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Sample records for huntington eugene robison

  1. American eugenics

    Directory of Open Access Journals (Sweden)

    Darko Polsek

    2002-12-01

    Full Text Available The article describes a troubled history of eugenics in the US, from its beginnings at the end of the 19th century, through the whole of the 20th. It is a part of a larger historical study on eugenics. It focuses on Davenport, Laughlin, Estabrook and the Eugenic Record Office, on the early racist eugenicists like Grant and Ross, and on sterilization legislation in the twenties and thirties. The intention however was to put the historical debate into a contemporary context, or at least to show that some eugenic ideas have lived long after everybody thought they were dead. There are some hints and quotations that show it might still be possible to misuse sterilisation in the US today.

  2. Huntington's Disease

    Science.gov (United States)

    Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of ...

  3. [Sterilization and eugenics].

    Science.gov (United States)

    Shasha, Shaul M

    2011-04-01

    The term "eugenics" was coined by Francis Galton in 1883 and was defined as the science of the improvement of the human race by better breeding. "Positive eugenics" referred to methods of encouraging the "most fit" to reproduce more often, while "negative eugenics" was related to ways of discouraging or preventing the "less fit" from reproducing by birth control and sterilization. Many western countries adopted eugenics programs including Britain, Canada, Norway, Australia, Switzerland and others. In Sweden more then 62,000 "unfits" were forcibly sterilized. Many states in the U.S.A. had adopted marriage laws with eugenics criteria including forced sterilization. Approximately 64,000 individuals were sterilized. Eugenics considerations also lay behind the adoption of the Immigration Restriction Act of 1924. The Largest plan on eugenics was adopted by the Nazi regime in Germany. Hundreds of thousands of people, who were viewed as being "unfit", were forcibly sterilized by different methods: Surgical sterilization or castration with severe complications and high mortality rates. X-ray irradiation. The method was suggested by Brack, and tested by Schuman using prisoners in Block No. 10 in Auschwitz and Birkenau. Experiments were also performed by Brack on prisoners using the "window method". "Klauberg method"--injection of irritating materials into the uterus. Experiments were conducted using the plant Caladium Seguinum which was believed to have sterilization and castration properties.

  4. Filming eugenics: teaching the history of eugenics through film.

    Science.gov (United States)

    Ooten, Melissa; Trembanis, Sarah

    2007-01-01

    In teaching eugenics to undergraduate students and general public audiences, film should he considered as a provocative and fruitful medium that can generate important discussions about the intersections among eugenics, gender, class, race, and sexuality. This paper considers the use of two films, A Bill of Divorcement and The Lynchburg Story, as pedagogical tools for the history of eugenics. The authors provide background information on the films and suggestions for using the films to foster an active engagement with the historical eugenics movement.

  5. Medical Genetics Is Not Eugenics

    Science.gov (United States)

    Cowan, Ruth Schwartz

    2008-01-01

    The connection that critics make between medical genetics and eugenics is historically fallacious. Activists on the political right are as mistaken as activists on the political left: Genetic screening was not eugenics in the past, is not eugenics in the present, and, unless its technological systems become radically transformed, will not be…

  6. Anton's syndrome and eugenics

    DEFF Research Database (Denmark)

    Kondziella, Daniel; Frahm-Falkenberg, Siska

    2011-01-01

    to the clinical neurosciences, including pioneering work in neurosurgery, neuropsychology, and child psychiatry. However, it has not been recognized in the English literature that Anton was also a dedicated advocate of eugenics and racial hygiene. This paper provides a case of Anton's syndrome and puts the works...

  7. Huntington's disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth; Law, Ian; Jønch, Aia

    2011-01-01

    In this open-label pilot study, the authors evaluated the effect of memantine on the distribution of brain glucose metabolism in four Huntington's disease (HD) patients as determined by serial 18-fluoro-deoxyglucose [F(18)]FDG-PET scans over a period of 3-4 months (90-129 days, with one patient...

  8. Huntington disease

    Science.gov (United States)

    ... President of the Florida Society of Neurology (FSN). Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Huntington's Disease Read more Latest Health News Read more Health ...

  9. Learning about Huntington's Disease

    Science.gov (United States)

    ... Mouse Models Of Huntington's Disease 1998 News Release Learning About Huntington's Disease What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. Huntington's Outreach ...

  10. [Eugenics: morality or pragmatism].

    Science.gov (United States)

    Gómez Fröde, Carina

    2013-01-01

    The subject of eugenics is as old as humanity itself, but since World War II it has been related almost automatically with the policies and practices implemented by the National Socialist regime. This happened despite the fact that these despicable practices were inspired by legislation in place in the United Sates since the 19th century and which, in some cases, were modified until the 1970's. Today, some state governments are still paying compensation to victims of these policies.

  11. [Eugenics: progress or backward movement?].

    Science.gov (United States)

    González de Cancino, Emilssen

    2007-01-01

    Throughout this article there is a critical analysis of how genetics presents a dilemma for "human progress". So much so, that the legal world aims to create unequivocal norms and guarantees in relation with eugenics in order to avoid attempting against human dignity. The document makes the reader reflect on the ethical problems that eugenics can entail.

  12. Down syndrome: coercion and eugenics.

    Science.gov (United States)

    McCabe, Linda L; McCabe, Edward R B

    2011-08-01

    Experts agree that coercion by insurance companies or governmental authorities to limit reproductive choice constitutes a eugenic practice. We discuss discrimination against families of children with Down syndrome who chose not to have prenatal testing or chose to continue a pregnancy after a prenatal diagnosis. We argue that this discrimination represents economic and social coercion to limit reproductive choice, and we present examples of governmental rhetoric and policies condoning eugenics and commercial policies meeting criteria established by experts for eugenics. Our purpose is to sensitize the clinical genetics community to these issues as we attempt to provide the most neutral nondirective prenatal genetic counseling we can, and as we provide postnatal care and counseling to children with Down syndrome and their families. We are concerned that if eugenic policies and practices targeting individuals with Down syndrome and their families are tolerated by clinical geneticists and the broader citizenry, then we increase the probability of eugenics directed toward other individuals and communities.

  13. Human enhancement: The new eugenics.

    Science.gov (United States)

    Vizcarrondo, Felipe E

    2014-08-01

    Supporters of human enhancement through genetic and other reproductive technologies claim that the new liberal eugenics, based on science and individual consent differs from the old eugenics which was unscientific and coercive. Supporters claim it is the parent's moral obligation to produce the best children possible. At this time, a defective gene that is identified in an unborn child cannot be repaired. To prevent the manifestation of the undesirable trait the unborn child is destroyed. The arguments in support of human enhancement are based on an ethic of consequence that could allow for nearly any means as long as the desired end is reached. Medical enhancement may affect the parent-child family unit; the parents' love for the child may be conditioned on the expected results. The new eugenics, although based on science, continues to pursue the same goal as the old eugenics, the development of a superior individual and the elimination of those considered inferior.

  14. Psychopathology in Huntington's disease

    NARCIS (Netherlands)

    Duijn, Erik van

    2010-01-01

    Dit proefschrift begint met een overzichtsartikel van oorspronkelijke onderzoek naar psychopathologie bij mutatiedragers voor de ziekte van Huntington. Aansluitend worden de resultaten van een cohortstudie naar de aanwezigheid en ernst van psychopathologie bij mensen met de ziekte van Huntington in

  15. Psychopathology in Huntington's disease

    NARCIS (Netherlands)

    Duijn, Erik van

    2010-01-01

    Dit proefschrift begint met een overzichtsartikel van oorspronkelijke onderzoek naar psychopathologie bij mutatiedragers voor de ziekte van Huntington. Aansluitend worden de resultaten van een cohortstudie naar de aanwezigheid en ernst van psychopathologie bij mensen met de ziekte van Huntington in

  16. Eugenics and modern biology: critiques of eugenics, 1910-1945.

    Science.gov (United States)

    Allen, Garland E

    2011-05-01

    Eugenics in most western countries in the first four decades of the 20th century was based on the idea that genes control most human phenotypic traits, everything from physical features such as polydactyly and eye colour to physiological conditions such as the A-B-O blood groups to mental and personality traits such as "feeblemindedness," alcoholism and pauperism. In assessing the development of the eugenics movement-its rise and decline between 1900 and 1950-it is important to recognise that its naïve assumptions and often flawed methodologies were openly criticised at the time by scientists and nonscientists alike. This paper will present a brief overview of the critiques launched against eugenicists' claims, particularly criticisms of the American school led by Charles B. Davenport. Davenport's approach to eugenics will be contrasted to his British counterpart, Karl Pearson, founder and first editor of the Annals of Eugenics. It was not the case that nearly everyone in the early 20th century accepted eugenic conclusions as the latest, cutting-edge science. There are lessons from this historical approach for dealing with similar naïve claims about genetics today. © 2011 The Author Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.

  17. Eugenics: The Threat of the Feeble Minded.

    Science.gov (United States)

    Winzer, Margaret; O'Connor, Anne

    1982-01-01

    The history of the eugenics movement is reviewed. The authors conclude that, despite changed terminology and a shifting emphasis, advocacy of eugenics and its discrimination against poor and mentally retarded persons still persists today. (MC)

  18. Eugenics in Education: Apologetics for Oppression

    Science.gov (United States)

    Hartlep, Nicholas D.

    2008-01-01

    For many people an esoteric educational topic is eugenics. This brief text analysis will provide a textual as well as contextual analysis of Dr. Ann Gibson Winfield's book (2007) Eugenics and Education in America: Institutionalized Racism and the Implications of History, Ideology, and Memory. Winfield objectively critiques eugenic apologetics.…

  19. Human Eugenics: Whose Perception of Perfection?

    Science.gov (United States)

    Mehta, Parendi

    2000-01-01

    Provides historical information on the science of eugenics beginning in ancient Greece. Discusses the use of "racial hygiene" by the Nazis' Third Reich and its effect on eugenics. Addresses the pros and cons of eugenics and genetic engineering. Includes an annotated bibliography. (CMK)

  20. Moderate eugenics and human enhancement.

    Science.gov (United States)

    Selgelid, Michael J

    2014-02-01

    Though the reputation of eugenics has been tarnished by history, eugenics per se is not necessarily a bad thing. Many advocate a liberal new eugenics--where individuals are free to choose whether or not to employ genetic technologies for reproductive purposes. Though genetic interventions aimed at the prevention of severe genetic disorders may be morally and socially acceptable, reproductive liberty in the context of enhancement may conflict with equality. Enhancement could also have adverse effects on utility. The enhancement debate requires a shift in focus. What the equality and/or utility costs of enhancement will be is an empirical question. Rather than philosophical speculation, more social science research is needed to address it. Philosophers, meanwhile, should address head-on the question of how to strike a balance between liberty, equality, and utility in cases of conflict (in the context of genetics).

  1. Huntington's disease phenocopy syndromes.

    Science.gov (United States)

    Wild, Edward J; Tabrizi, Sarah J

    2007-12-01

    Patients presenting with features of Huntington's disease but lacking the causative genetic expansion can be challenging diagnostically. The differential diagnosis of such Huntington's disease phenocopy syndromes has not recently been reviewed. Cohort studies have established the relative frequencies of known Huntington's disease phenocopy syndromes, whereas newly described ones have been characterized genetically, clinically, radiologically and pathologically. About 1% of suspected Huntington's disease cases emerge as phenocopy syndromes. Such syndromes are clinically important in their own right but may also shed light on the pathogenesis of Huntington's disease. Huntington's disease produces a range of clinical phenotypes, and the range of syndromes that may be responsible for Huntington's disease phenocopies is correspondingly wide. Cohort studies have established that, while the majority of phenocopy patients remain undiagnosed, in those patients where a genetic diagnosis is reached the commonest causes are SCA17, Huntington's disease-like syndrome 2 (HDL2), familial prion disease and Friedreich's ataxia. We review the features of the reported genetic causes of Huntington's disease phenocopy syndromes, including HDL1-3, SCA17, familial prion disease, spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy, chorea-acanthocytosis and iron-accumulation disorders. We present an evidence-based framework for the genetic testing of Huntington's disease phenocopy cases.

  2. "Eugenics talk" and the language of bioethics.

    Science.gov (United States)

    Wilkinson, S

    2008-06-01

    In bioethical discussions of preimplantation genetic diagnosis and prenatal screening, accusations of eugenics are commonplace, as are counter-claims that talk of eugenics is misleading and unhelpful. This paper asks whether "eugenics talk", in this context, is legitimate and useful or something to be avoided. It also looks at the extent to which this linguistic question can be answered without first answering relevant substantive moral questions. Its main conclusion is that the best and most non-partisan argument for avoiding eugenics talk is the Autonomy Argument. According to this, eugenics talk per se is not wrong, but there is something wrong with using its emotive power as a means of circumventing people's critical-rational faculties. The Autonomy Argument does not, however, tell against eugenics talk when such language is used to shock people into critical-rational thought. These conclusions do not depend on unique features of eugenics: similar considerations apply to emotive language throughout bioethics.

  3. Eugenics Past and Present: Remembering Buck v. Bell.

    Science.gov (United States)

    Berson, Michael J.; Cruz, Barbara

    2001-01-01

    Provides background information about the eugenics movement. Focuses on eugenics in the United States detailing the case, Buck v. Bell, and eugenics in Germany. Explores the present eugenic movement, focusing on "The Bell Curve," China's one child policy, and the use of eugenic sterilizations in the United States and Canada. Includes…

  4. Selling eugenics: the case of Sweden.

    Science.gov (United States)

    Bjorkman, Maria; Widmalm, Sven

    2010-12-20

    This paper traces the early (1910s to 1920s) development of Swedish eugenics through a study of the social network that promoted it. The eugenics network consisted mainly of academics from a variety of disciplines, but with medicine and biology dominating; connections with German scientists who would later shape Nazi biopolitics were strong. The paper shows how the network used political lobbying (for example, using contacts with academically accomplished MPs) and various media strategies to gain scientific and political support for their cause, where a major goal was the creation of a eugenics institute (which opened in 1922). It also outlines the eugenic vision of the institute's first director, Herman Lundborg. In effect the network, and in particular Lundborg, promoted the view that politics should be guided by eugenics and by a genetically superior elite. The selling of eugenics in Sweden is an example of the co-production of science and social order.

  5. Evangelizing Eugenics: A Brief Historiography of Popular and Formal American Eugenics Education (1908-1948)

    Science.gov (United States)

    Kohlman, Michael J.

    2012-01-01

    This article examines the history of the American Eugenics movement's penetration into the formal and popular educational milieu during the first half of the 20th Century, and includes a review of some recent scholarly research on eugenic themes in education and popular culture. Apologists have dismissed the American Eugenics movement as a…

  6. [The dispute over eugenics in interwar Poland].

    Science.gov (United States)

    Kawalec, K

    2000-01-01

    The eugenic problem seems not as well known as it was in the period between the world wars. The word "eugenics" was introduced into the scientific language by the British biologist, Francis Galton at the end of the XIX century. In general, it means the study of the methods of protecting and improving the quality of the human race by selective breeding. Galton's remarks initiated a wider (social and political) movement, which was active in some countries. The eugenic tendency was visible in American immigration policy before the Great War - making it difficult for people suffering from particular diseases to enter the USA. After the war, the eugenic movement became much stronger. In some countries (e.g. Sweden, Norway, Finland, Denmark, Switzerland, Germany, and over half of the states of the USA) some components of the eugenic programme were introduced into legislation. The eugenic movement also appeared in reconstructed Poland. In 1918 it published it own magazine "Zagadnienia Rasy" (Problems of Human Race), later "Eugenika Polska" (Polish Eugenics). This did not imply however, that interest in the eugenic programme was generally very strong. In fact, it was limited by the influence of the Catholic Church. Another significant factor was lost Polish - German hostility. In the late thirties eugenic slogans lost popularity because of their use in Germany racist policy.

  7. Eugenics and Curriculum: 1860-1929.

    Science.gov (United States)

    Selden, Steven

    1978-01-01

    Examines ideas about heredity, racism, and the development of the eugenics movement, which influenced curriculum thinkers in the period of the "naturalistic mind" and progressivism; the eugenics movement's influence upon education for the gifted; and continuing similar attitudes as to the limited effect of environment on individuals…

  8. Perspectives: Eugenics and Sterilization in the Heartland.

    Science.gov (United States)

    Wehmeyer, Michael L.

    2003-01-01

    Noting the Governor of Virginia's recent apology for his state's participation in eugenics, this article reviews the history of the sterilization of people with epilepsy and mental retardation in several states, and the importance of the Buck v. Bell (1927) Supreme Court decision in the promotion of eugenics. (Contains references.) (CR)

  9. [Sir Francis Galton: the father of eugenics].

    Science.gov (United States)

    Aubert-Marson, Dominique

    2009-01-01

    Not only was Sir Francis Galton a famous geographer and statistician, he also invented "eugenics" in 1883. Eugenics, defined as the science of improving racial stock, was developed from a new heredity theory, conceived by Galton himself, and from the evolution theory of Charles Darwin, transposed to human society by Herbert Spencer. Galton's eugenics was a program to artificially produce a better human race through regulating marriage and thus procreation. Galton put particular emphasis on "positive eugenics", aimed at encouraging the physically and mentally superior members of the population to choose partners with similar traits. In 1904, he presented his ideas in front of a vast audience of physicians and scientists in London. His widely-publicized lecture served as the starting point for the development of eugenics groups in Europe and the United States during the first half of the 20th century.

  10. Eugenics concept: from Plato to present.

    Science.gov (United States)

    Güvercin, C H; Arda, B

    2008-01-01

    All prospective studies and purposes to improve cure and create a race that would be exempt of various diseases and disabilities are generally defined as eugenic procedures. They aim to create the "perfect" and "higher" human being by eliminating the "unhealthy" prospective persons. All of the supporting actions taken in order to enable the desired properties are called positive eugenic actions; the elimination of undesired properties are defined as negative eugenics. In addition, if such applications and approaches target the public as a whole, they are defined as macro-eugenics. On the other hand, if they only aim at individuals and/or families, they are called micro-eugenics. As generally acknowledged, Galton re-introduced eugenic proposals, but their roots stretch as far back as Plato. Eugenic thoughts and developments were widely accepted in many different countries beginning with the end of the 19th to the first half of the 20th centuries. Initially, the view of negative eugenics that included compulsory sterilizations of handicapped, diseased and "lower" classes, resulted in tens of thousands being exterminated especially in the period of Nazi Germany. In the 1930s, the type of micro positive eugenics movement found a place within the pro-natalist policies of a number of countries. However, it was unsuccessful since the policy was not able to become effective enough and totally disappeared in the 1960s. It was no longer a fashionable movement and left a deep impression on public opinion after the long years of war. However, developments in genetics and its related fields have now enabled eugenic thoughts to reappear under the spotlight and this is creating new moral dilemmas from an ethical perspective.

  11. [The Henry E. Huntington Library.

    Science.gov (United States)

    Abraham, Terry

    The biographical sketch of Henry E. Huntington includes a description of the establishment of the Huntington Library and the purpose and scope of its collection. Although this is a free and public library, its use is restricted to qualified scholars having legitimate research needs. Photographic techniques were developed at the Huntington Library…

  12. Christianity and Eugenics: The Place of Religion in the British Eugenics Education Society and the American Eugenics Society, c.1907-1940.

    Science.gov (United States)

    Baker, Graham J

    2014-05-01

    Historians have regularly acknowledged the significance of religious faith to the eugenics movement in Britain and the USA. However, much of this scholarship suggests a polarised relationship of either conflict or consensus. Where Christian believers participated in the eugenics movement this has been represented as an abandonment of 'orthodox' theology, and the impression has been created that eugenics was a secularising force. In contrast, this article explores the impact of religious values on two eugenics organisations: the British Eugenics Education Society, and the American Eugenics Society. It is demonstrated that concerns over religion resulted in both these organisations modifying and tempering the public work that they undertook. This act of concealing and minimising the visibly controversial aspects of eugenics is offered as an addition to the debate over 'mainline' versus 'reform' eugenics.

  13. KRITIK TERHADAP ALIRAN SOCIOLOGICAL JURISPRUDENCE EUGEN EHRLICH

    OpenAIRE

    W.M. Herry Susilowati

    2000-01-01

    Eugen Ehrlich, seorang ahli hukum dan sosiologi dengan teorinya Sociological Jurisprudence, ingin membuktikan bahwa titik berat perkembangan hukum terletak pada masyarakat itu sendiri dengan konsep dasarnya “living law” yang mencerminkan nilai-nilai yang hidup dalam masyarakat (volkgeist). Dan apa yang dimaksud dengan volkgeist itu, Eugen Ehrlich tidak dapat memberikan jawaban secara memuaskan. Mochtar Kusumaatmadja mencoba mencari jalan keluar dengan teorinya yang dikenal dengan Teori Hukum ...

  14. Eugenics and Involuntary Sterilization: 1907-2015.

    Science.gov (United States)

    Reilly, Philip R

    2015-01-01

    In England during the late nineteenth century, intellectuals, especially Francis Galton, called for a variety of eugenic policies aimed at ensuring the health of the human species. In the United States, members of the Progressive movement embraced eugenic ideas, especially immigration restriction and sterilization. Indiana enacted the first eugenic sterilization law in 1907, and the US Supreme Court upheld such laws in 1927. State programs targeted institutionalized, mentally disabled women. Beginning in the late 1930s, proponents rationalized involuntary sterilization as protecting vulnerable women from unwanted pregnancy. By World War II, programs in the United States had sterilized approximately 60,000 persons. After the horrific revelations concerning Nazi eugenics (German Hereditary Health Courts approved at least 400,000 sterilization operations in less than a decade), eugenic sterilization programs in the United States declined rapidly. Simplistic eugenic thinking has faded, but coerced sterilization remains widespread, especially in China and India. In many parts of the world, involuntary sterilization is still intermittently used against minority groups.

  15. Eugene Paul Wigner's Nobel Prize

    CERN Document Server

    Kim, Y S

    2016-01-01

    In 1963, Eugene Paul Wigner was awarded the Nobel Prize in Physics for his contributions to the theory of the atomic nucleus and the elementary particles, particularly through the discovery and application of fundamental symmetry principles. There are no disputes about this statement. On the other hand, there still is a question of why the statement did not mention Wigner's 1939 paper on the Lorentz group, which was regarded by Wigner and many others as his most important contribution in physics. By many physicists, this paper was regarded as a mathematical exposition having nothing to do with physics. However, it has been more than one half century since 1963, and it is of interest to see what progress has been made toward understanding physical implications of this paper and its historical role in physics. Wigner in his 1963 paper defined the subgroups of the Lorentz group whose transformations do not change the four-momentum of a given particle, and he called them the little groups. Thus, Wigner's little g...

  16. Iowa and Eugene, Oregon, Orthopaedics

    Science.gov (United States)

    Buckwalter, Joseph A

    2003-01-01

    Over the last 50 years, the commitment of orthopaedic surgeons to basic and clinical research and evaluation of treatment outcomes has made possible remarkable improvements in the care of people with injuries and diseases of the limbs and spine. A group of Oregon orthopaedic surgeons has had an important role in these advances, especially in the orthopaedic specialties of sports medicine and hip reconstruction. Since Don Slocum (Iowa Orthopaedic Resident, 1934-1937), started practice in Eugene, Oregon, in 1939, three orthopaedic surgeons, Denny Collis, Craig Mohler and Paul Watson, who received their orthopaedic residency education at the University of Iowa, and three orthopaedic surgeons, Stan James, Tom Wuest and Dan Fitzpatrick, who received their undergraduate, medical school and orthopaedic residency education at the University of Iowa, have joined the group Dr. Slocum founded. These individuals, and their partners, established and have maintained a successful growing practice that serves the people of the Willamette valley, but in addition, they have made important contributions to the advancement of orthopaedics. PMID:14575262

  17. Social imaginaries: the literature of eugenics.

    Science.gov (United States)

    Sinclair, Alison

    2008-06-01

    This paper starts from a premise relating to the act of fictional writing about eugenics and the way it may be understood as the embodiment and enactment of social imaginaries. It proposes that literature (in the sense of fiction) frequently, if not habitually, expresses the underside of what is expressed in public discourse. That is, far from being the implement of state policy or intervention, it acts in counterpoint to the state, constituting a type of social fantasy in that it explores through the realm of the imagination what might happen. It becomes the arena for contestation, exploration, and nuancing as it essays how ideas from public, 'real' life, might transform when acted out. The paper considers two sorts of literary case. First it looks at that of 'naïve' literature, harnessed unashamedly to a specific sociological discourse of eugenics. Then, using primarily Ibsen, it considers a subset, the case of literature that does not set out to be explicitly in the service of the cause of eugenics, but is appropriated and disseminated from a platform of eugenics. Lastly, taking the example of Unamuno's Amor y pedagogía (1902) the paper considers literature that exists in a quite different sphere of public awareness. It shows awareness of the arguments and precepts of eugenics and related beliefs and practices, but acts as a transitional space (in the terms of Winnicott) to enable such ideas to be entertained and thought about, without a requirement of acceptance or belief.

  18. The public and private history of eugenics: an introduction.

    Science.gov (United States)

    Burke, Chloe S; Castaneda, Christopher J

    2007-01-01

    Inspired by our experience addressing the legacy of eugenics at California State University, Sacramento, this special issue presents an array of articles representative of diverse approaches to the historical investigation of eugenics. This article provides an introduction to the history of eugenics and explores the ways in which public history is particularly well suited to shape the historical memory of eugenics and encourage dialogue about contemporary biotechnologies.

  19. Eugenics and the Social Construction of Merit, Race, and Disability.

    Science.gov (United States)

    Selden, Steven

    2000-01-01

    Contends that eugenics is an example of normalization. Outlines an aspect of this process by analyzing: (1) the popular eugenic knowledge exhibited at U.S. state fairs; and (2) the mainstream eugenic knowledge found in the work of Leta S. Hollingworth who was an early leader in gifted education. (CMK)

  20. Eugenics in the community: gendered professions and eugenic sterilization in Alberta, 1928-1972.

    Science.gov (United States)

    Samson, Amy

    2014-01-01

    Scholarship on Alberta's Sexual Sterilization Act (1928-1972) has focused on the high-level politics behind the legislation, its main administrative body, the Eugenics Board, and its legal legacy, overlooking the largely female-dominated professions that were responsible for operating the program outside of the provincial mental health institutions. This paper investigates the relationship between eugenics and the professions of teaching, public health nursing, and social work. It argues that the Canadian mental hygiene and eugenics movements, which were fundamentally connected, provided these professions with an opportunity to maintain and extend their professional authority.

  1. Project Coast: eugenics in apartheid South Africa.

    Science.gov (United States)

    Singh, Jerome Amir

    2008-03-01

    It is a decade since the exposure of Project Coast, apartheid South Africa's covert chemical and biological warfare program. In that time, attention has been focused on several aspects of the program, particularly the production of narcotics and poisons for use against anti-apartheid activists and the proliferation of both chemical and biological weapons. The eugenic dimension of Project Coast has, by contrast, received scant attention. It is time to revisit the testimony that brought the suggestion of eugenic motives to light, reflect on some of the Truth and Reconciliation Commission's findings and search for lessons that can be taken from this troubled chapter in South Africa's history.

  2. Eugene Dening: Young Artist from Alberta

    Science.gov (United States)

    Sanders, James H.

    2009-01-01

    Eugene Dening, an emerging artist in Canada, recently earned his Bachelors degree at the Calvin College (Grand Rapids, MI). This essay on his artwork explores the value of art making to LGBT youth, those gay and lesbian artists who have influenced their work, and those queer and critical readings practices that one can apply to arts' viewing.…

  3. Eugene Dening: Young Artist from Alberta

    Science.gov (United States)

    Sanders, James H.

    2009-01-01

    Eugene Dening, an emerging artist in Canada, recently earned his Bachelors degree at the Calvin College (Grand Rapids, MI). This essay on his artwork explores the value of art making to LGBT youth, those gay and lesbian artists who have influenced their work, and those queer and critical readings practices that one can apply to arts' viewing.…

  4. Clinical neurogenetics: huntington disease.

    Science.gov (United States)

    Bordelon, Yvette M

    2013-11-01

    Huntington disease (HD) is an autosomal dominant, adult-onset, progressive neurodegenerative disease characterized by the triad of abnormal movements (typically chorea), cognitive impairment, and psychiatric problems. It is caused by an expanded CAG repeat in the gene encoding the protein huntingtin on chromosome 4 and causes progressive atrophy of the striatum as well as cortical and other extrastriatal structures. Genetic testing has been available since 1993 to confirm diagnosis in affected adults and for presymptomatic testing in at-risk individuals. This review covers HD signs, symptoms, and pathophysiology; current genetic testing issues; and current and future treatment strategies.

  5. Advertising eugenics: Charles M. Goethe's campaign to improve the race.

    Science.gov (United States)

    Schoenl, William; Peck, Danielle

    2010-06-01

    Over the last several decades historians have shown that the eugenics movement appealed to an extraordinarily wide constituency. Far from being the brainchild of the members of any one particular political ideology, eugenics made sense to a diverse range of Americans and was promoted by professionals ranging from geneticists and physicians to politicians and economists.(1) Seduced by promises of permanent fixes to national problems, and attracted to the idea of a scientifically legitimate form of social activism, eugenics quickly grew in popularity during the first decades of the twentieth century. Charles M. Goethe, the land developer, entrepreneur, conservationist and skilled advertiser who founded the Eugenics Society of Northern California, exemplifies the broad appeal of the eugenics movement. Goethe played an active role within the American eugenics movement at its peak in the 1920s. The last president of the Eugenics Research Association,(2) he also campaigned hard against Mexican immigration to the US and he continued open support for the Nazi regime's eugenic practices into the later 1930s.(3) This article examines Goethe's eugenic vision and, drawing on his correspondence with the leading geneticist Charles Davenport, explores the relationship between academic and non-academic advocates of eugenics in America. Published by Elsevier Ltd.

  6. [Eugen Bleuler and Carl Gustav Jung's habilitation].

    Science.gov (United States)

    Wilhelm, H R

    1996-01-01

    Eugen Bleuler's letter of recommendation for Carl Gustav Jung's appointment as a lecturer In January 1905, Eugen Bleuler (1857-1939) wrote a letter of recommendation to the Medical Faculty of the University of Zurich, urging them to accept the application of Carl Gustav Jung (1875-1961) as a lecturer there. Bleuler's letter mentions the contribution to Jung's writing made by Franz Riklin (1878-1938), although he does not define it precisely. It is safe to say that, judging from the way in which Bleuler expresses his opinions in this letter, this may be regarded at the very least as an early sign of his receptiveness to the psychoanalytical ideas of the time.

  7. A Canadian paradox: Tommy Douglas and eugenics.

    Science.gov (United States)

    Shevell, Michael

    2012-01-01

    Tommy Douglas is an icon of Canadian 20th Century political history and is considered by many as the "Father" of Medicare, a key component of our national identity. Throughout his career, he was associated at both the provincial and federal levels with progressive causes concerning disadvantaged populations. In his sociology Master's thesis written in the early 1930's, Douglas endorsed eugenic oriented solutions such as segregation and sterilization to address what was perceived to be an endemic and biologically determined problem. At first glance, this endorsement of eugenics appears to be paradoxical, but careful analysis revealed that this paradox has multiple roots in religion, political belief, historical exposure and our own desire to view our collective history in a favourable light.

  8. Better science and better race? Social Darwinism and Chinese eugenics.

    Science.gov (United States)

    Chung, Yuehtsen Juliette

    2014-12-01

    This essay explores the variegated roles played by racial, eugenic, and Social Darwinist discourse in China over roughly the last century. Using Japan as a parallel for comparison, it analyzes the introduction of the term "eugenics" into Japanese and Chinese. It then locates the deployment of eugenics and Social Darwinism as counterimperial discourse in East Asia. It offers a brief history of eugenics thinking in China across the twentieth century, focusing on the Chinese eugenicist Pan Guangdan, who used race as a category of analysis yet without any sense of hierarchy. He was critically aware of the scientific basis of eugenics and helped craft the study of eugenics in China, from biology to sociology, from economics to ethnology.

  9. Eugen Bleuler 150: Bleuler's reception of Freud.

    Science.gov (United States)

    Dalzell, Thomas G

    2007-12-01

    On the 150th anniversary of Eugen Bleuler's birth, this article examines his reception of Sigmund Freud and his use of Freudian theory to understand the symptoms of schizophrenia. In addition, in contrast to earlier interpretations of Bleuler's relationship with Freud in terms of an eventual personal and theoretical incompatibility, the article demonstrates that, although Bleuler did distance himself from the psychoanalytic movement, he remained consistent in his views on Freud's theories.

  10. Huntington's disease presenting as amyotrophic lateral sclerosis.

    LENUS (Irish Health Repository)

    Phukan, Julie

    2010-08-01

    We present the clinical, electrophysiological and molecular genetic findings of a 58-year-old male with genetically confirmed Huntington\\'s disease (HD) and concurrent clinically definite ALS by El Escorial criteria. The patient presented with asymmetric upper limb amyotrophy and weakness, and subsequently developed chorea and cognitive change. Genetic testing confirmed the presence of expanded trinucleotide repeats in huntingtin, consistent with a diagnosis of Huntington\\'s disease. This case confirms the rare coexistence of Huntington\\'s disease and motor neuron degeneration.

  11. What is HD - Huntington's Disease?

    Science.gov (United States)

    ... the person less able to work at their customary level and less functional in their regular activities ... not is intensely personal and there is no "right" answer. The Huntington's Disease Society of America recommends ...

  12. Stages of Huntington's Disease (HD)

    Science.gov (United States)

    ... the person less able to work at their customary level and less functional in their regular activities ... not is intensely personal and there is no "right" answer. The Huntington's Disease Society of America recommends ...

  13. KRITIK TERHADAP ALIRAN SOCIOLOGICAL JURISPRUDENCE EUGEN EHRLICH

    Directory of Open Access Journals (Sweden)

    W.M. Herry Susilowati

    2000-01-01

    Full Text Available Eugen Ehrlich, seorang ahli hukum dan sosiologi dengan teorinya Sociological Jurisprudence, ingin membuktikan bahwa titik berat perkembangan hukum terletak pada masyarakat itu sendiri dengan konsep dasarnya “living law” yang mencerminkan nilai-nilai yang hidup dalam masyarakat (volkgeist. Dan apa yang dimaksud dengan volkgeist itu, Eugen Ehrlich tidak dapat memberikan jawaban secara memuaskan. Mochtar Kusumaatmadja mencoba mencari jalan keluar dengan teorinya yang dikenal dengan Teori Hukum Pembangunan, yaitu bahwa “nilai-nilai yang hidup di masyarakat” berkaitan dengan “perasaan keadilan masyarakat” atau “kesadaran hukum masyarakat”. Di samping itu, teori Eugen Ehrlich (Teori Sociological Jurisprudence terdapat 3 (tiga kelemahan pokok yaitu: pertama, ajaran tersebut tidak dapat memberikan kriteria yang jelas yang membedakan norma hukum dari norma sosial yang lain; kedua, Ehrlich meragukan pisisi adat kebiasaan sebagai “sumber” hukum dan adat kebiasaan sebagai suatu bentuk hukum; ketiga, Ehrlich menolak mengikuti logika perbedaan antara norma-norma hukum negara yang khas dan norma-norma hukum dimana negara hanya memberi sanksi pada fakta sosial.

  14. Natural history of Huntington disease.

    Science.gov (United States)

    Dorsey, E Ray; Beck, Christopher A; Darwin, Kristin; Nichols, Paige; Brocht, Alicia F D; Biglan, Kevin M; Shoulson, Ira

    2013-12-01

    Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials. To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls. Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n =4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease. Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs. Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI, 0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by the product of frequency and severity score on the Unified Huntington's Disease Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with controls, baseline body mass index was lower in those with Huntington disease (25.8 vs 28.8; P Huntington disease all declined in a monotonic manner. These data quantify the natural history of the disease and may inform the design of trials aimed at reducing its burden. clinicaltrials.gov Identifier: NCT00313495.

  15. Back to the future: eugenics--a bibliographic essay.

    Science.gov (United States)

    Cullen, David

    2007-01-01

    The following essay is a review of the literature about the American eugenics movement produced by scholars over the last fifty years. The essay provides an explanation for today's renewed interest in the subject and for why the science of eugenics remains relevant to contemporary society. The essay examines the catalyst to re-examine the eugenics movement, the influence of Darwinian thought upon its development, the political and institutional support for its growth, the relationship between eugenics, sterilization, and sex, and how the twentieth-century promises of the science of better breeding was a precursor to the twenty-first-century promise of genetic engineering.

