicobacter pylori in the First and Third Worlds”. Scandinavian Journal of Gastroenterology 37, № 5 (2002).

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344

«Все то, что выброшено из человеческого тела, является нечистым и сразу же становится опасным для жизни человека», — писала санитарный инспектор Мэри Армстронг в 1878 году. Такие мысли, характерные для новой культурной одержимости опрятностью и чистотой, получили распространение в конце XVIII столетия. Возможно, новые моральные устои начали менять пути передачи H. pylori еще до того, как это сделала канализация, чистая вода и общественная гигиена. См.: G. H. Pelto, Y. Zhang, J. P. Habicht. “Premastication: The Second Arm of Infant and Young Child Feeding for Health and Survival?” Maternal & Child Nutrition 6, № 1 (2010).

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J. G. Fox et al. “Concurrent Enteric Helminth Infection Modulates Inflammation and Gastric Immune Responses and Reduces Helicobacter-Induced Gastric Atrophy”. Nature Medicine 6, № 5 (2000); Mark T. Whary et al. “Intestinal Helminthiasis in Colombian Children Promotes a T2 Response to Helicobacter pylori: Possible Implications for Gastric Carcinogenesis”. Cancer Epidemiology, Biomarkers & Prevention 14, № 6 (2005).

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M. J. Blaser, S. Falkow. “What Are the Consequences of the Disappearing Human Microbiota?” Nature Reviews Microbiology 7, № 12 (2009).

350

M. J. Blaser. “Antibiotic Overuse: Stop the Killing of Beneficial Bacteria”. Nature 476, № 7361 (2011).

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358

Джастин Сонненберг перефразировал (процитировал) слова более раннего первопроходца в этой области, микробиолога Дуэйна Сэвиджа.

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Размер теннисного корта для одиночной игры — 8,23 на 23,78 метра. Данные взяты из статьи: Kevin J. Maloy, Fiona Powrie. “Intestinal Homeostasis and Its Breakdown in Inflammatory Bowel Disease”. Nature 474, № 7351 (2011).

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Глиадин — одна из составляющих глютена. Соответствующая диета обычно называется безглютеновой. Прим. ред.

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Младенцев, родившихся путем кесарева сечения, колонизировали микробы, обитавшие на коже врачей и медсестер. Maria G. Dominguez-Bello et al. “Delivery Mode Shapes the Acquisition and Structure of the Initial Microbiota across Multiple Body Habitats in Newborns”. Proceedings of the National Academy of Sciences (2010).

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Есть вероятность, что особенности людей, родившихся с помощью кесарева сечения, не имеют никакого отношения к микробиоте. Эти особенности могут быть обусловлены относительно низким уровнем стресса в случае хирургической операции — способа родов, по-видимому, оставляющего «отключенными» те клетки, которые должны были «включиться». T. Schlinzig et al. “Epigenetic Modulation at Birth — Altered DNA-methylation in White Blood Cells after Caesarean Section”. Acta Paediatrica 98, № 7 (2009).

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Более подробную информацию о триклозане см.: H. Singer et al. “Triclosan: Occurrence and Fate of a Widely Used Biocide in the Aquatic Environment: Field Measurements in Wastewater Treatment Plants, Surface Waters, and Lake Sediments”. Environmental Science & Technology 36, № 23 (2002); K. McClellan, R. U. Halden. “Pharmaceuticals and Personal Care Products in Archived U.S. Biosolids from the 2001 EPA National Sewage Sludge Survey”. Water Research 44, № 2 (2010).

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То есть калорийной пищей с низкой биологической ценностью и высоким содержанием жиров и сахара. Прим. пер.

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Подтверждение того, что мы находимся на правильном пути, следует искать в собственной анатомии. Возьмем в качестве примера аппендикс, который долго считали бесполезным рудиментом эволюции человека. Уильям Паркер из Университета Дьюка считает, что этот отросток кишечника обеспечивает повторный посев дружественных микробов после неблагоприятных периодов. Если длительная диарея приводит к истощению микробиоты, аппендикс восстанавливает популяцию кишечных микробов из собственных запасов. R. Randal Bollinger et al. “Biofilms in the Large Bowel Suggest an Apparent Function of the Human Vermiform Appendix”. Journal of Theoretical Biology 249, № 4 (2007).

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Вот еще одно исследование, указывающее на важность микробного разнообразия: Hans Bisgaard et al. “Reduced Diversity of the Intestinal Microbiota During Infancy Is Associated with Increased Risk of Allergic Disease at School Age”. Journal of Allergy and Clinical Immunology 128, № 3 (2011).

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Падение Лидвины произошло в 1396 году. R. Medaer. “Does the History of Multiple Sclerosis Go Back as Far as the 14th Century?” Acta Neurologica Scandinavica 60, № 3 (1979).

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Eric J. Yager et al. “Gamma-Herpes Virus-Induced Protection Against Bacterial Infection Is Transient”. Viral Immunology 22, № 1 (2009).

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Более подробную информацию о полезных вирусах см.: Marilyn J. Roossinck. “The Good Viruses: Viral Mutualistic Symbioses”. Nature Reviews Microbiology 9, № 2 (2011).

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A. Paolillo et al. “The Effect of Bacille Calmette-Guerin on the Evolution of New Enhancing Lesions to Hypointense T1 Lesions in Relapsing Remitting MS”. Journal of Neurology 250, № 2 (2002); G. Ristori et al. “Use of Bacille Calmette-Guerin (BCG) in Multiple Sclerosis”. Neurology 53, № 7 (1999).

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482

J. Fleming et al. “Probiotic Helminth Administration in Relapsing-remitting Multiple Sclerosis: A Phase 1 Study,” Multiple Sclerosis 17, № 6 (2011).

483

Некоторые отмечают, что в случае появления вакцины от EBV она должна обеспечивать пожизненную защиту. В противном случае, когда в зрелом возрасте действие вакцины закончится, это будет иметь парадоксальные последствия в виде повышения риска развития как инфекционного мононуклеоза, так и рассеянного склероза. Эта глава в значительной мере основана на информации, почерпнутой из: Alberto Ascherio, Kassandra L. Munge. “Epstein-Barr Virus Infection and Multiple Sclerosis: A Review”. Journal of Neuroimmune Pharmacology 5, № 3 (2010).

484

Превосходный обзор идей Эрика Бартона см.: D. W. White, R. Suzanne Beard, E. S. Barton. “Immune Modulation During Latent Herpesvirus Infection”. Immunological Reviews 245, № 1 (2012).

485

Jonathan Silverberg et al. “Chickenpox in Childhood Is Associated with Decreased Atopic Disorders, IgE, Allergic Sensitization, and Leukocyte Subsets”. Pediatric Allergy and Immunology 23, № 1 (February 2012).

486

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487

Лео Каннер. «Аутистические нарушения аффективного контакта». Перевод Виктора Кагана. https://autism-russian.livejournal.com/19209.html. (Leo Kanner. “Autistic Disturbances of Affective Contact”. Nervous Child 2 (1943)) Более подробную информацию о Гансе Аспергере см.: J. H. Baskin, M. Sperber, B. H. Price. “Asperger Syndrome Revisited”. Reviews in Neurological Diseases 3, № 1 (2006).

488

Diagnostic and Statistical Manual of Mental Disorders (англ.), DSM-IV. Прим. пер.