  16. Obituary: Eugene Richard Tomer, 1932-2007

    Science.gov (United States)

    Dunkl, Charles F.

    2009-01-01

    Dr. Eugene R. Tomer passed away on 2 July 2007 at his home in San Francisco, California. The cause of death was cancer. Tomer was a consulting applied mathematician with a wide range of interests in dynamical astronomy, electromagnetic theory for use in communications, and computational methods of applied mathematics. He was a member of AAS, and the Society for Applied and Industrial Mathematics [SIAM]. With K. H. Prendergast, he co-wrote the influential paper "Self-consistent Models of Elliptical Galaxies," published in the Astronomical Journal 75 (1970), 674-679. This paper has been cited over eighty times. Tomer was born on 13 June 1932. He earned the Ph.D. in Mathematics at the University of California-Berkeley in 1978 (title of dissertation: On the C*-algebra of the Hermite Operator). In 1996 he and A. F. Peterson wrote "Meeting the Challenges Presented by Computational Electromagnetics," a publication of the Naval Postgraduate School at Monterey, California. This writer met Eugene at the 1992 Annual SIAM meeting in Los Angeles in connection with the Activity Group on Orthogonal Polynomials and Special Functions, which the writer chaired at the time. Eugene volunteered to edit the Newsletter of the group, which he did from July 1992 to July 1995. Thanks to his skills and efforts, the Newsletter became a carefully edited, professional publication. Eugene not only organized a Problems Column, attracting questions in pure and applied mathematics, but he also designed the logo for the group. He gave much time and effort to this service, in an era when copy had to be physically assembled and mailed to SIAM Headquarters. Eventually he felt he had done what he could for the Activity Group. He told me that he hoped the Group would get seriously involved with applications such as in astronomy, physics, and sciences that use special function solutions of differential equations. During Tomer's editorship, we communicated mostly by e-mail, our homes being far apart. He

  17. Huntington's disease in children.

    Science.gov (United States)

    Letort, Derek; Gonzalez-Alegre, Pedro

    2013-01-01

    Huntington's disease (HD) is a dominantly inherited, fatal neurodegenerative disease. This incurable illness is characterized by a triad of a movement disorder, cognitive decline and psychiatric manifestations. Although most patients with HD have disease onset in the adult years, a small but significant proportion present with pediatric HD. It has been long known that patients with early-onset HD commonly exhibit prominent parkinsonism, known as the Westphal variant of HD. However, even among patients with pediatric HD there are differential clinical features depending on the age of onset, with younger patients frequently presenting diagnostic challenges. In his chapter, the characteristics of patients with childhood- and adolescence-onset HD are discussed, focusing on the differential clinical features that can aid the clinical reach a correct diagnosis, the indications and rational use of genetic testing and the currently available options for symptomatic treatment.

  18. On Eugene A. Nida's Functional Equivalence%On Eugene A.Nida's Functional Equivalence

    Institute of Scientific and Technical Information of China (English)

    赵玲

    2016-01-01

    Eugene A. Nida's Functional Equivalence is a very useful theory in translation. This theory considers that translation is transference of the source language into the meaning of the target language in the way the author intended the text. It has a deep influence on translation.

  19. Eugenics, Mental Deficiency and Fabian Socialism between the Wars.

    Science.gov (United States)

    Ray, L. J.

    1983-01-01

    Eugenics was not exclusively the concern of conservatives; it also appealed to certain socialists, particularly those whose middle class status was dependent upon their expert services and who believed that social problems could be resolved scientifically. Reasons for the appeal of eugenics to this group are discussed. (IS)

  20. Science in the Publicity Laboratory: The Case of Eugenics.

    Science.gov (United States)

    Caudill, Edward

    The eugenicists of the 1920s and 1930s aggressively pursued media attention and sought policy change for their cause of improving the human race by selective breeding. Eugenics gained momentum in the United States when the American Eugenics Society (AES) was organized in 1921. Policy formation and information dissemination were central to the…

  1. Rational subjects, marriage counselling and the conundrums of eugenics.

    Science.gov (United States)

    Gerodetti, Natalia

    2008-06-01

    Against the background of degeneration and the perceived threat to the nation's health and stock, family politics came to constitute an important site for eugenic discourses and interventions. Eugenic regulation of reproductive sexuality and marriage was not only pursued through 'negative' eugenics but also through educational policies targeted at young adults and youth. Switzerland serves as a useful case to explore a general idea, namely the limitations for eugenicists of exploiting the concept of a rational subject in order to achieve their ends. Practices of 'positive eugenics' crucially hinged on the utilitarian principle of rationality underpinning positive eugenics which this paper seeks to elaborate. Eugenicists devised tools to deal efficiently with social problems on a collective as well as an individual basis by deploying technologies of government which conceived individuals to be members of a population who were each held responsible for the generation of healthy future generations. As a form of 'sustaining, multiplying and ordering life' eugenics thus relied on the premise that its ideas would be adopted through an appeal to rationality and, where this was insufficient, through a series of coercive measures. Relying on conviction and education about the merits of eugenics, however, posed particular problems to positive eugenic thinking and practice.

  2. [Eugenics, an element of the literary plots of dystopia].

    Science.gov (United States)

    Baum, Ewa; Musielak, Michał

    2007-01-01

    The work presents the ideas and assumptions of eugenics, a social philosophy established in 1883 by Francis Galton, which affected the social policies of numerous European countries in the first half of the 20th century. The work shows the effect of eugenics on the literary standards of European prose in the previous century. Two outstanding dystopian novels of the 20th century, The Brave New World by Aldous Huxley and 1984 by George Orwell, situate eugenics as a permanent element of the literary plot of dystopia. Apart from the typical features of this type of novel, for example: personal narration with a trace of irony, a totalitarian state and Newspeak, eugenics is an important element of the literary plot with is aim to exclude and marginalise certain social groups. Eugenics is also one of the main social ideas criticised by both the writers.

  3. The New Eugenics: Black Hyper-Incarceration and Human Abatement

    Directory of Open Access Journals (Sweden)

    James C. Oleson

    2016-10-01

    Full Text Available In the early twentieth century, the eugenics movement exercised considerable influence over domestic US public policy. Positive eugenics encouraged the reproduction of “fit” human specimens while negative eugenics attempted to reduce the reproduction of “unfit” specimens like the “feebleminded” and the criminal. Although eugenics became a taboo concept after World War II, it did not disappear. It was merely repackaged. Incarceration is no longer related to stated eugenic goals, yet incapacitation in prisons still exerts a prophylactic effect on human reproduction. Because minorities are incarcerated in disproportionately high numbers, the prophylactic effect of incarceration affects them most dramatically. In fact, for black males, the effect of hyper-incarceration might be so great as to depress overall reproduction rates. This article identifies some of the legal and extralegal variables that would be relevant for such an analysis and calls for such an investigation.

  4. Treatment of Huntington's disease.

    Science.gov (United States)

    Frank, Samuel

    2014-01-01

    Huntington's disease (HD) is a dominantly inherited progressive neurological disease characterized by chorea, an involuntary brief movement that tends to flow between body regions. HD is typically diagnosed based on clinical findings in the setting of a family history and may be confirmed with genetic testing. Predictive testing is available to family members at risk, but only experienced clinicians should perform the counseling and testing. Multiple areas of the brain degenerate, mainly involving the neurotransmitters dopamine, glutamate, and γ-aminobutyric acid. Although pharmacotherapies theoretically target these neurotransmitters, few well-conducted trials for symptomatic interventions have yielded positive results and current treatments have focused on the motor aspects of HD. Tetrabenazine is a dopamine-depleting agent that may be one of the more effective agents for reducing chorea, although it has a risk of potentially serious adverse effects. Some newer neuroleptic agents, such as olanzapine and aripiprazole, may have adequate efficacy with a more favorable adverse effect profile than older neuroleptic agents for treating chorea and psychosis. There are no current treatments to change the course of HD, but education and symptomatic therapies can be effective tools for clinicians to use with patients and families affected by HD.

  5. Dopamine and Huntington's disease.

    Science.gov (United States)

    Schwab, Laetitia C; Garas, Shady N; Garas, Shaady N; Drouin-Ouellet, Janelle; Mason, Sarah L; Stott, Simon R; Barker, Roger A

    2015-04-01

    Huntington's disease (HD) is an incurable, inherited, progressive neurodegenerative disorder that is defined by a combination of motor, cognitive and psychiatric features. Pre-clinical and clinical studies have demonstrated an important role for the dopamine (DA) system in HD with dopaminergic dysfunction at the level of both DA release and DA receptors. It is, therefore, not surprising that the drug treatments most commonly used in HD are anti-dopaminergic agents. Their use is based primarily on the belief that the characteristic motor impairments are a result of overactivation of the central dopaminergic pathways. While this is a useful starting place, it is clear that the behavior of the central dopaminergic pathways is not fully understood in this condition and may change as a function of disease stage. In addition, how abnormalities in dopaminergic systems may underlie some of the non-motor features of HD has also been poorly investigated and this is especially important given the greater burden these place on the patients' and families' quality of life. In this review, we discuss what is known about central dopaminergic pathways in HD and how this informs us about the mechanisms of action of the dopaminergic therapies used to treat it. By doing so, we will highlight some of the paradoxes that exist and how solving them may reveal new insights for improved treatment of this currently incurable condition, including the possibility that such drugs may even have effects on disease progression and pathogenesis.

  6. Huntington's Disease and Mitochondria.

    Science.gov (United States)

    Jodeiri Farshbaf, Mohammad; Ghaedi, Kamran

    2017-06-21

    Huntington's disease (HD) as an inherited neurodegenerative disorder leads to neuronal loss in striatum. Progressive motor dysfunction, cognitive decline, and psychiatric disturbance are the main clinical symptoms of the HD. This disease is caused by expansion of the CAG repeats in exon 1 of the huntingtin which encodes Huntingtin protein (Htt). Various cellular and molecular events play role in the pathology of HD. Mitochondria as important organelles play crucial roles in the most of neurodegenerative disorders like HD. Critical roles of the mitochondria in neurons are ATP generation, Ca(2+) buffering, ROS generation, and antioxidant activity. Neurons as high-demand energy cells closely related to function, maintenance, and dynamic of mitochondria. In the most neurological disorders, mitochondrial activities and dynamic are disrupted which associate with high ROS level, low ATP generation, and apoptosis. Accumulation of mutant huntingtin (mHtt) during this disease may evoke mitochondrial dysfunction. Here, we review recent findings to support this hypothesis that mHtt could cause mitochondrial defects. In addition, by focusing normal huntingtin functions in neurons, we purpose mitochondria and Huntingtin association in normal condition. Moreover, mHtt affects various cellular signaling which ends up to mitochondrial biogenesis. So, it could be a potential candidate to decline ATP level in HD. We conclude how mitochondrial biogenesis plays a central role in the neuronal survival and activity and how mHtt affects mitochondrial trafficking, maintenance, integrity, function, dynamics, and hemostasis and makes neurons vulnerable to degeneration in HD.

  7. Neuroimaging in Huntington's disease.

    Science.gov (United States)

    Niccolini, Flavia; Politis, Marios

    2014-06-28

    Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded trinucleotide CAG sequence in huntingtin gene (HTT) on chromosome 4. HD manifests with chorea, cognitive and psychiatric symptoms. Although advances in genetics allow identification of individuals carrying the HD gene, much is still unknown about the mechanisms underlying the development of overt clinical symptoms and the transitional period between premanifestation and manifestation of the disease. HD has no cure and patients rely only in symptomatic treatment. There is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease modifying drugs. Over the past years, neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have provided important advances in our understanding of HD. MRI provides information about structural and functional organization of the brain, while PET can detect molecular changes in the brain. MRI and PET are able to detect changes in the brains of HD gene carriers years ahead of the manifestation of the disease and have also proved to be powerful in assessing disease progression. However, no single technique has been validated as an optimal biomarker. An integrative multimodal imaging approach, which combines different MRI and PET techniques, could be recommended for monitoring potential neuroprotective and preventive therapies in HD. In this article we review the current neuroimaging literature in HD.

  8. On the concept of eugenics: preliminaries to a critical appraisal

    Directory of Open Access Journals (Sweden)

    Neri Demetrio

    1999-01-01

    Full Text Available This paper's main issue is linked to what can be foreseen as the increasing capability of medical genetics to modify the genetic composition of the human species through direct interventions in the human genome for medical and non-medical purposes, i.e., the 'risk' of a resurgence of eugenics. In current discussions on the topic (briefly presented in the first section, the 'phantom of eugenics' is raised several times, but there is a great deal of confusion on what counts as eugenics, partly because of broad conceptual disagreement over the notion itself. Furthermore, according to some scholars there is no hope of overcoming this unsatisfactory conceptual uncertainty. Partly challenging this opinion, the second and third sections of this paper attempt to identify some basic features which could be seen as intrinsically linked to the notion of eugenics, with the aim of reducing the range of conceptual disagreement as a preliminary step in bringing into focus what exactly is wrong with practicing eugenics. The subsequent sections deal with the substantive issue of whether or not to practice eugenics from the point of view of the interest of future generations in the human species' genetic composition. The main moral arguments for and against eugenics are examined from the point of view of our obligations towards future generations, and the conclusion is in favor of a cautious 'open-door' position.

  9. On the concept of eugenics: preliminaries to a critical appraisal

    Directory of Open Access Journals (Sweden)

    Demetrio Neri

    Full Text Available This paper's main issue is linked to what can be foreseen as the increasing capability of medical genetics to modify the genetic composition of the human species through direct interventions in the human genome for medical and non-medical purposes, i.e., the 'risk' of a resurgence of eugenics. In current discussions on the topic (briefly presented in the first section, the 'phantom of eugenics' is raised several times, but there is a great deal of confusion on what counts as eugenics, partly because of broad conceptual disagreement over the notion itself. Furthermore, according to some scholars there is no hope of overcoming this unsatisfactory conceptual uncertainty. Partly challenging this opinion, the second and third sections of this paper attempt to identify some basic features which could be seen as intrinsically linked to the notion of eugenics, with the aim of reducing the range of conceptual disagreement as a preliminary step in bringing into focus what exactly is wrong with practicing eugenics. The subsequent sections deal with the substantive issue of whether or not to practice eugenics from the point of view of the interest of future generations in the human species' genetic composition. The main moral arguments for and against eugenics are examined from the point of view of our obligations towards future generations, and the conclusion is in favor of a cautious 'open-door' position.

  10. Huntington Disease in Asia

    Institute of Scientific and Technical Information of China (English)

    Miao Xu; Zhi-Ying Wu

    2015-01-01

    Objective:The objective was to review the major differences of Huntington disease (HD) in Asian population from those in the Caucasian population.Data Sources:Data cited in this review were obtained from PubMed database and China National Knowledge Infrastructure (CNKI) from 1994 to 2014.All the papers were written in English or Chinese languages,with the terms of Asia/Asian,HD,genotype,epidemiology,phenotype,and treatment used for the literature search.Study Selection:From the PubMed database,we included the articles and reviews which contained the HD patients' data from Asian countries.From the CNKI,we excluded the papers which were not original research.Due to the language's restrictions,those data published in other languages were not included.Results:In total,50 papers were cited in this review,authors of which were from the mainland of China,Japan,India,Thailand,Taiwan (China),Korea,and western countries.Conclusions:The lower epidemiology in Asians can be partly explained by the less cytosine-adenine-guanine repeats,different haplotypes,and CCG polymorphisms.For the physicians,atypical clinical profiles such as the initial symptom of ataxia,movement abnormalities of Parkinsonism,dystonia,or tics need to be paid more attention to and suggest gene testing if necessary.Moreover,some pathogenesis studies may help progress some new advanced treatments.The clinicians in Asian especially in China should promote the usage of genetic testing and put more effects in rehabilitation,palliative care,and offer comfort of patients and their families.The unified HD rating scale also needs to be popularized in Asia to assist in evaluating the progression of HD.

  11. Mitochondrial dysfunction and Huntington disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.

  12. Is Huntington's disease a tauopathy?

    Science.gov (United States)

    Gratuze, Maud; Cisbani, Giulia; Cicchetti, Francesca; Planel, Emmanuel

    2016-04-01

    Tauopathies are a subclass of neurodegenerative diseases typified by the deposition of abnormal microtubule-associated tau protein within the cerebral tissue. Alzheimer's disease, progressive supranuclear palsy, chronic traumatic encephalopathy and some fronto-temporal dementias are examples of the extended family of tauopathies. In the last decades, intermittent reports of cerebral tau pathology in individuals afflicted with Huntington's disease-an autosomal dominant neurodegenerative disorder that manifests by severe motor, cognitive and psychiatric problems in adulthood-have also begun to surface. These observations remained anecdotal until recently when a series of publications brought forward compelling evidence that this monogenic disorder may, too, be a tauopathy. Collectively, these studies reported that: (i) patients with Huntington's disease present aggregated tau inclusions within various structures of the brain; (ii) tau haplotype influences the cognitive function of Huntington's disease patients; and (iii) that the genetic product of the disease, the mutant huntingtin protein, could alter tau splicing, phosphorylation, oligomerization and subcellular localization. Here, we review the past and current evidence in favour of the postulate that Huntington's disease is a new member of the family of tauopathies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Concluding Commentary: Response to Eugene and Kiyo

    Directory of Open Access Journals (Sweden)

    E. Jayne White

    2014-10-01

    Full Text Available At the risk of speaking on his behalf I could almost swear I heard Bakhtin laughing gleefully over my shoulder as I read this fascinating dialogue between Eugene and Kiyo.  His reason for this might be partly inspired by the glaring misunderstandings both men reveal through their associated interplay with key pedagogical concepts. While polemic in nature, it occurs to me, somewhat ironically, that each man makes the same careful, empirically located, argument from different cultural and philosophical standpoints. At the centre of their debate is the concept of pedagogy and its capacity to promote ‘authentic’ learning. Despite this shared agenda their interpretations of key terms are often at variance and, as a result, they passionately bang their heads against each other in vehement misunderstanding that makes for what Bakhtin (2004 would describe as “lively and expressive” debate (p. 24 on this topic.

  14. [Beyond eugenics: posthumanism as Homo patiens denials].

    Science.gov (United States)

    Ballesteros Llompart, Jesús

    2012-01-01

    Throughout history there have been attempts to overcome human limitations by means of technique. The novelty of the 20th century has been to try to extirpate all the faults, the suffering, the disease, and even the death. This power has been attributed successively to machines (the futurism), to the genetic information (the eugenism) and to the electronic information (the posthumanism). In all cases, it's unknown the distinction between inevitable faults, ontological deficiencies, as the reality of death, and avoidable ones, sociological deficiencies, as the deaths due to circumstances as lack of drinkable water, of medicaments, wars or any other type of violence. The due way of confronting the human faults is to try to eradicate their avoidable causes and at the same time to understand the sense of those that cannot be avoided, as occasion of the self-overcoming and the opening to the Transcendence.

  15. [The analysis of the eugenic culture in ancient China].

    Science.gov (United States)

    Jiang, Gong-Cheng; Zong, Hong

    2010-09-01

    There was a centuries-old culture of eugenics in ancient China. We should have comprehensive and objective cognition of this tradition. The ancient people did not generally advocate marrying at a mature age as do people of modern times. They not only considered the prepotency, but also were influenced by other complicated social factors on the problem of mate selection. Although advocates of coition techniques claimed the purpose of prepotency, the eugenic effect of coition techniques deserved to be suspect. Regarding the aspect of embryo conservation and care, the most significant thing was not so-called "prenatal education", but various antenatal care methods which were proposed by TCM scholars. By making a comparison with modern eugenics, the ancient eugenics had the characteristics of valuing the male child only, commiserating with deformity and being based on familial values.

  16. Between Germanic and Latin eugenics: Portugal, 1930-1960

    Directory of Open Access Journals (Sweden)

    Richard Mark Cleminson

    Full Text Available Abstract This article assesses critically the participation of Portuguese eugenicists in “Latin eugenics” and traces the continuities and discontinuities with respect to this model. In particular, it focuses on a number of examples of more “Germanic” eugenics in contrast and in comparison to Latin versions of eugenics. In the former category, Eusébio Tamagnini, José Ayres de Azevedo and Leopoldina Ferreira de Paulo are considered; in the latter category, especially the work of Almerindo Lessa on “racial mixing” is considered. The conclusions suggest that we should seek diversity in both Latin and northern European eugenic models while at the same time placing Portugal within the array of possible versions of eugenics during the first half of the twentieth century.

  17. Assisted procreation and its relationship to genetics and eugenics.

    Science.gov (United States)

    Ricci, Mariella Lombardi

    2009-01-01

    The article below is intended to reflect on whether or not a eugenic tendency constitutes an intrinsic element of human fertilization in vitro. The author outlines ideas and circumstances which characterized the foundation and propagation of eugenics between the eighteenth and nineteenth centuries. A brief discussion follows on some of the standard procedures of in vitro fertilization, and in particular, those which manifest a trace or hint of eugenics--heterologous fertilization and sperm banking, preimplantation genetic diagnosis (PGD) and embryo selection--practices which, nonetheless, are used on a large scale and shed light on both the essence of procreative medicine and on the current cultural environment. The objective of the article is to explore whether it is possible to eliminate the eugenic connotations without foregoing the benefits of technical and scientific progress.

  18. Eugenics in Buenos Aires: discourses, practices, and historiography.

    Science.gov (United States)

    Armus, Diego

    2016-12-01

    Since the early 1990s, a series of studies underscored the overwhelming presence of positive eugenics in modern Argentina. These works emphasized the marginal role which discourse on eugenics took on violent methods for selection. In recent years, this point of view has shifted, emphasizing the conceptual viscosity of eugenics as well as the presence of negative eugenic discourses. This paper discusses these historiographic trends, and also dwells on the narratives that those perspectives articulated in relation to the question of sterilization and regulation of marriage of those who had tuberculosis in Buenos Aires during the first half of the twentieth century. This example stresses the need to examine discourse as well as practices in understanding and making sense of the past.

  19. Eugenics without the state: anarchism in Catalonia, 1900-1937.

    Science.gov (United States)

    Cleminson, Richard

    2008-06-01

    Current historiography has considered eugenics to be an emanation from state structures or a movement which sought to appeal to the state in order to implement eugenic reform. This paper examines the limitations of that view and argues that it is necessary to expand our horizons to consider particularly working-class eugenics movements that were based on the dissemination of knowledge about sex and which did not aspire to positions of political power. The paper argues that anarchism, with its contradictory practice afforded by the convulsive social situation of the Civil War in Spain, allows us to assess critically the parameters of the social action of eugenics, its many alliances, and its struggle for existence in changing political circumstances not of its own making.

  20. Neurodegenerative disorders: Parkinson's disease and Huntington's disease

    Science.gov (United States)

    Hague, S; Klaffke, S; Bandmann, O

    2005-01-01

    Parkinson's disease and Huntington's disease are both model diseases. Parkinson's disease is the most common of several akinetic-rigid syndromes and Huntington's disease is only one of an ever growing number of trinucleotide repeat disorders. Molecular genetic studies and subsequent molecular biological studies have provided fascinating new insights into the pathogenesis of both disorders and there is now real hope for disease modifying treatment in the not too distant future for patients with Parkinson's disease or Huntington's disease. PMID:16024878

  1. Neurodegenerative disorders: Parkinson's disease and Huntington's disease.

    Science.gov (United States)

    Hague, S M; Klaffke, S; Bandmann, O

    2005-08-01

    Parkinson's disease and Huntington's disease are both model diseases. Parkinson's disease is the most common of several akinetic-rigid syndromes and Huntington's disease is only one of an ever growing number of trinucleotide repeat disorders. Molecular genetic studies and subsequent molecular biological studies have provided fascinating new insights into the pathogenesis of both disorders and there is now real hope for disease modifying treatment in the not too distant future for patients with Parkinson's disease or Huntington's disease.

  2. Huntington's disease presenting as amyotrophic lateral sclerosis.

    Science.gov (United States)

    Phukan, Julie; Ali, Elfatih; Pender, Niall P; Molloy, Fiona; Hennessy, Michael; Walsh, Ronan J; Hardiman, Orla

    2010-08-01

    We present the clinical, electrophysiological and molecular genetic findings of a 58-year-old male with genetically confirmed Huntington's disease (HD) and concurrent clinically definite ALS by El Escorial criteria. The patient presented with asymmetric upper limb amyotrophy and weakness, and subsequently developed chorea and cognitive change. Genetic testing confirmed the presence of expanded trinucleotide repeats in huntingtin, consistent with a diagnosis of Huntington's disease. This case confirms the rare coexistence of Huntington's disease and motor neuron degeneration.

  3. Huntington Disease: Molecular Diagnostics Approach.

    Science.gov (United States)

    Bastepe, Murat; Xin, Winnie

    2015-10-06

    Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at-risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed.

  4. Cortical myoclonus in Huntington's disease.

    Science.gov (United States)

    Thompson, P D; Bhatia, K P; Brown, P; Davis, M B; Pires, M; Quinn, N P; Luthert, P; Honovar, M; O'Brien, M D; Marsden, C D

    1994-11-01

    We describe three patients with Huntington's disease, from two families, in whom myoclonus was the predominant clinical feature. The diagnosis was confirmed at autopsy in two cases and by DNA analysis in all three. These patients all presented before the age of 30 years and were the offspring of affected fathers. Neurophysiological studies documented generalised and multifocal action myoclonus of cortical origin that was strikingly stimulus sensitive, without enlargement of the cortical somatosensory evoked potential. The myoclonus improved with piracetam therapy in one patient and a combination of sodium valproate and clonazepam in the other two. Cortical reflex myoclonus is a rare but disabling component of the complex movement disorder of Huntington's disease, which may lead to substantial diagnostic difficulties.

  5. Molecular Imaging of Huntington's Disease.

    Science.gov (United States)

    Ciarmiello, Andrea; Giovacchini, Giampiero; Giovannini, Elisabetta; Lazzeri, Patrizia; Borsò, Elisa; Mannironi, Antonio; Mansi, Luigi

    2017-08-01

    The onset and the clinical progression of Huntington Disease (HD) is influenced by several events prompted by a genetic mutation that affects several organs tissues including different regions of the brain. In the last decades years, Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) helped to deepen the knowledge of neurodegenerative mechanisms that guide to clinical symptoms. Brain imaging with PET represents a tool to investigate the physiopathology occurring in the brain and it has been used to predict the age of onset of the disease and to evaluate the therapeutic efficacy of new drugs. This article reviews the contribution of PET and MRI in the research field on Huntington's disease, focusing in particular on some most relevant achievements that have helped recognize the molecular changes, the clinical symptoms and evolution of the disease. J. Cell. Physiol. 232: 1988-1993, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Antipsychotic drugs in Huntington's disease.

    Science.gov (United States)

    Unti, E; Mazzucchi, S; Palermo, G; Bonuccelli, U; Ceravolo, R

    2017-03-01

    The aim of this review is to overview the pharmacological features of neuroleptics experienced in the treatment of Huntington's disease (HD) symptoms. Despite a large number of case reports, randomized controlled trials (RCT) and drug comparison studies are lacking. Areas covered: After evaluating current guidelines and clinical unmet needs we searched PubMed for the term 'Huntington's disease' cross referenced with the terms 'Antipsychotic drugs' 'Neuroleptic drugs' and single drug specific names. Expert commentary: In clinical practice antipsychotics represent the first choice in the management of chorea in the presence of psychiatric symptoms, when poor compliance is suspected or when there is an increased risk of adverse events due to tetrabenazine. Antipsychotics are considered valid strategies, with the second generation preferred to reduce extrapyramidal adverse events, however they may cause more metabolic side effects. In the future 'dopamine stabilizers', such as pridopidine, could replace antipsychotics modulating dopamine transmission.

  7. Neuropsychiatric Burden in Huntington's Disease.

    Science.gov (United States)

    Paoli, Ricardo Augusto; Botturi, Andrea; Ciammola, Andrea; Silani, Vincenzo; Prunas, Cecilia; Lucchiari, Claudio; Zugno, Elisa; Caletti, Elisabetta

    2017-06-16

    Huntington's disease is a disorder that results in motor, cognitive, and psychiatric problems. The symptoms often take different forms and the presence of disturbances of the psychic sphere reduces patients' autonomy and quality of life, also impacting patients' social life. It is estimated that a prevalence between 33% and 76% of the main psychiatric syndromes may arise in different phases of the disease, often in atypical form, even 20 years before the onset of chorea and dementia. We present a narrative review of the literature describing the main psychopathological patterns that may be found in Huntington's disease, searching for a related article in the main database sources (Medline, ISI Web of Knowledge, Scopus, and Medscape). Psychiatric conditions were classified into two main categories: affective and nonaffective disorders/symptoms; and anxiety and neuropsychiatric features such as apathy and irritability. Though the literature is extensive, it is not always convergent, probably due to the high heterogeneity of methods used. We summarize main papers for pathology and sample size, in order to present a synoptic vision of the argument. Since the association between Huntington's disease and psychiatric symptoms was demonstrated, we argue that the prevalent and more invalidating psychiatric components should be recognized as early as possible during the disease course in order to best address psychopharmacological therapy, improve quality of life, and also reduce burden on caregivers.

  8. Reflections on the Historiography of American Eugenics: Trends, Fractures, Tensions.

    Science.gov (United States)

    Paul, Diane B

    2016-12-01

    By the 1950s, eugenics had lost its scientific status; it now belonged to the context rather than to the content of science. Interest in the subject was also at low ebb. But that situation would soon change dramatically. Indeed, in an essay-review published in 1993, Philip Pauly commented that a "eugenics industry" had come to rival the "Darwin industry" in importance, although the former seemed less integrated than the latter. Since then, the pace of publication on eugenics, including American eugenics, has only accelerated, while the field has become even more fractured, moving in multiple and even contradictory directions. This essay explores the trajectory of work on the history of American eugenics since interest in the subject revived in the 1960s, noting trends and also fractures. The latter are seen to result partly from the fact that professional historians no longer own the subject, which has attracted the interest of scholars in several other disciplines as well as scientists, political activists, and journalists, and also from the fact that the history of eugenics has almost always been policy-oriented. Historians' desire to be policy-relevant and at the same time attentive to context, complexity, and contingency has generated tensions at several levels: within individuals, among historians, and between professional historians and others who also engage with the history of eugenics. That these tensions are resolved differently by different authors and even by the same authors at different times helps explain why the fragmentation that Pauly noted is not likely to be overcome anytime soon.

  9. Huntington's disease: review and anesthetic case management.

    OpenAIRE

    Cangemi, C. F.; Miller, R. J.

    1998-01-01

    Huntington's disease is a dominantly inherited progressive autosomal disease that affects the basal ganglia. Symptoms appear later in life and manifest as progressive mental deterioration and involuntary choreiform movements. Patients with Huntington's disease develop a progressive but variable dementia. Dysphagia, the most significant related motor symptom, hinders nutrition intake and places the patient at risk for aspiration. The combination of involuntary choreoathetoid movements, depress...

  10. Drug-induced hyperthermia in Huntington's disease

    NARCIS (Netherlands)

    Gaasbeek, D; Naarding, Paul; Stor, T; Kremer, H P H

    Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic

  11. Drug-induced hyperthermia in Huntington's disease.

    NARCIS (Netherlands)

    Gaasbeek, D.; Naarding, P.; Stor, T.; Kremer, H.P.H.

    2004-01-01

    Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic

  12. Drug-induced hyperthermia in Huntington's disease.

    NARCIS (Netherlands)

    Gaasbeek, D.; Naarding, P.; Stor, T.; Kremer, H.P.H.

    2004-01-01

    Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic m

  13. Apathy is not depression in Huntington's disease

    NARCIS (Netherlands)

    Naarding, Paul; Janzing, Joost G E; Eling, Paul; van der Werf, Sieberen; Kremer, Berry

    2009-01-01

    Apathy and depression are common neuropsychiatric features of Huntington's disease. The authors studied a group of 34 Huntington's disease patients. In addition to the conventional classification according to DSM-IV criteria of depression, emphasis was put on a dimensional approach using scores on

  14. Huntington's disease: clinical characteristics, pathogenesis and therapies.

    Science.gov (United States)

    Nakamura, Ken; Aminoff, Michael J

    2007-02-01

    Huntington's disease is a devastating disorder with no known cure. The disease results from an expanded sequence of CAG repeats in the huntingtin gene and leads to a movement disorder with associated cognitive and systemic deficits. Huntington's disease is diagnosed by genetic testing and disease progression can be followed with a variety of imaging modalities. The accumulation of aggregated huntingtin with associated striatal degeneration is evident at autopsy. The pathophysiology of Huntington's disease remains unknown, although protein aggregation, excitotoxicity, deficits in energy metabolism, transcriptional dysregulation and apoptosis may all be involved. Current pharmacologic therapy for Huntington's disease is limited and exclusively symptomatic. However, the disease is being heavily researched, and a wide range of disease-modifying therapies is currently under development. The efficacy of these therapies is being evaluated in transgenic models of Huntington's disease and in preliminary clinical trials.

  15. Flinders Petrie and Eugenics at UCL

    Directory of Open Access Journals (Sweden)

    Kathleen L. Sheppard

    2010-05-01

    Full Text Available William Matthew Flinders Petrie is considered the father of scientific archaeology and is credited with developing a chronology of Ancient Egypt using the nondescript artefacts that other archaeologists had ignored. He occupied the first chair of Egyptology in England, and was also well-known for the museum built around his personal collection of Egyptian artifacts at University College London. Petrie's archaeological work has been studied by scholars, from various disciplines, for its scholarly, cultural, and historical value, while Petrie's life and career outside of archaeology have been the subject of relatively little study. Petrie himself wrote two life stories: the first, 'Ten Years Digging in Egypt, 1881–1891' (1892, detailed the years before his professorship at UCL; in 1932 he published his second, more complete autobiography, 'Seventy Years in Archaeology'. After he died in 1942 there were various obituaries and memorials that outlined his life and major achievements in archaeology. There was very little written about Petrie the man until 1985, when Margaret Drower's 'Flinders Petrie: A Life in Archaeology' was published; it remains the most comprehensive work on Petrie's life. A thin volume of the correspondence of Hilda and Flinders Petrie also allows a glimpse into life on excavation. In short, much of what is known about Petrie focuses on his excavations in Egypt, his time as Professor of Egyptology at University College London, or the museum that bears his name. Subsequently, as a historical matter, Petrie's work in the discipline of eugenics has rarely been discussed as part of his career.

  16. The Testing and Militarization of K-12 Education: Eugenic Assault on Urban School Populations

    Science.gov (United States)

    Hartlep, Nicholas Daniel

    2010-01-01

    This paper attempts to discuss eugenics in education and how this eugenic legacy continues to haunt American schooling and nonwhite students. Eugenic praxes and pedagogy continue to proliferate inside the American school systems' teachers may be unaware that they are teaching in such a way that maintains this ethos. This paper and seminar's…

  17. Eugen Goldstein and his Laboratory Work at the Berlin Observatory

    Science.gov (United States)

    Hedenus, Michael

    At the end of the 19th century the astronomer and director of the Berlin Observatory, Wilhelm Foerster, started an extraordinary research project: He asked the physicist Eugen Goldstein to examine the nature of electricity in space experimentally. Eugen Goldstein (1850-1930) was one of the most deserving pioneers in the field of electricity, e. g. he discovered the canal rays and he introduced the term ``cathode ray''. He became assistent at the Berlin Observatory and his official duty was the research on relations between electricity and cosmic phenomena. As a result Goldstein successfully reproduced comet tails in gas discharge tubes. My speech is about the biography of Eugen Goldstein and his work at the Berlin Observatory. I will discuss some of his experiments and show a reproduction of his artificial comet tails.

  18. The sex reform movement and eugenics in interwar Poland.

    Science.gov (United States)

    Gawin, Magdalena

    2008-06-01

    This paper focuses on the relations between a liberal group of sex reformers, consisting of writers and literary critics, and physicians from the Polish Eugenics Society in interwar Poland. It illustrates the paradoxes of the mutual co-operation between these two groups during the 1930s and analyses the reason why compulsory sterilisation was rejected by politicians. From the early 1930s two movements began to forge an alliance in Poland: the sexual reform movement which advocated freedom of the individual, and eugenics, which called for limiting the freedom of the individual for the collective good. This paper draws attention to several issues which emerged as part of this collaboration: population politics, the relationship between reformers, eugenicists and state institutions, and the question of how both movements--eugenics and sexual reform--perceived the question of sexuality, birth control and abortion. It will also focus on those aspects of their thinking that led to mutual co-operation.

  19. Eugenics, genetics, and mental illness stigma in Chinese Americans.

    Science.gov (United States)

    WonPat-Borja, Ahtoy J; Yang, Lawrence H; Link, Bruce G; Phelan, Jo C

    2012-01-01

    The increasing interest in the genetic causes of mental disorders may exacerbate existing stigma if negative beliefs about a genetic illness are generally accepted. China's history of policy-level eugenics and genetic discrimination in the workplace suggests that Chinese communities will view genetic mental illness less favorably than mental illness with non-genetic causes. The aim of this study is to identify differences between Chinese Americans and European Americans in eugenic beliefs and stigma toward people with genetic mental illness. We utilized data from a 2003 national telephone survey designed to measure how public perceptions of mental illness differ if the illness is described as genetic. The Chinese American (n = 42) and European American (n = 428) subsamples were analyzed to compare their support of eugenic belief items and measures of stigma. Chinese Americans endorsed all four eugenic statements more strongly than European Americans. Ethnicity significantly moderated the relationship between genetic attribution and three out of five stigma outcomes; however, genetic attribution actually appeared to be de-stigmatizing for Chinese Americans while it increased stigma or made no difference for European Americans. Our findings show that while Chinese Americans hold more eugenic beliefs than European Americans, these attributions do not have the same effect on stigma as they do in Western cultures. These results suggest that future anti-stigma efforts must focus on eugenic attitudes as well as cultural beliefs for Chinese Americans, and that the effects of genetic attributions for mental illness should be examined relative to other social, moral, and religious attributions common in Chinese culture.

  20. Huntington's Disease: An Immune Perspective

    Directory of Open Access Journals (Sweden)

    Annapurna Nayak

    2011-01-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein. The effects of immune activation in HD nervous system are a relatively unexplored area of research. This paper summarises immunological features associated with development and progression of HD.

  1. Huntington disease: pathogenesis and treatment.

    Science.gov (United States)

    Dayalu, Praveen; Albin, Roger L

    2015-02-01

    Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, culminating in death. It is caused by an expanded CAG repeat in the huntingtin gene. Even years before symptoms become overt, mutation carriers show subtle but progressive striatal and cerebral white matter atrophy by volumetric MRI. Although there is currently no direct treatment of HD, management options are available for several symptoms. A better understanding of HD pathogenesis, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments. This article reviews the current knowledge of HD pathogenesis and treatment.

  2. Psychiatric symptoms and CAG expansion in Huntington`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Weber, M.W.; Schmid, W.; Spiegel, R. [Univ. of Zuerich (Switzerland)

    1996-02-16

    The mutation responsible for Huntington`s disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers. 40 refs., 1 fig., 2 tabs.

  3. Eugen Goldstein and his laboratory work at Berlin Observatory

    Science.gov (United States)

    Hedenus, M.

    2002-07-01

    At the end of the 19th century, the astronomer Wilhelm Foerster, director of Berlin Observatory, initiated an extraordinary research project: He asked the physicist Eugen Goldstein to examine experimentally the nature of electricity in space. Eugen Goldstein (1850-1930) was one of the most deserving pioneers in the field of electricity. He discovered, e.g., the canal rays, and he introduced the term cathode ray. He became assistent at Berlin Observatory, and his official duty was the research on relations between electricity and cosmic phenomena. As a result, Goldstein successfully reproduced comet tails in gas discharge tubes.

  4. Exhibiting eugenics: response and resistance to a hidden history.

    Science.gov (United States)

    Brave, Ralph; Sylva, Kathryn

    2007-01-01

    Human Plants, Human Harvest: The Hidden History of California Eugenics is the first-ever exhibition on the history of eugenics in California. The disappearance of this history for half a century, and the consequent absence of a "collective menory", were the primary factors determining the exhibit's sttrcture and content. Responses to the exhibit confirmed that most visitors "never knew" about this history. The exhibit is described in some detail, with selected imagery from the exhibit reproduced. After the initial exhibition, responses of other museums and foundation officials revealed a continuing resistance to this history being publicly displayed, though the sources of resistance varied.

  5. Designing a brave new world: eugenics, politics, and fiction.

    Science.gov (United States)

    Woiak, Joanne

    2007-01-01

    Aldous Huxley composed Brave New World in the context of the Depression and the eugenics movement in Britain. Today his novel is best known as satirical and predictive, but an additional interpretation emerges from Huxley's nonfiction writings in which the liberal hurmanist expressed some surprising opinions about eugenics, citizenship, and meritocracy. He felt that his role as an artist and public intellectual was to formulate an evolving outlook on urgent social, scientific, and moral issues. His brave new world can therefore be understood as a serious design for social reform, as well as a commentary about the social uses of scientific knowledge.

  6. [Molecular therapeutic strategies for Huntington's disease].

    Science.gov (United States)

    Milewski, Michał; Hoffman-Zacharska, Dorota; Ball, Jerzy

    2015-01-01

    Huntington's disease is a progressive neurodegenerative disorder of genetic origin that still lacks an effective treatment. Recently, a number of new attempts have been undertaken to develop a successful molecular therapy for this incurable condition. The novel approaches employ, among others, some new methods to selectively silence the mutated gene or to neutralize its toxic protein product. This paper reviews all major strategies that are currently considered for molecular therapy of Huntington's disease while discussing their potential effectiveness regarding the treatment of both the Huntington's disease and a large group of related neurodegenerative disorders associated with abnormal protein aggregation.

  7. Genetic modifiers of Huntington's disease.

    Science.gov (United States)

    Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

    2014-09-15

    Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs.

  8. Eugenic utopias/dystopias, reprogenetics, and community genetics.

    Science.gov (United States)

    Raz, Aviad E

    2009-05-01

    The impetus for this review is the intriguing realisation that eugenics, viewed as dystopian and authoritarian in most of the 20th century, is in the process of being reinterpreted today--in the context of reproductive genetics--as utopian and liberal. This review offers an analytical framework for mapping the growing literature on this subject in order to provide a summary for both teaching and research in medical sociology. Recent works are subsumed and explored in three areas: historical criticism of the 'old eugenics'; the continuation of this stream in the form of criticism of reprogenetics as a new, 'backdoor' eugenic regime of bio-governmentality--an area which also includes the application of Foucauldian and feminist perspectives; and the recent enthusiasm regarding 'liberal eugenics,' claiming that reprogenetic decisions should be left to individual consumers thus enhancing their options in the health market. The review concludes by discussing and illustrating potential research directions in this field, with a focus on the social and ethical aspects of 'community genetics' and its emerging networks of individuals genetically at risk.

  9. Final-Offer Arbitration: "Sudden Death" in Eugene

    Science.gov (United States)

    Long, Gary; Feuille, Peter

    1974-01-01

    A case study on final offer arbitration experiences in Eugene, Oregon, is presented and discussed. Basic criticisms leveled against the final-offer system are opposed by the authors and evidence is given in support of the use of final-offer arbitration. (DS)

  10. The Real "Toll" of A. G. Bell: Lessons about Eugenics

    Science.gov (United States)

    Greenwald, Brian H.

    2009-01-01

    Historian Brian Greenwald offers a revisionist interpretation of Bell. He reviews Bell's role and influence within the American eugenics movement and shows that Bell had the respect of the most prominent American eugenicists. His intimate knowledge of deafness, from personal experience with his mother and wife and from his studies of deaf people…

  11. Chris Woodhead: A New Champion of Eugenic Theories

    Science.gov (United States)

    Chitty, Clyde

    2009-01-01

    Eugenic Theories are clearly alive and well in present-day society--or this is at least true of those theories relating to the passing on of abilities and talents from one generation to the next. This depressing thought was prompted by a reading of Chris Woodhead's latest book "A Desolation of Learning."

  12. What Was Wrong with Eugenics? Conflicting Narratives and Disputed Interpretations

    Science.gov (United States)

    Paul, Diane B.

    2014-01-01

    Although it is often taken for granted that eugenics is odious, exactly what makes it so is far from obvious. The existence of considerable interpretative flexibility is evident in the disparate policy lessons for contemporary reproductive genetics (or "reprogenetics") that have been derived from essentially the same set of historical…

  13. Echoes of a Forgotten Past: Eugenics, Testing, and Education Reform.

    Science.gov (United States)

    Stoskopf, Alan

    2002-01-01

    Review of the work of Goddard, Terman, and Thorndike and the role of eugenics and the intelligence quotient in testing points out dangers to be avoided in the current testing climate, such as use of the business model, single-number scores, and tracking. (Contains 42 references.) (SK)

  14. The Legitimizing Function of Judicial Rhetoric in the Eugenics Controversy.

    Science.gov (United States)

    Hasian, Marouf, Jr.; Croasmun, Earl

    1992-01-01

    Investigates the possibility that judicial policymaking is responsive to the situational exigencies created in part through public discourse. Investigates the elite and public perspectives regarding the eugenics controversy in the 1920s to explore the emergent relationship between the public and technical spheres of argument. (SR)

  15. "The Bell Curve" and Carrie Buck: Eugenics Revisited.

    Science.gov (United States)

    Smith, J. David

    1995-01-01

    The 1994 publication of "The Bell Curve" by R. Herrnstein and C. Murray is compared to other examples of eugenic principles, including the sterilization of "feebleminded" Carrie Buck, family degeneracy studies focusing on lower class Caucasian families, and other works that view the poorest and least educated members of society…

  16. Huntington's disease: review and anesthetic case management.

    Science.gov (United States)

    Cangemi, C F; Miller, R J

    1998-01-01

    Huntington's disease is a dominantly inherited progressive autosomal disease that affects the basal ganglia. Symptoms appear later in life and manifest as progressive mental deterioration and involuntary choreiform movements. Patients with Huntington's disease develop a progressive but variable dementia. Dysphagia, the most significant related motor symptom, hinders nutrition intake and places the patient at risk for aspiration. The combination of involuntary choreoathetoid movements, depression, and apathy leads to cachexia. Factors of considerable concern to the anesthesiologist who treats patients with Huntington's disease may include how to treat frail elderly people incapable of cooperation, how to treat patients suffering from malnourishment, and how to treat patients with an increased risk for aspiration or exaggerated responses to sodium thiopental and succinylcholine. The successful anesthetic management of a 65-yr-old woman with Huntington's disease who presented for full-mouth extractions is described.

  17. Huntington's Disease: Speech, Language and Swallowing

    Science.gov (United States)

    ... Disease Society of America Huntington's Disease Youth Organization Movement Disorder Society National Institute of Neurological Disorders and Stroke Typical Speech and Language Development Learning More Than One Language Adult Speech and Language Child Speech and Language Swallowing ...

  18. Impaired mitochondrial trafficking in Huntington's disease

    OpenAIRE

    Li, Xiao-Jiang; Orr, Adam L.; Li, Shihua

    2009-01-01

    Abstract Impaired mitochondrial function has been well documented in Huntington?s disease. Mutant huntingtin is found to affect mitochondria via various mechanisms including the dysregulation of gene transcription and impairment of mitochondrial function or trafficking. The lengthy and highly branched neuronal processes constitute complex neural networks in which there is a large demand for mitochondria-generated energy. Thus, the impaired mitochondria trafficking in neuronal cells...

  19. Clinical presentation of juvenile Huntington disease

    Directory of Open Access Journals (Sweden)

    Ruocco Heloísa H.

    2006-01-01

    Full Text Available OBJECTIVE: To describe the clinical presentation a group of patients with juvenile onset of Huntington disease. METHOD: All patients were interviewed following a structured clinical questioner. Patients were genotyped for the trinucleotide cytosine-adenine-guanine (CAG repeat in the Huntington Disease gene. High resolution brain MRI was performed in all patients. RESULTS: We identified 4 patients with juvenile onset of disease among 50 patients with Huntington disease followed prospectively in our Neurogenetics clinic. Age at onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal inheritance of the disease. Expanded Huntington disease allele sizes varied from 41 to 69 trinucleotide repeats. The early onset patients presented with rigidity, bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume loss of caudate and putamen nuclei (p=0.001 and reduced cerebral and cerebellum volumes (p=0.01. CONCLUSION: 8% of Huntington disease patients seen in our clinic had juvenile onset of the disease. They did not present with typical chorea as seen in adult onset Huntington disease. There was a predominance of rigidity and bradykinesia. Two other important clinical features were seizures and ataxia, which related with the imaging findings of early cortical atrophy and cerebellum volume loss.

  20. Ethical issues and Huntington's disease.

    Science.gov (United States)

    Kromberg, Jennifer G R; Wessels, Tina-Marié

    2013-10-11

    The practice of genetic counselling gives rise to many ethical dilemmas, and counsellors need to be familiar with the principles of biomedical ethics. The primary principles include respect for autonomy, beneficence, non-maleficence and justice. A case of identical twins at 50% risk for Huntington's disease, in which only one twin sought predictive testing for this dominantly inherited disease, created several ethical dilemmas. Another case where predictive testing was carried out on two young children, at high risk, by a laboratory at the request of an adoption agency and a doctor, with a view to giving information to the foster parents, also posed many ethical conundrums for the counsellor. The ethical issues that arose in these cases are discussed in this paper. 

  1. Cholesterol metabolism in Huntington disease.

    Science.gov (United States)

    Karasinska, Joanna M; Hayden, Michael R

    2011-09-06

    The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease.

  2. Juvenile Huntington disease in Argentina.

    Science.gov (United States)

    Gatto, Emilia Mabel; Parisi, Virginia; Etcheverry, José Luis; Sanguinetti, Ana; Cordi, Lorena; Binelli, Adrian; Persi, Gabriel; Squitieri, Ferdinando

    2016-01-01

    We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors.

  3. Language impairment in Huntington's disease.

    Science.gov (United States)

    Azambuja, Mariana Jardim; Radanovic, Marcia; Haddad, Mônica Santoro; Adda, Carla Cristina; Barbosa, Egberto Reis; Mansur, Letícia Lessa

    2012-06-01

    Language alterations in Huntington's disease (HD) are reported, but their nature and correlation with other cognitive impairments are still under investigation. This study aimed to characterize the language disturbances in HD and to correlate them to motor and cognitive aspects of the disease. We studied 23 HD patients and 23 controls, matched for age and schooling, using the Boston Diagnostic Aphasia Examination, Boston Naming Test, the Token Test, Animal fluency, Action fluency, FAS-COWA, the Symbol Digit Modalities Test, the Stroop Test and the Hooper Visual Organization Test (HVOT). HD patients performed poorer in verbal fluency (poral comprehension (preading comprehension (p=0.034) and narrative writing (p<0.0001). There was a moderate correlation between the Expressive Component and Language Competency Indexes and the HVOT (r=0.519, p=0.011 and r=0.450, p=0.031, respectively). Language alterations in HD seem to reflect a derangement in both frontostriatal and frontotemporal regions.

  4. Huntington's disease: a clinical review

    Directory of Open Access Journals (Sweden)

    Roos Raymund AC

    2010-12-01

    Full Text Available Abstract Huntington disease (HD is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD. The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which

  5. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  6. Silencing Huntington's chorea: Is RNA Interference a Potential Cure?

    OpenAIRE

    Metz, Gerlinde A.; Whishaw, Ian Q.; Afra Foroud; Nafisa M Jadavji

    2006-01-01

    In 1872, George Huntington described Huntington's disease as characterized by motor, cognitive and psychiatric impairments. Huntington's disease is a dominant and autosomal mutation on chromosome 4 featuring the insertion of numerous CAG repeats. CAG codes for the amino acid, glutmanine that forms part of the Huntingtin protein (htt). Excess glutamine attachments make htt prone to accumulate in neurons. Three genes can be considered when developing therapies for Huntington's disease. They inc...

  7. Arnold Gesell's progressive vision: child hygiene, socialism and eugenics.

    Science.gov (United States)

    Harris, Ben

    2011-08-01

    In October 1913, The American Magazine published an article by Arnold Gesell that portrayed Alma, Wisconsin (his hometown) as overflowing with the mentally and morally unfit. In "The Village of a Thousand Souls", Gesell called for the observation and segregation of the unfit as a eugenic measure. This article explores the reasons behind this infamous article by someone who became a famous developmental psychologist and pediatrician. Gesell's papers at the Library of Congress reveal his socialist views of poverty, injustice, and human development. The archives of his father's photography studio at the Wisconsin Historical Society reveal his manipulation of the photographic record to fit his negative view of Alma. Typical of the era, Gesell's Progressive vision combined social control and negative eugenics with egalitarianism and the benevolent engineering of the environment.

  8. Propulsion by light: visions of the German pioneer Eugen Saenger

    Science.gov (United States)

    Bohn, Willy L.

    2005-03-01

    Although the laser was not yet invented Eugen Sanger, one of the most prominent German personalities in the early development of hypersonic flight and rocket technology suggested to use photons for the propulsion of spacecrafts in the fifties. In contrast to current schemes which are mostly aimed at laser induced ablation processes, Eugen Sanger started with the idea of using the radiation pressure itself for propulsion purposes. A review of his pioneering work in that area will be supported by numerous historical documents and personal remembrance showing his effort to promote unconventional ideas. The paper also emphasizes how some of the original concepts are being revisited and partly implemented by using today's laser technology.

  9. Disability, gene therapy and eugenics - a challenge to John Harris

    OpenAIRE

    Reindal, S. M.

    2000-01-01

    This article challenges the view of disability presented by Harris in his article, "Is gene therapy a form of eugenics?"1 It is argued that his definition of disability rests on an individual model of disability, where disability is regarded as a product of biological determinism or "personal tragedy" in the individual. Within disability theory this view is often called "the medical model" and it has been criticised for not being able to deal with the term "disability", but only with impairme...

  10. Comparing Eugene P. Wigner, Raymond Duval and Richard P. Feynman

    OpenAIRE

    IURATO, Giuseppe

    2013-01-01

    Inspired by some basic formal aspects of standard model of fundamental physics, in this paper, putting into comparison the Eugene Wigner's theoretical definition of elementary particle with some aspects of the semiotic theory according to Raymond Duval, it will be possible to lay out the former into the latter theory which will get a further epistemological foundation also on the basis of the experimental validations of the standard model itself. Moreover, a final comparison with some epistem...

  11. Exercise effects in Huntington disease.

    Science.gov (United States)

    Frese, Sebastian; Petersen, Jens A; Ligon-Auer, Maria; Mueller, Sandro Manuel; Mihaylova, Violeta; Gehrig, Saskia M; Kana, Veronika; Rushing, Elisabeth J; Unterburger, Evelyn; Kägi, Georg; Burgunder, Jean-Marc; Toigo, Marco; Jung, Hans H

    2017-01-01

    Huntington disease (HD) is a relentlessly progressive neurodegenerative disorder with symptoms across a wide range of neurological domains, including cognitive and motor dysfunction. There is still no causative treatment for HD but environmental factors such as passive lifestyle may modulate disease onset and progression. In humans, multidisciplinary rehabilitation has a positive impact on cognitive functions. However, a specific role for exercise as a component of an environmental enrichment effect has been difficult to demonstrate. We aimed at investigating whether endurance training (ET) stabilizes the progression of motor and cognitive dysfunction and ameliorates cardiovascular function in HD patients. Twelve male HD patients (mean ± SD, 54.8 ± 7.1 years) and twelve male controls (49.1 ± 6.8 years) completed 26 weeks of endurance training. Before and after the training intervention, clinical assessments, exercise physiological tests, and a body composition measurement were conducted and a muscle biopsy was taken from M. vastus lateralis. To examine the natural course of the disease, HD patients were additionally assessed 6 months prior to ET. During the ET period, there was a motor deficit stabilization as indicated by the Unified Huntington's Disease Rating Scale motor section score in HD patients (baseline: 18.6 ± 9.2, pre-training: 26.0 ± 13.7, post-training: 26.8 ± 16.4). Peak oxygen uptake ([Formula: see text]) significantly increased in HD patients (∆[Formula: see text] = +0.33 ± 0.28 l) and controls (∆[Formula: see text] = +0.29 ± 0.41 l). No adverse effects of the training intervention were reported. Our results confirm that HD patients are amenable to a specific exercise-induced therapeutic strategy indicated by an increased cardiovascular function and a stabilization of motor function.

  12. [Application of case-based method in genetics and eugenics teaching].

    Science.gov (United States)

    Li, Ya-Xuan; Zhao, Xin; Zhang, Fei-Xiong; Hu, Ying-Kao; Yan, Yue-Ming; Cai, Min-Hua; Li, Xiao-Hui

    2012-05-01

    Genetics and Eugenics is a cross-discipline between genetics and eugenics. It is a common curriculum in many Chinese universities. In order to increase the learning interest, we introduced case teaching method and got a better teaching effect. Based on our teaching practices, we summarized some experiences about this subject. In this article, the main problem of case-based method applied in Genetics and Eugenics teaching was discussed.

  13. When the time seems ripe: eugenics, the annals, and the subtle persistence of typological thinking.

    Science.gov (United States)

    Weiss, Kenneth M; Lambert, Brian W

    2011-05-01

    This journal began in 1925 as the Annals of Eugenics. Much has changed since then. The original Editors' primary eugenic objective was not achieved, and eugenics justifiably became notorious for racism and gross abuse of human rights. But one founding aim was to publish advances in statistical genetics, and that objective prospered in the journal's pages from its beginning to the present day. The online availability of the original issues will be useful to those interested in the history of both eugenics and human genetics and will provide a reminder of how the careless use of genetical concepts can go astray.

  14. Energy Edge Post-Occupancy Evaluation Project: The Eugene Water and Electric Board Building (EWEB) Eugene, Oregon

    Energy Technology Data Exchange (ETDEWEB)

    1990-06-01

    The Workspace Satisfaction Survey measures occupant satisfaction with the thermal, lighting, acoustical, and air quality aspects of the work environment. In addition to ratings of these ambient environmental features, occupants also rate their satisfaction with a number of functional and aesthetic features of the office environment as well as their satisfaction with specific kinds of workspaces (e.g., computer rooms, the lobby, employee lounge, etc.) Each section on ambient conditions includes questions on the frequency with which people experience particular kinds of discomforts or problems, how much the discomfort bothers them, and how much it interferes with their work. Occupants are also asked to identify how they cope with discomfort or environmental problems, and to what extent these behaviors enable them to achieve more satisfactory conditions. Results of this survey of occupants of the four story Eugene Water Electric Boards (EWEB) main office building on the banks of the Wilamette River in Eugene, Oregon are the subject of this report.

  15. Biochemical aspects of Huntington's chorea.

    Science.gov (United States)

    Caraceni, T; Calderini, G; Consolazione, A; Riva, E; Algeri, S; Girotti, F; Spreafico, R; Branciforti, A; Dall'olio, A; Morselli, P L

    1977-01-01

    Fifteen patients affected by Huntington's chorea were divided into two groups, 'slow' and 'fast', according to IQ scores on the Wechsler-Bellevue scale, and scores on some motor performance tests. A possible correlation was looked for between some biochemical data (cerebrospinal fluid (CSF), homovanillic acid (HVA), and 5-hydroxyindolacetic acid (5HIAA) levels, plasma dopamine-beta-hydroxylase (DBH), dopamine (DA) uptake by platelets), and clinical data (duration of illness, severity of symptoms, age of patients, IQ scores, 'slow' and 'fast' groups). The CSF, HVA, and 5HIAA levels were found to be significantly lowered in comparison with normal controls. DBH activity and DA uptake by platelets did not differ significantly from normal subjects. Treatment with haloperidol in all patients and with dipropylacetic acid in three patients did not appear to modify the CSF, HVA, and 5HIAA concentrations, the plasma DBH activity, or the DA uptake. There were no significant differences in the CSF, HVA, and 5HIAA contents between the two groups of patients, and there was no correlation between biochemical data and clinical features. PMID:143508

  16. Protein oxidation in Huntington disease.

    Science.gov (United States)

    Sorolla, M Alba; Rodríguez-Colman, María José; Vall-llaura, Núria; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

    2012-01-01

    Huntington disease (HD) is an inherited neurodegenerative disorder caused by expansion of CAG repeats in the huntingtin gene, affecting initially the striatum and progressively the cortex. Oxidative stress, and consequent protein oxidation, has been described as important to disease progression. This review focuses on recent advances in the field, with a particular emphasis on the identified target proteins and the role that their oxidation has or might have in the pathophysiology of HD. Oxidation and the resulting inactivation and/or degradation of important proteins can explain the impairment of several metabolic pathways in HD. Oxidation of enzymes involved in ATP synthesis can account for the energy deficiency observed. Impairment of protein folding and degradation can be due to oxidation of several heat shock proteins and Valosin-containing protein. Oxidation of two enzymes involved in the vitamin B6 metabolism could result in decreased availability of pyridoxal phosphate, which is a necessary cofactor in transaminations, the kynurenine pathway and the synthesis of glutathione, GABA, dopamine and serotonin, all of which have a key role in HD pathology. In addition, protein oxidation often contributes to oxidative stress, aggravating the molecular damage inside the cell. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  17. Error processing in Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Christian Beste

    Full Text Available BACKGROUND: Huntington's disease (HD is a genetic disorder expressed by a degeneration of the basal ganglia inter alia accompanied with dopaminergic alterations. These dopaminergic alterations are related to genetic factors i.e., CAG-repeat expansion. The error (related negativity (Ne/ERN, a cognitive event-related potential related to performance monitoring, is generated in the anterior cingulate cortex (ACC and supposed to depend on the dopaminergic system. The Ne is reduced in Parkinson's Disease (PD. Due to a dopaminergic deficit in HD, a reduction of the Ne is also likely. Furthermore it is assumed that movement dysfunction emerges as a consequence of dysfunctional error-feedback processing. Since dopaminergic alterations are related to the CAG-repeat, a Ne reduction may furthermore also be related to the genetic disease load. METHODOLOGY/PRINCIPLE FINDINGS: We assessed the error negativity (Ne in a speeded reaction task under consideration of the underlying genetic abnormalities. HD patients showed a specific reduction in the Ne, which suggests impaired error processing in these patients. Furthermore, the Ne was closely related to CAG-repeat expansion. CONCLUSIONS/SIGNIFICANCE: The reduction of the Ne is likely to be an effect of the dopaminergic pathology. The result resembles findings in Parkinson's Disease. As such the Ne might be a measure for the integrity of striatal dopaminergic output function. The relation to the CAG-repeat expansion indicates that the Ne could serve as a gene-associated "cognitive" biomarker in HD.

  18. Predictive testing for Huntington's disease.

    Science.gov (United States)

    Tibben, Aad

    2007-04-30

    Worldwide, predictive testing for Huntington's disease has become an accepted clinical application that has allowed many individuals from HD-families to proceed with their life without the uncertainty of being at risk. International guidelines have extensively contributed to establishing counselling programmes of high quality, and have served as a model for other genetic disorders. Psychological follow-up studies have increased the insight into the far-reaching impact of test results for all individuals involved. Although the guidelines have served as a useful frame of reference, clinical experience has shown the importance of a case-by-case approach to do justice to the specific needs of the individual test candidate. Issues such as ambiguous test results, lack of awareness in a test candidate of early signs of the disease, non-compliance to the test protocol, or the test candidate's need for information on the relationship between age at onset and CAG-repeat require careful consideration. Receiving a test result is only one of the transition points in the life of an individual at risk; such result needs to be valued from a life-cycle perspective.

  19. Huntington's Disease and Striatal Signaling.

    Science.gov (United States)

    Roze, Emmanuel; Cahill, Emma; Martin, Elodie; Bonnet, Cecilia; Vanhoutte, Peter; Betuing, Sandrine; Caboche, Jocelyne

    2011-01-01

    Huntington's Disease (HD) is the most frequent neurodegenerative disease caused by an expansion of polyglutamines (CAG). The main clinical manifestations of HD are chorea, cognitive impairment, and psychiatric disorders. The transmission of HD is autosomal dominant with a complete penetrance. HD has a single genetic cause, a well-defined neuropathology, and informative pre-manifest genetic testing of the disease is available. Striatal atrophy begins as early as 15 years before disease onset and continues throughout the period of manifest illness. Therefore, patients could theoretically benefit from therapy at early stages of the disease. One important characteristic of HD is the striatal vulnerability to neurodegeneration, despite similar expression of the protein in other brain areas. Aggregation of the mutated Huntingtin (HTT), impaired axonal transport, excitotoxicity, transcriptional dysregulation as well as mitochondrial dysfunction, and energy deficits, are all part of the cellular events that underlie neuronal dysfunction and striatal death. Among these non-exclusive mechanisms, an alteration of striatal signaling is thought to orchestrate the downstream events involved in the cascade of striatal dysfunction.

  20. Therapeutic advances in Huntington's Disease.

    Science.gov (United States)

    Shannon, Kathleen M; Fraint, Avram

    2015-09-15

    Huntington's disease is a rare hereditary degenerative disease with a wide variety of symptoms that encompass movement, cognition, and behavior. The genetic mutation that causes the disease has been known for more than 20 y, and animal models have illuminated a host of intracellular derangements that occur downstream of protein translation. A number of clinical trials targeting these metabolic consequences have failed to produce a single effective therapy, although clinical trials continue. New strategies targeting the protein at the level of transcription, translation, and posttranslational modification and aggregation engender new hope that a successful strategy will emerge, but there is much work ahead. Some of the clinical manifestations of the illness, particularly chorea, affective symptoms, and irritability, are amenable to palliative strategies, but physicians have a poor evidence base on which to select the best agents. Clinical trials since 2013 have dashed hopes that coenzyme Q10 or creatine might have disease-modifying properties but suggested other agents were safe or hinted at efficacy (cysteamine, selisistat, hydroxyquinoline) and could proceed into later-stage disease modification trials. The hunt for effective symptom relief suggested that pridopidine might be shown effective given the right outcome measure. This review summarizes recent progress in HD and highlights promising new strategies for slowing disease progression and relieving suffering in HD. © 2015 International Parkinson and Movement Disorder Society.

  1. Huntington's disease: a clinical review.

    Science.gov (United States)

    McColgan, Peter; Tabrizi, Sarah J

    2017-08-17

    Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6-13.7 individuals per 100,000. It is characterised by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently underway. This may bring us one step closer to treating and potentially preventing this devastating condition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Movement sequencing in Huntington disease.

    Science.gov (United States)

    Georgiou-Karistianis, Nellie; Long, Jeffrey D; Lourens, Spencer G; Stout, Julie C; Mills, James A; Paulsen, Jane S

    2014-08-01

    To examine longitudinal changes in movement sequencing in prodromal Huntington's disease (HD) participants (795 prodromal HD; 225 controls) from the PREDICT-HD study. Prodromal HD participants were tested over seven annual visits and were stratified into three groups (low, medium, high) based on their CAG-Age Product (CAP) score, which indicates likely increasing proximity to diagnosis. A cued movement sequence task assessed the impact of advance cueing on response initiation and execution via three levels of advance information. Compared to controls, all CAP groups showed longer initiation and movement times across all conditions at baseline, demonstrating a disease gradient for the majority of outcomes. Across all conditions, the high CAP group had the highest mean for baseline testing, but also demonstrated an increase in movement time across the study. For initiation time, the high CAP group showed the highest mean baseline time across all conditions, but also faster decreasing rates of change over time. With progress to diagnosis, participants may increasingly use compensatory strategies, as evidenced by faster initiation. However, this occurred in conjunction with slowed execution times, suggesting a decline in effectively accessing control processes required to translate movement into effective execution.

  3. Language impairment in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mariana Jardim Azambuja

    2012-06-01

    Full Text Available Language alterations in Huntington's disease (HD are reported, but their nature and correlation with other cognitive impairments are still under investigation. This study aimed to characterize the language disturbances in HD and to correlate them to motor and cognitive aspects of the disease. We studied 23 HD patients and 23 controls, matched for age and schooling, using the Boston Diagnostic Aphasia Examination, Boston Naming Test, the Token Test, Animal fluency, Action fluency, FAS-COWA, the Symbol Digit Modalities Test, the Stroop Test and the Hooper Visual Organization Test (HVOT. HD patients performed poorer in verbal fluency (p<0.0001, oral comprehension (p<0.0001, repetition (p<0.0001, oral agility (p<0.0001, reading comprehension (p=0.034 and narrative writing (p<0.0001. There was a moderate correlation between the Expressive Component and Language Competency Indexes and the HVOT (r=0.519, p=0.011 and r=0.450, p=0.031, respectively. Language alterations in HD seem to reflect a derangement in both frontostriatal and frontotemporal regions.

  4. Mapping energy poverty in Huntington, West Virginia

    Science.gov (United States)

    Callicoat, Elizabeth Anne

    Energy poverty is a growing phenomenon culminating from the combination of low to mid household income, deteriorating housing structures and rising household energy costs. Energy prices are increasing for all households, but the burden is proportionally larger for those with low to mid income. These groups must sacrifice to afford energy, and are often unable or do not have the autonomy to make structural improvements, especially if they rent their home. Data on residential dwellings from the Cabell County Tax Assessor's Office was used within a geographic information system to map where energy poverty likely exists within the city limits of Huntington, WV. It was found that one fifth of Huntington households are at a high risk of energy poverty, primarily located across the northern section of the city and in the center, surrounding Marshall University, Downtown and Cabell Huntington Hospital.

  5. Unusual early-onset Huntingtons disease.

    Science.gov (United States)

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  6. Development of biomarkers for Huntington's disease.

    Science.gov (United States)

    Weir, David W; Sturrock, Aaron; Leavitt, Blair R

    2011-06-01

    Huntington's disease is an autosomal dominant, progressive neurodegenerative disorder, for which there is no disease-modifying treatment. By use of predictive genetic testing, it is possible to identify individuals who carry the gene defect before the onset of symptoms, providing a window of opportunity for intervention aimed at preventing or delaying disease onset. However, without robust and practical measures of disease progression (ie, biomarkers), the efficacy of therapeutic interventions in this premanifest Huntington's disease population cannot be readily assessed. Current progress in the development of biomarkers might enable evaluation of disease progression in individuals at the premanifest stage of the disease; these biomarkers could be useful in defining endpoints in clinical trials in this population. Clinical, cognitive, neuroimaging, and biochemical biomarkers are being investigated for their potential in clinical use and their value in the development of future treatments for patients with Huntington's disease.

  7. Monkey hybrid stem cells develop cellular features of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Lorthongpanich Chanchao

    2010-02-01

    Full Text Available Abstract Background Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research. Results To test this hypothesis, a pluripotent Huntington's disease monkey hybrid cell line (TrES1 was established from a tetraploid Huntington's disease monkey blastocyst generated by the fusion of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological features that paralleled neural development. It expressed mutant huntingtin and stem cell markers, was capable of differentiating to neural cells, and developed teratoma in severely compromised immune deficient (SCID mice. Interestingly, the expression of mutant htt, the accumulation of oligomeric mutant htt and the formation of intranuclear inclusions paralleled neural development in vitro , and even mutant htt was ubiquitously expressed. This suggests the development of Huntington's disease cellular features is influenced by neural developmental events. Conclusions Huntington's disease cellular features is influenced by neural developmental events. These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis.

  8. Maternal transmission in sporadic Huntington's disease.

    OpenAIRE

    Sánchez, A; Milà, M.; Castellví-Bel, S; Rosich, M; Jiménez, D; Badenas, C.; ESTIVILL, X.

    1997-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disorder caused by the expansion of a (CAG)n repeat in the IT15 gene. Three per cent of cases are sporadic and in those in which family studies have been performed, the origin of the mutation was always paternal. The first sporadic case of Huntington's disease is presented in which a premutated maternal allele of 37 CAG repeats was transmitted expanded to the proband (43 CAG repeats). Molecular analysis of the IT15 gene is extrem...

  9. Pathogenic insights from Huntington's disease-like 2 and other Huntington's disease genocopies.

    Science.gov (United States)

    Margolis, Russell L; Rudnicki, Dobrila D

    2016-12-01

    Huntington's disease-like 2 (HDL2) is a rare, progressive, autosomal dominant neurodegenerative disorder that genetically, clinically, and pathologically closely resembles Huntington's disease. We review HDL2 pathogenic mechanisms and examine the implications of these mechanisms for Huntington's disease and related diseases. HDL2 is caused by a CTG/CAG repeat expansion in junctophilin-3. Available data from cell and animal models and human brain suggest that HDL2 is a complex disease in which transcripts and proteins expressed bidirectionally from the junctophilin-3 locus contribute to pathogenesis through both gain-and loss-of-function mechanisms. Recent advances indicate that the pathogenesis of Huntington's disease is equally complex, despite the emphasis on toxic gain-of-function properties of the mutant huntingtin protein. Studies examining in parallel the genetic, clinical, neuropathological, and mechanistic similarities between Huntington's disease and HDL2 have begun to identify points of convergence between the pathogenic pathways of the two diseases. Comparisons to other diseases that are phenotypically or genetically related to Huntington's disease and HDL2 will likely reveal additional common pathways. The ultimate goal is to identify shared therapeutic targets and eventually develop therapies that may, at least in part, be effective across multiple similar rare diseases, an essential approach given the scarcity of resources for basic and translational research.