489

S. Ozonoff et al. “A Prospective Study of the Emergence of Early Behavioral Signs of Autism”. Journal of the American Academy of Childhood Adolescent Psychiatry 49, № 3 (2010).

490

Catherine Rice. “Prevalence of Autism Spectrum Disorders — Autism and Developmental Disabilities Monitoring Network, United States, 2006”. Atlanta: Center for Disease Control MMWR, 2009.

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Данные о расходах в связи с аутизмом взяты из: Michael Ganz. “The Costs of Autism” // Understanding Autism: From Basic Neuroscience to Treatment, ed. Steven O. Moldin and John L. R. Rubenstein. Boca Raton: CRC/Taylor & Frances, 2006.

492

Irva Hertz-Picciotto, Lora Delwiche. “The Rise in Autism and the Role of Age at Diagnosis”. Epidemiology 20, № 1 (2009).

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Frank DeStefano et al. “Age at First Measles-mumps-rubella Vaccination in Children with Autism and School-matched Control Subjects: A Population-based Study in Metropolitan Atlanta”. Pediatrics 113, № 2 (2004).

495

L. Dales et al. “Time Trends in Autism and in MMR Immunization Coverage in California”. JAMA 285, № 9 (2001).

496

В Японии распространенность аутизма выросла почти в четыре раза с 19,6 из 10 000 детей, родившихся в 1988 году, до 81,4 из 10 000 детей, родившихся в 1996 году. Обратите внимание на то, что в абсолютном выражении этот уровень заболеваемости гораздо ниже соответствующего показателя на Западе, так же как и в случае астмы, воспалительных заболеваний кишечника и других иммуноопосредованных заболеваний. Тем не менее, подобно этим заболеваниям, распространенность аутизма неуклонно растет. Hideo Honda, Yasuo Shimizu, Michael Rutter. “No Effect of MMR Withdrawal on the Incidence of Autism: A Total Population Study”. Journal of Child Psychology and Psychiatry, and Allied Disciplines 46, № 6 (2005).

497

Dorota Mrozek-Budzyn, Agnieszka Kiełtyka, Renata Majewska. “Lack of Association between Measles-mumps-rubella Vaccination and Autism in Children: A Case-control Study”. Pediatric Infectious Disease Journal 29, № 5 (2010).

498

Fiona Godlee, Jane Smith, Harvey Marcovitch. “Wakefield’s Article Linking MMR Vaccine and Autism Was Fraudulent”. British Medical Journal 342 (2011).

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501

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R. P. Warren et al. “Immune Abnormalities in Patients with Autism”. Journal of Autism and Developmental Disorders 16, № 2 (1986); W. W. Daniels et al. “Increased Frequency of the Extended or Ancestral Haplotype B44-SC30-DR4 in Autism”. Neuropsychobiology 32, № 3 (1995); Anthony R. Torres et al. “The Transmission Disequilibrium Test Suggests Tat HLA-DR4 and DR13 Are Linked to Autism Spectrum Disorder”. Human Immunology 63, № 4 (2002); William G. Johnson et al. “HLA-DR4 as a Risk Allele for Autism Acting in Mothers of Probands Possibly During Pregnancy”. Archives of Pediatrics & Adolescent Medicine 163, № 6 (2009).

503

Li-Ching Lee et al. “HLA-DR4 in Families with Autism”. Pediatric Neurology 35, № 5 (2006).

504

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505

Loren A. Martin et al. “Stereotypes and Hyperactivity in Rhesus Monkeys Exposed to IgG from Mothers of Children with Autism”. Brain, Behavior, and Immunity 22, № 6 (2008).

506

E. Courchesne et al. “Unusual Brain Growth Patterns in Early Life in Patients with Autistic Disorder: An MRI Study”. Neurology 57, № 2 (2001).

507

Eric Courchesne, Kathleen Campbell, Stephanie Solso. “Brain Growth Across the Life Span in Autism: Age-specific Changes in Anatomical Pathology”. Brain Research 1380 (2011).

508

Cynthia Mills Schumann et al. “Amygdala Enlargement in Toddlers with Autism Related to Severity of Social and Communication Impairments”. Biological Psychiatry 66, № 10 (2009).

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Diana L. Vargas et al. “Neuroglial Activation and Neuroinflammation in the Brain of Patients with Autism”. Annals of Neurology 57, № 1 (2005).

511

Harvey S. Singer et al. “Prenatal Exposure to Antibodies from Mothers of Children with Autism Produces Neurobehavioral Alterations: A Pregnant Dam Mouse Model”. Journal of Neuroimmunology 211, nos. 1–2 (2009).

512

Kevin G. Becker. “Autism, Asthma, Inflammation, and the Hygiene Hypothesis”. Medical Hypotheses 69, № 4 (2007).

513

Содержательный обзор этой темы см.: Nicolette A. Hodyl et al. “Prenatal Programming of the Innate Immune Response Following in Utero Exposure to Inflammation: A Sexually Dimorphic Process?” Expert Review of Clinical Immunology 7, № 5 (2011).

514

Alan S. Brown, Ezra S. Susser. “In Utero Infection and Adult Schizophrenia”. Mental Retardation and Developmental Disabilities Research Reviews 8, № 1 (2002).

515

Некоторые данные взяты из статьи: P. H. Patterson. Infectious Behavior: Brain-Immune Connections in Autism, Schizophrenia, and Depression. Источник: S. Chess. “Autism in Children with Congenital Rubella”. Journal of Autism and Childhood Schizophrenia 1, № 1 (1971).

516

Elaine Y. Hsiao, Paul H. Patterson. “Activation of the Maternal Immune System Induces Endocrine Changes in the Placenta via IL-6”. Brain, Behavior, and Immunity 25 (2010). По результатам других исследований было установлено, что у аутистов повышен уровень интерлейкина-6, а также что интерлейкин-6 приводит к изменению процесса миграции нейронов. H. Wei et al. “IL-6 Is Increased in the Cerebellum of Autistic Brain and Alters Neural Cell Adhesion, Migration and Synaptic Formation”. Journal of Neuroinflammation 8 (2011).

517

Alan S. Brown et al. “Serologic Evidence of Prenatal Influenza in the Etiology of Schizophrenia”. Archives of General Psychiatry 61, № 8 (2004). Alan S. Brown, Paul H. Patterson. “Maternal Infection and Schizophrenia: Implications for Prevention”. Schizophrenia Bulletin 37, № 2 (2011).

518

Lisa A. Croen et al. “Maternal Autoimmune Diseases, Asthma and Allergies, and Childhood Autism Spectrum Disorders: A Case-control Study”. Archives of Pediatrics & Adolescent Medicine 159, № 2 (2005). Связь между аутизмом и инфекционными заболеваниями матери была обнаружена уже после эпидемии краснухи, разразившейся в 60-х годах. В ходе самого крупного на данный момент исследования были проанализированы данные о 1,6 миллиона будущих матерей и их детей, родившихся в Дании за период с 1980 по 2005 год. По результатам этого анализа было установлено, что в случае госпитализации матери с вирусной инфекцией во время первого триместра беременности вероятность рождения ребенка-аутиста увеличивалась в три раза. Бактериальная инфекция во время второго триместра увеличивала эту вероятность почти в два раза. Не было конкретного вируса или бактерии, заражение которыми могло бы стать прогнозирующим фактором развития аутизма у детей; риск развития этого заболевания повышался только в случае госпитализации в связи с тем ли иным инфекционным заболеванием. Hjördis O. Atladóttir et al. “Maternal Infection Requiring Hospitalization During Pregnancy and Autism Spectrum Disorders”. Journal of Autism and Developmental Disorders 40, № 12 (2010).