  10. Impaired motor speech performance in Huntington's disease.

    Science.gov (United States)

    Skodda, Sabine; Schlegel, Uwe; Hoffmann, Rainer; Saft, Carsten

    2014-04-01

    Dysarthria is a common symptom of Huntington's disease and has been reported, besides other features, to be characterized by alterations of speech rate and regularity. However, data on the specific pattern of motor speech impairment and their relationship to other motor and neuropsychological symptoms are sparse. Therefore, the aim of the present study was to describe and objectively analyse different speech parameters with special emphasis on the aspect of speech timing of connected speech and non-speech verbal utterances. 21 patients with manifest Huntington's disease and 21 age- and gender-matched healthy controls had to perform a reading task and several syllable repetition tasks. Computerized acoustic analysis of different variables for the measurement of speech rate and regularity generated a typical pattern of impaired motor speech performance with a reduction of speech rate, an increase of pauses and a marked disability to steadily repeat single syllables. Abnormalities of speech parameters were more pronounced in the subgroup of patients with Huntington's disease receiving antidopaminergic medication, but were also present in the drug-naïve patients. Speech rate related to connected speech and parameters of syllable repetition showed correlations to overall motor impairment, capacity of tapping in a quantitative motor assessment and some score of cognitive function. After these preliminary data, further investigations on patients in different stages of disease are warranted to survey if the analysis of speech and non-speech verbal utterances might be a helpful additional tool for the monitoring of functional disability in Huntington's disease.

  11. Destination and source memory in Huntington's disease

    NARCIS (Netherlands)

    El Haj, M.; Caillaud, M.; Verny, C.; Fasotti, L.; Allain, P.

    2016-01-01

    Destination memory refers to the recall of the destination of previously relayed information, and source memory refers to the recollection of the origin of received information. We compared both memory systems in Huntington's disease (HD) participants. For this, HD participants and healthy adults

  12. Kas Huntington oli prohvet? / Priit Simson

    Index Scriptorium Estoniae

    Simson Priit, 1977-

    2008-01-01

    Autor käsitleb Samuel Huntingtoni teese ning leiab, et tegelikult Huntington ei pakkunud õigustust islamiriikide ründamisele, vaid pigem hoiatas tsivilisatsioonide siseasjusse sekkumise, tekkida võiva ahelreaktsiooni eest, kus üks tsivilisatsiooni liige tõmbab sõtta ka teise

  13. Wearable Sensors in Huntington Disease: A Pilot Study.

    Science.gov (United States)

    Andrzejewski, Kelly L; Dowling, Ariel V; Stamler, David; Felong, Timothy J; Harris, Denzil A; Wong, Cynthia; Cai, Hang; Reilmann, Ralf; Little, Max A; Gwin, Joseph T; Biglan, Kevin M; Dorsey, E Ray

    2016-06-18

    The Unified Huntington's Disease Rating Scale (UHDRS) is the principal means of assessing motor impairment in Huntington disease but is subjective and generally limited to in-clinic assessments. To evaluate the feasibility and ability of wearable sensors to measure motor impairment in individuals with Huntington disease in the clinic and at home. Participants with Huntington disease and controls were asked to wear five accelerometer-based sensors attached to the chest and each limb for standardized, in-clinic assessments and for one day at home. A second chest sensor was worn for six additional days at home. Gait measures were compared between controls, participants with Huntington disease, and participants with Huntington disease grouped by UHDRS total motor score using Cohen's d values. Fifteen individuals with Huntington disease and five controls completed the study. Sensor data were successfully captured from 18 of the 20 participants at home. In the clinic, the standard deviation of step time (time between consecutive steps) was increased in Huntington disease (p Huntington disease, and participants with Huntington disease grouped by motor impairment.

  14. Silencing Huntington's chorea: Is RNA Interference a Potential Cure?

    Directory of Open Access Journals (Sweden)

    Gerlinde A. Metz

    2006-01-01

    Full Text Available In 1872, George Huntington described Huntington's disease as characterized by motor, cognitive and psychiatric impairments. Huntington's disease is a dominant and autosomal mutation on chromosome 4 featuring the insertion of numerous CAG repeats. CAG codes for the amino acid, glutmanine that forms part of the Huntingtin protein (htt. Excess glutamine attachments make htt prone to accumulate in neurons. Three genes can be considered when developing therapies for Huntington's disease. They include targeting the symptoms of the disease, the progression of the disease and the cause of the disease. By using RNA interference (RNAi, the cause of the disease can be targeted. RNAi is a method that could potentially silence the formation of abnormal htt. This paper will discuss how RNAi could potentially cure Huntington's disease, by describing the genetic and proteinomic basis of Huntington's disease, the function of RNAi in Huntington's disease and the problems of benefits of RNAi. Preliminary work using RNAi in transgenic mice has shown a decrease in the behavioural expression of the mutant Huntington gene. There are several limitations associated with using RNAi as a gene therapy. For example, the effects of RNAi are short lived. A transposition system such as Sleeping Beauty can be used to increase the integration of the gene, however, for patients who currently have Huntington's disease, RNAi may potentially be used in combination with drugs or other treatments to target both symptoms and the underlying cause of Huntington's disease. This combination could eventually alleviate many painful symptoms associated with Huntington's disease and could even stop the progressive neurodegeneration of Huntington's disease. This review concludes that a substantial amount of new research is still necessary before RNAi is directly applicable to human patients with Huntington's disease.

  15. A Cabinet of Mathematical Curiosities at Teachers College: David Eugene Smith's Collection

    Science.gov (United States)

    Murray, Diane R.

    2012-01-01

    This dissertation is a history of David Eugene Smith's collection of historical books, manuscripts, portraits, and instruments related to mathematics. The study analyzes surviving documents, images, objects, college announcements and catalogs, and secondary sources related to Smith's collection. David Eugene Smith (1860-1944) travelled…

  16. Eugenics and education: Implications of ideology, memory, and history for education in the United States

    Science.gov (United States)

    Winfield, Ann Gibson

    Eugenics has been variously described "as an ideal, as a doctrine, as a science (applied human genetics), as a set of practices (ranging from birth control to euthanasia), and as a social movement" (Paul 1998 p. 95). "Race Suicide" (Roosevelt 1905) and the ensuing national phobia regarding the "children of worm eaten stock" (Bobbitt 1909) prefaced an era of eugenic ideology whose influence on education has been largely ignored until recently. Using the concept of collective memory, I examine the eugenics movement, its progressive context, and its influence on the aims, policy and practice of education. Specifically, this study examines the ideology of eugenics as a specific category and set of distinctions, and the role of collective memory in providing the mechanism whereby eugenic ideology may shape and fashion interpretation and action in current educational practice. The formation of education as a distinct academic discipline, the eugenics movement, and the Progressive era coalesced during the first decades of the twentieth century to form what has turned out to be a lasting alliance. This alliance has had a profound impact on public perception of the role of schools, how students are classified and sorted, degrees and definitions of intelligence, attitudes and beliefs surrounding multiculturalism and a host of heretofore unexplored ramifications. My research is primarily historical and theoretical and uses those material and media cultural artifacts generated by the eugenics movement to explore the relationship between eugenic ideology and the institution of education.

  17. Resistance in School and Society: Public and Pedagogical Debates about Eugenics, 1900-1947.

    Science.gov (United States)

    Selden, Steven

    1988-01-01

    This article reviews positions of scientists, educators and publicists who resisted eugenics and determinism. The nature nurture controversy is discussed, as well as the impact of eugenics on American classrooms. Specific attention is given to four resisters: Dewey, Bagley, Jennings, and Lippmann. (IAH)

  18. Science and Society in the Eugenic Thought of H. J. Muller

    Science.gov (United States)

    Allen, Garland E.

    1970-01-01

    Traces the growth of theories of eugenics during the twentieth century, focussing on the work of H. J. Muller. Concludes that "Muller's lasting contribution was to write the hereditarian attitudes associated with traditional eugenics and the environmentalist's viewpoint associated with modern sociology to obtain a humane and reasoned approach to…

  19. A Metabolic Study of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Rajasree Nambron

    Full Text Available Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III and controls.Control (n = 15, premanifest (n = 14 and stage II/III (n = 13 participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a, fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine there is a suggestion (p values between 0.02 and 0.05 that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that

  20. Eugenics, sterilization, and historical memory in the United States.

    Science.gov (United States)

    Stern, Alexandra Minna

    2016-12-01

    From the 1920s to the 1950s, California sterilized approximately 20,000 people in state homes and hospitals based on a eugenic law that authorized medical superintendents to perform reproductive surgeries on patients deemed unfit and "suffering from a mental affliction likely to be inherited." Working with a unique resource - a dataset created from 19,000 sterilization recommendations - my team and I have reconstructed patterns and experiences of institutionalization of sterilizations. This article presents several of our important initial findings related to ethnic and gender bias in sterilization policies, and reflects on the relevance of the history for contemporary issues in genomics and social justice.

  1. The Emergence of Genetic Counseling in Sweden: Examples from Eugenics and Medical Genetics.

    Science.gov (United States)

    Björkman, Maria

    2015-09-01

    This paper examines the intertwined relations between eugenics and medical genetics from a Swedish perspective in the 1940s and 1950s. The Swedish case shows that a rudimentary form of genetic counseling emerged within eugenic practices in the applications of the Swedish Sterilization Act of 1941, here analyzed from the phenomenon of "heredophobia" (ärftlighetsskräck). At the same time genetic counseling also existed outside eugenic practices, within the discipline of medical genetics. The paper argues that a demand for genetic counseling increased in the 1940s and 1950s in response to a sense of reproductive responsibility engendered by earlier eugenic discourse. The paper also questions the claim made by theoreticians of biopolitics that biological citizens have emerged only during the last decades, especially in neoliberal societies. From the Swedish case it is possible to argue that this had already happened earlier in relation to the proliferation of various aspects of eugenics to the public.

  2. Molecular diagnostic analysis for Huntington's disease: a prospective evaluation.

    OpenAIRE

    MacMillan, J C; Davies, P.; Harper, P S

    1995-01-01

    The availability of mutation analysis for the CAG repeat expansion associated with Huntington's disease has prompted clinicians in various specialties to request testing of samples from patients displaying clinical features that might be attributable to Huntington's disease. A series of 38 cases presenting with clinical features thought possibly to be due to Huntington's disease were analysed prospectively. In 53% of such cases presenting initially with chorea and 62.5% with psychiatric sympt...

  3. Beyond eugenics: the forgotten scandal of hybridizing humans and apes.

    Science.gov (United States)

    Etkind, Alexander

    2008-06-01

    This paper examines the available evidence on one of the most radical ideas in the history of eugenics and utopianism. In the mid-1920s, the zoology professor Ilia Ivanov submitted to the Soviet government a project for hybridizing humans and apes by means of artificial insemination. He received substantial financing and organized expeditions to Africa to catch apes for his experiments. His project caused an international sensation. The American Association for the Advancement of Atheism announced its fund-raising campaign to support Ivanov's project but gave it a scandalously racist interpretation. Ivanov's own motivation remained unclear, as did the motivation of those in the Bolshevik government who supported Ivanov until his arrest in 1930. This paper discusses three hypothetical reasons for Ivanov's adventure: first, hybridization between humans and apes, should it be successful, would support the atheist propaganda of the Bolsheviks; second, regardless of the success of hybridization, Ivanov would catch and bring to Russia apes, which were necessary for the rejuvenation programs that were fashionable among the Bolshevik elite; and third, hybridization, should it be successful, would pave the way to the New Socialist Man whose 'construction by scientific means' was the official purpose of the Bolsheviks. Ivanov's ideas were arguably important for the American proponent of reform eugenics, Herman Muller, and for the Soviet anthropologist Boris Porshnev.

  4. Normal CAG and CCG repeats in the Huntington`s disease genes of Parkinson`s disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Rubinsztein, D.C.; Leggo, J.; Barton, D.E. [Cambridge Univ. (United Kingdom)] [and others

    1995-04-24

    The clinical features of Parkinson`s disease, particularly rigidity and bradykinesia and occasionally tremor, are seen in juvenile-onset Huntington`s disease. Therefore, the CAG and CCG repeats in the Huntington`s disease gene were investigated in 45 Parkinson`s disease patients and compared to 40 control individuals. All of the Parkinson`s disease chromosomes fell within the normal size ranges. In addition, the distributions of the two repeats in the Parkinson`s disease patients did not differ significantly from those of the control population. Therefore, abnormalities of these trinucleotide repeats in the Huntington`s disease gene are not likely to contribute to the pathogenesis of Parkinson`s disease. 12 refs., 2 figs.

  5. Sterilization and birth control in the shadow of eugenics: married, middle-class women in Alberta, 1930-1960s.

    Science.gov (United States)

    Dyck, Erika

    2014-01-01

    The history of eugenic sterilization connotes draconian images of coerced and involuntary procedures robbing men and women of their reproductive health. While eugenics programs often fit this characterization, there is another, smaller, and less obvious legacy of eugenics that arguably contributed to a more empowering image of reproductive health. Sexual sterilization surgeries as a form of contraception began to gather momentum alongside eugenics programs in the middle of the 20th century and experiences among prairie women serve as an illustrative example. Alberta maintained its eugenics program from 1929 to 1972 and engaged in thousands of eugenic sterilizations, but by the 1940s middle-class married women pressured their Albertan physicians to provide them with sterilization surgeries to control fertility, as a matter of choice. The multiple meanings and motivations behind this surgery introduced a moral quandary for physicians, which encourages medical historians to revisit the history of eugenics and its relationship to the contemporaneous birth control movement.

  6. The strength of a loosely defined movement: eugenics and medicine in imperial Russia.

    Science.gov (United States)

    Krementsov, Nikolai

    2015-01-01

    This essay examines the 'infiltration' of eugenics into Russian medical discourse during the formation of the eugenics movement in western Europe and North America in 1900-17. It describes the efforts of two Russian physicians, the bacteriologist and hygienist Nikolai Gamaleia (1859-1949) and the psychiatrist Tikhon Iudin (1879-1949), to introduce eugenics to the Russian medical community, analysing in detail what attracted these representatives of two different medical specialties to eugenic ideas, ideals, and policies advocated by their western colleagues. On the basis of a close examination of the similarities and differences in Gamaleia's and Iudin's attitudes to eugenics, the essay argues that lack of cohesiveness gave the early eugenics movement a unique strength. The loose mix of widely varying ideas, ideals, methods, policies, activities and proposals covered by the umbrella of eugenics offered to a variety of educated professionals in Russia and elsewhere the possibility of choosing, adopting and adapting particular elements to their own national, professional, institutional and disciplinary contexts, interests and agendas.

  7. Confronting the stigma of eugenics: genetics, demography and the problems of population.

    Science.gov (United States)

    Ramsden, Edmund

    2009-12-01

    Building upon the work of Thomas Gieryn and Erving Goffman, this paper will explore how the concepts of stigma and boundary work can be usefully applied to history of population science. Having been closely aligned to eugenics in the early 20th century, from the 1930s both demographers and geneticists began to establish a boundary between their own disciplines and eugenic ideology. The eugenics movement responded to this process of stigmatization. Through strategies defined by Goffman as 'disclosure' and 'concealment', stigma was managed, and a limited space for eugenics was retained in science and policy. Yet by the 1960s, a revitalized eugenics movement was bringing leading social and biological scientists together through the study of the genetic demography of characteristics such as intelligence. The success of this programme of 'stigma transformation' resulted from its ability to allow geneticists and demographers to conceive of eugenic improvement in ways that seemed consistent with the ideals of individuality, diversity and liberty. In doing so, it provided them with an alternative, and a challenge, to more radical and controversial programmes to realize an optimal genotype and population. The processes of stigma attribution and management are, however, ongoing, and since the rise of the nature-nurture controversy in the 1970s, the use of eugenics as a 'stigma symbol' has prevailed.

  8. The Characteristics of Korea’s Eugenic Movement in the Colonial Period Represented in the Bulletin, Woosaeng

    Directory of Open Access Journals (Sweden)

    SHIN Young-Jeon

    2006-12-01

    Full Text Available Woosaeng, meaning "eugenic" in Korean, was a bulletin published by the Korean Eugenics Association in 1934. With detailed review of the contributors to Woosaeng, its publication background and the contents, the characteristics of Korea's eugenic movement in 1930's and its historical implications of public health are studied. Intellectuals, especially some medical doctors educated abroad, played the pivotal role in publishing Woosaeng and leading the eugenic movement in 1930's. Lee Gabsoo, a medical doctor educated in Germany, is identified as the key person in the whole process. Most of contributors including Lee considered medical science, especially genetics, as the foundation of eugenics and had strong confidence in their belief. A variety of eugenic movements and activities, including enactment of the national eugenic law around the world, was introduced to the Korean society through Woosaeng and it reinforced the eugenic activities in Korea. Although colonial Korea at the time was being heavily imposed with Japan's culture, the eugenic activities were also influenced by Germany and the US through the contributors educated oversea. The overall content and tone of Woosaeng, revealed its 'soft' characteristics, yet it also implied its vulnerability to 'hard' eugenics. Korea's eugenic movement around Woosaeng faces turnover right before 'The Go Fast Imperialism' period. The high class intellectuals tamed by Japanese colonial paradigm in eugenics took the lead and ended up having a significant influence upon the activities around Woosaeng. And even after Koreans' liberation from Japan's annexation, they were able to retain their influence in public health area in the Korean society. In summary, Woosaeng guided us to understand the characteristics of Korea's eugenic movement in 1930's and the historical context of public health in Korea. Moreover, Woosaeng provided a large amount of information about the eugenic movements around the world as well

  9. Large genetic animal models of Huntington's Disease.

    Science.gov (United States)

    Morton, A Jennifer; Howland, David S

    2013-01-01

    The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research.

  10. Revisiting the neuropsychiatry of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Antonio Lucio Teixeira

    Full Text Available ABSTRACT Huntington's disease (HD is an autosomal dominant neurodegenerative disease classified under the choreas. Besides motor symptoms, HD is marked by cognitive and behavioral symptoms, impacting patients' functional capacity. The progression of cognitive impairment and neuropsychiatric symptoms occur in parallel with neurodegeneration. The nature of these symptoms is very dynamic, and the major clinical challenges include executive dysfunction, apathy, depression and irritability. Herein, we provide a focused updated review on the cognitive and psychiatric features of HD.

  11. [Sporadic juvenile forms of Huntington's chorea].

    Science.gov (United States)

    Zinchenko, A P; Goncharov, V D; Burtianskii, D L; Zakhar'ev, Iu M

    1980-01-01

    Six patients with Huntington's chorea in the age of 15-24 years old, suffered from diffusive choreic hyperkynesis with slowly progressive dementia. The development of this disease in childhood and adolescence was atypical, as nobody in the family and in kin sufferred from it and it was difficult to diagnose the disease. Recognition of the disease was promoted by pneumoencephalography, electromyography and memory investigation.

  12. [Constant or break? On the relations between human genetics and eugenics in the Twentieth Century].

    Science.gov (United States)

    Germann, Pascal

    2015-07-01

    The history of human genetics has been a neglected topic in history of science and medicine for a long time. Only recently, have medical historians begun to pay more attention to the history of human heredity. An important research question deals with the interconnections between human genetics and eugenics. This paper addresses this question: By focusing on a Swiss case study, the investigation of the heredity of goiter, I will argue that there existed close but also ambiguous relations between heredity research and eugenics in the twentieth century. Studies on human heredity often produced evidence that challenged eugenic aims and ideas. Concurrently, however, these studies fostered visions of genetic improvement of human populations.

  13. Eugenics--a side effect of progressivism? analysis of the role of scientific and medical elites in the rise and fall of eugenics in pre-war Poland.

    Science.gov (United States)

    Blach, Olga

    2010-06-01

    The eminent geneticist, Benno Muller-Hill, described eugenics as"explosive mixture between something we might call hard science, that is, human genetics, and the sphere of political action. On the one hand, geneticists needed politicians to implement their ideas. On the other hand, Hitler and the Nazis needed scientists who could say that anti-Semitism has scientific theoretical foundations." For some Polish eugenicists, the Third Reich was not the home of the Nuremberg Laws, but a country that "boldly embarked on racial hygiene." This enthusiastic attitude of Polish intellectual circles towards Nazi eugenic laws was characteristic of the status of pre-war science in Poland, which in many areas, such as anthropology and psychiatry, remained strongly influenced by the paradigm of German science. While the professional and scientific context of the day promoted eugenic and racist ideas within the framework of the academic milieu and the curriculum of the medical and scientific community, eugenicists in Poland tended to refrain from anti-Semitic and racist phraseology. Indeed, the Polish eugenic movement was class- rather than race-orientated. The hybrid language of eugenics, combining social sensitivity with repulsion and contempt for the sick and the weak, illustrated the ambiguous stance of the Polish eugenicists on politics and science in Nazi Germany, for the Third Reich provided the German eugenicists with what had always been an unfulfilled dream to the Polish eugenicists--political power and the ability to implement their ideas.

  14. Eugenics, sterilization, and historical memory in the United States

    Directory of Open Access Journals (Sweden)

    Alexandra Minna Stern

    Full Text Available Abstract From the 1920s to the 1950s, California sterilized approximately 20,000 people in state homes and hospitals based on a eugenic law that authorized medical superintendents to perform reproductive surgeries on patients deemed unfit and “suffering from a mental affliction likely to be inherited.” Working with a unique resource – a dataset created from 19,000 sterilization recommendations – my team and I have reconstructed patterns and experiences of institutionalization of sterilizations. This article presents several of our important initial findings related to ethnic and gender bias in sterilization policies, and reflects on the relevance of the history for contemporary issues in genomics and social justice.

  15. 俄罗斯杀毒大王Eugene Kaspersky

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    现在的病毒越来越厉害,给社会造成的损失也越来越大。但与此同时,这也给防病毒软件企业提供了发展的特续动力。除了赛门铁克、趋势科技等国际性厂商外,还有一个著名的厂商不能不提起,这就是俄罗斯的防毒公司Kaspersky Lab。这家公司的创始人和核心技术研究负责人就是Eugene Kaspersky,他也是俄罗斯软件业的代表人物。

  16. Altered cholesterol and fatty acid metabolism in Huntington disease.

    Science.gov (United States)

    Block, Robert C; Dorsey, E Ray; Beck, Christopher A; Brenna, J Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.

  17. Arithmetic Word-Problem-Solving in Huntington's Disease

    Science.gov (United States)

    Allain, P.; Verny, C.; Aubin, G.; Pinon, K.; Bonneau, D.; Dubas, F.; Gall, D.L.

    2005-01-01

    The purpose of this study was to examine executive functioning in patients with Huntington's disease using an arithmetic word-problem-solving task including eight solvable problems of increasing complexity and four aberrant problems. Ten patients with Huntington's disease and 12 normal control subjects matched by age and education were tested.…

  18. Comprehension of Complex Discourse in Different Stages of Huntington's Disease

    Science.gov (United States)

    Saldert, Charlotta; Fors, Angelika; Stroberg, Sofia; Hartelius, Lena

    2010-01-01

    Background: Huntington's disease not only affects motor speech control, but also may have an impact on the ability to produce and understand language in communication. Aims: The ability to comprehend basic and complex discourse was investigated in three different stages of Huntington's disease. Methods & Procedures: In this experimental group…

  19. Quality babies. China's "eugenics" guidelines are as old as civilization.

    Science.gov (United States)

    1994-01-12

    Inaccurate translations inadvertently misrepresent policy directives from China. Professional moralizers respond to the new laws with indignation. For example, an editorial in a US newspaper said that Americans objected to China's eugenic guidelines to prevent inferior quality infants. Yet, in the US and other developed countries, parents, and adult siblings do no allow their mentally retarded family members to procreate. Quiet abortions occur. In the US, deformed newborns are classified as stillborns. In the 1950s in the US, state governments allowed sterilization of handicapped people and even alcoholics. The moralizers expect China to accomplish in 10 years what developed countries did in 100 years. China has a one-child policy to which many so-called human rights advocates object. Yet, China cannot sustain a population of 2 billion with the living standards to which it aspires. Granted, however, that China does create its own image problems. It needs to invest more in public relations, maybe employ image-building professionals from the US and Europe to circumvent the unintentional use of emotionally charged, historically loaded, or inappropriate terms and, therefore, to prevent the international media from overreacting. Nevertheless, moral dilemmas do exist with eugenics policies. Genetic markers can detect chromosomal abnormalities leading to mental retardation as well as later-life abnormalities; e.g., colon cancer. Markers may perhaps someday detect a propensity to criminal behavior, homosexuality, or alcoholism. Governments could forbid all genetic testing, resulting in families accepting whatever nature sends, but with the advancement of science, this is unrealistic. If it is banned in one country, people will go to a country where it is available. Since parents in both the US and China want healthy, good-looking and intelligent children US editorialists should not moralize about China while US couples have access to the most up-to-date genetic technology.

  20. Eugenics, sexual pedagogy and social change: constructing the responsible subject of governmentality in the Spanish Second Republic.

    Science.gov (United States)

    Jiménez-Alonso, Belén

    2008-06-01

    This study focuses on eugenics in Spain, and more specifically on the 'official' eugenics whose platform was the Primeras Jornadas Eugénicas Españolas (First Spanish Eugenic Days, FSED). The aim of this paper is to relate eugenics to 'governmentality' rather than to State politics alone and to 'Latin eugenics' rather than to 'mainline eugenics'. On the one hand, the FSED were largely centred on the development of a new sexual code which would set Catholic sexual morality aside. For this reason, sexual pedagogy was one of the most relevant topics during the FSED, personal responsibility becoming the first step to social change. The concern about making people play an active role in their own self-regulation is typical of governmentality. The latter refers to societies where power is decentered and where the objective is to structure the field of action of others (the conduct of conduct). On the other hand, the FSED emphasised preventive eugenics such as welfare programmes and health campaigns rather than negative eugenics such as the sterilisation of the unfit. The situation in Spain was mirrored in countries such as Brazil, Argentina and Mexico, which allows us to think about them in terms of 'Latin eugenics' rather than 'mainline eugenics' from countries such as Great Britain, Germany and the USA.

  1. Examination of Huntington's disease in a Chinese family.

    Science.gov (United States)

    Yu, Mingxia; Li, Xiaogai; Wu, Sanyun; Shen, Ji; Tu, Jiancheng

    2014-02-15

    We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington's disease. Among 17 family members across three generations, four patients (II2, II6, III5, and III9) show typical Huntington's disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members (II2, II6, and III5). Moreover, genetic analysis identified abnormally amplified CAG sequence repeats (> 40) in two members (III5 and III9). Among borderline cases, with clinical symptoms and brain imaging features of Huntington's disease, two cases were identified (II2 and II6), but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington's disease. Our findings suggest that clinical diagnosis of Huntington's disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis.

  2. Eesti aja arhitektuur : Eugen Habermann 125. Herbert Johanson 125 / Ike Volkov

    Index Scriptorium Estoniae

    Volkov, Ike, 1951-

    2010-01-01

    Näitus Eesti Arhitektuurimuuseumis 04. 12. 2009-07. 03. 2010. Eugen Habermannist ja Herbert Johansonist, nende tegevusest ja loomingust. Selle aja ja praegustest probleemidest ning lahendusvõimalustest

  3. Eesti aja arhitektuur : Eugen Habermann 125. Herbert Johanson 125 / Ike Volkov

    Index Scriptorium Estoniae

    Volkov, Ike, 1951-

    2010-01-01

    Näitus Eesti Arhitektuurimuuseumis 04. 12. 2009-07. 03. 2010. Eugen Habermannist ja Herbert Johansonist, nende tegevusest ja loomingust. Selle aja ja praegustest probleemidest ning lahendusvõimalustest

  4. From nation to family: two careers in the recasting of eugenics.

    Science.gov (United States)

    Slavishak, Edward

    2009-01-01

    By examining the professional lives of two popularizers of eugenic thought from the 1910s to the 1940s, this study illustrates the broader change from "mainline" to "reform" eugenics in the United States. Roswell Hill Johnson's university teaching, laboratory research, and later marriage counseling work contrasted greatly with George Seibel's forays into eugenic theater moral reform, and mass physical fitness movements. Yet both men shifted from a strict position of mandating other people's behavior in the name of national health and racial integrity to a more therapeutic stance that cast individual decisions in the context of managed family life. This study shows that for some, the transformation of eugenics in the 1930s meant adapting the traditional focus on superiority, inferiority, and reproduction by design to the language of a commercial marketplace.

  5. Communication and Huntington's Disease: Qualitative Interviews and Focus Groups with Persons with Huntington's Disease, Family Members, and Carers

    Science.gov (United States)

    Hartelius, Lena; Jonsson, Maria; Rickeberg, Anneli; Laakso, Katja

    2010-01-01

    Background: As an effect of the cognitive, emotional and motor symptoms associated with Huntington's disease, communicative interaction is often dramatically changed. No study has previously included the subjective reports on this subject from individuals with Huntington's disease. Aims: To explore the qualitative aspects of how communication is…

  6. 3-NP-induced neurodegeneration studies in experimental models of Huntington's disease : apoptosis in Huntington's disease

    NARCIS (Netherlands)

    Vis, Johanna Catharina

    2005-01-01

    This thesis investigates the possible role of apoptosis, or programmed cell death, in Huntington's disease (HD). HD is caused by an expanded CAG repeat in the N-terminal region of the huntingtin protein leading to specific neostriatal neurodegeneration. The sequence of events that leads to this sele

  7. An Interview with Dr. Eugene Garfield (Chinese Version)%Eugene Garfield博士访谈(译文)

    Institute of Scientific and Technical Information of China (English)

    任胜利

    2005-01-01

    Eugene Garfield博士是美国著名文献信息检索专家,也是科学引文索引(SCI)之父。关于他的生平及传奇经历,本刊在今年卷首新开辟的“人物”专栏已有详细介绍(见2005年第5卷第1期:79~81)。本文源自对Garfield博士在“A Year of Celebration & Century of Science Launch”的访谈,编者希望能对有志于推进中国科技论文和期刊发展的作者、科技期刊从业者和管理者有所启示。

  8. When Harvard said no to eugenics: the J. Ewing Mears Bequest, 1927.

    Science.gov (United States)

    Lombardo, Paul A

    2014-01-01

    James Ewing Mears (1838-1919) was a founding member of the Philadelphia Academy of Surgery. His 1910 book, The Problem of Race Betterment, laid the groundwork for later authors to explore the uses of surgical sterilization as a eugenic measure. Mears left $60,000 in his will to Harvard University to support the teaching of eugenics. Although numerous eugenic activists were on the Harvard faculty, and two of its Presidents were also associated with the eugenics movement, Harvard refused the Mears gift. The bequest was eventually awarded to Jefferson Medical College in Philadelphia. This article explains why Harvard turned its back on a donation that would have supported instruction in a popular subject. Harvard's decision illustrates the range of opinion that existed on the efficacy of eugenic sterilization at the time. The Mears case also highlights a powerful irony: the same week Harvard turned down the Mears legacy, the U.S. Supreme Court endorsed eugenic sterilization in the landmark case of Buck v. Bell. Justice Oliver Wendell Holmes, Jr., graduate of Harvard and former member of its law faculty wrote the opinion in that case, including the famous conclusion: "Three generations of imbeciles are enough."

  9. Eugenic and sexual folklores and the castration of sex offenders in the Netherlands (1938-1968).

    Science.gov (United States)

    van der Meer, Theo

    2008-06-01

    This contribution questions the positive/negative eugenics dichotomy that typifies the historiography on the eugenic movement in the Netherlands and the claim that this movement was mostly marginal because only positive eugenics was pursued. From 1938 to 1968 in the Netherlands, after a decade of debates, 400 sex offenders who had been committed to asylums for the criminally insane were 'voluntarily' and 'therapeutically' castrated. For political reasons debates on castration, meant to create consensus, eliminated any reference to or connotation with eugenics, yet these policies were unthinkable without them. This article shows that thinking about social and sexual problems and their solutions in the 1930s were permeated by eugenic folklore which in turn was informed by sexual folklore. Both eugenic and sexual lore, as common sense, or as ways of knowing, were about individual and collective loss of self control which was referred to with a catch-all phrase: 'hypersexuality'. Although sexual classifications used in diagnosing sex offenders suggested the existence of discrete sexual categories, homosexuality for instance was not seen as a sexual alternative or as an identity but as the extent to which an offender suffered from a form of hypersexuality that threatened the fabric of society.

  10. Characterization of conservative somatic instability of the CAG repeat region in Huntington`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, F.V.; Calikoglu, A.S.; Whetsell, L.H. [H.A. Chapman Research Institute of Medical Genetics, Tulsa, OK (United States)

    1994-09-01

    Instability and enlargement of a CAG repeat region at the beginning of the huntingtin gene (IT-15) has been linked with Huntington`s disease. The CAG repeat size shows a highly significant correlation with age-of-onset of clinicial features in individuals with 40 or more repeats who have Huntington disease. The clinical status of nonsymptomatic individuals with 30 to 39 CAG repeats is considered ambiguous. In order to define more carefully the nature of the HD expansion instability, we examined patients in our HD population using a discriminating fluorescence-based PCR approach. The degree of somatic mutation increases with both earlier age of onset and the size of the inherited allele. A single prominent band one repeat larger than the index peak was typical in individuals with 40-41 CAG repeats. Three to four larger bands are typically discerned in individuals with 50 or more repeats. In an extreme example, an individual with approximately 95 repeats had at least 8 prominent bands. Plotting the degree of somatic mutation relative to the size of the HD allele shows somatic mutation activity increases with size. By this approach 40-60% of the alleles in a 40-41 CAG repeat HD loci is represented in the primary allele. In contrast, the primary allele represents a relatively minor proportion of the total alleles for expansions greater than 50 CAG repeats (10-20%). The limited range of somatic mutation suggest that the instability is restricted to very early stages of embryogenesis before tissue development diverges or that persistent somatic instability occurs at a slow rate. Therefore, the properties of somatic instability in Huntington`s disease have aspects that are both in common but also different from that found in other trinucleotide repeat expanding diseases such as myotonic muscular dystrophy and fragile X syndrome.

  11. Eugenics discourse and racial improvement in Republican China (1911-1949).

    Science.gov (United States)

    Sihn, Kyu-hwan

    2010-12-31

    This paper aimed to examine the advent of eugenics and its characteristics in republican China. Although eugenics was introduced into China as a discourse to preserve and improve race by the 1898 reformers such as Yan Fu (1854-1921) and Yi Nai (1875-?) in the late imperial period, it was not until the republican period that eugenics discourse started to combine with the discourse and movement related to social reform. The May 4th intellectuals put forward criticisms of Confucian patriarchy, propagating science and democracy. They pointed out that the large family system was a source of every social evil, and argued the need for a small family system based on monogamy. The aim of the small family system was to improve both the race and the environment. Such thinkers argued that freedom of love and the liberation of individuality were necessary for this end. Zhou Jianren (1888-1984), Lu Xun's youngest brother and representative eugenicist in the May 4th period, combined eugenics with freedom of love and the liberation of individuality. Pan Guangdan (1899-1967) and Zhou Jianren debated the eugenics controversy in the 1920s. They raised the freedom of love and the liberation of individuality as central issues related to the eugenics controversy. The eugenics debate was developed into the controversy between biological determinism and environmentalism in the late 1920s. However, these issues did not continue to be brought up in the 1930s. The main issues concerning the eugenics controversy in the 1930s were cultural identity and the population problem. Particularly in the 1930s, the scope of birth control as the solution to the population problem was extended from the individual person and family to nation and race. For eugenicists like Pan Guangdan, birth control violated the aim of eugenics and brought about the degeneration of the race. However, such theorists did not deny the value of birth control itself. The supporters of birth control thought that selecting

  12. The meaning of eugenics: reflections on the government of genetic knowledge in the past and the present.

    Science.gov (United States)

    Koch, Lene

    2004-09-01

    The recent development of molecular genetics has created concern that society may experience a new eugenics. Notions about eugenics and what took place in the 1930s and 1940s are actively shaping questions about which uses of new genetics should be considered illegitimate. Drawing upon a body of historiographical literature on Scandinavian eugenics, this paper argues that the dominant view of eugenics as morally and scientifically illegitimate is not tenable when it comes to the uses of compulsion, political motivation, and scientific acceptability. In spite of a general condemnation of eugenics, health authorities today are trying to prevent individuals with deviant behavior from reproducing or at least from rearing children. This may not be argued with reference to the risk of transmitting defective genes, but rather the risk of producing undesirable social problems. Drawing on a Foucauldian approach, the paper concludes that eugenics and new genetics should be seen as two historically specific forms of biopower.

  13. Altered Fractional Anisotropy in Early Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Silky Singh

    2013-02-01

    Full Text Available Huntington's disease (HD is a dominantly inherited neurodegenerative disease best known for chorea. The disorder includes numerous other clinical features including mood disorder, eye movement abnormalities, cognitive disturbance, pendular knee reflexes, motor impersistence, and postural instability. We describe a mild case of HD early in the disease course with depression and subtle neurological manifestations. In addition, we review MRI and diffusion tensor imaging features in this patient. The bicaudate ratio, a measure of caudate atrophy, was increased. Fractional anisotropy values of the bilateral caudate and putamen were increased, signifying neurodegeneration of these structures in HD.

  14. Huntingtin processing in pathogenesis of Huntington disease

    Institute of Scientific and Technical Information of China (English)

    Zhenghong QIN; Zhenlun GU

    2004-01-01

    Huntington's disease (HD) is caused by an expansion of the polyglutamine tract in the protein named huntingtin.The expansion of polyglutamine tract induces selective degeneration of striatal projection neurons and cortical pyramidal neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and cytoplasmic aggregates in association with other cellular proteins in vulnerable neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent. These pathological features are related to protein misfolding and impairments in protein processing and degradation in neurons. This review focused on the role of proteases in huntingtin cleavage and degradation and the contribution of altered processing of mutant huntingtin to HD pathogenesis.

  15. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington's disease.

    Science.gov (United States)

    Paul, Bindu D; Sbodio, Juan I; Xu, Risheng; Vandiver, M Scott; Cha, Jiyoung Y; Snowman, Adele M; Snyder, Solomon H

    2014-05-01

    Huntington's disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes. Huntington's disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington's disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity. Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine γ-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington's disease tissues, which may mediate Huntington's disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington's disease tissues and in intact mouse models of Huntington's disease, suggesting therapeutic potential.

  16. Unawareness of motor phenoconversion in Huntington disease.

    Science.gov (United States)

    McCusker, Elizabeth A; Gunn, David G; Epping, Eric A; Loy, Clement T; Radford, Kylie; Griffith, Jane; Mills, James A; Long, Jeffrey D; Paulsen, Jane S

    2013-09-24

    To determine whether Huntington disease (HD) mutation carriers have motor symptoms (complaints) when definite motor onset (motor phenoconversion) is diagnosed and document differences between the groups with and without unawareness of motor signs. We analyzed data from 550 HD mutation carriers participating in the multicenter PREDICT-HD Study followed through the HD prodrome. Data analysis included demographics, the Unified Huntington's Disease Rating Scale (UHDRS) and the Participant HD History of symptoms, self-report of progression, and cognitive, behavioral, and imaging measures. Unawareness was identified when no motor symptoms were self-reported but when definite motor HD was diagnosed. Of 38 (6.91%) with onset of motor HD, almost half (18/38 = 47.36%) had no motor symptoms despite signs of disease on the UHDRS motor rating and consistent with unawareness. A group with motor symptoms and signs was similar on a range of measures to the unaware group. Those with unawareness of HD signs reported less depression. Patients with symptoms had more striatal atrophy on imaging measures. Only half of the patients with newly diagnosed motor HD had motor symptoms. Unaware patients were less likely to be depressed. Self-report of symptoms may be inaccurate in HD at the earliest stage.

  17. High Protein Diet and Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Chiung-Mei Chen

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder caused by the huntingtin (HTT gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT exists in the liver and causes urea cycle deficiency. A low protein diet (17% restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories than in mice (~22%. We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein for 5 days, followed by a high protein diet (HPD, 26.3% protein for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington's Disease Rating Scale (UHDRS. The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378 in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.

  18. Eugene F. Fama: Nobel prize for 2013: Capital market efficiency

    Directory of Open Access Journals (Sweden)

    Pantelić Svetlana

    2015-01-01

    Full Text Available In 2013 the Nobel Prize in Economic Sciences was awarded to the American economists, Eugene Fama, Lars Peter Hansen and Robert Shiller. The monetarists, Fama and Hansen, from the University of Chicago, and the Neo- Keynesian, Shiller, from the Yale University, according to the Swedish Royal Academy, won this prestigious prize for their research providing mathematical and economic models to determine (irregularities in the stock value trends at the stock exchanges. With his colleagues, in the 1960s Fama established that, in the short term, it is extremely difficult to forecast stock prices, given that new information gets embedded in the prices rather quickly. Shiller, however, determined that, although it is almost impossible to predict the stock prices for a period of few days, this is not true for a period of several years. He discovered that the stock prices fluctuate much more substantially than corporation dividents, and that the relationship between prices and dividends tends to decline when high, and to grow when low. This pattern does not apply only to stocks, but also to bonds and other forms of capital.

  19. [Neurocosmetics, transhumanism and eliminative materialism: toward new ways of eugenics].

    Science.gov (United States)

    Echarte Alonso, Luis E

    2012-01-01

    In this paper I present similarities and connections between Transhumanism and Eliminative Materialism. Concretely, I study the arguments with which in both positions it is defended a merely instrumental idea of human body and, because of that, one infinitely mouldable. First, I show the social relevance of this idea and its projections in phenomena as medicalization of human condition and, especially, cosmetic psychopharmacology. Besides, I denounce that such influences are caused by illegitimate transference of authority between philosophical and scientific forums. Second, according to my analysis, these new postmodern fashions of chemical sentimentalism (related with radical changes on personal identity and human nature) drive to new eugenic forms what I name autoeugenics. Finally, I call attention to the important role of utopian speeches about the science of tomorrow and super-human civilization in a Carpe Diem society. In my conclusions, I claim that historical reasoning or warnings about what is coming are not efficient strategies to control neither new psychopharmacological habits nor passivity generated by them. Returning social confidence in the power of reason to achieve reality (and other human beings) is, in my opinion, the best way to rehabilitate a more and more devalued human action.

  20. Karl Pearson and eugenics: personal opinions and scientific rigor.

    Science.gov (United States)

    Delzell, Darcie A P; Poliak, Cathy D

    2013-09-01

    The influence of personal opinions and biases on scientific conclusions is a threat to the advancement of knowledge. Expertise and experience does not render one immune to this temptation. In this work, one of the founding fathers of statistics, Karl Pearson, is used as an illustration of how even the most talented among us can produce misleading results when inferences are made without caution or reference to potential bias and other analysis limitations. A study performed by Pearson on British Jewish schoolchildren is examined in light of ethical and professional statistical practice. The methodology used and inferences made by Pearson and his coauthor are sometimes questionable and offer insight into how Pearson's support of eugenics and his own British nationalism could have potentially influenced his often careless and far-fetched inferences. A short background into Pearson's work and beliefs is provided, along with an in-depth examination of the authors' overall experimental design and statistical practices. In addition, portions of the study regarding intelligence and tuberculosis are discussed in more detail, along with historical reactions to their work.

  1. From eugenics to scientometrics: Galton, Cattell, and men of science.

    Science.gov (United States)

    Godin, Benoît

    2007-10-01

    In 1906, James McKeen Cattell, editor of Science, published a directory of men of science. American Men of Science was a collection of biographical sketches of thousands of men of science in the USA and was published periodically. It launched, and was used in, the very first systematic quantitative studies on science. Cattell used two concepts for his statistics: productivity, defined as the number of men of science a nation produces, and performance or merit, defined as scientific contributions to research as judged by peers. These are the two dimensions that still define measurement of scientific productivity today: quantity and quality. This paper analyzes the emergence of statistics on science and the very first uses to which they were put. It argues that the measurement of science emerged out of interest in great men, heredity and eugenics, and the contribution of eminent men to civilization. Among these eminent men were men of science, the population of whom was thought to be in decline and insufficiently appreciated and supported. Statistics on men of science thus came to be collected to document the case, and to contribute to the advancement of science and the scientific profession.

  2. Association of Huntington's disease and schizophrenia-like psychosis in a Huntington's disease pedigree

    OpenAIRE

    Guimarães João; Xavier Miguel; Corrêa Bernardo

    2006-01-01

    Abstract Background Huntington's disease (HD) is a dominantly inherited, neurodegenerative disorder due to expansion of a polymorphic trinucleotide repeat in the short arm of chromosome 4. Clinical manifestations consist of a triad of choreic movements, cognitive decline and psychiatric syndromes starting in the fourth to fifth decade. Psychiatric manifestations vary and may precede motor and cognitive changes. Personality changes and depression occur most commonly. Paranoid schizophrenia-lik...

  3. O desenvolvimento político em Huntington e Fukuyama Huntington and Fukuyama on political development

    Directory of Open Access Journals (Sweden)

    Natália Nóbrega de Mello

    2010-01-01

    Full Text Available O artigo contrasta as teses de Huntington e Fukuyama sobre desenvolvimento político. As obras analisadas, Ordem política nas sociedades em mudança e O fim da história, inscrevem-se entre duas conjunturas decisivas - 1968 e 1989. Huntington desmontou a equivalência entre desenvolvimento político e modernização e Fukuyama reafirmou a democracia como o destino de todos os países e, desse modo, como o fim da história. Nesta comparação, dois eixos se sobressaem: o contexto de produção das obras e a alternância entre os polos teóricos da democracia e da estabilidade. Procura-se demonstrar como, apesar de reinserir a democracia no desenvolvimento político, a instabilidade continua a ser um foco privilegiado de análise no pensamento de Fukuyama.The article contrasts the theories of Huntington and Fukuyama on political development. The analyzed works, Political order in changing societies and The end of history, fall between two decisive historical moments - in 1968 and 1989. Huntington disassembled the equivalence between political development and modernization; Fukuyama reaffirmed democracy as the destiny of all countries and, as such, it is the end of history. In this comparison, two axes call our attention: the production context of these works and the alternation between the theoreticals poles of democracy and stability. The article shows how, although reenters democracy in the political development theory, instablility remains a prime focus of analysis in Fukuyama's thought.

  4. Américo Negrette and Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mariana Moscovich

    2011-08-01

    Full Text Available The authors present a historical review of the seminal clinical contribution of Professor Américo Negrette, a Venezuelan neurologist, to the evolution of scientific knowledge about Huntington's disease.

  5. 1H magnetic resonance spectroscopy in preclinical Huntington disease

    NARCIS (Netherlands)

    van Oostrom, Joost C. H.; Sijens, Paul E.; Roos, Raymund A. C.; Leenders, Klaus L.

    2007-01-01

    Huntington disease (HD) is a hereditary brain disease, causing progressive deterioration after a preclinical phase. The pathophysiology of early brain abnormalities around disease onset is largely unknown. Some preclinical mutation carriers (PMC) show structural or metabolic changes on brain imaging

  6. Juvenile Huntington's disease: a case report and literature review.

    Science.gov (United States)

    Reyes Molón, L; Yáñez Sáez, R M; López-Ibor Alcocer, M I

    2010-01-01

    Huntington's disease is the most frequent neurodegenerative disease with a prevalence of fewer than 10 cases per 10,000 inhabitants; the juvenile form is responsible for less than 10% of all cases. Huntington's disease belongs to the group known as "triad syndromes," which evolve with cognitive, motor and neuropsychiatric manifestations. Around 30% of patients debut with behavioral symptoms, which are a major challenge for management by patients, families, and caregivers. Huntington's disease (HD) is reviewed and a case of juvenile onset is reported in this article. The characteristics of juvenile-onset Huntington's disease (HD) differ from those of adult-onset HD, as chorea does not occur, although bradykinesia, dystonia, and signs of cerebellar disorder, such as rigidity, are present, frequently in association with convulsive episodes and psychotic manifestations.

  7. Genetics Home Reference: Huntington disease-like syndrome

    Science.gov (United States)

    ... 21915. Citation on PubMed Wild EJ, Tabrizi SJ. Huntington's disease phenocopy syndromes. Curr Opin Neurol. 2007 Dec;20(6):681-7. Review. Citation on PubMed Reviewed : August 2008 Published : August ...

  8. Episodic Memory Decline in Huntington's Disease, A Binding Deficit?

    NARCIS (Netherlands)

    El Haj, M.; Caillaud, M.; Fasotti, L.; Verny, C.; Allain, P.

    2013-01-01

    Background: Huntington's disease (HD) is characterized by episodic memory deterioration. Objective: Our paper investigates the cognitive mechanisms that might underlie this decline. To this aim, we tested two executive hypotheses, the binding and the inhibition hypotheses. Methods: Fifteen HD patien

  9. Parcels and Land Ownership, Published in 2011, Huntington County Government.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Parcels and Land Ownership dataset as of 2011. The extent of these data is generally Huntington County, IN. This metadata was auto-generated through the Ramona...

  10. O paradigma de Huntington e o realismo político Huntington's paradigm and political realism

    Directory of Open Access Journals (Sweden)

    José R. Novaes Chiappin

    1994-12-01

    Full Text Available Examina-se a proposta de Huntington de um novo paradigma da política internacional (centrado na idéia de "civilizações" em substituição ao paradigma do realismo. Demonstra-se que se trata, na realidade, de um subparadigma do realismo e, portanto, a ele subordinado. Aplica-se isso à mudança da concepção estratégica de "contenção", que passa a aplicar-se às civilizações não-ocidentais e não mais ao expansionismo soviético.Huntington's proposal of a new paradigm for international politics (focused on the idea of "civilizations", meant to replace the paradigm of realism, is examined. It is shown that the proposed new paradigm should in fact be viewed as as sub-paradigm of the realist one. In particular, it is pointed out that Huntington's proposal, in a realist vein, draws on the idea of "containment", which is now directed (instead of its former target, the soviet expansionism to non-Western civilizations.

  11. Eugenics, politics and the state: social democracy and the Swiss 'gardening state'.

    Science.gov (United States)

    Mottier, Véronique

    2008-06-01

    This article explores the connections between eugenics, politics and the state, taking the Swiss case as a particular focus. It is argued that Switzerland provides a historical example of what Bauman [Bauman, Z. (1989). Modernity and the Holocaust. Cambridge: Polity Press.] describes as 'gardening states': states that are concerned with eliminating the 'bad weeds' from the national garden and thereby constructing sharply exclusionary national identities. The Swiss experiments with eugenics (1920s-1960s) can be seen as an example of an ongoing struggle against 'difference'. Against this backdrop I will examine, first, the ways in which state regulation of reproductive sexuality, and other eugenic measures, became central mechanisms for dealing with cultural and other 'differences' in the Swiss nation. Second, I will analyse the gendered nature of such mechanisms, as well as the preoccupation with racial 'difference' exemplified by eugenic policies towards 'Gypsies'. To conclude, I will examine the impact of political institutions and political ideology, in particular, social democracy, on these eugenic gardening efforts.

  12. From 'beastly philosophy' to medical genetics: eugenics in Russia and the Soviet Union.

    Science.gov (United States)

    Krementsov, Nikolai

    2011-01-01

    This essay offers an overview of the three distinct periods in the development of Russian eugenics: Imperial (1900-1917), Bolshevik (1917-1929), and Stalinist (1930-1939). Began during the Imperial era as a particular discourse on the issues of human heredity, diversity, and evolution, in the early years of the Bolshevik rule eugenics was quickly institutionalized as a scientific discipline--complete with societies, research establishments, and periodicals--that aspired an extensive grassroots following, generated lively public debates, and exerted considerable influence on a range of medical, public health, and social policies. In the late 1920s, in the wake of Joseph Stalin's 'Great Break', eugenics came under intense critique as a 'bourgeois' science and its proponents quickly reconstituted their enterprise as 'medical genetics'. Yet, after a brief period of rapid growth during the early 1930s, medical genetics was dismantled as a 'fascist science' towards the end of the decade. Based on published and original research, this essay examines the factors that account for such an unusual--as compared to the development of eugenics in other locales during the same period--historical trajectory of Russian eugenics.

  13. Eugenics from the New Deal to the Great Society: genetics, demography and population quality.

    Science.gov (United States)

    Ramsden, Edmund

    2008-12-01

    The relationship between biological and social scientists as regards the study of human traits and behavior has often been perceived in terms of mutual distrust, even antipathy. In the interwar period, population study seemed an area that might allow for closer relations between them-united as they were by a concern to improve the eugenic quality of populations. Yet these relations were in tension: by the early post-war era, social demographers were denigrating the contributions of biologists to the study of population problems as embodying the elitist ideology of eugenics. In response to this loss of credibility, the eugenics movement pursued a simultaneous program of withdrawal and expansion: its leaders helped focus concern with biological quality onto the developing field of medical genetics, while at the same moment, extended their scope to improving the social quality of populations through birth control policies, guided by demography. While this approach maintained boundaries between the social and the biological, in the 1960s, a revitalized American Eugenics Society helped reunite leading demographers and geneticists. This paper will assess the reasons for this period of influence for eugenics, and explore its implications for the social and biological study of human populations.

  14. Prenatal diagnosis as a tool and support for eugenics: myth or reality in contemporary French society?

    Science.gov (United States)

    Gaille, Marie; Viot, Géraldine

    2013-02-01

    Today, French public debate and bioethics research reflect an ongoing controversy about eugenics. The field of reproductive medicine is often targeted as pre-implantation genetic diagnosis (PGD), prenatal diagnosis, and prenatal detection are accused of drifting towards eugenics or being driven by eugenics considerations. This article aims at understanding why the charge against eugenics came at the forefront of the ethical debate. Above all, it aims at showing that the charge against prenatal diagnosis is groundless. The point of view presented in this article has been elaborated jointly by a geneticist and a philosopher. Besides a survey of the medical, bioethical, philosophical and social sciences literature on the topic, the methodology is founded on a joint analysis of geneticist's various consults. Evidence from office visits demonstrated that prenatal diagnosis leads to case-by-case decisions. As we have suggested, this conclusion does not mean that prenatal diagnosis is devoid of ethical issues, and we have identified at least two. The first is related to the evaluation of a decision to abort. The second line of ethical questions arises from the fact that the claim for "normality" hardly hides normative and ambiguous views about disability. As a conclusion, ethical dilemmas keep being noticeable in the field of reproductive medicine and genetic counselling, but an enquiry about eugenic tendencies probably does not allow us to understand them in the proper way.

  15. Subtle changes among presymptomatic carriers of the Huntington's disease gene

    OpenAIRE

    S. Kirkwood; Siemers, E.; Hodes, M; Conneally, P; Christian, J.; Foroud, T

    2000-01-01

    OBJECTIVES—To compare the neurological and psychometric characteristics of presymptomatic gene carriers and non-gene carriers who are at risk for developing Huntington's disease so as to characterise early signs of disease and to identify markers of neurological function that could be used to assess the impact of experimental therapies on the progression of disease, even among those who are clinically presymptomatic.
METHODS—A sample of people at risk for Huntington's dis...

  16. Samuel Huntington, Clash of Civilizations: A Book Review

    OpenAIRE

    Yrd. Doç. Dr. Cengiz Kartýn

    2015-01-01

    Samuel Huntington's The Clash of Civilizations was written in 1993 by him. Study is a work containing the article and the responses to this article. Work is composed of two main parts. Makes the important point of this study is the process that began with the September 11 attacks by some strategists that is exactly the way towards a world where it is hidden in Huntington's fictionalized articulate.

  17. Linking SNPs to CAG repeat length in Huntington's disease patients.

    Science.gov (United States)

    Liu, Wanzhao; Kennington, Lori A; Rosas, H Diana; Hersch, Steven; Cha, Jang-Ho; Zamore, Phillip D; Aronin, Neil

    2008-11-01

    Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples.

  18. Neuropathological diagnosis and CAG repeat expansion in Huntington's disease.

    OpenAIRE

    Xuereb, J H; MacMillan, J C; Snell, R; Davies, P.; Harper, P S

    1996-01-01

    OBJECTIVE--To correlate the degree of CAG repeat expansion with neuropathological findings in Huntington's disease. METHODS--The CAG repeat polymorphism was analysed in a large series of brain samples from 268 patients with a clinical diagnosis of Huntington's disease in which full neuropathological data was available. RESULTS--Analysis by polymerase chain reaction was successful in 63% of samples (169 of 268). Repeat expansions were detected in 152 of 153 (99%) samples with a neuropathologic...

  19. Levodopa responsive parkinsonism in an adult with Huntington's disease

    OpenAIRE

    Racette, B.; Perlmutter, J

    1998-01-01

    A patient is reported on with Huntington's disease who, as an adult, first developed severe parkinsonism with bradykinesia, rigidity, postural instability and festinating gait. His clinical signs were similar to those of the Westphal variant of Huntington's disease except that he also had resting tremor and a supranuclear gaze palsy. Magnetic resonance imaging showed caudate and putamen atrophy. Genetic analysis disclosed 49 triple CAG repeats in allele 1 and 17 in allele 2 ...

  20. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O;

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... eminences grown as free-floating roller-tube cultures can be successfully grafted in a rat Huntington model and that a clinical MR scanner offers a useful noninvasive tool for studying striatal graft development....

  1. [Olanzapine improves chorea in patients with Huntington's disease].

    Science.gov (United States)

    Jiménez-Jiménez, F J; de Toledo, M; Puertas, I; Barón, M; Zurdo, M; Barcenilla, B

    The main treatment for choreatic movements associated to Huntington s disease are the neuroleptic drugs, however, its use causes long term troubles. We describe two patients with a predominantly choreic Huntington s disease, who experience improvement of choreatic movements after introduction of olanzapine to their treatment, being this drug well tolerated. The improvement of chorea suggests that olanzapine has a dopaminergic D2 receptors blocking action.

  2. A case report of juvenile Huntington disease

    Directory of Open Access Journals (Sweden)

    Anita Choudhary

    2017-09-01

    Full Text Available Huntington disease (HD is a progressive neurodegenerative disorder, characterized by autosomal dominant inheritance, movement disorder, dementia, and behavioural disturbances. It is caused by a mutation in IT15 gene on chromosome 4p16.3, which leads to unstable CAG trinucleotide repeat expansion. The onset of juvenile HD occurs before the 2nd decade of life and comprises approximately 10% of total HD patients. Juvenile HD differs in symptomatology and is usually transmitted from paternal side with genetic anticipation phenomenon. Magnetic resonance imaging (MRI of the brain shows specific changes of early affection of caudate nucleus and putamen. Multidisciplinary approach with symptomatic treatment of specific symptoms is the current available management. Gene editing and gene silencing treatment are under trial. Hereby, we introduce a case of an 8-year-old boy, who presented with typical symptoms of juvenile HD, positive family history with genetic anticipation phenomenon and characteristic MRI findings.

  3. Plants and phytochemicals for Huntington's disease.

    Science.gov (United States)

    Choudhary, Sunayna; Kumar, Puneet; Malik, Jai

    2013-07-01

    Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor dysfunction, including chorea and dystonia, emotional disturbances, memory, and weight loss. The medium spiny neurons of striatum and cortex are mainly effected in HD. Various hypotheses, including molecular genetics, oxidative stress, excitotoxicity, metabolic dysfunction, and mitochondrial impairment have been proposed to explain the pathogenesis of neuronal dysfunction and cell death. Despite no treatment is available to fully stop the progression of the disease, there are treatments available to help control the chorea. The present review deals with brief pathophysiology of the disease, plants and phytochemicals that have shown beneficial effects against HD like symptoms. The literature for the current review was collected using various databases such as Science direct, Pubmed, Scopus, Sci-finder, Google Scholar, and Cochrane database with a defined search strategy.

  4. The choreography of neuroinflammation in Huntington's disease.

    Science.gov (United States)

    Crotti, Andrea; Glass, Christopher K

    2015-06-01

    Currently, the concept of 'neuroinflammation' includes inflammation associated with neurodegenerative diseases, in which there is little or no infiltration of blood-derived immune cells into the brain. The roles of brain-resident and peripheral immune cells in these inflammatory settings are poorly understood, and it is unclear whether neuroinflammation results from immune reaction to neuronal dysfunction/degeneration, and/or represents cell-autonomous phenotypes of dysfunctional immune cells. Here, we review recent studies examining these questions in the context of Huntington's disease (HD), where mutant Huntingtin (HTT) is expressed in both neurons and glia. Insights into the cellular and molecular mechanisms underlying neuroinflammation in HD may provide a better understanding of inflammation in more complex neurodegenerative disorders, and of the contribution of the neuroinflammatory component to neurodegenerative disease pathogenesis.

  5. Huntington disease: DNA analysis in brazilian population

    Directory of Open Access Journals (Sweden)

    RASKIN SALMO

    2000-01-01

    Full Text Available Huntington disease (HD is associated with expansions of a CAG trinucleotide repeat in the HD gene. Accurate measurement of a specific CAG repeat sequence in the HD gene in 92 Brazilian controls without HD, 44 Brazilian subjects with clinical findings suggestive of HD and 40 individuals from 6 putative HD families, showed a range from 7 to 33 repeats in normal subjects and 39 to 88 repeats in affected subjects. A trend between early age at onset of first symptoms and increasing number of repeats was seen. Major increase of repeat size through paternal inheritance than through maternal inheritance was observed. Data generated from this study may have significant implications for the etiology, knowledge of the incidence, diagnosis, prognosis, genetic counseling and treatment of HD Brazilian patients.

  6. Huntington's Disease: Pathogenic Mechanisms and Therapeutic Targets.

    Science.gov (United States)

    Wright, Dean J; Renoir, Thibault; Gray, Laura J; Hannan, Anthony J

    2017-01-01

    Huntington's disease (HD) is a tandem repeat disorder involving neurodegeneration and a complex combination of symptoms. These include psychiatric symptoms, cognitive deficits culminating in dementia, and the movement disorder epitomised by motor signs such as chorea. HD is caused by a CAG repeat expansion encoding an extended tract of the amino acid glutamine in the huntingtin protein. This polyglutamine expansion appears to induce a 'change of function', possibly a 'gain of function', in the huntingtin protein, which leads to various molecular and cellular cascades of pathogenesis. In the current review, we will briefly describe these broader aspects of HD pathogenesis, but will then focus on specific aspects where there are substantial bodies of experimental evidence, including oxidative stress, mitochondrial dysfunction, glutamatergic dysfunction and neuroinflammation. Furthermore, we will review recent preclinical therapeutic approaches targeting some of these pathogenic pathways, their clinical implications and future directions.

  7. Huntington's Disease: Relationship Between Phenotype and Genotype.

    Science.gov (United States)

    Sun, Yi-Min; Zhang, Yan-Bin; Wu, Zhi-Ying

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disease with the typical manifestations of involuntary movements, psychiatric and behavior disorders, and cognitive impairment. It is caused by the dynamic mutation in CAG triplet repeat number in exon 1 of huntingtin (HTT) gene. The symptoms of HD especially the age at onset are related to the genetic characteristics, both the CAG triplet repeat and the modified factors. Here, we reviewed the recent advancement on the genotype-phenotype relationship of HD, mainly focus on the characteristics of different expanded CAG repeat number, genetic modifiers, and CCG repeat number in the 3' end of CAG triplet repeat and their effects on the phenotype. We also reviewed the special forms of HD (juvenile HD, atypical onset HD, and homozygous HD) and their phenotype-genotype correlations. The review will aid clinicians to predict the onset age and disease course of HD, give the genetic counseling, and accelerate research into the HD mechanism.

  8. Huntington's Disease: Calcium Dyshomeostasis and Pathology Models.

    Science.gov (United States)

    Kolobkova, Y A; Vigont, V A; Shalygin, A V; Kaznacheyeva, E V

    2017-01-01

    Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and mental impairment. At the molecular level, HD is caused by a mutation in the first exon of the gene encoding the huntingtin protein. The mutation results in an expanded polyglutamine tract at the N-terminus of the huntingtin protein, causing the neurodegenerative pathology. Calcium dyshomeostasis is believed to be one of the main causes of the disease, which underlies the great interest in the problem among experts in molecular physiology. Recent studies have focused on the development of animal and insect HD models, as well as patient-specific induced pluripotent stem cells (HD-iPSCs), to simulate the disease's progression. Despite a sesquicentennial history of HD studies, the issues of diagnosis and manifestation of the disease have remained topical. The present review addresses these issues.

  9. Cerebrospinal Fluid Biomarkers for Huntington's Disease.

    Science.gov (United States)

    Byrne, Lauren M; Wild, Edward J

    2016-01-01

    Cerebrospinal fluid (CSF) is enriched in brain-derived components and represents an accessible and appealing means of interrogating the CNS milieu to study neurodegenerative diseases and identify biomarkers to facilitate the development of novel therapeutics. Many such CSF biomarkers have been proposed for Huntington's disease (HD) but none has been validated for clinical trial use. Across many studies proposing dozens of biomarker candidates, there is a notable lack of statistical power, consistency, rigor and validation. Here we review proposed CSF biomarkers including neurotransmitters, transglutaminase activity, kynurenine pathway metabolites, oxidative stress markers, inflammatory markers, neuroendocrine markers, protein markers of neuronal death, proteomic approaches and mutant huntingtin protein itself. We reflect on the need for large-scale, standardized CSF collections with detailed phenotypic data to validate and qualify much-needed CSF biomarkers for clinical trial use in HD.

  10. Contribution of Neuroepigenetics to Huntington's Disease.

    Science.gov (United States)

    Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

    2017-01-01

    Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process.

  11. Neuronal Ca(2+) dyshomeostasis in Huntington disease.

    Science.gov (United States)

    Giacomello, Marta; Oliveros, Juan C; Naranjo, Jose R; Carafoli, Ernesto

    2013-01-01

    The expansion of the N-terminal poly-glutamine tract of the huntingtin (Htt) protein is responsible for Huntington disease (HD). A large number of studies have explored the neuronal phenotype of HD, but the molecular aethiology of the disease is still very poorly understood. This has hampered the development of an appropriate therapeutical strategy to at least alleviate its symptoms. In this short review, we have focused our attention on the alteration of a specific cellular mechanism common to all HD models, either genetic or induced by treatment with 3-NPA, i.e. the cellular dyshomeostasis of Ca(2+). We have highlighted the direct and indirect (i.e. transcriptionally mediated) effects of mutated Htt on the maintenance of the intracellular Ca(2+) balance, the correct modulation of which is fundamental to cell survival and the disturbance of which plays a key role in the death of the cell.

  12. Emancipation through interaction--how eugenics and statistics converged and diverged.

    Science.gov (United States)

    Louçã, Francisco

    2009-01-01

    The paper discusses the scope and influence of eugenics in defining the scientific programme of statistics and the impact of the evolution of biology on social scientists. It argues that eugenics was instrumental in providing a bridge between sciences, and therefore created both the impulse and the institutions necessary for the birth of modern statistics in its applications first to biology and then to the social sciences. Looking at the question from the point of view of the history of statistics and the social sciences, and mostly concentrating on evidence from the British debates, the paper discusses how these disciplines became emancipated from eugenics precisely because of the inspiration of biology. It also relates how social scientists were fascinated and perplexed by the innovations taking place in statistical theory and practice.

  13. Medicine, eugenics, and the Supreme Court: from coercive sterilization to reproductive freedom.

    Science.gov (United States)

    Lombardo, P A

    1996-01-01

    This article shows how the current language of reproductive rights, including the determination of US constitutional protections, can be traced to three cases heard by the US Supreme Court that challenged eugenic state legislation written between 1924 and 1935. The introduction defines "eugenics" as the notion that the human race can be improved and social ills gradually eliminated by selective procreation and notes that eugenicists were extremely effective in using the law as their ally and effected the adoption of nearly 100 eugenic statutes by the states between 1900 and 1970. Part 2 examines the classification of social deviance as a social ill that could be overcome by the application of eugenic principles bolstered by scientific explanations about defective "germ-plasm." The third part of the article illustrates the legal impact of US eugenicists in 1924 when the Federal Immigration Restriction Act was adopted with national origin quotas that remained in place until 1965. This year also saw adoption of two eugenic laws enacted in Virginia that would be later challenged in the Supreme Court. Part 4 details one of these cases, Buck vs. Bell, that challenged Virginia's Eugenical Sterilization Act. In upholding the Virginia statute, the Supreme Court allowed the forced sterilization of a young woman in the first and only instance in which the Court allowed a physician to act as an agent of state government in the performance of an undesired and unnecessary operation. Part 5 describes how the Supreme Court overturned Oklahoma's law mandating the sterilization of "hereditary criminals" in Skinner vs. Oklahoma. The 1967 ruling in Loving vs. Virginia overturning Virginia's Racial Integrity Act preventing interracial marriage is presented in part 6. The article ends by tracing the impact of these cases on the constitutionalization of reproductive rights in the US.

  14. A Response to Eugene and Kiyo’s Dialogue-Disagreement on Dialogic Pedagogy

    Directory of Open Access Journals (Sweden)

    Beth Ferholt

    2014-10-01

    Full Text Available Thank you for asking me to respond to the text that you have created, Eugene and Kiyo. I will write about the “freedom from,” which Eugene raises and which Kiyo addresses at the end of the text. Kiyo points out that when the teacher’s primary active engagement with the learner is to respect the learner’s freedom from, then ‘engaging with others actively to facilitate their learning and the development of their agency’ (pedagogy itself is hindering the development of self-generated authorship (or making people responsive.

  15. Quantitative 7T phase imaging in premanifest Huntington disease.

    Science.gov (United States)

    Apple, A C; Possin, K L; Satris, G; Johnson, E; Lupo, J M; Jakary, A; Wong, K; Kelley, D A C; Kang, G A; Sha, S J; Kramer, J H; Geschwind, M D; Nelson, S J; Hess, C P

    2014-09-01

    In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease. © 2014 by American Journal of Neuroradiology.

  16. Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

    NARCIS (Netherlands)

    Cubo, E.; Gonzalez, M.; Puerto, I. del; Yebenes, J.G. de; Arconada, O.F.; Gabriel y Galan, J.M.; Kremer, H.P.H.; Warrenburg, B.P.C. van de

    2012-01-01

    BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disea

  17. 75 FR 33617 - Notice of Proposed Settlement Agreement and Opportunity for Public Comment: West Huntington Spill...

    Science.gov (United States)

    2010-06-14

    ... AGENCY Notice of Proposed Settlement Agreement and Opportunity for Public Comment: West Huntington Spill... United States Department of Justice on behalf of EPA, in connection with the West Huntington Spill Site, Huntington, West Virginia (``Site''). DATES: Written comments on the proposed settlement agreement must...

  18. Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

    NARCIS (Netherlands)

    Cubo, E.; Gonzalez, M.; Puerto, I. del; Yebenes, J.G. de; Arconada, O.F.; Gabriel y Galan, J.M.; Kremer, H.P.H.; Warrenburg, B.P.C. van de

    2012-01-01

    BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's

  19. Disease stage, but not sex, predicts depression and psychological distress in Huntington's disease

    DEFF Research Database (Denmark)

    Dale, Maria; Maltby, John; Shimozaki, Steve

    2016-01-01

    OBJECTIVE: Depression and anxiety significantly affect morbidity in Huntington's disease. Mice. models of Huntington's disease have identified sex differences in mood-like behaviours that vary across disease lifespan, but this interaction has not previously been explored in humans with Huntington...

  20. Huntington's disease: from molecular pathogenesis to clinical treatment.

    Science.gov (United States)

    Ross, Christopher A; Tabrizi, Sarah J

    2011-01-01

    Huntington's disease is a progressive, fatal, neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, which encodes an abnormally long polyglutamine repeat in the huntingtin protein. Huntington's disease has served as a model for the study of other more common neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. These disorders all share features including: delayed onset; selective neuronal vulnerability, despite widespread expression of disease-related proteins during the whole lifetime; abnormal protein processing and aggregation; and cellular toxic effects involving both cell autonomous and cell-cell interaction mechanisms. Pathogenic pathways of Huntington's disease are beginning to be unravelled, offering targets for treatments. Additionally, predictive genetic testing and findings of neuroimaging studies show that, as in some other neurodegenerative disorders, neurodegeneration in affected individuals begins many years before onset of diagnosable signs and symptoms of Huntington's disease, and it is accompanied by subtle cognitive, motor, and psychiatric changes (so-called prodromal disease). Thus, Huntington's disease is also emerging as a model for strategies to develop therapeutic interventions, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset.