519

L. Heuer et al. “Association of an MET Genetic Variant with Autism-associated Maternal Autoantibodies to Fetal Brain Proteins and Cytokine Expression”. Translational Psychiatry 1 (2011).

520

U. Meyer et al. “Adult Behavioral and Pharmacological Dysfunctions Following Disruption of the Fetal Brain Balance Between Pro-inflammatory and IL-10-Mediated Anti-inflammatory Signaling”. Molecular Psychiatry 13, № 2 (2008).

521

Auriel A. Willette et al. “Brain Enlargement and Increased Behavioral and Cytokine Reactivity in Infant Monkeys Following Acute Prenatal Endotoxemia”. Behavioural Brain Research 219, № 1 (2011).

522

Вот как выглядит аргументация Мейера и Фелдона в полном виде. Немного отличающиеся нарушения в работе иммунной системы приводят либо к аутизму, либо к шизофрении. Если будущая мать не может отключить воспаление, это приводит к развитию аутизма. Если же у матери развивается серьезное заболевание (как в случае вирусной инфекции), она устраняет угрозу, а затем возвращается в состояние иммунного гомеостаза, что вызывает не аутизм, а предрасположенность к шизофрении. В зрелом возрасте такие люди могут столкнуться с неким триггером («вторичной травмой»), под воздействием которого у них появится психическое расстройство. Urs Meyer, Joram Feldon, Olaf Dammann. “Schizophrenia and Autism: Both Shared and Disorder-specific Pathogenesis via Perinatal Inflammation?” Pediatric Research 69 (2011).

523

P. Munk-Jørgensen, P. B. Mortensen. “Is Schizophrenia Really on the Decrease?” European Archives of Psychiatry and Clinical Neuroscience 242, № 4 (1993).

524

J. M. Suvisaari et al. “Decline in the Incidence of Schizophrenia in Finnish Cohorts Born from 1954 to 1965”. Archives of General Psychiatry 56, № 8 (1999); J. Suvisaari et al. “Association between Prenatal Exposure to Poliovirus Infection and Adult Schizophrenia”. American Journal of Psychiatry 156, № 7 (1999).

525

R. M. Cotterill. “Fever in Autistics”. Nature 313, № 6002 (1985).

526

Gary Brown. “The Sometimes Son: Fever May Temporarily Cure Autism”. The Humanist (1999).

527

Laura K. Curran et al. “Behaviors Associated with Fever in Children with Autism Spectrum Disorders”. Pediatrics 120, № 6 (2007).

528

Jonathan Kipnis et al. “T-сell Deficiency Leads to Cognitive Dysfunction: Implications for Therapeutic Vaccination for Schizophrenia and Other Psychiatric Conditions”. Proceedings of the National Academy of Sciences 101, № 21 (2004).

529

Noël C. Derecki et al. “Regulation of Learning and Memory by Meningeal Immunity: A Key Role for IL-4”. Journal of Experimental Medicine 207, № 5 (2010).

530

Michael G. Chez et al. “Elevation of Tumor Necrosis Factor alpha in Cerebrospinal Fluid of Autistic Children”. Pediatric Neurology 36, № 6 (2007).

531

Paul Ashwood et al. “Brief Report: Plasma Leptin Levels Are Elevated in Autism: Association with Early Onset Phenotype?” Journal of Autism and Developmental Disorders 38, № 1 (2008).

532

Amanda M. Enstrom et al. “Differential Monocyte Responses to TLR Ligands in Children with Autism Spectrum Disorders”. Brain, Behavior, and Immunity 24, № 1 (2010).

533

Paul Ashwood et al. “Decreased Transforming Growth Factor Beta-1 in Autism: A Potential Link between Immune Dysregulation and Impairment in Clinical Behavioral Outcomes”. Journal of Neuroimmunology 204, nos. 1–2 (2008).

534

Gehan A. Mostafa, Abeer Al Shehab, Nermeen R. Fouad. “Frequency of CD4+CD25 high Regulatory T-cells in Peripheral Blood of Egyptian Children with Autism”. Journal of Child Neurology 25, № 3 (2009).

535

Michael G. Chez, Natalie Guido-Estrada. “Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy”. Neurotherapeutics 7, № 3 (2010).

536

Sudhir Gupta, Daljeet Samra, Sudhanshu Agrawal. “Adaptive and Innate Immune Responses in Autism: Rationale for Therapeutic Use of Intravenous Immunoglobulin”. Journal of Clinical Immunology 30, Suppl. 1 (2010).

537

M. S. Maddur et al. “Immunomodulation by Intravenous Immunoglobulin: Role of Regulatory T-cells”. Journal of Clinical Immunology 30, Suppl. 1 (2010).

538

Более подробную информацию о дисфункции кишечника в случае аутизма можно найти здесь: Valicenti-McDermott et al. “Gastrointestinal Symptoms in Children with an Autism Spectrum Disorder and Language Regression”. Pediatric Neurology 39, № 6 (December 2008): 392–398.

539

Аргументы в пользу того, что у детей-аутистов действительно отмечается дисфункция желудочно-кишечного тракта, можно найти здесь: Amy C. Brown, Lewis Mehl-Madrona. “Autoimmune and Gastrointestinal Dysfunctions: Does a Subset of Children with Autism Reveal a Broader Connection?” Expert Review of Gastroenterology & Hepatology 5, № 4 (2011).

540

Harumi Jyonouchi et al. “Evaluation of an Association Between Gastrointestinal Symptoms and Cytokine Production Against Common Dietary Proteins in Children with Autism Spectrum Disorders”. Journal of Pediatrics 146, № 5 (2005).

541

Timothy Buie et al. “Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals with ASDs: A Consensus Report”. Pediatrics 125, Suppl. 1 (2010).

542

R. H. Sandler et al. “Relief of Psychiatric Symptoms in a Patient with Crohn’s Disease after Metronidazole Therapy”. Clinical Infectious Diseases 30, № 1 (2000).

543

Stephen J. Genuis, Tomas P. Bouchard. “Celiac Disease Presenting as Autism”. Journal of Child Neurology 25, № 1 (2010); S. J. Genuis. “Is Autism Reversible?” Acta Paediatrica 98, № 10 (2009).

544

Giulia Barcia et al. “Autism and Coeliac Disease”. Journal of Autism and Developmental Disorders 38, № 2 (2008).

545

Enzo Emanuele et al. “Low-grade Endotoxemia in Patients with Severe Autism”. Neuroscience Letters 471, № 3 (2010).

546

R. H. Sandler et al. “Short-term Benefit from Oral Vancomycin Treatment of Regressive-onset Autism”. Journal of Child Neurology 15, № 7 (2000).

547

Sydney M. Finegold. “Desulfovibrio Species Are Potentially Important in Regressive Autism”. Medical Hypotheses 77, № 2 (2011); Sydney M. Finegold. “State of the Art; Microbiology in Health and Disease. Intestinal Bacterial Flora in Autism”. Anaerobe (2011); Sydney M. Finegold et al. “Pyrosequencing Study of Fecal Microflora of Autistic and Control Children”. Anaerobe 16, № 4 (2010).

548

K. A. Foley et al. “Propionic Acid Alters Startle Response Magnitude in Adolescent Rats” (2011).

549

Rochellys Diaz Heijtz et al. “Normal Gut Microbiota Modulates Brain Development and Behavior”. Proceedings of the National Academy of Sciences 108, № 7 (2011).

550

M. R. Buehler. “A Proposed Mechanism for Autism: An Aberrant Neuroimmune Response Manifested as a Psychiatric Disorder”. Medical Hypotheses 76, № 6 (2011).

551

T. Haahtela. “Allergy Is Rare Where Butterflies Flourish in a Biodiverse Environment”. Allergy 64, № 12 (2009).

552

Хороший обзор этой темы см.: E. Magen et al. “Can Worms Defend Our Hearts? Chronic Helminthic Infections May Attenuate the Development of Cardiovascular Diseases”. Medical Hypotheses 64, № 5 (2005).

553

M. J. Doenhoff et al. “An Anti-atherogenic Effect of Schistosoma mansoni Infections in Mice Associated with a Parasite-induced Lowering of Blood Total Cholesterol”. Parasitology 125, № 5 (2002).

554

V. S. Zhdanov et al. “Development of Atherosclerosis over a 25-Year Period: An Epidemiological Autopsy Study in Males of 11 Towns”. International Journal of Cardiology 68, № 1 (1999); K. S. Woo et al. “Westernization of Chinese Adults and Increased Subclinical Atherosclerosis”. Arteriosclerosis, Thrombosis, and Vascular Biology 19, № 10 (1999).

555

A. R. Walker. “Survival Rate at Middle Age in Developing and Western Populations”. Postgraduate Medical Journal 50, № 579 (1974).

556

В Финляндии ученые обнаружили, что перенесенная в начале жизни инфекция может защитить от сердечно-сосудистых заболеваний на склоне лет. В то время как у финнов с антителами к взрослым вирусам действительно чаще развивались сердечные заболевания (что поддерживает парадигму о существовании прямой зависимости между инфекционными и сердечными заболеваниями), у тех из них, кто чаще болел в детстве, более низкий риск развития сердечно-сосудистых заболеваний. При этом чем больше число болезней, которыми человек страдал в детстве, тем ниже у него риск сердечных заболеваний в пожилом возрасте. Erkki Pesonen et al. “Dual Role of Infections as Risk Factors for Coronary Heart Disease”. Atherosclerosis 192, № 2 (2007).

557

Tomas W. McDade et al. “Early Origins of Inflammation: Microbial Exposures in Infancy Predict Lower Levels of C-reactive Protein in Adulthood”. Proceedings of the Royal Society B: Biological Sciences 277, № 1684 (2010).

558

Tomas W. McDade, Stacy Tessler Lindau, Kristen Wroblewski. “Predictors of C-reactive Protein in the National Social Life, Health, and Aging Project”. Journals of Gerontology: Series B, Psychological Sciences and Social Sciences 66, № 1 (2011).

559

Yael T. Joffe et al. “Tumor Necrosis Factor-alpha Gene-308 G/A Polymorphism Modulates the Relationship Between Dietary Fat Intake, Serum Lipids, and Obesity Risk in Black South African Women”. Journal of Nutrition 140, № 5 (2010).

560

Davina Wu et al. “Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis”. Science 332, № 6026 (2011). Более подробную информацию о гельминтах и восстановлении тканей см.: F. Chen et al. “An Essential Role for T H2-type Responses in Limiting Acute Tissue Damage During Experimental Helminth Infection”. Nature Medicine 18, № 2 (2012).

561

Rick M. Maizels, Judith E. Allen. “Immunology: Eosinophils Forestall Obesity”. Science 332, № 6026 (2011).

562

S. H. Vermund, S. MacLeod. “Is Pinworm a Vanishing Infection? Laboratory Surveillance in a New York City Medical Center from 1971 to 1986”. American Journal of Diseases of Children 142, № 5 (1988).

563

S-L. Huang, P-F. Tsai, Y-F. Yeh. “Negative Association of Enterobius Infestation with Asthma and Rhinitis in Primary School Children in Taipei”. Clinical and Experimental Allergy 32, № 7 (2002).

564

Kathrin Eller et al. “Potential Role of Regulatory T-cells in Reversing Obesity-Linked Insulin Resistance and Diabetic Nephropathy”. Diabetes 60, № 11 (2011).

565

Интересно то, что высокий индекс массы тела у матери является предиктором бронхиальной обструкции только в случае детей, у родителей которых еще нет аллергии. Swatee P. Patel et al. “Associations between Pre-pregnancy Obesity and Asthma Symptoms in Adolescents”. Journal of Epidemiology & Community Health (2011).

566

O. Schaefer. “When the Eskimo Comes to Town”. Nature Today 6 (1971); H. Herxheimer, O. Schaefer. “Letter: Asthma in Canadian Eskimos”. New England Journal of Medicine 291, № 26 (1974).

567

O. Schaefer. “Etiology of Appendicitis”. British Medical Journal 1, № 6172 (1979).

568

J. A. Hildes, O. Schaefer. “The Changing Picture of Neoplastic Disease in the Western and Central Canadian Arctic (1950–1980)”. Canadian Medical Association Journal 130, № 1 (1984).

569

“Occupation, Health, and Mortality in the Light of the Registrar-General’s Decennial Supplement”. Lancet 211, № 5449 (1928; Francesco Colotta et al. “Cancer-related Inflammation, the Seventh Hallmark of Cancer: Links to Genetic Instability”. Carcinogenesis 30, № 7 (2009).

570

Graham A. W. Rook, Angus Dalgleish. “Infection, Immunoregulation, and Cancer”. Immunological Reviews 240, № 1 (2011); Leena C. Von Hertzen, H. Joensuu, T. Haahtela. “Microbial Deprivation, Inflammation and Cancer”. Cancer Metastasis Reviews 30, № 2 (2011).

571

Anamaria Savu et al. “Breast Cancer and Microbial Cancer Incidence in Female Populations around the World: A Surprising Hyperbolic Association”. International Journal of Cancer 123, № 5 (2008).

572

Paulo S. Pinheiro et al. “Cancer Incidence in First Generation U.S. Hispanics: Cubans, Mexicans, Puerto Ricans, and New Latinos”. Cancer Epidemiology, Biomarkers & Prevention 18, № 8 (2009).

573

W. Li et al. “Occupational Risk Factors for Pancreatic Cancer among Female Textile Workers in Shanghai, China”. Occupational and Environmental Medicine 63, № 12 (2006); George Astrakianakis et al. “Lung Cancer Risk among Female Textile Workers Exposed to Endotoxin”. Journal of the National Cancer Institute 99, № 5 (2007); Roberta M. Ray et al. “Occupational Exposures and Breast Cancer among Women Textile Workers in Shanghai”. Epidemiology 18, № 3 (2007); Karen J. Wernli et al. “Occupational Exposures and Ovarian Cancer in Textile Workers”. Epidemiology 19, № 2 (2008).