  1. Investigational agents for the management of Huntington's disease.

    Science.gov (United States)

    Müller, Thomas

    2017-02-01

    An inherited, chronic progressive, neurodegenerative disorder is Huntington's disease, characterized by motor, cognitive, and psychiatric symptoms. Predictive genetic testing allows earlier diagnosis and identification of gene carriers for Huntington's disease. These individuals are ideal candidates for testing of therapeutic interventions for disease modification. Areas covered: According to queries in Pubmed, Embase and clinical register databases, research and clinical studies emerge on symptomatic and neuroprotective therapies in Huntington's disease. This review discusses novel agents for symptomatic therapy and disease modification. They are currently in phase I and II of drug development Expert opinion: There are promising, safe and well tolerated compounds for amelioration of motor and neuropsychiatric symptoms, but their efficacy still needs to be proven in clinical trials. Deterioration of mutant huntingtin expression, antiapoptotic or cell death inhibition as disease modifying concepts was efficacious in models of Huntington's disease. However, the risk for clinical trial failures is high not only due to ineffectiveness of the tested agent. Negative study outcomes may also result from design misconceptions, underestimation of the heterogeneity of Huntington's disease, too short study durations and too small study cohorts.

  2. Obituary: Harding Eugene (Gene) Smith, Jr., 1947-2007

    Science.gov (United States)

    Lonsdale, Carol; Soifer, Tom

    2009-01-01

    Harding Eugene Smith Junior, or Gene, as he was known to family, friends, and colleagues, passed away after an automobile accident in Encinitas, California, on 16 August 2007. He was 60 years old. Gene had recently retired from UCSD after thirty years of service. A memorial service was held at Quail Botanical Gardens in Encinitas, California, on 23 August 2007. A web page is dedicated to his memory at http://harding.smith.muchloved.com, where contributions of memories are invited. Gene was born in San Jose, California in 1947, to Harding Eugene Smith Senior, and Bernice Smith (nee Smith). Harding Smith Senior was an air-force navigator; therefore Gene spent his childhood moving from one air-force base to another. Although an only child, Gene was very close to his cousin Meg, whom he lived nearby to in Gilroy for a time, and the two were like brother and sister. The elder Harding Smith was lost in action over Cambodia in the mid-sixties. Gene was a dedicated student, a boy scout, and a Presidential Scholar. He majored in Physics at Caltech, where he also took a lively interest in the football team and the Glee Club, and was elected a House Officer. To his close friends, he was known at Caltech as Smitty, and the closest of them was Rob Drew, who gave a glimpse into that period of Gene's life at the memorial: "Gene arrived early at campus his first year, in response to an invitation to join the football team. Gene's size and features reminded the head coach of a long-forgotten player named 'Johnson.' After a few days of confusion, Gene simply replaced the name on his helmet. 'Johnson!' coach would yell, 'get in there!' If Johnson was going to get to play, Gene was going to be the best Johnson available!" Gene spent the summer of 1966 working at Kitt Peak, where his lifetime love of observing with ground-based telescopes began, though he learned some things the hard way, such as the fact that trying to squeeze 40,000 numbers onto a computer that stored only 32

  3. The Killing Thought in the Eugenic Era and Today: A Commentary on Hollander's Essay.

    Science.gov (United States)

    Wolfensberger, Wolf

    1989-01-01

    Two responses to Hollander (EC 220 057) and the author's counter-response note similarities between "mercy killing" of people with mental retardation and deliberate abortion of the unborn, misuse of the history of eugenics, and a defense of the author's historical scholarship. (DB)

  4. Hereditarian Ideas and Eugenic Ideals at the National Deaf-Mute College

    Science.gov (United States)

    Ennis, William Thomas, III

    2015-01-01

    For the past two centuries deaf people in the United States have faced more or less intense skepticism about their marriages to each other, largely due to fears of inherited deafness. These fears, while always present, have waxed and waned over time, becoming most prominent during the eugenics era of the late nineteenth and early twentieth…

  5. Reflections on Mental Retardation and Eugenics, Old and New: Mensa and the Human Genome Project.

    Science.gov (United States)

    Smith, J. David

    1994-01-01

    This article addresses the moral and ethical issues of mental retardation and a continuing legacy of belief in eugenics. It discusses the involuntary sterilization of Carrie Buck in 1927, support for legalized killing of subnormal infants by 47% of respondents to a Mensa survey, and implications of the Human Genome Project for the field of mental…

  6. Eugene Wigner – A Gedanken Pioneer of the Second Quantum Revolution

    Directory of Open Access Journals (Sweden)

    Zeilinger Anton

    2014-01-01

    Full Text Available Eugene Wigner pointed out very interesting consequences of quantum physics in elegant gedanken experiments. As a result of technical progress, these gedanken experiments have become real experiments and contribute to the development of novel concepts in quantum information science, often called the second quantum revolution.

  7. In Memory of Professors Chen Yaozhen (Eugene Chan) and Mao Wenshu (Winifred Mao)

    Institute of Scientific and Technical Information of China (English)

    Lezheng Wu

    2002-01-01

    @@ It has been 16 and 14 years respectively since Professor Chen Yaozhen (Eugene Chan) and Pro-fessor Mao Wenshu (Winifred Mao) passed away. We recollect the great and extraordinary lives ofthese two seniors, their outstanding achievements and contributions as well as the unforgettable andvaluable academic heritages left by them to the ophthalmology in China.

  8. Ethnic, Familial and Catholic Elements in Eugene O'Neill's Long Day's Journey Into Night

    Institute of Scientific and Technical Information of China (English)

    纪小军

    2010-01-01

    In the plays of Eugene O'Neill. American's leading and foremost creative playwright, can be found the influence of his Irish and Catholic background. This paper attempts to explore the influence of O'Neill's ethnic, familial and religious background upon his thinly disguised autobiographical materpiece Long Day' s Journey Into Night.

  9. EUGENICS, THE GIRARDIAN THEORY OF SACRIFICE, AND THE NEW DARWINIAN ETHICS

    Directory of Open Access Journals (Sweden)

    THOMAS RYBA

    2011-11-01

    Full Text Available In this paper I argue that, though many ethical systems recognizesacrifice as moral action, the utilitarian appropriation of Neo-Darwinian theory especially as it justifies eugenics as a “winnowing of the human stock” is in Girardian terms analogous to the sacrificial scapegoating of innocents. This argument is accomplished in four steps. (1 I show that within some ethical systems sacrifice is recognized as moral behavior driven by a specific axiology (or theory of value (2 I discuss some of the meta-ethical problems connected with Neo-Darwinian naturalism and naturalism, in general. (3 I show how modern varieties of naturalism and Darwinian naturalism, inparticular are especially inclined to lead to a moral justification of eugenic scapegoating and how Girardian theory is helpful in identifying the moral disorder connected with eugenics. (4 Finally, I conclude by arguing that Darwin’s thought is susceptible to another kind of interpretation, one that need not lead to the valorization of eugenics.

  10. An Interview with Eugene Genovese: The Rise of a Marxist Historian.

    Science.gov (United States)

    Radosh, Ronald

    1978-01-01

    Eugene D. Genovese, the new president of the Organization of American Historians, and the first Marxist to hold that post, is interviewed. Among the topics discussed are the Bertell Ollman incident at the University of Maryland, academic freedom and political discrimination on campus, campus activism, and Genovese's academic career. (JMD)

  11. Professionalization and the Null Curriculum: The Case of the Popular Eugenics Movement and American Educational Studies.

    Science.gov (United States)

    Selden, Steven

    1987-01-01

    Presents an essay review of three recent books on eugenics, a once popular quasiscientific and politically conservative social movement devoted to the improvement of humankind through programs of selective breeding and marriage restriction. States that educators must study and come to grips with the meaning of this movement in order to appreciate…

  12. A not-so-new eugenics. Harris and Savulescu on human enhancement.

    Science.gov (United States)

    Sparrow, Robert

    2011-01-01

    John Harris and Julian Savulescu, leading figures in the "new' eugenics, argue that parents are morally obligated to use genetic and other technologies to enhance their children. But the argument they give leads to conclusions even more radical than they acknowledge. Ultimately, the world it would lead to is not all that different from that championed by eugenicists one hundred years ago.

  13. Reflections on Mental Retardation and Eugenics, Old and New: Mensa and the Human Genome Project.

    Science.gov (United States)

    Smith, J. David

    1994-01-01

    This article addresses the moral and ethical issues of mental retardation and a continuing legacy of belief in eugenics. It discusses the involuntary sterilization of Carrie Buck in 1927, support for legalized killing of subnormal infants by 47% of respondents to a Mensa survey, and implications of the Human Genome Project for the field of mental…

  14. Thoughts on the Changing Meaning of Disability: New Eugenics or New Wholeness?

    Science.gov (United States)

    Smith, J. David

    1999-01-01

    Reviews the impact of eugenics on people with disabilities and the danger that they will be further devalued in a world of increasing genetic manipulation. Margaret Mead's concept of providing opportunities for all people to learn how to participate wholly in society and the need for an ethical revolution are discussed. (CR)

  15. The Human Genome Project and Eugenics: Identifying the Impact on Individuals with Mental Retardation.

    Science.gov (United States)

    Kuna, Jason

    2001-01-01

    This article explores the impact of the mapping work of the Human Genome Project on individuals with mental retardation and the negative effects of genetic testing. The potential to identify disabilities and the concept of eugenics are discussed, along with ethical issues surrounding potential genetic therapies. (Contains references.) (CR)

  16. Eugenics for the doctors: medicine and social control in 1930s Turkey.

    Science.gov (United States)

    Salgirli, Sanem Güvenç

    2011-07-01

    This article aims to add a new dimension to the analysis of the relationship between medicine and eugenics via a discussion of the community of Turkish physicians in the period between the two World Wars. It argues that even though the relationship between the two fields has been discussed before in terms of the professional ideology of doctors, the medical community itself has not come under scrutiny by scholars. It is the purpose of this article to show eugenics as the main unifying edifice of that community and argue that eugenics is to be found in the patterns of social reproduction of the doctors as part of the professional middle class in addition to being those who transfer knowledge of medicine. As can be seen in Turkey in the 1930s, the doctors, in their efforts to construct themselves as the pioneers of modern scientific medicine, as well as the new ruling class of the country, used eugenics extensively both as a means of self-identification, and as a way to build a professional class "fit" to rule the country.

  17. Eugenics and Education: A Note on the Origins of the Intelligence Testing Movement in England.

    Science.gov (United States)

    Lowe, Roy

    1980-01-01

    Examines influence of Francis Galton and the Eugenics Education Society in the intelligence testing movement in England (early 1900s). For eugenicists, the central issue confronting society was the problem of racial deterioration. They responded with modification of the Binet-Simon tests and developed tests to examine the whole ability range.…

  18. The Killing Thought in the Eugenic Era and Today: A Commentary on Hollander's Essay.

    Science.gov (United States)

    Wolfensberger, Wolf

    1989-01-01

    Two responses to Hollander (EC 220 057) and the author's counter-response note similarities between "mercy killing" of people with mental retardation and deliberate abortion of the unborn, misuse of the history of eugenics, and a defense of the author's historical scholarship. (DB)

  19. Education Policy and Biological Science: Genetics, Eugenics, and the College Textbook, c. 1908-1931.

    Science.gov (United States)

    Selden, Steven

    1985-01-01

    A revolution in genetics is occurring, but when looking ahead, we must not romanticize the past. The social history of genetics, and American education's association with eugenics, make it necessary that we understand that both education and science are informed by social attitudes. (MT)

  20. The Hunt for Disability: The New Eugenics and the Normalization of School Children.

    Science.gov (United States)

    Baker, Bernadette

    2002-01-01

    Examines issues of sameness, difference, equality, and democracy in present public school systems, focusing on the question of (dis)ability and implications of rethinking (dis)ability as an ontological issue before its inscription as an educational one concerning the politics of inclusion. The paper analyzes old and new discourses of eugenics as…

  1. [On the medical and publishing activities of the community of Saint Eugene].

    Science.gov (United States)

    2012-01-01

    The article deals with the role the physicians played in organization and functioning of the Community of Saint Eugene in St. Petersburg in 1882-1918. The typography production of the Community being of interest for history of medicine is examined.

  2. Watching the 'eugenic experiment' unfold: the mixed views of British eugenicists toward Nazi Germany in the early 1930s.

    Science.gov (United States)

    Hart, Bradley W

    2012-01-01

    Historians of the eugenics movement have long been ambivalent in their examination of the links between British hereditary researchers and Nazi Germany. While there is now a clear consensus that American eugenics provided significant material and ideological support for the Germans, the evidence remains less clear in the British case where comparatively few figures openly supported the Nazi regime and the left-wing critique of eugenics remained particularly strong. After the Second World War British eugenicists had to push back against the accusation that their science was intrinsically dictatorial or totalitarian and, as a result, many of their early perceptions of the Nazis were ignored or rationalised away. Further, historians in recent years have focused more directly on the social reformist elements of eugenics, discussing the links between hereditary science and the birth control and feminist movements in addition to others. While undoubtedly making valuable contributions to the scholarly understanding of the eugenic milieu in the interwar years, these studies have neglected to recontextualize the sentiments of British eugenicists who did indeed view the Nazi government positively in the early years of the 1930s. This article argues that there was a significant, though not numerically sizable, faction in the British eugenics movement, though mostly outside the Eugenics Society itself, in the early 1930s that viewed the Nazi Germany as an admirable state for its implementation of eugenic principles. One of these figures was later interned by his own government for being too closely aligned with the German regime, though he argued that this affinity was driven by the quest for scientific truth rather than politics. Eugenics in Britain thus contained a greater diversity of views toward Germany than scholars have previously assumed, warranting more research into the individuals and organizations harbouring these views.

  3. Single sperm analysis of the trinucleotide repeat in the Huntington`s disease gene

    Energy Technology Data Exchange (ETDEWEB)

    Leeflang, E.P.; Zhang, L.; Hubert, R. [Univ. of Southern California, Los Angeles, CA (United States)] [and others

    1994-09-01

    Huntington`s disease (HD) is one of several genetic diseases caused by trinucleotide repeat expansion. The CAG repeat is very unstable, with size changes occurring in more than 80% of transmissions. The degree of instability of this repeat in the male germline can be determined by analysis of individual sperm cells. An easy and sensitive PCR assay has been developed to amplify this trinucleotide repeat region from single sperm using two rounds of PCR. As many as 90% of the single sperm show amplification for the HD repeat. The PCR product can be easily detected on an ethidium bromide-stained agarose gel. Single sperm samples from an HD patient with 18 and 49 repeats were studied. We observed size variations for the expanded alleles while the size of the normal allele in sperm is very consistent. We did not detect any significant bias in the amplification of normal alleles over the larger HD alleles. Our preliminary study supports the observation made by PCR of total sperm that instability of the HD trinucleotide repeat occurs in the germline. HD preimplantation diagnosis on single embryo blastomeres may also possible.

  4. 22 Years of predictive testing for Huntington's disease: the experience of the UK Huntington's Prediction Consortium.

    Science.gov (United States)

    Baig, Sheharyar S; Strong, Mark; Rosser, Elisabeth; Taverner, Nicola V; Glew, Ruth; Miedzybrodzka, Zosia; Clarke, Angus; Craufurd, David; Quarrell, Oliver W

    2016-10-01

    Huntington's disease (HD) is a progressive neurodegenerative condition. At-risk individuals have accessed predictive testing via direct mutation testing since 1993. The UK Huntington's Prediction Consortium has collected anonymised data on UK predictive tests, annually, from 1993 to 2014: 9407 predictive tests were performed across 23 UK centres. Where gender was recorded, 4077 participants were male (44.3%) and 5122 were female (55.7%). The median age of participants was 37 years. The most common reason for predictive testing was to reduce uncertainty (70.5%). Of the 8441 predictive tests on individuals at 50% prior risk, 4629 (54.8%) were reported as mutation negative and 3790 (44.9%) were mutation positive, with 22 (0.3%) in the database being uninterpretable. Using a prevalence figure of 12.3 × 10(-5), the cumulative uptake of predictive testing in the 50% at-risk UK population from 1994 to 2014 was estimated at 17.4% (95% CI: 16.9-18.0%). We present the largest study conducted on predictive testing in HD. Our findings indicate that the vast majority of individuals at risk of HD (>80%) have not undergone predictive testing. Future therapies in HD will likely target presymptomatic individuals; therefore, identifying the at-risk population whose gene status is unknown is of significant public health value.

  5. A study on the trinucleotide repeat associated with Huntington`s disease in the Chinese

    Energy Technology Data Exchange (ETDEWEB)

    Bing-wen Soong; Jih-tsuu Wang [Neurological Institute, Taipei (Taiwan, Province of China)

    1994-09-01

    Analysis of the polymorphic (CAG)n repeat in the hungingtin gene in the chinese confirmed the presence of an expanded repeat on all Huntington`s disease chromosomes. Measurement of the specific CAG repeat sequence in 34 HD chromosomes from 15 unrelated families and 190 control chromosomes from the Chinese population showed a range from 9 to 29 repeats in normal subjects and 40 to 58 in affected subjects. The size distributions of normal and affected alleles did not overlap. A clear correlation bewteen early onset of symptoms and very high repeat number was seen, but the spread of the age-at-onset in the major repeat range producing characteristic HD it too wide to be of diagnostic value. There was also variability in the transmitted repeat size for both sexes in the HD size range. Maternal HD alleles showed a moderate instability with a preponderance of size decrease, while paternal HD alleles had a tendency to increase in repeat size on transmission, the degree of which appeared proportional to the initial size.

  6. The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population.

    Science.gov (United States)

    Baine, Fiona K; Krause, Amanda; Greenberg, L Jacquie

    2016-01-01

    Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa. © 2016 S. Karger AG, Basel.

  7. Association of Huntington's disease and schizophrenia-like psychosis in a Huntington's disease pedigree

    Directory of Open Access Journals (Sweden)

    Guimarães João

    2006-02-01

    Full Text Available Abstract Background Huntington's disease (HD is a dominantly inherited, neurodegenerative disorder due to expansion of a polymorphic trinucleotide repeat in the short arm of chromosome 4. Clinical manifestations consist of a triad of choreic movements, cognitive decline and psychiatric syndromes starting in the fourth to fifth decade. Psychiatric manifestations vary and may precede motor and cognitive changes. Personality changes and depression occur most commonly. Paranoid schizophrenia-like symptoms occur in 6% to 25% of cases. Case report We describe a 55 year-old woman with an 8 yearlong history of behavioural changes, multi-thematic delusions and auditory hallucinations. History and mental state examination were suggestive of paranoid schizophrenia. Neurological examination revealed discrete, involuntary movements affecting her arms and trunk. Genotyping detected an expanded allele (43 trinucleotide repeats. A three-generation-long family history of chorea and schizophrenia-like psychosis was found. Conclusion HD-families have been reported in which schizophrenia-like syndromes emerged in all or most HD-affected members long before they developed extra-pyramidal or cognitive changes. This has been attributed to more than mere coincidence. We hypothesise that in these families the HD gene is transmitted along with a low load of small-effect "psychosis genes" which, in the presence of the severe cognitive changes of HD, manifest as a schizophrenia-like phenotype. Further research is needed in order to clarify the links between genetic loading and the emergence of psychotic symptoms in Huntington's disease.

  8. Exclusion testing in pregnancy for Huntington's disease.

    Science.gov (United States)

    Tyler, A; Quarrell, O W; Lazarou, L P; Meredith, A L; Harper, P S

    1990-01-01

    The results of DNA analysis are presented for a series of 90 couples, with one partner at 50% risk for Huntington's disease (HD), who were referred for exclusion testing in pregnancy over a three year period. Thirty-seven couples were studied in detail. The aims of the study were to evaluate attitudes towards prenatal testing, before pregnancy and afterwards, and the effectiveness of our counseling and methods of organising the service. Problems which could arise in relation to presymptomatic testing are documented. It is concluded that exclusion testing is a valuable form of prediction for some couples, particularly where family structure does not permit prediction for the person at risk. The need for intensive counselling was highlighted by the difficulties experienced by many couples in understanding how the test worked. Particular ethical and organisational problems may arise which require careful consideration beforehand and some recommendations are made. The proportion of couples who will continue to request exclusion testing as pre-symptomatic testing becomes more widely applicable remains unknown. PMID:2145437

  9. Cell-based technologies for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mônica Santoro Haddad

    Full Text Available ABSTRACT Huntington's disease (HD is a fatal genetic disorder, which causes the progressive breakdown of neurons in the human brain. HD deteriorates human physical and mental abilities over time and has no cure. Stem cell-based technologies are promising novel treatments, and in HD, they aim to replace lost neurons and/or to prevent neural cell death. Herein we discuss the use of human fetal tissue (hFT, neural stem cells (NSCs of hFT origin or embryonic stem cells (ESCs and induced pluripotent stem cells (IPSCs, in clinical and pre-clinical studies. The in vivo use of mesenchymal stem cells (MSCs, which are derived from non-neural tissues, will also be discussed. All these studies prove the potential of stem cells for transplantation therapy in HD, demonstrating cell grafting and the ability to differentiate into mature neurons, resulting in behavioral improvements. We claim that there are still many problems to overcome before these technologies become available for HD patient treatment, such as: a safety regarding the use of NSCs and pluripotent stem cells, which are potentially teratogenic; b safety regarding the transplantation procedure itself, which represents a risk and needs to be better studied; and finally c technical and ethical issues regarding cells of fetal and embryonic origin.

  10. Comprehension of prosody in Huntington's disease.

    Science.gov (United States)

    Speedie, L J; Brake, N; Folstein, S E; Bowers, D; Heilman, K M

    1990-07-01

    Patients with Huntington's Disease (HD) who were without dementia were compared to unilateral stroke patients and controls as previously reported in 1983, to discover if they had a prosodic defect. Subjects were presented tape-recorded speech filtered sentences and asked to indicate the tone of voice as happy, sad or angry (affective prosody), or as a question, command or statement (propositional prosody). HD patients were impaired in comprehension of both types of prosody compared to controls but were not different from stroke patients. A second study compared early HD patients with at-risk siblings and spouse controls on comprehension of affective and propositional prosody, discrimination of both types of prosody, rhythm discrimination and tonal memory (Seashore tests). HD patients were impaired in both comprehension and discrimination of all types of prosody. HD patients were less accurate than at-risk patients on the tonal memory task but not on the rhythm discrimination task. These findings suggest compromise in ability to understand the more subtle prosodic aspects of communication which may contribute to social impairment of HD patients very early in the course of the disease.

  11. Hypothalamic-endocrine aspects in Huntington's disease.

    Science.gov (United States)

    Petersén, Asa; Björkqvist, Maria

    2006-08-01

    Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic-pituitary-adrenal axis occurs as well as pancreatic beta-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions.

  12. DNA instability in replicating Huntington's disease lymphoblasts

    Directory of Open Access Journals (Sweden)

    Frati Luigi

    2009-02-01

    Full Text Available Abstract Background The expanded CAG repeat in the Huntington's disease (HD gene may display tissue-specific variability (e.g. triplet mosaicism in repeat length, the longest mutations involving mitotic (germ and glial cells and postmitotic (neurons cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths. Results Although most lymphoblastoid cell lines (88% showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting in cis to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations. Conclusion Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.

  13. Genetic diagnosis of Huntington's disease: cases report

    Institute of Scientific and Technical Information of China (English)

    Liao Ting-ting; Wu Wei; Wan Qi; Cui Yu-gui; Liu Jia-yin

    2011-01-01

    Objective:To assess the efficiency of the PCR combined DNA sequencing to ascertain CAG repeat size of Huntington's disease(HD)gene as for gene diagnosis of HD.Method:Three patients with HD were diagnosed genetically with the technology of polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis by assessing the CAG repeat size of HD gene.DNA sequencing then was used as verification test for HD gene.Results:Nine members of three nuclear families were included in this study,three patients were HD proband.In those families,CAG repeats of all spouse of propositus were in normal range.CAG repeats of all propositus and their descendants with the normal allele were in normal range,while CAG copy number of the other mobigenous allele was obviously abnormal.Conclusion:PCR combined DNA sequencing can be used to effectively ascertain CAG repeat of HD gene.CAG-repeat expansion mutations were accounted for 99% of HD cases,so HD can be accurately diagnosed by this method.

  14. Genetic Testing for Huntington's Disease in Parkinsonism.

    Science.gov (United States)

    Rahman, M S; Nagai, Y; Popiel, H A; Fujikake, N; Okamoto, Y; Ahmed, M U; Islam, M A; Islam, M T; Ahmed, S; Rahman, K M; Uddin, M J; Dey, S K; Ahmed, Q; Hossain, M A; Jahan, N; Toda, T

    2010-10-01

    The study was conducted to find out Huntington's disease (HD) by genetic analysis from those presenting with parkinsonism in the Neurology department of Mymensingh Medical College & Hospital. A sample of about 5ml blood was collected by veni puncture in EDTA tube with informed consent from 9 patients & 7 healthy individuals after approval of the institutional ethics committee for genetic study. The neurological disorder along with a complete history and physical findings were recorded in a prescribed questionnaire by the neurologists of Mymensingh Medical College & Hospital. Extraction of genomic DNA from the venous blood using FlexiGene DNA kit (Qiagen, Japan) was performed in Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh. The extracted DNA was stored and accumulated and then these DNA were sent to Division of Clinical Genetics, Department of Medical Genetics, Osaka University Medical School, Suita, Osaka 565 0871, Japan for PCR and further analysis. PCR amplification of the CAG repeat in the 1T15 gene was performed with primers HD1 and HD3. HD PCR products revealed the DNA product of about 110bp (no. of CAG repeats=21) to 150bp (no. of CAG repeats=34) in both healthy individual and suspected PD patient DNA.

  15. Pridopidine for the treatment of Huntington's disease.

    Science.gov (United States)

    Shannon, Kathleen M

    2016-01-01

    Huntington's disease is a rare dominantly-inherited neurodegenerative disease with motor, cognitive and behavioral manifestations. It results from an expanded unstable trinucleotide repeat in the coding region of the huntingtin gene. Treatment is symptomatic, but a poor evidence baseguides selection of therapeutic agents. Non-choreic derangements in voluntary movement contribute to overall motor disability and are poorly addressed by current therapies. Pridopidine is a novel agent in the dopidine class believed to have 'state dependent' effects at dopamine receptors, thus show promise in the treatment of these disorders of voluntary movement. This review discusses the pharmacokinetics and pharmacodynamics of pridopidine and reviews clinical trials supporting development of the drug for HD. This information was culled from literature searches for dopidines, pridopidine, and HD experimental therapeutics in PubMed and at http://www.clinicaltrials.org . There is a compelling need to discover new treatments for motor disability in HD, particularly for non-choreic motor symptoms. While pridopidine failed to achieve its primary efficacy outcomes in 2 large trials, reproducible effects on secondary motor outcomes have fueled an ongoing trial studying higher doses and more focused clinical endpoints. This and phase III trials will define define the utility of pridopidine for HD.

  16. Lessons Learned from the Transgenic Huntington's Disease Rats

    Directory of Open Access Journals (Sweden)

    Rinske Vlamings

    2012-01-01

    Full Text Available Huntington's disease (HD is a fatal inherited disorder leading to selective neurodegeneration and neuropsychiatric symptoms. Currently, there is no treatment to slow down or to stop the disease. There is also no therapy to effectively reduce the symptoms. In the investigation of novel therapies, different animal models of Huntington's disease, varying from insects to nonhuman primates, have been created and used. Few years ago, the first transgenic rat model of HD, carrying a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter, was introduced. We have been using this animal model in our research and review here our experience with the behavioural, neurophysiological, and histopathological phenotype of the transgenic Huntington's disease rats with relevant literature.

  17. Variation within the Huntington's disease gene influences normal brain structure.

    Directory of Open Access Journals (Sweden)

    Mark Mühlau

    Full Text Available Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain.

  18. Proceedings of the National Silviculture Workshop: Density of Stocking Control; Eugene, Oregon; October 13-15, 1976

    Science.gov (United States)

    Jack H. Usher; Daniel B. Jones; A. R. Stage; Benjamin A. Roach; Gilbert B. Schubert; Darrell W. Crawford; Gilbert H. Schubert; Walter Fox; Edward A. Smith; Richard E. Lowrey Sofes; Richard F. Watt

    1976-01-01

    The 1976 National Silviculture Workshop was held in Eugene, Oregon, on October 13-15, 1976. The objectives were to discuss second growth management of individual stands, with particular emphasis on the control of stand density.

  19. Mäletamine, aeglus ja kontrollimatu kapitalism / Eugen Ruge ; intervjueerinud Dieter Neidlinger ; saksa keelest eesti keelde vahendanud Aija Sakova

    Index Scriptorium Estoniae

    Ruge, Eugen, 1954-

    2016-01-01

    Intervjuu kirjandusfestivalil "Prima vista" esineva saksa kirjaniku Eugen Rugega tema romaanides "Kahaneva valguse aegu" ("In Zeiten des abnehmenden Lichts") ja "Cabo de Gata" ning käsil olevast teosest

  20. [Eugen Helimski, Urlike Kahrs. Nordselkupisches Wörterbuch von F. G. Mal'cev (1903)] / Ago Künnap

    Index Scriptorium Estoniae

    Künnap, Ago, 1941-

    2003-01-01

    Raamatust: Helimski, Eugen, Kahrs, Urlike. Nordselkupisches Wörterbuch von F. G. Mal'cev (1903). Hamburg, 2001. (Hamburger Sibirische und Finnisch-Ugrische Materialen / Habent Sua Fata Manuscripts; 1)

  1. [Eugen Helimski, Urlike Kahrs. Nordselkupisches Wörterbuch von F. G. Mal'cev (1903)] / Ago Künnap

    Index Scriptorium Estoniae

    Künnap, Ago, 1941-

    2003-01-01

    Raamatust: Helimski, Eugen, Kahrs, Urlike. Nordselkupisches Wörterbuch von F. G. Mal'cev (1903). Hamburg, 2001. (Hamburger Sibirische und Finnisch-Ugrische Materialen / Habent Sua Fata Manuscripts; 1)

  2. "Hopelessly entangled in Nordic pre-suppositions": Catholic participation in the American Eugenics Society in the 1920s.

    Science.gov (United States)

    Leon, Sharon M

    2004-01-01

    While American Catholics stand out as some of the few voices of cultural opposition to the eugenics movement in the United States, Catholics and eugenicists actively engaged in conversational exchanges during the late 1920s. In association with the Committee on Cooperation with Clergymen of the American Eugenics Society, John A. Ryan and John Montgomery Cooper engaged in a process that Sander Gilman and Nancy Leys Stepan call "recontextualization," whereby they challenged the social and scientific basis for eugenics policy initiatives while constantly urging American eugenicists to rid their movement of racial and class prejudice. In the process, they participated in a revealing debate on immigration restriction, charity, racial hierarchies, feminism, birth control, and sterilization that points to both the instances of convergence and divergence of Catholic and eugenic visions for the national community.

  3. Mäletamine, aeglus ja kontrollimatu kapitalism / Eugen Ruge ; intervjueerinud Dieter Neidlinger ; saksa keelest eesti keelde vahendanud Aija Sakova

    Index Scriptorium Estoniae

    Ruge, Eugen, 1954-

    2016-01-01

    Intervjuu kirjandusfestivalil "Prima vista" esineva saksa kirjaniku Eugen Rugega tema romaanides "Kahaneva valguse aegu" ("In Zeiten des abnehmenden Lichts") ja "Cabo de Gata" ning käsil olevast teosest

  4. Tetrabenazine is neuroprotective in Huntington's disease mice

    Directory of Open Access Journals (Sweden)

    Tang Tie-Shan

    2010-04-01

    Full Text Available Abstract Background Huntington's disease (HD is a neurodegenerative disorder caused by a polyglutamine (polyQ expansion in Huntingtin protein (Htt. PolyQ expansion in Httexp causes selective degeneration of striatal medium spiny neurons (MSN in HD patients. A number of previous studies suggested that dopamine signaling plays an important role in HD pathogenesis. A specific inhibitor of vesicular monoamine transporter (VMAT2 tetrabenazine (TBZ has been recently approved by Food and Drug Administration for treatment of HD patients in the USA. TBZ acts by reducing dopaminergic input to the striatum. Results In previous studies we demonstrated that long-term feeding with TBZ (combined with L-Dopa alleviated the motor deficits and reduced the striatal neuronal loss in the yeast artificial chromosome transgenic mouse model of HD (YAC128 mice. To further investigate a potential beneficial effects of TBZ for HD treatment, we here repeated TBZ evaluation in YAC128 mice starting TBZ treatment at 2 months of age ("early" TBZ group and at 6 months of age ("late" TBZ group. In agreement with our previous studies, we found that both "early" and "late" TBZ treatments alleviated motor deficits and reduced striatal cell loss in YAC128 mice. In addition, we have been able to recapitulate and quantify depression-like symptoms in TBZ-treated mice, reminiscent of common side effects observed in HD patients taking TBZ. Conclusions Our results further support therapeutic value of TBZ for treatment of HD but also highlight the need to develop more specific dopamine antagonists which are less prone to side-effects.

  5. Everyday cognition in prodromal Huntington disease.

    Science.gov (United States)

    Williams, Janet K; Kim, Ji-In; Downing, Nancy; Farias, Sarah; Harrington, Deborah L; Long, Jeffrey D; Mills, James A; Paulsen, Jane S

    2015-03-01

    Assessment of daily functions affected by cognitive loss in prodromal Huntington's disease (HD) is necessary in practice and clinical trials. We evaluated baseline and longitudinal sensitivity of the Everyday Cognition (ECog) scales in prodromal HD and compared self- and companion-ratings. Everyday cognition was self-assessed by 850 participants with prodromal HD and 768 companions. We examined internal structure using confirmatory factor analysis (CFA) on baseline data. For longitudinal analysis, we stratified participants into Low, Medium, and High disease progression groups. We examined ECog scores for group differences and participant-and-companion differences using linear mixed effects regression (LMER). Comparison with the Total Functional Capacity (TFC) scale was made. CFA revealed good fit of a 5-factor model having a global factor (total score), and subfactors (subscales) of memory, language, visuospatial perception, and executive function. At study entry, participants and companions in the Medium and High groups reported significantly worsened everyday cognition as well as significant functional decline over time. Losses became more pronounced and participant and companion ratings diverged as individuals progressed. TFC showed significant functional loss over time in the High group but not in the Medium group. Disease progression is associated with reduced self- and companion-reported everyday cognition in prodromal HD participants who are less than 13 years to estimated motor onset. Our findings suggest companion ratings are more sensitive than participants' for detecting longitudinal change in daily cognitive function. ECog appears more sensitive to specific functional changes in the prodrome of HD than the TFC. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  6. To know eugenics and turn away eugenic mistake%认识优生学,走出优生的误区

    Institute of Scientific and Technical Information of China (English)

    陈基平

    2005-01-01

    目的正确认识何谓优生学.方法了解优生学的产生和发展过程,纠正社会上对优生的一些误解.结果优生优育不等同于"eugenics".结论优生是指通过保健、咨询、教育等手段,来帮助父母生出一个身心健康的孩子.

  7. An improved assay for the determination of Huntington`s disease allele size

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, C.; Klinger, K.; Miller, G. [Intergrated Genetics, Framingham, MA (United States)

    1994-09-01

    The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra- or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.

  8. The Counselor and Genetic Disease: Huntington's Disease as a Model.

    Science.gov (United States)

    Wexler, Nancy S.

    This speech offers a brief description of Huntington's Disease (HD): its causes, symptoms, and incidence. It then concentrates on the psychological problems of persons one of whose parents had the disease, and the role of the counselor in helping these humans cope with their fears about contacting it themselves. A relatively detailed case study is…

  9. Age, CAG repeat length, and clinical progression in Huntington's disease.

    Science.gov (United States)

    Rosenblatt, Adam; Kumar, Brahma V; Mo, Alisa; Welsh, Claire S; Margolis, Russell L; Ross, Christopher A

    2012-02-01

    The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow-up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini-Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment.

  10. Biological Markers of Cognition in Prodromal Huntington's Disease: A Review

    Science.gov (United States)

    Papp, Kathryn V.; Kaplan, Richard F.; Snyder, Peter J.