574

G. Mastrangelo et al. “Lung and Other Cancer Site Mortality in a Cohort of Italian Cotton Mill Workers”. Occupational and Environmental Medicine 65, № 10 (2008); G. Mastrangelo, V. Marzia, G. Marcer, “Reduced Lung Cancer Mortality in Dairy Farmers: Is Endotoxin Exposure the Key Factor?” American Journal of Industrial Medicine 30, № 5 (1996).

575

Susan E. Erdman, Teoflos Poutahidis. “Cancer Inflammation and Regulatory T-cells”. International Journal of Cancer 127, № 4 (2010); Susan E. Erdman et al. “Unifying Roles for Regulatory T-cells and Inflammation in Cancer”. International Journal of Cancer 126, № 7 (2010).

576

P. M. Rothwell et al. “Effect of Daily Aspirin on Long-term Risk of Death Due to Cancer: Analysis of Individual Patient Data from Randomised Trials”. Lancet 377, № 9759 (2011).

577

Edward F. McCarthy. “The Toxins of William B. Coley and the Treatment of Bone and Soft-tissue Sarcomas”. Iowa Orthopaedic Journal 26 (2006).

578

U. Hobohm. “Fever Therapy Revisited”. British Journal of Cancer 92, № 3 (2005).

579

K. F. Kölmel et al. “Infections and Melanoma Risk: Results of a Multicentre EORTC Case-control Study”. Melanoma Research 9, № 5 (1999).

580

C. Garbe, U. Leiter. “Melanoma Epidemiology and Trends”. Clinical Dermatology 27, № 1 (2009).

581

B. Krone, J. M. Grange. “Melanoma, Darwinian Medicine and the Inner World”. Journal of Cancer Research and Clinical Oncology 136, № 12 (2010).

582

Ellen T. Chang et al. “Childhood Social Environment and Hodgkin’s Lymphoma: New Findings from a Population-based Case-control Study”. Cancer Epidemiology, Biomarkers & Prevention 13, № 8 (2004).

583

Mel Greaves. “Infection, Immune Responses and the Etiology of Childhood Leukemia”. Nature Reviews Cancer 6, № 3 (2006).

584

C. Gilham et al. “Day Care in Infancy and Risk of Childhood Acute Lymphoblastic Leukemia: Findings from UK Case-control Study”. British Medical Journal (Clinical Research Ed.) 330, № 7503 (2005).

585

S. J. O’Keefe et al. “Rarity of Colon Cancer in Africans Is Associated with Low Animal Product Consumption, Not Fiber”. American Journal of Gastroenterology 94, № 5 (1999).

586

S. J. O’Keefe et al. “Products of the Colonic Microbiota Mediate the Effects of Diet on Colon Cancer Risk”. Journal of Nutrition 139, № 11 (2009).

587

J. B. Greer, S. J. O’Keefe. “Microbial Induction of Immunity, Inflammation, and Cancer”. Frontiers in Physiology 1 (2011).

588

M. El-Zein et al. “History of Asthma or Eczema and Cancer Risk among Men: A Population-based Case-control Study in Montreal, Quebec, Canada”. Annals of Allergy, Asthma & Immunology 104, № 5 (2010).

589

Fanny Legrand et al. “Human Eosinophils Expert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells”. Journal of Immunology 185, № 12 (2010).

590

A. E. Prizment et al. “Inverse Association of Eosinophil Count with Colorectal Cancer Incidence: Atherosclerosis Risk in Communities Study”. Cancer Epidemiology Biomarkers and Prevention 20, № 9 (2011).

591

У носителей вариантов генов, повышающих уровень гормонов роста, более высокий риск развития онкологических заболеваний. Elizabeth C. Leroy et al. “Genes in the Insulin and Insulin-like Growth Factor Pathway and Odds of Metachronous Colorectal Neoplasia”. Human Genetics 129, № 5 (2011). С другой стороны, среди людей с нарушенной сигнализацией гормонов роста рак встречается поразительно редко. В ходе исследования жителей отдаленных эквадорских деревень, у которых произошла мутация рецептора гормона роста (именно поэтому они маленького роста), было установлено, что они не страдают онкологическими заболеваниями. Jaime Guevara-Aguirre et al. “Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-aging Signaling, Cancer, and Diabetes in Humans”. Science: Translational Medicine 3, № 70 (2011).

592

Многие представленные здесь идеи в отношении рака и уровня гормонов взяты из: Tessa M. Pollard. Western Diseases: An Evolutionary Perspective. Cambridge and New York: Cambridge University Press, 2008, 75–98. Информацию об уровне гормонов у мужчин в разных условиях см.: P. T. Ellison et al. “Population Variation in Age-related Decline in Male Salivary Testosterone”. Human Reproduction 17, № 12 (2002).

593

Превосходный обзор информации о тестостероне и иммунитете: Michael P. Muehlenbein, Richard G. Bribiescas. “Testosterone-mediated Immune Functions and Male Life Histories”. American Journal of Human Biology 17, № 5 (2005).

594

T. W. McDade et al. “Maintenance Versus Growth: Investigating the Costs of Immune Activation Among Children in Lowland Bolivia”. American Journal of Physical Anthropology 136, № 4 (2008); Aaron D. Blackwell et al. “Life History, Immune Function, and Intestinal Helminths: Trade-offs Among Immunoglobulin E, C-reactive Protein, and Growth in an Amazonian Population”. American Journal of Human Biology 22, № 6 (2010).

595

Lise Aksglaede et al. “Age at Puberty and the Emerging Obesity Epidemic”. PLoS ONE 4, № 12 (2009).

596

A. Nuñez-de la Mora et al. “Childhood Conditions Influence Adult Progesterone Levels”. PLoS Medicine 4, № 5 (2007).

597

D. M. Parkin et al. “Global Cancer Statistics, 2002”. CA: A Cancer Journal for Clinicians 55, № 2 (2005).

598

J. E. Dunn. “Cancer Epidemiology in Populations of the United States — with Emphasis on Hawaii and California — and Japan”. Cancer Research 35, № 11 (1975); J. Lee et al. “Cancer Incidence among Korean-American Immigrants in the United States and Native Koreans in South Korea”. Cancer Control 14, № 1 (2007).

599

R. G. Ziegler et al. “Migration Patterns and Breast Cancer Risk in Asian-American Women”. Journal of the National Cancer Institute 85, № 22 (1993).

600

C. A. Lowry et al. “Identification of an Immune-responsive Mesolimbocortical Serotonergic System: Potential Role in Regulation of Emotional Behavior”. Neuroscience 146, № 2 (2007).

601

J. Stanford. “Successful Immunotherapy with Mycobacterium vaccae in the Treatment of Adenocarcinoma of the Lung”. European Journal of Cancer 44, № 2 (2008).

602

Charles L. Raison, Lucile Capuron, Andrew H. Miller. “Cytokines Sing the Blues: Inflammation and the Pathogenesis of Depression”. Trends in Immunology 27, № 1 (2006); Charles L. Raison et al. “Depressive Symptoms and Viral Clearance in Patients Receiving Interferon-alpha and Ribavirin for Hepatitis C”. Brain, Behavior and Immunity 19, № 1 (2005).

603

Andrew H. Miller, Vladimir Maletic, Charles L. Raison. “Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression”. Biological Psychiatry 65, № 9 (2009).

604

B. E. Leonard. “The Immune System, Depression and the Action of Antidepressants”. Progress in Neuro-Psychopharmacology & Biological Psychiatry 25, № 4 (2001).

605

Graham A. W. Rook, Christopher A. Lowry, Charles L. Raison. “Lymphocytes in Neuroprotection, Cognition and Emotion: Is Intolerance Really the Answer?” Brain, Behavior and Immunity 25, № 4 (2011).

606

Julie A. Pasco et al. “Association of High-sensitivity C-reactive Protein with de Novo Major Depression”. British Journal of Psychiatry 197 (2010).

607

M. R. Hayatbakhsh et al. “Association of Psychiatric Disorders, Asthma and Lung Function in Early Adulthood”. Journal of Asthma 47, № 7 (2010).

608

Michael Diamond, John P. Kelly, Thomas J. Connor. “Antidepressants Suppress Production of the Th1 Cytokine Interferon-gamma, Independent of Monoamine Transporter Blockade”. European Neuropsychopharmacology 16, № 7 (2006).

609

E. Naumova et al. “‘Immunogenetics of Aging’: Report on the Activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop,” Tissue Antigens 77, № 3 (2011).

610

Carmela Rita Balistreri et al. “LPS-Mediated Production of Pro/anti-inflammatory Cytokines and Eicosanoids in Whole Blood Samples: Biological Effects of +896A/G TLR4 Polymorphism in a Sicilian Population of Healthy Subjects”. Mechanisms of Ageing and Development 132, № 3 (2011).

611

Maris Kuningas et al. “Selection for Genetic Variation Inducing Pro-inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population”. PLoS ONE 4, № 11 (2009).

612

Lucia Malaguarnera et al. “Human Chitotriosidase Polymorphism Is Associated with Human Longevity in Mediterranean Nonagenarians and Centenarians”. Journal of Human Genetics 55, № 1 (2010).

613

Yu-Rong Fu et al. “Effects of Bifidobacterium bifidum on Adaptive Immune Senescence in Aging Mice”. Microbiology and Immunology 54, № 10 (2010).

614

A. A. Hogewoning et al. “Prevalence and Risk Factors of Inflammatory Acne Vulgaris in Rural and Urban Ghanaian Schoolchildren”. British Journal of Dermatology 161, № 2 (2009).

615

“Let them Eat Worms”. New Scientist, August 3, 2011.

616

Основано на интервью автора. Джаспер Лоуренс рассказывал свою историю на разных ресурсах. Один из сайтов: http://wormtherapy.wordpress.com/2011/01/19/the-story-of-how-i-decided-to-infect-myself-with-hookworms-andthe-founding-of-autoimmune-therapies-2-2-2/.

617

Джаспер Лоуренс опубликовал свою историю о поездке в Камерун здесь: http://www.kuro5hin.org/story/2006/4/30/91945/8971.

618

Lauren Cox. “Allergy Desperation: I’ll Take a Parasite, Please”. http://abcnews.go.com/Health/AllergiesNews/story?id=8114307&page=1&singlePage=true#.TwMqUUoyc7g.

619

Elizabeth Svoboda. “David Pritchard: The Worms Crawl In”. The New York Times, July 1, 2008.

620

Данные взяты из документов FDA, полученных по запросу в соответствии с законом о свободе информации.

621

Ричард Докинз. Эгоистичный ген. М.: Corpus (АСТ), АСТ, 2017.

622

Tim Adams. “Gut Instinct: The Miracle of the Parasitic Hookworm”. Guardian/Observer, May 22, 2010.

623

Уловку Джаспера Лоуренса можно увидеть здесь: http://curezone.com/forums/am.asp?i=1025654&s=2#i21. Он использовал имя пользователя FQ1513 здесь и на других сайтах.

624

J. R. Feary et al. “Experimental Hookworm Infection: A Randomized Placebo-controlled Trial in Asthma”. Clinical and Experimental Allergy 40, № 2 (2010).

625

В программе Radiolab было два сюжета о Джаспере Лоуренсе. Первый можно найти здесь: http://www.radiolab.org/2009/sep/07/sculptors-of-monumentalnarrative/. Продолжение этой истории представлено на: http://www.radiolab.org/blogs/radiolab-blog/2010/apr/02/an-update-on-hookworms/.

626

Сотрудники FDA побеседовали с некоторыми клиентами Лоуренса после его бегства. Один из них отметил, что предпочел бы купить гельминта, одобренного FDA, но такого просто не было.

627

M. Zuk. Riddled with Life. Orlando: Harcourt, 2007.

628

John Croese et al. “Allergy Controls the Population Density of Necator americanus in the Small Intestine”. Gastroenterology 131, № 2 (2006); John Croese, Richard Speare. “Intestinal Allergy Expels Hookworms: Seeing Is Believing”. Trends in Parasitology 22, № 12 (2006).

629

Ученые реже обнаруживают защитное воздействие человеческой аскариды (Ascaris lumbricoides) и во многих случаях отмечают, что эти гельминты приводят к обострению аллергии. См.: J. Calvert, P. Burney. “Ascaris, Atopy, and Exercise-induced Bronchoconstriction in Rural and Urban South African Children”. Journal of Allergy and Clinical Immunology 125, № 1 (2010). См. также: E. Pinelli et al. “Infection with the Roundworm Toxocara canis Leads to Exacerbation of Experimental Allergic Airway Inflammation”. Clinical and Experimental Allergy 38, № 4 (2008).

630

R. S. Zeiger et al. “Effect of Combined Maternal and Infant Food-Allergen Avoidance on Development of Atopy in Early Infancy: A Randomized Study”. Journal of Allergy and Clinical Immunology 84, № 1 (1989).

631

Большая часть истории Гидеона Лэка изложена здесь: Jerome Groopman. “The Peanut Puzzle”. The New Yorker, February 2, 2011.

632

George du Toit et al. “Early Consumption of Peanuts in Infancy Is Associated with a Low Prevalence of Peanut Allergy”. Journal of Allergy and Clinical Immunology 122, № 5 (2008).

633

Gideon Lack et al. “Factors Associated with the Development of Peanut Allergy in Childhood”. New England Journal of Medicine 348, № 11 (2003).

634

Bianca E. P. Snijders et al. “Age at First Introduction of Cow Milk Products and Other Food Products in Relation to Infant Atopic Manifestations in the First 2 Years of Life: The KOALA Birth Cohort Study”. Pediatrics 122, № 1 (2008).

635

Ananth Tygarajan, Arvil W. Burks. “American Academy of Pediatrics Recommendations on the Effects of Early Nutritional Interventions on the Development of Atopic Disease”. Current Opinion in Pediatrics 20, № 6 (2008).

636

См.: Irwin Mclean. “The Allergy Gene”. Scientist, December 1, 2010.

637

John Henderson et al. “The Burden of Disease Associated with Filaggrin Mutations: A Population-based, Longitudinal Birth Cohort Study”. Journal of Allergy and Clinical Immunology 121, № 4 (2008).

638

K. Bonnelykke et al. “Filaggrin Gene Variants and Atopic Diseases in Early Childhood Assessed Longitudinally from Birth”. Pediatric Allergy and Immunology 21, № 6 (2010).

639

Toshifumi Nomura et al. “Specific Filaggrin Mutations Cause Ichthyosis Vulgaris and Are Significantly Associated with Atopic Dermatitis in Japan”. Journal of Investigative Dermatology 128, № 6 (2008).