    2011-01-01

    Huntington's disease (HD), an autosomal-dominant genetic disorder, has historically been viewed as a degenerative movement disorder but it also includes psychiatric symptoms and progressive cognitive decline. There has been a lack of consensus in the literature about whether or not cognitive signs can be detected in carriers before clinical…

  11. Huntington II Simulation Program-POLUT. Teacher's Guide.

    Science.gov (United States)

    Braun, L.; And Others

    This teacher's guide is written to accompany the Huntington II Simulation Program - POLUT. POLUT is a program written in BASIC which provides simulation of the interaction between water and waste. It creates a context within which the user can control specific variables which effect the quality of a water resource. The teacher's guide provides…

  12. Exploring Genetic Factors Involved in Huntington Disease Age of Onset

    DEFF Research Database (Denmark)

    Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel;

    2015-01-01

    Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of ...

  13. Clinical and genetic features of Huntington disease in Sri Lanka.

    Science.gov (United States)

    Sumathipala, Dulika S; Jayasekara, Rohan W; Dissanayake, Vajira H W

    2013-12-05

    Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka. Data of 35 consecutive patients tested from 2007 to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was analyzed retrospectively. Clinical data and genetic diagnostic results were reviewed. Statistical analysis was performed using descriptive statistics. Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and 64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2 patients with Juvenile onset (60 years) Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 -91%). Three patients had psychiatric and behavioral disorders. The age difference between onset and genetic diagnosis showed significant delay in females compared to males (p Huntington disease in the Sri Lankan study population were similar to that previously reported in literature.

  14. PSYCHIATRIC ASPECTS OF HUNTINGTON DISEASE – CASE REPORTS

    Directory of Open Access Journals (Sweden)

    Mirela Batta

    2004-04-01

    Full Text Available Background. Huntington disease occurrs rarely, it can be encountered not only by neurologists and psychiatrists but also by other medical practitioners. Its characteristic features are involuntary movements, cognitive disorders and gradual development of dementia. Diagnosis is given on the basis of these clinical features, positive familial anamnesis, with the laboratory exclusion of other neuropsychiatric diseases and with the help of neuroimaging methods (in particular NMR. The disease can be only confirmed by means of genetic analysis.Patients and methods. In this article, four cases of patients with Huntington disease and diverse psychiatric disorders that were hospitalised at the psychiatric department of the Maribor General Hospital between October 2002 and March 2003 are described. All the patients fulfilled the valid criteria for the diagnosis of Huntington disease. However, they differed according to their accompanying psychiatric psychopathology, age and social problems.Conclusions. The purpose of this article is to draw attention to different psychiatric symptoms and clinical manifestations of Huntington disease that are often misleading in the diagnostic process. In addition, exigency of early diagnostics, guidelines for referrals to genetic testing and psychiatric monitoring of these patients are emphasised.

  15. Expression pattern of apoptosis-related markers in Huntington's disease

    NARCIS (Netherlands)

    Vis, José C; Schipper, Ellis; de Boer-van Huizen, Roelie T; Verbeek, Marcel M; de Waal, Rob M W; Wesseling, Pieter; ten Donkelaar, Hans J; Kremer, Berry

    2005-01-01

    Inappropriate apoptosis has been implicated in the mechanism of neuronal death in Huntington's disease (HD). In this study, we report the expression of apoptotic markers in HD caudate nucleus (grades 1-4) and compare this with controls without neurological disease. Terminal transferase-mediated biot

  16. Hitler's bible: an analysis of the relationship between American and German eugenics in pre-war Nazi Germany.

    Science.gov (United States)

    Brown, Susan

    2009-06-01

    Throughout the last century the wellbeing of those with disability has been threatened by the idea of eugenics. The most notable and extreme example of this could be considered to have been carried out during World WarTwo, within Nazi eugenic programmes. These resulted in the sterilisation and killing of hundreds of thousands of disabled people. Through research of a wide range of sources it has been established that much of the inspiration and encouragement for this rapidly progressing movement in Germany initially came from America, most notably from California. American eugenicists expressed interest, and at times jealousy, at the speed of the progression in German eugenics. German Sterilisation laws were drafted following careful study of American experiments and research, while financial support from a number of American individuals encouraged further German research. Correspondence between influential leaders, including Hitler, Grant and Whitney, Verschuer and Popenoe, on both sides also added to the developing relationship. In conclusion, although there are a number of vital differences between the progress of the eugenics programme in America and in pre-war Nazi Germany, and eugenics in America never produced the massive genocide that occurred in Germany, it is clear that the research, encouragement and enthusiasm from America had a profound influence on the rapidly growing Nazi eugenics movement.

  17. From species ethics to social concerns: Habermas's critique of "liberal eugenics" evaluated.

    Science.gov (United States)

    Árnason, Vilhjálmur

    2014-10-01

    Three arguments of Habermas against "liberal eugenics" -- the arguments from consent, responsibility, and instrumentalization -- are critically evaluated and explicated in the light of his discourse ethics and social theory. It is argued that these arguments move partly at a too deep level and are in part too individualistic and psychological to sufficiently counter the liberal position that he sets out to criticize. This is also due to limitations that prevent discourse ethics from connecting effectively to the moral and political domains, e.g., through a discussion of justice. In spite of these weaknesses, Habermas's thesis is of major relevance and brings up neglected issues in the discussion about eugenic reproductive practices. This relevance has not been duly recognized in bioethics, largely because of the depth of his speculations of philosophical anthropology. It is argued that Habermas's notion of the colonization of the lifeworld could provide the analytical tool needed to build that bridge to the moral and political domain.

  18. 'These pushful days': time and disability in the age of eugenics.

    Science.gov (United States)

    Baynton, Douglas C

    2011-01-01

    At the turn of the twentieth century, social attitudes toward disability turned sharply negative. An international eugenics movement brought about restrictive immigration laws in the United States and other immigrant nations. One cause was the changing understanding of time, both historical and quotidian, that accompanied the advent of evolutionary theory and a competitive industrial economy. As analogies of competition became culturally ubiquitous, new words to talk about disability such as 'handicapped', 'retarded', 'abnormal', 'degenerate', and 'defective', came into everyday use, all of them explicitly or implicitly rooted in new ways of thinking about time. The intense fear of disability that characterised the eugenics movement grew, in good part, from this new and unsettling vision of time.

  19. Propulsion by light: a tribute to the German pioneer Eugen Saenger (Plenary Paper)

    Science.gov (United States)

    Bohn, Willy L.

    2004-09-01

    Although the laser was not yet invented Eugen Saenger, one of the most prominent German personalities in the early development of rocket science and technology suggested to use photons for the propulsion of spacecrafts in the fifties. In contrast to current schemes which are basically aimed at laser induced ablation processes, Eugen Saenger started with the idea of using the radiation pressure itself for propulsion purposes. A review of his pioneering work in that area will be supported by numerous historical documents and personal remembrance showing his effort to promote unconventional ideas. The paper also emphasizes how some of the original concepts are being revisited and partly implemented by using today"s laser technology.

  20. From political economy to sociology: Francis Galton and the social-scientific origins of eugenics.

    Science.gov (United States)

    Renwick, Chris

    2011-09-01

    Having coined the word 'eugenics' and inspired leading biologists and statisticians of the early twentieth century, Francis Galton is often studied for his contributions to modern statistical biology. However, whilst documenting this part of his work, historians have frequently neglected crucial aspects of what motivated Galton to establish his eugenics research programme. Arguing that his work was shaped more by social than by biological science, this paper addresses these oversights by tracing the development of Galton's programme, from its roots in a debate about political economy to his appeals for it to be taken up by sociologists. In so doing, the paper not only returns Galton's ideas to their original context but also provides a reason to reflect on the place of the social sciences in history-of-science scholarship.

  1. [The 100-year anniversary of Eugene Jamot's (1879-1937) admittance to the Pharo School].

    Science.gov (United States)

    Milleliri, J M; Louis, F J

    2010-04-01

    For the 100-year anniversary of Dr. Eugene Jamot's (1879-1937) admittance to the Pharo School (then known as the Training School of the Colonial Army Health Corps), the authors describe the life of a French military physician working in Africa. Eugene Jamot devoted 22 years of his life to fighting sleeping sickness. Using a standardized approach that has become a textbook example, he was highly successful in controlling this dreaded tropical disease. Despite being criticized by some officials of the colonial administration and becoming the target of an obvious smear campaign because of his strong personality and growing fame, Jamot handed down a set of values that are recognized by most physicians working to improve the living conditions of the unfortunately still suffering African population.

  2. Employing Real Time PCR for the Diagnosis of Huntington Disease

    Directory of Open Access Journals (Sweden)

    Frouzandeh Mahjoubi

    2013-07-01

    Full Text Available Background: Huntington disease (HD is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia. The onset age of this disease is varied but usually is between the ages 40-50. Huntington's disease is caused by a triplet-repeat expansion in the IT15 gene (also known as huntingtin or HD which is located on chromosome 4p3.1. Since many clinical picture of HD are indistinguishable from other distinct genetic disorders molecular test such as PCR is the only way to confirm the disease. The aim of this study was to introduce a new and fast technique for the diagnosis of Huntington disease.Materials and Methods: Blood specimens were collected from individuals suspected for Huntington disease and also people with no symptoms and family history of this disease. DNAs were extracted according to standard protocol. Using conventional PCR, patient positive for Huntington disease were diagnosed. Then employing real time PCR on the basis of difference between melting temperature (Tm a new and fast diagnostic method was introduced.Results: Among 29 patients suspected to be HD only 8 HD patients were confirmed using PCR and real time PCR. The numbers of CAG repeat were between 42-50 and melting temperatures were between 89-92.Conclusion: The concept of using melting temperature in real time PCR protocol presented in here could be employed for the rapid diagnosis of the diseases caused by the increased in triple repeat sequences. It is fast, robust and has the potential use for the prenatal diagnosis.

  3. Major Superficial White Matter Abnormalities in Huntington's Disease

    Science.gov (United States)

    Phillips, Owen R.; Joshi, Shantanu H.; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Narr, Katherine; Shattuck, David W.; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

    2016-01-01

    Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease. PMID:27242403

  4. Huntington舞蹈病一家系临床遗传学分析%Clinical-Genetic Analysis of the Huntington Chorea

    Institute of Scientific and Technical Information of China (English)

    罗纯

    2012-01-01

    目的 通过分析Huntington舞蹈病一家系临床资料并对症前高风险成员进行再发风险预测,为该病的基因诊断和遗传咨询提供科学依据.方法 全面的家系调查、深入的系谱分析和主动的遗传优生咨询.结果 以先证者为线索深入调查此家系4代39人,家系中有Htington舞蹈病患者7例,3男4女;高风险者7名,需进一步进行基因诊断.结论 此病为常染色体显性遗传病;体现了延迟显性、遗传印记和遗传早现等遗传学特征;对家系高风险者进行婚育指导和症前、孕前、产前诊断对避免患儿的出生具有重要意义.%OBJECTIVE To analyze the clinical data of a Huntington Chorea family and predicting the recurrence risk before symptomatic recurrence for high-risk members, provide scientific basis for genetic disease diagnosis and counseling. METHODS Comprehensive family survey, in-depth genetic pedigree analysis and proactive eugenic counseling were conducted. RESULTS We took the proband as a clue to look into the four generations of a family with 39 people, 7 of them (3 males and 4 females) had Huntington Chorea, another 7 had high risk who were subjects to further genetic diagnosis. CONCLUSION The Huntington Chorea is autosomal dominant inheritance. It features delayed dominance, genetic imprinting, genetic anticipation and other genetic characteristics. For families at high risk, it is critical to provide guidance on marriage and child rearing, pre-pregnancy and prenatal diagnosis in order to avoid the birth of children with the disease.

  5. A gift of prophecy essays in celebration of the life of Robert Eugene Marshak

    CERN Document Server

    1994-01-01

    Robert Eugene Marshak (1916-92) devoted much of his life to helping other people carry out scientific research and gather to discuss their work. In addition to his scientific statesmanship, he was an extraordinarily gifted research scientist, and many of his scientific contributions have been prophetic. This book pays homage to his creativity and continuing work, with contributions from many of the people whose lives have been influenced by him.

  6. [Eugenics' extension in the Spanish health care system through the prenatal diagnosis].

    Science.gov (United States)

    Rodríguez Martín, Esteban

    2012-01-01

    The wide implantation of strategies of sifted or prenatal selection close to laws that protect the destruction of the human life before the childbirth in the whole world, they are giving place to an increasing number of eugenic abortions. In Spain, the law 2/2010 of the sexual and reproductive health and voluntary interruption of pregnancy there has supposed the liberalization of the eugenic abortion without term limit. In we make concrete, the sanitary national and international policies of prenatal selection of Down's Syndrome, which they chase to facilitate the total or partial destruction before the childbirth of this human group, submitting it to a few particular conditions of existence during his prenatal life in those who will be an object of a series of technologies of selection, they might be qualified of genocidal policies if we consider the definition of genocide given by United Nations. In consequence, the sanitary agent who takes part without objection in the above mentioned programs promoted by the principal agents, meets turned into a necessary cooperator of the abortion who justifies itself in the supposition of "foetal risk". We can conclude that we are present at an eugenic drift of the prenatal diagnosis that is opposite to the ethical beginning of the medical profession.

  7. The doers of good. Scandinavian historians revise the social history of eugenics(1997-2001).

    Science.gov (United States)

    Zylberman, Patrick

    2008-01-01

    Late disclosure of the large scale of sterilization practices in the Nordic countries created an outburst of scandal: did these policies rely on coercion? To what extent? Who in the end was responsible? Sterilization practices targeted underprivileged people first. The mentally retarded and women were their first victims. Operations were very frequently determined by other people's manipulative or coercive influences. Should the blame be put on the Social-Democrats in power throughout the period (except in Finland and Estonia)? Apart from Denmark, perhaps, local physicians and local services, more than governments, seemed to have strongly supported sterilization practices. Teetotalers and feminists shared responsibilities. How can one explain that eugenics finally declined? Based on a sound application of the Hardy-Weinberg law, the science of the eugenicists was correct. Was it politics? But uncovering of the Nazi crimes had only a very small impact on eugenics. Some authors underline the fact that the Nordic scientific institutions were particularly suited to liberal values. Others point to the devastating effect on eugenics once hereditarist psychiatry fell from favor in the middle of the sixties.

  8. Eugenic World Building and Disability: The Strange World of Kazuo Ishiguro's Never Let Me Go.

    Science.gov (United States)

    Garland-Thomson, Rosemarie

    2017-06-01

    A crucial challenge for critical disability studies is developing an argument for why disabled people should inhabit our democratic, shared public sphere. The ideological and material separation of citizens into worthy and unworthy based on physiological variations imagined as immutable differences is what I call eugenic world building. It is justified by the idea that social improvement and freedom of choice require eliminating devalued human traits in the interest of reducing human suffering, increasing life quality, and building a more desirable citizenry. In this essay, I outline the logic of inclusive and eugenic world building, define and explain the role of the "normate" in eugenic logic, and provide a critical disability studies reading of the 2005 novel Never Let Me Go by Kazuo Ishiguro and its 2010 film adaptation. I argue that the ways of being in the world we think of as disabilities must be understood as the natural variations, abilities, and limitations inherent in human embodiment. When this happens, disability will be understood not as a problem to be eliminated but, rather, as a valid way of being in the world that must be accommodated through a sustaining and sustainable environment designed to afford access for a wide range of human variations.

  9. Targeting the Cholinergic System to Develop a Novel Therapy for Huntington's Disease.

    Science.gov (United States)

    D'Souza, Gary X; Waldvogel, Henry J

    2016-12-15

    In this review, we outline the role of the cholinergic system in Huntington's disease, and briefly describe the dysfunction of cholinergic transmission, cholinergic neurons, cholinergic receptors and cholinergic survival factors observed in post-mortem human brains and animal models of Huntington's disease. We postulate how the dysfunctional cholinergic system can be targeted to develop novel therapies for Huntington's disease, and discuss the beneficial effects of cholinergic therapies in pre-clinical and clinical studies.

  10. Crime in Huntington's disease: a study of registered offences among patients, relatives, and controls

    OpenAIRE

    Jensen, P; Fenger, K; Bolwig, T; Sorensen, S. A.

    1998-01-01

    OBJECTIVES—Criminal behaviour has been described as a problem in Huntington's disease, but systematic studies including control groups have been missing. Based on information from Danish registries, rates and types of crime committed by patients with Huntington's disease, non-affected relatives, and controls were studied.
METHODS—99 males and 151 females with Huntington's disease were compared with 334 non-affected first degree relatives (134 men and 200 women) and to matche...

  11. Human heredity and politics: A comparative institutional study of the Eugenics Record Office at Cold Spring Harbor (United States), the Kaiser Wilhelm Institute for Anthropology, Human Heredity, and Eugenics (Germany), and the Maxim Gorky Medical Genetics Institute (USSR).

    Science.gov (United States)

    Adams, Mark B; Allen, Garland E; Weiss, Sheila Faith

    2005-01-01

    Despite the fact that much has been written in recent years about the science of heredity under the Third Reich, there is as yet no satisfying analysis of two central questions: What, if anything, was peculiarly "Nazi" about human genetics under National Socialism? How, under whatever set of causes, did at least some of Germany's most well-known and leading biomedical practioners become engaged in entgrenzte Wissenschaft (science without moral boundaries)? This paper attempts to provide some answers to these two questions comparing three institutes that studied eugenics and human heredity in the 1920s and 1930s: the Eugenics Record Office at Cold Spring Harbor, New York, directed by Charles B. Davenport; the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics, in Berlin, directed by Eugen Fischer; and the Maxim Gorky Medical Genetics Institute in Moscow, directed by Solomon G. Levit. The institutes are compared on the basis of the kind and quality of their research in eugenics and medical genetics, organizational structure, leadership, patronage (private or state), and the economic-social-political context in which they functioned.

  12. Family caregivers' views on coordination of care in Huntington's disease

    DEFF Research Database (Denmark)

    Røthing, Merete; Malterud, Kirsti; Frich, Jan C

    2015-01-01

    BACKGROUND: Collaboration between family caregivers and health professionals in specialised hospitals or community-based primary healthcare systems can be challenging. During the course of severe chronic disease, several health professionals might be involved at a given time, and the patient......'s illness may be unpredictable or not well understood by some of those involved in the treatment and care. AIM: The aim of this study was to explore the experiences and expectations of family caregivers for persons with Huntington's disease concerning collaboration with healthcare professionals. METHODS......: To shed light on collaboration from the perspectives of family caregivers, we conducted an explorative, qualitative interview study with 15 adult participants experienced from caring for family members in all stages of Huntington's disease. Data were analysed with systematic text condensation, a cross...

  13. Psychodynamic theory and counseling in predictive testing for Huntington's disease.

    Science.gov (United States)

    Tassicker, Roslyn J

    2005-04-01

    This paper revisits psychodynamic theory, which can be applied in predictive testing counseling for Huntington's Disease (HD). Psychodynamic theory has developed from the work of Freud and places importance on early parent-child experiences. The nature of these relationships, or attachments are reflected in adult expectations and relationships. Two significant concepts, identification and fear of abandonment, have been developed and expounded by the psychodynamic theorist, Melanie Klein. The processes of identification and fear of abandonment can become evident in predictive testing counseling and are colored by the client's experience of growing up with a parent affected by Huntington's Disease. In reflecting on family-of-origin experiences, clients can also express implied expectations of the future, and future relationships. Case examples are given to illustrate the dynamic processes of identification and fear of abandonment which may present in the clinical setting. Counselor recognition of these processes can illuminate and inform counseling practice.

  14. Abnormalities in the tricarboxylic Acid cycle in Huntington disease and in a Huntington disease mouse model.

    Science.gov (United States)

    Naseri, Nima N; Xu, Hui; Bonica, Joseph; Vonsattel, Jean Paul G; Cortes, Etty P; Park, Larry C; Arjomand, Jamshid; Gibson, Gary E

    2015-06-01

    Glucose metabolism is reduced in the brains of patients with Huntington disease (HD). The mechanisms underlying this deficit, its link to the pathology of the disease, and the vulnerability of the striatum in HD remain unknown. Abnormalities in some of the key mitochondrial enzymes involved in glucose metabolism, including the pyruvate dehydrogenase complex (PDHC) and the tricarboxylic acid (TCA) cycle, may contribute to these deficits. Here, activities for these enzymes and select protein levels were measured in human postmortem cortex and in striatum and cortex of an HD mouse model (Q175); mRNA levels encoding for these enzymes were also measured in the Q175 mouse cortex. The activities of PDHC and nearly all of the TCA cycle enzymes were dramatically lower (-50% to 90%) in humans than in mice. The activity of succinate dehydrogenase increased with HD in human (35%) and mouse (23%) cortex. No other changes were detected in the human HD cortex or mouse striatum. In Q175 cortex, there were increased activities of PDHC (+12%) and aconitase (+32%). Increased mRNA levels for succinyl thiokinase (+88%) and isocitrate dehydrogenase (+64%) suggested an upregulation of the TCA cycle. These patterns of change differ from those reported in other diseases, which may offer unique metabolic therapeutic opportunities for HD patients.

  15. Pluripotent hybrid stem cells from transgenic Huntington's disease monkey.

    Science.gov (United States)

    Laowtammathron, Chuti; Chan, Anthony W S

    2013-01-01

    Huntington's disease (HD) is a devastating disease that currently has no cure. Transgenic HD monkeys have developed key neuropathological and cognitive behavioral impairments similar to HD patients. Thus, pluripotent stem cells derived from transgenic HD monkeys could be a useful comparative model for clarifying HD pathogenesis and developing novel therapeutic approaches, which could be validated in HD monkeys. In order to create personal pluripotent stem cells from HD monkeys, here we present a tetraploid technique for deriving pluripotent hybrid HD monkey stem cells.

  16. Striatal degeneration impairs language learning: evidence from Huntington's disease.

    Science.gov (United States)

    De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C

    2008-11-01

    Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly

  17. Long-term outcome of presymptomatic testing in Huntington disease

    OpenAIRE

    Gargiulo, Marcela; Lejeune, Séverine; Tanguy, Marie-Laure; Lahlou-Laforêt, Khadija; Faudet, Anne; Cohen, David; Feingold, Josué; Durr, Alexandra

    2008-01-01

    Our study on long-term outcome of presymptomatic testing for Huntington disease had two aims: the comparison of the psychological well-being and social adjustment of carriers and non-carriers of the mutation, and the identification of psychological determinants to improve care/support of testees. We performed a cross-sectional study of 351 persons who underwent presymptomatic testing. Those who had motor signs were excluded from the comparison of asymptomatic carrier and non-carriers. A struc...

  18. The structural involvement of the cingulate cortex in premanifest and early Huntington's disease.

    Science.gov (United States)

    Hobbs, Nicola Z; Pedrick, Amy V; Say, Miranda J; Frost, Chris; Dar Santos, Rachelle; Coleman, Allison; Sturrock, Aaron; Craufurd, David; Stout, Julie C; Leavitt, Blair R; Barnes, Josephine; Tabrizi, Sarah J; Scahill, Rachael I

    2011-08-01

    The impact of Huntington's disease neuropathology on the structure of the cingulate is uncertain, with evidence of both cortical enlargement and atrophy in this structure in early clinical disease. We sought to determine differences in cingulate volume between premanifest Huntington's disease and early Huntington's disease groups compared with controls using detailed manual measurements. Thirty controls, 30 subjects with premanifest Huntington's disease, and 30 subjects with early Huntington's disease were selected from the Vancouver site of the TRACK-HD study. Subjects underwent 3 Tesla magnetic resonance imaging and motor, cognitive, and neuropsychiatric assessment. The cingulate was manually delineated and subdivided into rostral, caudal, and posterior segments. Group differences in volume and associations with performance on 4 tasks thought to utilize cingulate function were examined, with adjustment for appropriate covariates. Cingulate volumes were, on average, 1.7 mL smaller in early Huntington's disease (P=.001) and 0.9 mL smaller in premanifest Huntington's disease (P=.1) compared with controls. Smaller volumes in subsections of the cingulate were associated with impaired recognition of negative emotions (P=.04), heightened depression (P=.009), and worse visual working memory performance (P=.01). There was no evidence of associations between volume and ability on a performance-monitoring task. This study disputes previous findings of enlargement of the cingulate cortex in Huntington's disease and instead suggests that the cingulate undergoes structural degeneration during early Huntington's disease with directionally consistent, nonsignificant differences seen in premanifest Huntington's disease. Cingulate atrophy may contribute to deficits in mood, emotional processing, and visual working memory in Huntington's disease.

  19. A laboratory for Latin eugenics: the Italian Committee for the Study of Population Problems and the international circulation of eugenic knowledge, 1920s-1940s

    Directory of Open Access Journals (Sweden)

    Luc André Berlivet

    Full Text Available Abstract The aim of this article is to shed light on the rise to international prominence of the Italian statistician and eugenicist Corrado Gini and his appointment as the inaugural president of the Latin International Federation of Eugenic Societies in October 1935. It explores the numerous pioneering, still little known, investigations he undertook with a few Italian scientists and some foreign scholars, in order to analyze the role played by “isolation,” and “racial hybridization” in the formation and degeneration of human races. After outlining Gini’s professional and political trajectory, the article focuses on the scientific expeditions launched by the Italian Committee for the Study of Population Problems between 1933 and 1940 under his stewardship.

  20. Preimplantation genetic diagnosis for Huntington's disease with exclusion testing.

    Science.gov (United States)

    Sermon, Karen; De Rijcke, Martine; Lissens, Willy; De Vos, Anick; Platteau, Peter; Bonduelle, Maryse; Devroey, Paul; Van Steirteghem, André; Liebaers, Inge

    2002-10-01

    Huntington's disease is an autosomal dominant, late-onset disorder, for which the gene and the causative mutation have been known since 1993. Some at-risk patients choose for presymptomatic testing and can make reproductive choices accordingly. Others however, prefer not to know their carrier status, but may still wish to prevent the birth of a carrier child. For these patients, exclusion testing after prenatal sampling has been an option for many years. A disadvantage of this test is that unaffected pregnancies may be terminated if the parent at risk (50%) has not inherited the grandparental Huntington gene, leading to serious moral and ethical objections. As an alternative, preimplantation genetic diagnosis (PGD) on embryos obtained in vitro may be proposed, after which only embryos free of risk are replaced. Embryos can then be selected, either by the amplification of the CAG repeat in the embryos without communicating results to the patients (ie non-disclosure testing), which brings its own practical and moral problems, or exclusion testing. We describe here the first PGD cycles for exclusion testing for Huntington's disease in five couples. Three couples have had at least one PGD cycle so far. One pregnancy ensued and a healthy female baby was delivered.

  1. iPSC-based drug screening for Huntington's disease.

    Science.gov (United States)

    Zhang, Ningzhe; Bailus, Barbara J; Ring, Karen L; Ellerby, Lisa M

    2016-05-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. The disease generally manifests in middle age with both physical and mental symptoms. There are no effective treatments or cures and death usually occurs 10-20 years after initial symptoms. Since the original identification of the Huntington disease associated gene, in 1993, a variety of models have been created and used to advance our understanding of HD. The most recent advances have utilized stem cell models derived from HD-patient induced pluripotent stem cells (iPSCs) offering a variety of screening and model options that were not previously available. The discovery and advancement of technology to make human iPSCs has allowed for a more thorough characterization of human HD on a cellular and developmental level. The interaction between the genome editing and the stem cell fields promises to further expand the variety of HD cellular models available for researchers. In this review, we will discuss the history of Huntington's disease models, common screening assays, currently available models and future directions for modeling HD using iPSCs-derived from HD patients. This article is part of a Special Issue entitled SI: PSC and the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Informativeness of Early Huntington Disease Signs about Gene Status.

    Science.gov (United States)

    Oster, Emily; Eberly, Shirley W; Dorsey, E Ray; Kayson-Rubin, Elise; Oakes, David; Shoulson, Ira

    2015-01-01

    The cohort-level risk of Huntington disease (HD) is related to the age and symptom level of the cohort, but this relationship has not been made precise. To predict the evolving likelihood of carrying the Huntington disease (HD) gene for at-risk adults using age and sign level. Using data from adults with early signs and symptoms of HD linked to information on genetic status, we use Bayes' theorem to calculate the probability that an undiagnosed individual of a certain age and sign level has an expanded CAG repeat. Both age and sign levels have substantial influence on the likelihood of HD onset, and the probability of eventual diagnosis changes as those at risk age and exhibit (or fail to exhibit) symptoms. For example, our data suggest that in a cohort of individuals age 26 with a Unified Huntington's Disease Rating Scale (UHDRS) motor score of 7-10 70% of them will carry the HD mutation. For individuals age 56, the same motor score suggests only a 40% chance of carrying the mutation. Early motor signs of HD, overall and the chorea subscore, were highly predictive of disease onset at any age. However, body mass index (BMI) and cognitive performance scores were not as highly predictive. These results suggest that if researchers or clinicians are looking for early clues of HD, it may be more foretelling to look at motor rather than cognitive signs. Application of similar approaches could be used with other adult-onset genetic conditions.

  3. Contribution of imaging studies and neuro physiologic investigations to the diagnosis of Huntington`s chorea; L`imagerie medicale et les explorations neuro-physiologiques dans le diagnostic de la choree de Huntington

    Energy Technology Data Exchange (ETDEWEB)

    Paquet, J.M.; Turpin, J.CI. [Centre Hospitalier Universitaire, 51 - Reims (France)

    1997-05-01

    Although Huntington`s disease was described in 1872, its diagnosis continues to rest on clinical grounds. Recently developed techniques for imaging the brain (computed tomography and magnetic resonance imaging) or studying its function (single photon emission computed tomography and positron emission tomography) have demonstrated only non specific abnormalities at the early stages of the disease, thus failing to improve the pre-symptomatic diagnosis. Neuro-physiologic investigations (evoked potentials, electromyogram, electroencephalogram) have been similarly unrewarding. Investigations are useful only as an laid to the differential diagnosis. Molecular biology technology is the only available tool for identifying high-risk individuals and establishing a definitive diagnosis of Huntington`s disease. (authors). 10 refs.

  4. Inherently Undesirable: American Identity and the Role of Negative Eugenics in the Education of Visually Impaired and Blind Students in Ohio, 1870-1930

    Science.gov (United States)

    Free, Jennifer L.

    2012-01-01

    To date, studies of eugenics artificially confine their focus to the movement's application to race, socio-economic status, and the forced sterilization of the so-called feebleminded. However, the segregationist aspect of the eugenics design in the United States brought with it damaging policies toward individuals with physical and mental…

  5. Eugenics and migration: a case study of Salvation Army literature about Canada and Britain, c.1890-1921.

    Science.gov (United States)

    Baker, Graham J

    2014-01-01

    The eugenics movement attracted a wide range of supporters. This article explores this theme with relation to literature about the charitable work of the Salvation Army in Britain and Canada c.1890-1921, with a focus upon the emigration scheme outlined in William Booth's book In Darkest England and the Way Out. These writings indicate the widespread dispersal of eugenic ideology, and demonstrate the flexibility with which these theories were interpreted in this period. It will be shown that the Salvation Army adopted elements of both hereditarian and environmentalist views regarding racial health. These arguments were unified by the claim that the work of the organization made a worthy contribution to public health, both in the present and in the future. This case study sheds new light upon the history of a prominent evangelical Christian organization and upon the development of the international eugenics movement.

  6. Eugenics as Indian removal: sociohistorical processes and the de(con)struction of American Indians in the southeast.

    Science.gov (United States)

    Gonzales, Angela; Kertész, Judy; Tayac, Gabrielle

    2007-01-01

    Although research on the history of the eugenics movement in the United States is legion, its impact on state policies that identified and defined American Indians has yet to be fully addressed. The exhibit, Our Lives: Comtemporary Life and Identities (ongoing until September 21, 2014) at the National Museum of the American Indian provides a provocative vehicle for examining how eugenics-informed public policy during the first quarter of the twentieth century served to "remove" from official records Native peoples throughout the Southeast. One century after Indian Removal of the antebellum era, Native peoples in the American Southeast provide an important but often overlooked example of how racial policies, this time rooted in eugenics, effected a documentary erasure of Native peoples and communities.

  7. Attitude and opinion of volunteer blood donors regarding access to eugenic

    Directory of Open Access Journals (Sweden)

    Konstantina Chatzilaou

    2009-02-01

    Full Text Available PURPOSE: The assessment of the attitude and views of blood donors in relation to eugenics. As well as the relation of eugenics to several demographical factors such as educational level, sex age and religious beliefs.MATERIAL AND METHOD: The subjects of study were 252 blood donors, who voluntarily gave blood and its byproducts in a Blood Donation Center in Athens. The data was collected through an anonymous questionnaire especially designed for the purpose of this study.RESULTS: The overwhelming majority of volunteer blood-donors agree in percentage greater than 50%, that society will probably never offer sufficient support to individuals with disabilities and that a woman should be submitted to prenatal control to determine if she medically advised in relation to her age and family background. 79% agrees that they would want to learn more about the moral questions that arise from the application of genetics to human.Independent variables that influence the attitude towards eugenics were found to be the importance of religion, the level of education, the sex and the number of children.Also, there was a connection of religion and the number of children with the knowledge of moral questions on genetics.CONCLUSIONS: Prenatal control should be carried out only when serious genetic illnesses or illnesses whose treatment is imperative to start early are expected. The attitude of citizens towards individuals with disabilities should change radically so that the biases and social stereotypes are raised. A better provision of information of the public on the moral questions that derive from the application of genetics to humans is also suggested.

  8. Mexican Americans and the American Nation: A Response to Professor Huntington

    Science.gov (United States)

    Telles, Edward

    2006-01-01

    This essay is based on a talk I delivered at Texas A&M University on December 10, 2005, in response to an earlier lecture at the university by Professor Samuel P. Huntington. It relies on social science evidence to first address Huntington's contention that Mexicans are overwhelming American borders. It then turns to evidence that Mexican…

  9. PROBLEMS OF MODERNIZATION IN THE WORKS OF S. HUNTINGTON: THEORY AND PRACTICE

    Directory of Open Access Journals (Sweden)

    Britikova E. A.

    2016-06-01

    Full Text Available The article discusses the interpretation of the mechanisms of modernization of the American scientist - Samuel Huntington, which sees modernization as a complex process with a very uncertain result. As a representative of the multilinear approach, Samuel Huntington proves the uniqueness of the modernization paths of each individual national system

  10. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    Science.gov (United States)

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  11. Eugene P. Wigner’s Visionary Contributions to Generations-I through IV Fission Reactors

    Directory of Open Access Journals (Sweden)

    Carré Frank

    2014-01-01

    Full Text Available Among Europe’s greatest scientists who fled to Britain and America in the 1930s, Eugene P. Wigner made instrumental advances in reactor physics, reactor design and technology, and spent nuclear fuel processing for both purposes of developing atomic weapons during world-war II and nuclear power afterwards. Wigner who had training in chemical engineering and self-education in physics first gained recognition for his remarkable articles and books on applications of Group theory to Quantum mechanics, Solid state physics and other topics that opened new branches of Physics.

  12. A paradigmatic disagreement in "Dialogue on Dialogic Pedagogy" by Eugene Matusov and Kiyotaka Miyazaki

    Directory of Open Access Journals (Sweden)

    Ana Marjanovic-Shane

    2014-10-01

    Full Text Available I read with a great pleasure the heated dialogue on Dialogic Pedagogy between Eugene Matusov and Kiyotaka Miyazaki. It provided me with one of those rare occasions where I could both witness, and also join, the workings of two minds as they struggled with and against each other to construct, de-construct, and reconstruct their visions of dialogic pedagogical approaches to education. As I was reading, I had a lot of questions and remarks. I try to summarize them here – while many are still left on the margins of the original manuscript.

  13. Eugene P. Wigner's Visionary Contributions to Generations-I through IV Fission Reactors

    Science.gov (United States)

    Carré, Frank

    2014-09-01

    Among Europe's greatest scientists who fled to Britain and America in the 1930s, Eugene P. Wigner made instrumental advances in reactor physics, reactor design and technology, and spent nuclear fuel processing for both purposes of developing atomic weapons during world-war II and nuclear power afterwards. Wigner who had training in chemical engineering and self-education in physics first gained recognition for his remarkable articles and books on applications of Group theory to Quantum mechanics, Solid state physics and other topics that opened new branches of Physics.