640

Alan Irvine, Irwin McLean, Donald Leung. “Filaggrin Mutations Associated with Skin and Allergic Diseases”. New England Journal of Medicine 365 (2011).

641

S. J. Brown et al. “Loss-of-function Variants in the Filaggrin Gene Are a Significant Risk Factor for Peanut Allergy”. Journal of Allergy and Clinical Immunology 127, № 3 (2011).

642

A. de Benedetto et al. “Tight Junction Defects in Patients with Atopic Dermatitis”. Journal of Allergy and Clinical Immunology 127, № 3 (2011).

643

Padraic G. Fallon et al. “A Homozygous Frameshift Mutation in the Mouse Flg Gene Facilitates Enhanced Percutaneous Allergen Priming”. Nature Genetics 41, № 5 (2009).

644

J. Strid et al. “Epicutaneous Exposure to Peanut Protein Prevents Oral Tolerance and Enhances Allergic Sensitization”. Clinical and Experimental Allergy 35, № 6 (2005); Tierry Olivry et al. “Stratum Corneum Removal Facilitates Experimental Sensitization to Mite Allergens in Atopic Dogs”. Veterinary Dermatology 22, № 2 (2011).

645

Alan D. Irvine, W. H. Irwin McLean. “Breaking the (Un)sound Barrier: Filaggrin Is a Major Gene for Atopic Dermatitis”. Journal of Investigative Dermatology 126, № 6 (2006).

646

Sarita Sehra et al. “IL-4 Regulates Skin Homeostasis and the Predisposition toward Allergic Skin Inflammation”. Journal of Immunology 184, № 6 (2010); Michael D. Howell et al. “Cytokine Modulation of Atopic Dermatitis Filaggrin Skin Expression”. Journal of Allergy and Clinical Immunology 124, № 3 (2009).

647

Carsten Flohr, Lindsey Yeo. “Atopic Dermatitis and the Hygiene Hypothesis Revisited”. Current Problems in Dermatology 41 (2011).

648

O. Herbarth et al. “Helicobacter pylori Colonisation and Eczema”. Journal of Epidemiology and Community Health 89.

649

Sunia Foliaki et al. “Antibiotic Use in Infancy and Symptoms of Asthma, Rhinoconjunctivitis, and Eczema in Children 6 and 7 Years Old: International Study of Asthma and Allergies in Childhood Phase III”. Journal of Allergy and Clinical Immunology 124, № 5 (2009).

650

C. Roduit et al. “Prenatal Animal Contact and Gene Expression of Innate Immunity Receptors at Birth Are Associated with Atopic Dermatitis”. Journal of Allergy and Clinical Immunology 127, № 1 (2011).

651

C. Flohr et al. “Reduced Helminth Burden Increases Allergen Skin Sensitization but Not Clinical Allergy: A Randomized, Double-blind, Placebo-controlled Trial in Vietnam”. Clinical and Experimental Allergy 40, № 1 (2010).

652

J. Muir. My First Summer in the Sierra. Houghton Miffin, 1911, 211. Я благодарен кинорежиссеру Шэрон Шаттак за то, что она сообщила мне об этом.

653

Тема формирования иммунитета к кишечным паразитам рассматривается в: Maria Yazdanbakhsh, David L. Sacks. “Why Does Immunity to Parasites Take So Long to Develop?” Nature Reviews Immunology 10, № 2 (2010).

654

Я привожу несколько оптимистичные данные об уровне детской смертности, опираясь на информацию о смертности в Швеции XVIII столетия. http://www.mortality.org/hmd/SWE/STATS/cMx_5x10.txt (дата доступа: 01.01.2012).

655

Некоторые народы, живущие в инфекционной среде обитания (такие, как пигмеи из тропических лесов в центральных районах Африки), достигают пубертатного возраста раньше других племен. Это одна из стратегий выживания в крайне инфекционной среде: рожать детей как можно раньше. Однако есть исключение из этого правила. Более подробную информацию о компромиссах между ростом и формированием иммунной системы см.: Robert Walker et al. “Growth Rates and Life Histories in Twenty-two Small-scale Societies”. American Journal of Human Biology 18, № 3 (2006).

656

В наше время нигерийцы, контактирующие с паразитами, не всегда более низкорослые, но растут они не так быстро. Omolola Ayoola et al. “Relative Height and Weight among Children and Adolescents of Rural Southwestern Nigeria”. Annals of Human Biology 36, № 4 (2009).

657

J. M. Grange et al. “Historical Declines in Tuberculosis: Nature, Nurture and the Biosocial Model”. International Journal of Tuberculosis and Lung Disease 5, № 3 (2001).

658

Тема полиомиелита рассматривается более подробно в: N. Nathanson, O. M. Kew. “From Emergence to Eradication: The Epidemiology of Poliomyelitis Deconstructed”. American Journal of Epidemiology 172, № 11 (20110). Результаты исследования по теме распространенности полиомиелита в Марокко, проведенного в середине ХХ столетия, можно найти здесь: J. R. Paul, D. M. Horstmann. “A Survey of Poliomyelitis Virus Antibodies in French Morocco”. American Journal of Tropical Medicine and Hygiene 4, № 3 (1955).

659

J. H. Savage et al. “Triclosan, a Common Ingredient in Household Products, Is Associated with Allergic Sensitization”. Journal of Allergy and Clinical Immunology 129, № 2 (2012).

660

K. B. Paul et al. “Developmental Triclosan Exposure Decreases Maternal and Neonatal Thyroxine in Rats”. Environmental Toxicology and Chemistry 29, № 12 (2010).

661

E. M. Clayton et al. “The Impact of Bisphenol A and Triclosan on Immune Parameters in the U.S. Population, NHANES 2003–2006”. Environmental Health Perspectives 119, № 3 (2011); J. M. Braun et al. “Impact of Early-life Bisphenol A Exposure on Behavior and Executive Function in Children”. Pediatrics 128, № 5 (2011).

662

Adam J. Spanier et al. “Prenatal Bisphenol A Is a Risk Factor for Early Transient Wheeze” (2011).

663

T. Midoro-Horiuti et al. “Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups”. Environmental Health Perspectives 118, № 2 (2010).

664

V. Braniste et al. “Impact of Oral Bisphenol A at Reference Doses on Intestinal Barrier Function and Sex Differences after Perinatal Exposure in Rats”. Proceedings of the National Academy of Sciences 107, № 1 (2010).

665

Christie Aschwanden. “Studies Suggest an Acetaminophen-Asthma Link”. The New York Times, December 19, 2011.

666

Richard W. Beasley et al. “Acetaminophen Use and Risk of Asthma, Rhinoconjunctivitis, and Eczema in Adolescents: International Study of Asthma and Allergies in Childhood Phase Three”. American Journal of Respiratory and Critical Care Medicine 183, № 2 (2011); J. T. McBride. “The Association of Acetaminophen and Asthma Prevalence and Severity”. Pediatrics 128, № 6 (2011).

667

Matthew S. Perzanowski et al. “Prenatal Acetaminophen Exposure and Risk of Wheeze at Age 5 Years in an Urban Low-income Cohort”. Torax 65, № 2 (2010); Seif O. Shaheen et al. “Prenatal and Infant Acetaminophen Exposure, Antioxidant Gene Polymorphisms, and Childhood Asthma”. Journal of Allergy and Clinical Immunology 126, № 6 (2010).

668

K. Becker, S. Schultz. “Similarities in Features of Autism and Asthma and a Possible Link to Acetaminophen Use”. Medical Hypotheses (2009).

669

J. E. Sordillo et al. “Multiple Microbial Exposures in the Home May Protect Against Asthma or Allergy in Childhood”. Clinical and Experimental Allergy 40, № 6 (2010).

670

См. главы Кетлин Барнс и Кетлин Уртадо в книге: Wenda Trevathan, Euclid O. Smith, James J. McKenna. Evolutionary Medicine. New York: Oxford University Press, 1999. Вопросы эволюции, аллергии, заражения гельминтами в бедных городских районах и астмы у животных более подробно рассматриваются в главах 5 и 9.

671

Питер Хотез из Sabin Vaccine Institute поспорил бы с этим. Он считает, что паразиты все же вызывают аллергию у обитателей бедных районов американских городов. В данном случае речь идет о гельминте Toxocara canis, носителями которого являются собаки. Яйца этих гельминтов могут попасть в организм с током воздуха. Хотез обнаружил, что городские жители гораздо чаще контактируют с этим гельминтом. Однако гельминтная теория аллергических заболеваний не утверждает, что любой старый паразит может обеспечить защиту. Лишь адаптированные к человеку гельминты могут надлежащим образом настроить иммунную систему. Кроме того, только хроническое заражение обеспечивает необходимую иммуномодуляцию. Информацию о том, как Toxocara canis усугубляет астму, см.: E. Pinelli et al. “Infection with the Roundworm Toxocara canis Leads to Exacerbation of Experimental Allergic Airway Inflammation”. Clinical and Experimental Allergy 38, № 4 (2007). Рассуждения Хотеза о заражении гельминтами (в частности, T. canis) в бедных районах американских городов можно найти в: P. J. Hotez. “Neglected Infections of Poverty in the United States of America”. PLoS Neglected Tropical Diseases 2, № 6 (2008).

672

Вот еще несколько примеров: Candelaria Vergara et al. “African Ancestry Is Associated with Risk of Asthma and High Total Serum IgE in a Population from the Caribbean Coast of Colombia”. Human Genetics 125, nos. 5–6 (2009). В некоторых этнических группах, обитающих в Западной Африке, более широко представлены варианты генов, связанные с аутоиммунными заболеваниями. См. Patrizia Lulli et al. “HLA-DRB1 and DQB1 Loci in Tree West African Ethnic Groups: Genetic Relationship with Sub-Saharan African and European Populations”. Human Immunology 70, № 11 (2009).

673

P. J. Cooper et al. “Asthma in Latin America: A Public Heath Challenge and Research Opportunity”. Allergy 64, № 1 (2009).

674

Emmanuel O. D. Addo-Yobo et al. “Exercise-induced Bronchospasm and Atopy in Ghana: Two Surveys Ten Years Apart”. PLoS Medicine 4, № 2 (2007). См. также результаты последних исследований ISAAC: Heather J. Zar et al. “The Changing Prevalence of Asthma, Allergic Rhinitis and Atopic Eczema in African Adolescents from 1995 to 2002”. Pediatric Allergy and Immunology 18, № 7 (2007).

675

Triine Annus et al. “Modest Increase in Seasonal Allergic Rhinitis and Eczema Over 8 Years among Estonian Schoolchildren”. Pediatric Allergy and Immunology 16, № 4 (2005).

676

Ajit Varki. “Colloquium Paper: Uniquely Human Evolution of Sialic Acid Genetics and Biology”. Proceedings of the National Academy of Sciences 107, Suppl. 2 (2010).

677

J. S. Suchodolski. “Microbes and Gastrointestinal Health of Dogs and Cats”. Journal of Animal Science (2010).

678

Darien J. Feary, Diana M. Hassel. “Enteritis and Colitis in Horses”. Veterinary Clinics of North America Equine Practice 22, № 2 (2006).

679

Anna Ledin et al. “High Plasma IgE Levels within the Scandinavian Wolf Population, and Its Implications for Mammalian IgE Homeostasis”. Molecular Immunology 45, № 7 (2008).

680

Eman Hamza et al. “Increased IL-4 and Decreased Regulatory Cytokine Production Following Relocation of Icelandic Horses from a High to Low Endoparasite Environment”. Veterinary Immunology and Immunopathology 133, № 1 (2010).

681

G. M. Halpern et al. “Diagnosis of Inhalant Allergy in a Chimpanzee Using ‘in Vivo’ and ‘in Vitro’ Tests”. Allergologia et Immunopathologia 17, № 5 (1989).

682

M. Hog, I. Schindera. “Neurodermatitis in Primates: A Case Description of a Female Gorilla”. Hautarzt; Zeitschrif für Dermatologie, Venerologie, und verwandte Gebiete 40, № 3 (1989).

683

F. Lankester et al. “Fatal Ulcerative Colitis in a Western Lowland Gorilla”. Journal of Medical Primatology 37, № 6 (2008).

684

C. A. Rubio, G. B. Hubbard. “Chronic Colitis in Macaca fascicularis: Similarities with Chronic Colitis in Humans” In Vivo 16, № 3 (2002); C. A. Rubio, G. B. Hubbard. “Chronic Colitis in Baboons: Similarities with Chronic Colitis in Humans”. In Vivo 15, № 1 (2001).

685

Alfonso S. Gozalo et al. “Pathology of Captive Moustache Tamarins (Saguinus mystax)”. Comparative Medicine 58, № 2 (2008).

686

H. Uno et al. “Colon Cancer in Aged Captive Rhesus Monkeys (Macaca mulatta)”. American Journal of Primatology 44, № 1 (1998).

687

J. D. Wood et al. “Colitis and Colon Cancer in Cottontop Tamarins (Saguinus oedipus) Living Wild in Teir Natural Habitat”. Digestive Diseases and Sciences 43, № 7 (1998).

688

Gentaro Uenishi et al. “Molecular Analyses of the Intestinal Microbiota of Chimpanzees in the Wild and in Captivity”. American Journal of Primatology 69, № 4 (2007).

689

Philip McKenna et al. “The Macaque Gut Microbiome in Health, Lentiviral Infection, and Chronic Enterocolitis”. PLoS Pathogens 4, № 2 (2008).

690

Michael K. Axthelm et al. “Japanese Macaque Encephalomyelitis: A Spontaneous Multiple Sclerosis-like Disease in a Nonhuman Primate”. Annals of Neurology 70, № 3 (2011).

691

Роберт Сапольски. Записки примата: необычайная жизнь ученого среди павианов. М.: Альпина нон-фикшн, 2018.

692

Joshua Kramer et al. “Alopecia in Rhesus Macaques Correlates with Immunophenotypic Alterations in Dermal Inflammatory Infiltrates Consistent with Hypersensitivity Etiology”. Journal of Medical Primatology 39, № 2 (2010).

693

James E. Gern. “Barnyard Microbes and Childhood Asthma”. New England Journal of Medicine 364, № 8 (2011).

694

G. C. Williams, R. M. Nesse. “The Dawn of Darwinian Medicine”. Quarterly Review of Biology 66, № 1 (1991). Другие источники и дополнительные материалы можно найти на epidemicofabsence.com.