  14. Colombia en el contexto eugenésico latinoamericano 1900-1950

    Directory of Open Access Journals (Sweden)

    Juan Vianey Tovar Mosquera

    2016-01-01

    Full Text Available Introducción. La Eugenesia es un acontecimiento histórico que logró mover, una vez más, los fundamentos éticos tradicionales de la humanidad, cuestionando nuestra concepción de lo humano, haciendo de la diferencia, la debilidad o la enfermad una amenaza tangible urgente de normalizar o exterminar. Objetivo. Estudiar la forma como se desarrolló el movimiento eugenésico en Latinoamérica, en países como Argentina, Brasil, Colombia, Cuba, Chile, México y Perú. Materiales y métodos. Artículo de revisión de corte histórico; se seleccionó bibliografía que permitiera 1 brindar acercamiento al origen y principios de la Eugenesia; 2 investigaciones y artículos publicados en los países en mención que dan cuenta del desarrollo del movimiento eugenésico y de las políticas e instituciones con ocasión del mismo; 3 documentos históricos de intelectuales, políticos y educadores colombianos de la primera mitad del siglo XX para evaluar su adhesión al darwinismo social y al paradigma degeneracionista; 4 revisión de la legislación de la primera mitad del siglo XX en Colombia para analizar la materialización de principios eugenésicos y finalmente 5 se abordaron documentos que permiten consolidar una reflexión en torno a los graves problemas éticos y sociales que implicó la Eugenesia como un paradigma determinista biológica y socialmente. Resultados y discusión. Se evidencia que el movimiento eugenésico permeó el contexto latinoamericano definiendo, en la primera mitad del siglo XX, la política pública de los diferentes estados en materia educativa, médica, económica y migratoria, entre otras; generando graves problemas de estigmatización racial y moral.

  15. [Towards social eugenics. Ideology and bioethics in the construction of the social policy].

    Science.gov (United States)

    Fernández Riquelme, Sergio

    2009-01-01

    The social eugenics is the real face of the biomedical application of an ideological paradigm, self-styled like "progressive", that claims the radical transformation of the western society from laicist and utilitarians positions. This article tries to decipher the historical roots, the bioethical language and the political - social implications of this paradigm, which questions the essential dignity of any human life in benefit of "new rights", constructed ex professo. For it, it exposes three analytical dimensions of his "historical possibilities" (retrospective, perspective and Forward studies), taking as an example the role of the social Policy, and especially, the doctrinal and institutional paradoxes of the "Welfare state" in Spain.

  16. Contraception or eugenics? Sterilization and "mental retardation" in the 1970s and 1980s.

    Science.gov (United States)

    Ladd-Taylor, Molly

    2014-01-01

    Nonconsensual sterilization is usually seen as the by-product of a classist and racist society; disability is ignored. This article examines the 1973 sterilization of two young black girls from Alabama and other precedent-setting court cases involving the sterilization of "mentally retarded" white women to make disability more central to the historical analysis of sterilization. It analyzes the concept of mental retardation and the appeal of a surgical solution to birth control, assesses judicial deliberations over the "right to choose" contraceptive sterilization when the capacity to consent is in doubt, and reflects on the shadow of eugenics that hung over the sterilization debate in the 1970s and 1980s.

  17. The reception of Eugen Bleuler in British psychiatry, 1892-1954.

    LENUS (Irish Health Repository)

    Dalzell, Thomas

    2012-02-01

    This article draws on over 60 years of British medical journals and psychiatry textbooks to indicate the chronological stages of the reception of Eugen Bleuler in British psychiatry. Bleuler was already well known in Britain before his schizophrenia book appeared, with the journals containing numerous references, mainly positive, to his work. The psychiatry textbooks, however, were slower to integrate his contribution. This paper argues that this was not due to Bleuler\\'s placing Freud on a par with Kraepelin, but because of the early negative reaction to Kraepelin\\'s dementia praecox concept, despite Bleuler\\'s wider and less ominous conception of the illness.

  18. Huntington disease and Huntington disease-like in a case series from Brazil.

    Science.gov (United States)

    Castilhos, R M; Souza, A F D; Furtado, G V; Gheno, T C; Silva, A L; Vargas, F R; Lima, M-A F D; Barsottini, O; Pedroso, J L; Godeiro, C; Salarini, D; Pereira, E T; Lin, K; Toralles, M-B; Saute, J A M; Rieder, C R; Quintas, M; Sequeiros, J; Alonso, I; Saraiva-Pereira, M L; Jardim, L B

    2014-10-01

    The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

  19. From the 'Village of a Thousand Souls' to 'Race Crossing in Jamaica': Arnold Gesell, eugenics and child development.

    Science.gov (United States)

    Weizmann, Fredric

    2010-01-01

    Perhaps best known for providing age-related norms in early development, norms that are still used as a basis for measures of developmental maturity, Arnold Gesell was a key figure in developmental psychology from the 1920s through the 1950s. After examining Gesell's reputation and status in the field, we explore Gesell's changing relationship to eugenics, both in terms of Gesell's often contradictory attitudes about the role of hereditary and environmental influences in development, and in terms of the broader relationship between the eugenics movement and science.

  20. Measurement of caudate nucleus area - a more accurate measurement for Huntington's disease

    Energy Technology Data Exchange (ETDEWEB)

    Wardlaw, J.M.; Abernethy, L.J. (Royal Infirmary, London (United Kingdom). Dept. of Radiology); Sellar, R.J. (Western General Hospital, Edinburgh (United Kingdom). Dept. of Neuroradiology)

    1991-08-01

    Caudate nucleus atrophy occurs in Huntington's disease and methods of measuring this have been described using axial CT, but these are indirect and lack sensitivity. We measured caudate nucleus area (blind to the subjects' clinical state) in 30 subjects with or at risk of Huntington's disease, and in 100 normal age matched controls. Fifteen subjects with established symptomatic Huntington's disease, 3 with early symptoms, and 3 presymptomatic subjects (2 showing a high probability for the Huntington's disease gene on genetic testing, and one who has since developed symptoms) were correctly identified. Three normal (gene negative) family members were also correctly identified. Outcome is awaited in 6. CT caudate area measurement is simple and reproducible and we have found it to be a useful confirmatory test for Huntington's disease. (orig.).

  1. Clinical and counselling implications of preimplantation genetic diagnosis for Huntington's disease in the UK.

    Science.gov (United States)

    Lashwood, A; Flinter, F

    2001-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disorder that usually occurs in adult life. Individuals at risk can have a gene test before the onset of symptoms, and prenatal diagnosis is available. Preimplantation genetic diagnosis (PGD) for Huntington's disease is now available for couples in whom one partner has the gene for Huntington's disease. A licence to practise PGD is required from the Human Fertilisation and Embryology Authority, and there are several complex issues relating to PGD for Huntington's disease that require consideration. The partner of the Huntington's disease gene carrier should have a presymptomatic test to ensure accuracy in a PGD cycle. There should be a delay between blood sampling and testing for Huntington's disease to allow time for reflection and withdrawal from testing. All PGD treatment has an associated risk of misdiagnosis. If confirmatory prenatal testing is not undertaken after a successful PGD cycle, no confirmation of diagnosis will be obtained at birth. Guidelines indicate that individuals who are at risk cannot be tested before 18 years. There is concern over the ability of a child or adolescent to make an informed choice about testing before this age. Confirmatory testing at birth after PGD would be in direct contravention of these guidelines. In the UK, the law requires consideration of the welfare of children born after assisted conception treatment. Presenting symptoms of Huntington's disease may affect the parenting abilities of an affected individual. There is a need for an assessment of a patient's current Huntington's disease status and their planned provision of care of children if Huntington's disease affects parenting. It has been necessary to create a detailed working protocol for the management of PGD for Huntington's disease to address these issues.

  2. [Eugenic abortion could explain the lower infant mortality in Cuba compared to that in Chile].

    Science.gov (United States)

    Donoso S, Enrique; Carvajal C, Jorge A

    2012-08-01

    Cuba and Chile have the lower infant mortality rates of Latin America. Infant mortality rate in Cuba is similar to that of developed countries. Chilean infant mortality rate is slightly higher than that of Cuba. To investigate if the lower infant mortality rate in Cuba, compared to Chile, could be explained by eugenic abortion, considering that abortion is legal in Cuba but not in Chile. We compared total and congenital abnormalities related infant mortality in Cuba and Chile during 2008, based on vital statistics of both countries. In 2008, infant mortality rates in Chile were significantly higher than those of Cuba (7.8 vs. 4.7 per 1,000 live born respectively, odds ratio (OR) 1.67; 95% confidence intervals (Cl) 1.52-1.83). Congenital abnormalities accounted for 33.8 and 19.2% of infant deaths in Chile and Cuba, respectively. Discarding infant deaths related to congenital abnormalities, infant mortality rate continued to be higher in Chile than in Cuba (5.19 vs. 3.82 per 1000 live born respectively, OR 1.36; 95%CI 1.221.52). Considering that antenatal diagnosis is widely available in both countries, but abortion is legal in Cuba but not in Chile, we conclude that eugenic abortion may partially explain the lower infant mortality rate observed in Cuba compared to that observed in Chile.

  3. Racial Metabolism: Eugenic Studies in Jamaica and Yucatán, between 1920 and 1940

    Directory of Open Access Journals (Sweden)

    Joel Vargas Domínguez

    2015-10-01

    Full Text Available Objective: this paper shows the configuration of research conducted by the Carnegie Institution of Washington (CIW, in Jamaica and Yucatan, about basal metabolism on the onset of the twen­tieth century. I argue that this physiological research, conducted outside the usual laboratory spaces, used and articulated eugenics and racialized notions about the bodies under examination.Content: from the standpoint of the history of science I have analyzed the publications, reports and correspondence of the members of the Carnegie Institution expeditions. Conclusions: I show that basal metabolism was a measure constructed and used in the first half of the twentieth cen­tury with a strong eugenic and racial bias. Francis G. Benedict, Charles B. Davenport and Morris Steggerda from the CIW conducted these expeditions not only from the medical but also from the anthropological standpoint, in order to answer the question whether there was a climatic or racial effect on the body of the subjects analyzed. The results of the research were incorporated to the formulas used to evaluate the nutritional status of populations, fact that might have con­sequences nowadays on the way we understand metabolic “normality”.

  4. From eugenics to lysenkoism: the evolution of Stanisław Skowron.

    Science.gov (United States)

    Dejong-Lambert, William

    2009-01-01

    This article describes the relationship between Polish geneticist Stanisław Skowron's views on eugenics during the interwar period, his experiences in Nazi concentration camps during World War II, and his response to Trofim D. Lysenko's ban on genetic research in Soviet-allied states after 1948. Skowron was educated at the Jagiellonian University in Krakow and received funding from the Rockefeller Foundation to study in the United States, Italy, Denmark, and Great Britain from 1924 to 1926. His exposure to research being conducted outside of Poland made him an important figure in Polish genetics. During this time Skowron also began to believe that an understanding of biological principles of heredity could play an important role in improving Polish society and became a supporter of eugenics. In 1939 he was arrested along with other faculty members at the Jagiellonian and sent to Sachsenhausen and Dachau. In 1947 he published the first book updating Polish biologists on recent developments in genetics; however, after learning of the outcome of the 1948 session of the Lenin All-Union Academy of Agricultural Sciences in Moscow, Skowron emerged as on of the most vocal advocates for Michurinism. I argue that Skowron's conversion to Lysenkoism was motivated by more than fear or opportunism, and is better understood as the product of his need to rationalize his own support for a theory he could not possibly have believed was correct.

  5. Investigation of Eugenic Knowledge and Eugenic Health Service Demand among Popula-tion Planning to Get Pregnant%计划怀孕人群优生知识及优生保健服务需求调查

    Institute of Scientific and Technical Information of China (English)

    官燮; 李鹏

    2015-01-01

    目的:通过了解计划怀孕人群优生知识知晓现状和优生需求,为计划怀孕夫妇提供有针对性的孕前优生健康教育使和优生保健服务.方法于2013年6-8月期间,使用同一调查问卷对参与国家免费孕前优生健康检查项目的1003名参检人员进行调查.结果优生知识总得分不及格率70.1%,良好13.2%.调查对象中能正确回答孕期绝对不能使用的疫苗仅12.8%.不同年龄、不同文化程度调查对象对优生知识知晓情况比较差异有统计学意义(P <0.05).调查对象中根据自己意愿希望生育宝宝的占86.0%;能做到花很多精力在孩子身上的占89.6%;参检人员对优生服务的需求率较高(96.0%).结论在开展优生保健服务工作中,应加强指导和教育,有针对性地向育龄参检人群宣传优生保健知识.%Objectives To understand the awareness situation of eugenic knowledge and the demand of eugenic service among population planning to get pregnant,and to provide targeted eugenic knowledge and eugenic service for this population.Methods 1 003 objects who participated in the National Free Pregnant Eugenics Health Check Program were surveyed by using the same questionnaire from June to August in 2013.Results The failing rate of the eugenics knowledge was 70.1%,and the good grade rate was 13.2%.Only 12.8% of the objects could correctly answer which vaccines could not be used absolutely during pregnancy.The awareness status of eugenics knowledge was different among different age,different cultural level objects (P <0.05).86.0% of the objects wanted to give birth based on their own willing,and 89.6% of the objects could spend a lot of vigor on children.The demand rate of eugenic service was high (96.0%).Conclusions The guidance and the education should be strengthened in the work of eugenics health services,and the targeted eugenic knowledge should be spread for the childbearing age pop-ulation.

  6. Current status of PET imaging in Huntington's disease.

    Science.gov (United States)

    Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

    2016-06-01

    To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading "Huntington Disease" combined with text and key words "Huntington Disease", "Neuroimaging" and "PET". Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([(18)F]FDG and [(15)O]H2O), presynaptic ([(18)F]fluorodopa, [(11)C]β-CIT and [(11)C]DTBZ) and postsynaptic ([(11)C]SCH22390, [(11)C]FLB457 and [(11)C]raclopride) dopaminergic function, phosphodiesterases ([(18)F]JNJ42259152, [(18)F]MNI-659 and [(11)C]IMA107), and adenosine ([(18)F]CPFPX), cannabinoid ([(18)F]MK-9470), opioid ([(11)C]diprenorphine) and GABA ([(11)C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed for monitoring potential neuroprotective and preventive treatment in HD.

  7. El trabajo interdisciplinar en la enfermedad de Huntington

    OpenAIRE

    Fernández Hawrylak, María; Grau Rubio, Claudia; Hernández Lozano, David; Fernández Sastre, Beatriz

    2014-01-01

    Se argumenta la importancia del trabajo en equipo en la atención de las personas afectadas por la Enfermedad de Huntington y de sus familias, y se describen las principales funciones de los distintos profesionales que han de cubrir sus necesidades en cada una de las etapas de la enfermedad en función de las alteraciones y secuelas. Siguiendo esta premisa, se presenta el trabajo de intervención basado en la complementariedad de distintos profesionales que atienden y cuidan a las personas afect...

  8. ENFERMEDAD DE HUNTINGTON: MODELOS EXPERIMENTALES Y PERSPECTIVAS TERAPÉUTICAS

    OpenAIRE

    TERESA SERRANO SÁNCHEZ; LISETTE BLANCO LEZCANO; ROCÍO GARCÍA MINET; ESTEBAN ALBERTI AMADOR; IVÁN DÍAZ ARMESTO; NANCY PAVÓN FUENTE; LOURDES LORIGADOS PEDRE; MARÍA ELENA GONZÁLEZ FRAGUELA; JORGE FELIPE MONTERO LEÓN; LISIS MARTÍNEZ MARTÍ; MARÍA DE LOS ANGELES ROBINSON AGRAMONTE; LILIANA FRANCIS TURNER

    2011-01-01

    La enfermedad de Huntington (EH) es un trastorno degenerativo de Weiss de origen hereditario. Hasta el momento no existe un tratamiento efectivo para la enfermedad que inexorablemente después de transcurridos 15 a 20 años, evoluciona hacia incapa- cidad total o muerte. En este trabajo se revisan las características clínicas y morfológicas de la EH y los modelos experimentales más utilizados para su estudio tomando como fuente, artículos indexados en la base de datos Medline publicados en los ...

  9. Huntington's disease as caused by 34 CAG repeats.

    Science.gov (United States)

    Andrich, Jürgen; Arning, Larissa; Wieczorek, Stefan; Kraus, Peter H; Gold, Ralf; Saft, Carsten

    2008-04-30

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by an abnormal expansion of a polymorphic stretch of CAG repeats in the coding 5' part of the HD gene on chromosome 4p. Expansions of CAG blocks beyond 35 repeats are associated with the clinical presentation of HD. There is an intermediate range of rare alleles between 27 and 35 CAG repeats with a higher risk for further expansion in subsequent generations. Here, we report a 75-year-old male with clinical features of HD and 34 CAG repeat units.

  10. Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?

    Science.gov (United States)

    Hoffner, Guylaine; Djian, Philippe

    2015-12-01

    Huntington disease is a dominantly inherited disease of the central nervous system. The mutational expansion of polyglutamine beyond a critical length produces a toxic gain of function in huntingtin and results in neuronal death. In the course of the disease, expanded huntingtin is proteolyzed, becomes abnormally folded, and accumulates in oligomers, fibrils, and microscopic inclusions. The aggregated forms of the expanded protein are structurally diverse. Structural heterogeneity may explain why polyglutamine-containing aggregates could paradoxically be either toxic or neuroprotective. When defined, the toxic structures could then specifically be targeted by prophylactic or therapeutic drugs aimed at inhibiting polyglutamine aggregation.

  11. Reduced gluconeogenesis and lactate clearance in Huntington's disease

    DEFF Research Database (Denmark)

    Josefsen, Knud; Nielsen, Signe M B; Campos, André

    2010-01-01

    We studied systemic and brain glucose and lactate metabolism in Huntington's disease (HD) patients in response to ergometer cycling. Following termination of exercise, blood glucose increased abruptly in control subjects, but no peak was seen in any of the HD patients (2.0 ± 0.5 vs. 0.0 ± 0.2mM, P...... for gluconeogenesis in HD, possibly contributing to the clinical symptoms of HD. We propose that blood glucose concentration in the recovery from exercise can be applied as a liver function test in HD patients....

  12. The Cambridge MRI database for animal models of Huntington disease.

    Science.gov (United States)

    Sawiak, Stephen J; Morton, A Jennifer

    2016-01-01

    We describe the Cambridge animal brain magnetic resonance imaging repository comprising 400 datasets to date from mouse models of Huntington disease. The data include raw images as well as segmented grey and white matter images with maps of cortical thickness. All images and phenotypic data for each subject are freely-available without restriction from (http://www.dspace.cam.ac.uk/handle/1810/243361/). Software and anatomical population templates optimised for animal brain analysis with MRI are also available from this site.

  13. Preserving Precious Instruments in Mathematics History: The Educational Museum of Teachers College and David Eugene Smith's Collection

    Science.gov (United States)

    Murray, Diane R.

    2011-01-01

    A history is given of the Educational Museum of Teachers College, which began in 1886, and David Eugene Smith's extensive collection of mathematical tools used in the Museum's exhibits is discussed. Historic mathematical instruments including, the astrolabe, abacus and counting rods, and the slide rule are examined. The author uses digitized…

  14. 76 FR 33341 - Notice of Intent to prepare a Resource Management Plan for the West Eugene Wetlands Planning Area...

    Science.gov (United States)

    2011-06-08

    ... costs of management. Preliminary planning criteria include: 1. Lands addressed in the RMP will be public... Bureau of Land Management Notice of Intent to prepare a Resource Management Plan for the West Eugene Wetlands Planning Area in the State of Oregon and Associated Environmental Impact Statement AGENCY: Bureau...

  15. Eugene O'Neill "Pikk päevatee kaob öösse" / Ellu Eik ; interv. Ene Paaver

    Index Scriptorium Estoniae

    Eik, Ellu

    2008-01-01

    Seoses Eesti Draamateatri suvelavastusega "Pikk päevatee kaob öösse" (autor Eugene O'Neill ja lavastaja Merle Karusoo) räägib Lääne-Tallinna Keskhaigla Sõltuvusravikeskuse psühhiaater Ellu Eik sõltuvuse tagamaadest ja mõjudest

  16. Proceedings of the National Silviculture Workshop: Economics Of Silvicultural Investments; Eugene, OR; May 16-20, 1983

    Science.gov (United States)

    Clark Row; Charles Palmer; Robert M. Randall; Tom Ortman; James P. Merzenich; Gary Manning; George Howe; Jim McDivitt; Chris Hansen; Willard R. Fey; Vernon L. Robinson; K. E. Sleavin; K. N. Johnson; Roger D. Fight; L. O. (Pete) Stanger; Lee Medema; Christopher D. Risbrudt; Richard W. Guldin; Richard Greenhalgh; Mike Skinner; John Fiske; Thomas J. Mills; John H. Beuter

    1983-01-01

    The 1983 Silviculture Workshop was held in Eugene, Oregon, and the Willamette National Forest. The purpose of the workshop was to review and discuss the requirements by laws, regulations, and Forest Service policy of the need for and uses of economic analyses in silvicultural program planning and development.

  17. Eugene O'Neill "Pikk päevatee kaob öösse" / Ellu Eik ; interv. Ene Paaver

    Index Scriptorium Estoniae

    Eik, Ellu

    2008-01-01

    Seoses Eesti Draamateatri suvelavastusega "Pikk päevatee kaob öösse" (autor Eugene O'Neill ja lavastaja Merle Karusoo) räägib Lääne-Tallinna Keskhaigla Sõltuvusravikeskuse psühhiaater Ellu Eik sõltuvuse tagamaadest ja mõjudest

  18. 78 FR 21547 - Approval and Promulgation of Air Quality Implementation Plans; Oregon: Eugene-Springfield PM10

    Science.gov (United States)

    2013-04-11

    ..., children and older adults are the most likely to be affected by particle pollution exposure. However, even... a comprehensive wood burning curtailment program. EPA took final action to approve the State's... control measures in the Eugene- Springfield moderate PM 10 SIP include a mandatory home wood...

  19. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Science.gov (United States)

    Miller, James R C; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J

    2015-01-01

    Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  20. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    James R C Miller

    Full Text Available Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  1. Presymptomatic testing for Huntington's disease: a world wide survey. The World Federation of Neurology Research Group on Huntington's Disease.

    OpenAIRE

    1993-01-01

    World wide data on presymptomatic testing for Huntington's disease using closely linked DNA markers show that 1479 persons at risk received completed test results up to the end of 1991. Testing has been carried out in 19 countries, with at least 88 centres involved, and numbers have levelled off after a peak in 1990. Only 5% of those at risk have been tested in six countries with the longest established programmes. Continued monitoring of international data will be of value in assessing the s...

  2. Maltreatment of people with serious mental illness in the early 20th century: a focus on Nazi Germany and eugenics in America.

    Science.gov (United States)

    Fischer, Bernard A

    2012-12-01

    Prejudice and stigma against people with mental illness can be seen throughout history. The worst instance of this prejudice was connected to the rise of the eugenics movement in the early 20th century. Although the Nazi German T-4 program of killing people with mental illness was the most egregious culmination of this philosophy, the United States has its own dark eugenics history-nearing a slippery slope all too similar to that of the Nazis. Mental health care clinicians need to examine this period to honor the memory of the victims of eugenics and to guarantee that nothing like this will ever happen again.

  3. Polymorphisms in the CAG repeat--a source of error in Huntington disease DNA testing.

    Science.gov (United States)

    Yu, S; Fimmel, A; Fung, D; Trent, R J

    2000-12-01

    Five of 400 patients (1.3%), referred for Huntington disease DNA testing, demonstrated a single allele on CAG alone, but two alleles when the CAG + CCG repeats were measured. The PCR assay failed to detect one allele in the CAG alone assay because of single-base silent polymorphisms in the penultimate or the last CAG repeat. The region around and within the CAG repeat sequence in the Huntington disease gene is a hot-spot for DNA polymorphisms, which can occur in up to 1% of subjects tested for Huntington disease. These polymorphisms may interfere with amplification by PCR, and so have the potential to produce a diagnostic error.

  4. Presymptomatic diagnosis in Huntington's disease: the Mexican experience.

    Science.gov (United States)

    Alonso, Maria Elisa; Ochoa, Adriana; Sosa, Ana Luisa; Rodríguez, Yaneth; Chávez, Mireya; Boll, Catherine; Yescas, Petra; Macías, Rosario; Rasmussen, Astrid

    2009-12-01

    Huntington's disease (HD) is an autosomal dominant progressive, disabling neurodegenerative disorder, for which there is no effective treatment. Predictive testing (PT) for this illness began in 1986 and by 1993 it became more precise after cloning of the gene and the discovery of a CAG repeat expansion as the underlying cause. The objective of this paper is to illustrate the implementation and results of a PT program in a group of at-risk Mexican individuals with 12 years of follow-up. Our PT program conforms to the guidelines proposed by the International Huntington Association and the HD Working group of the World Federation of Neurology. Seventy-five individuals requested the testing, four of them did not fulfill the inclusion criteria, and five abandoned the program voluntarily before receiving the test results. Therefore, 66 results were delivered to 41 noncarriers and 25 mutation carriers. We did not have any catastrophic event, but 4 individuals with normal results and 11 mutation carriers were depressed. Even if this is a small sample, it is the first report of PT in a Latin-American population in which we have been faced with the same problems referred to in larger series.

  5. Pluripotent Stem Cells Models for Huntington's Disease: Prospects and Challenges

    Institute of Scientific and Technical Information of China (English)

    Richard L. Carter; Anthony W.S. Chan

    2012-01-01

    Pluripotent cellular models have shown great promise in the study of a number of neurological disorders.Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types,providing a system for researchers to monitor disease progression during neurogenesis,along with serving as a platform for drug discovery.A number of stem cell derived models have been employed to establish in vitro research models of Huntington's disease that can be used to investigate cellular pathology and screen for drug and cell-based therapies.Although some progress has been made,there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved,In this article we review current stem cell models that have been reported,as well as discuss the issues that impair these studies.We also highlight the prospective application of Huntington's disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.

  6. Progress in studies of gene therapy for Huntington's disease

    Directory of Open Access Journals (Sweden)

    JIN Fan-ying

    2012-06-01

    Full Text Available Huntington's disease (HD is a kind of inherited neurodegenerative disorder characterized by movement problems, cognitive decline and psychiatry disturbance. HD is caused by mutation in gene IT -15 involving the expansion of a trinucleotide (CAG repeat encoding glutamine, which leads to abnormal conformation of huntingtin (Htt protein and finally emerge cytotoxic functions. Currently, HD remains a fatal untreatable disease. Gene therapy for HD discussed in this review is under preclinical studies. Silencing of mutant IT-15 via RNA interference (RNAi or antisense oligonucleotide (ASO has shown some effectiveness in mouse model studies. Increasing the clearance of mutant Htt protein could be achieved by viral-mediated delivery of anti-Htt intrabodies (iAbs or induction of autophagy, and beneficial results have been observed. Ectopic expression of neurotrophic factors, such as nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF, mediated either by viral vectors or transplantation of genetically modified cells, has also been proved to be effective. Other gene-modifying methods aiming at correction of transcriptional dysregulation by histone modification, activation of endogenous neural stem cells, and normalization of calcium signaling and mitochondrial function, are also under intensive research. Gene therapy for Huntington's disease is promising, yet a long way remains from preclinical studies to clinical trials.

  7. Clinical diagnosis and management in early Huntington's disease: a review

    Directory of Open Access Journals (Sweden)

    Schiefer J

    2015-03-01

    Full Text Available Johannes Schiefer,1,* Cornelius J Werner,1,* Kathrin Reetz1,2 1Euregional Huntington Center, 2Jülich Aachen Research Alliance (JARA – Translational Brain Medicine, Department of Neurology, RWTH Aachen University, Aachen, Germany *These authors contributed equally to this work Abstract: This review focuses on clinical diagnosis and both pharmacological and nonpharmacological therapeutic options in early stages of the autosomal dominant inherited neurodegenerative Huntington's disease (HD. The available literature has been reviewed for motor, cognitive, and psychiatric alterations, which are the three major symptom domains of this devastating progressive disease. From a clinical point of view, one has to be aware that the HD phenotype can vary highly across individuals and during the course of the disease. Also, symptoms in juvenile HD can differ substantially from those with adult-onset of HD. Although there is no cure of HD and management is limited, motor and psychiatric symptoms often respond to pharmacotherapy, and nonpharmacological approaches as well as supportive care are essential. International treatment recommendations based on study results, critical statements, and expert opinions have been included. This review is restricted to symptomatic and supportive approaches since all attempts to establish a cure for the disease or modifying therapies have failed so far. Keywords: Neurodegeneration, clinical picture, early symptoms, therapy, treatment

  8. Ethical considerations of genetic presymptomatic testing for Huntington's disease.

    Science.gov (United States)

    Coustasse, Alberto; Pekar, Alicia; Sikula, Andrew; Lurie, Sue

    2009-01-01

    The aim of this literature review was to determine if there is adequate ethical justification for presymptomatic genetic testing on potential Huntington's disease patients. Huntington's disease is a neurological genetic disorder characterized by midlife onset which consists of cognitive, physical, and emotional deterioration. Although genetic testing has traditionally been guided by the principle of autonomy, severe psychological consequences such as depression, anxiety, survival guilt, and suicide have complicated the ethical issue of providing a presymptomatic yet definitive diagnosis for an incurable disease. An analysis of available articles yielded inconclusive findings, namely due to insufficient evidence, self-selection bias of test participants, or lack of a longitudinal design. Additional results indicated psychological distress is not solely associated with test result, but rather with individual characteristics including, but not limited to, psychological history, test motivation, level of preparation, social support, and age. In the interest of upholding the principles of autonomy, beneficence, nonmaleficence, and justice, it is recommended that medical professionals follow strict protocol, provide extensive counseling, and employ vigilance when assessing at-risk individuals for HD presymptomatic test eligibility to ensure psychological well-being.

  9. Comprehensive care in Huntington's disease: a physician's perspective.

    Science.gov (United States)

    Nance, Martha A

    2007-04-30

    Huntington's disease is a slowly progressive neurodegenerative disorder with wide-ranging effects on affected individuals and their families. Until a cure is found for the disease, patients and their families will continue to need care over years, even generations. The ideal care for HD is provided by a team, led by a physician, with input from rehabilitation therapists, nurses, psychologists, genetic counselors, social workers, and other health care providers. The goals of care are to maximize the quality of life at all points through the course of the disease, in part by anticipating problems that are likely to arise at the next stage of the illness. We describe below an approach to comprehensive care, and introduce the concept of the "Huntington disease molecule", in which the patient, in the center, is surrounded by a shell of immediate and extended family members, with bonds extended in multiple directions to provider who can give appropriate medical care, education, crisis management, research opportunities, address family issues, maximize function, and prepare for the future.

  10. Deep brain stimulation in Huntington's disease: assessment of potential targets.

    Science.gov (United States)

    Sharma, Mayur; Deogaonkar, Milind

    2015-05-01

    Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder that has very few effective therapeutic interventions. Since the disease has a defined neural circuitry abnormality, neuromodulation could be an option. Case reports, original research, and animal model studies were selected from the databases of Medline and PubMed. All related studies published up to July 2014 were included in this review. The following search terms were used: "Deep brain stimulation," "DBS," "thalamotomy," "pallidal stimulation," and "Huntington's Disease," "HD," "chorea," or "hyperkinetic movement disorders." This review examines potential nodes in the HD circuitry that could be modulated using deep brain stimulation (DBS) therapy. With rapid evolution of imaging and ability to reach difficult targets in the brain with refined DBS technology, some phenotypes of HD could potentially be treated with DBS in the near future. Further clinical studies are warranted to validate the efficacy of neuromodulation and to determine the most optimal target for HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Functional impairment of precerebral arteries in Huntington disease.

    Science.gov (United States)

    Kobal, Jan; Cankar, Ksenija; Pretnar, Janja; Zaletel, Marjan; Kobal, Lucijan; Teran, Natasa; Melik, Ziva

    2017-01-15

    Cardiovascular pathology of Huntington disease (HD) appears to be complex; while microvascular dysfunction seems to appear early, deaths from cardiomyopathy and stroke might occur in the late phase of HD. Our study evaluated global risk factors for coronary heart disease (CHD), structure and function of precerebral arteries in 41 HD subjects and 41 matched controls. HD subjects were divided into groups by the United Huntington disease rating scale (presymptomatic-PHD, early-EHD, midstage-MHD and late-LHD). CHD risk factors assessment and Doppler examination of precerebral arteries were performed, including measurements of the carotid artery intima-media thickness (IMT), and parameters indicating local carotid artery distensibility (stiffness index β, pulse wave velocity, pressure strain elasticity module and carotid artery compliance). In the HD and controls we identified a comparable number of non-obstructive plaques (50% lumen narrowing) were found. There was significantly increased IMT in MHD. In PHD and EHD the parameters of arterial stiffness were significantly higher and the carotid artery compliance was significantly lower. Our results reveal functional vascular pathology in PHD, EHD, and MHD. Precerebral arteries dysfunction in HD therefore appears to be mostly functional and in agreement with recently described autonomic nervous system changes in HD. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Clinical and genetic data of Huntington disease in Moroccan patients.

    Science.gov (United States)

    Bouhouche, Ahmed; Regragui, Wafaa; Lamghari, Hind; Khaldi, Khadija; Birouk, Nazha; Lytim, Safaa; Bellamine, Soufiane; Kriouile, Yamna; Bouslam, Naima; Haddou, El Hachmia Ait Ben; Faris, Mustapha Alaoui; Benomar, Ali; Yahyaoui, Mohamed

    2015-12-01

    Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10/100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin. Clinical and genetics data of 21 consecutive patients recruited from 2009 to 2014 from the outpatient clinic of six medical centers were analyzed. Statistical analysis was performed using descriptive statistics. Twenty one patients from 17 families were diagnosed positive for the IT15 gene CAG expansion. Clinical symptoms were predominantly motor (19/21). Twelve patients had psychiatric and behavioral disorders, and 11 patients had cognitive disorders essentially of memory impairment. Analysis of genetic results showed that 5 patients had reduced penetrant (RP) alleles and 16 had fully penetrant (FP) alleles. The mean CAG repeat length in patients with RP alleles was 38.4 ± 0.54, and 45.37 ± 8.30 in FP alleles. The age of onset and the size of the CAG repeat length showed significant inverse correlation (p <0.001, r = -0.754). Clinical and genetic data of Moroccan patients are similar to those of Caucasian populations previously reported in the literature.

  13. "Our power to remodel civilization": the development of eugenic feminism in Alberta, 1909-1921.

    Science.gov (United States)

    Gibbons, Sheila

    2014-01-01

    In addition to being a prominent political figure in equal rights legislation, Emily Murphy was a vital contributor to programs which sought to improve the human race through forced sterilization. These negative aspects of this period in feminist history tend to be described as outside of the women's sphere, representing instead the patriarchal realm of men. However, both eugenics and the first-wave feminist ambitions for equal political rights were connected through an agrarian construction of "mothers of the race." As "mothers of the race," women in Alberta were responsible for the physical and moral betterment of the nation, and were directly engaged in concepts of intelligent motherhood, healthy childhood, and an overarching moral philosophy that was politically driven.

  14. A multilocus analysis provides evidence for more than one species within Eugenes fulgens (Aves: Trochilidae).

    Science.gov (United States)

    Zamudio-Beltrán, Luz E; Hernández-Baños, Blanca E

    2015-09-01

    The status of subspecies in systematic zoology is the focus of controversy. Recent studies use DNA sequences to evaluate the status of subspecies within species complexes and to recognize and delimit species. Here, we assessed the phylogenetic relationships, the taxonomic status of the proposed subspecies, and the species limits of the monotypic hummingbird genus Eugenes (E. fulgens with traditionally recognized subspecies E. f. fulgens, E. f. viridiceps, and E. f. spectabilis), using nuclear (Beta Fibrinogen BFib, Ornithine Decarboxylase ODC, and Muscle Skeletal Receptor Tyrosine Kinase MUSK) and mitochondrial (NADH dehydrogenase subunit 2 ND2, NADH dehydrogenase subunit 4 ND4, and Control Region CR) markers. We performed Bayesian and Bayesian Phylogenetics and Phylogeography analyses and found genetic differences between the three groups, suggesting the existence of two cryptic species (E. fulgens and E. viridiceps) and one phenotypically differentiated species (E. spectabilis). Our analyses show that the E. viridiceps and E. fulgens groups are more closely related with one another than with E. spectabilis.

  15. Eugenics and racial biology in Sweden and the USSR: contacts across the Baltic Sea.

    Science.gov (United States)

    Rudling, Per Anders

    2014-01-01

    The 1920s saw a significant exchange between eugenicists in Sweden and the young Soviet state. Sweden did not take part in World War I, and during the years following immediately upon the Versailles peace treaty, Swedish scholars came to serve as an intermediary link between, on the one hand, Soviet Russia and Weimar Germany, and, on the other hand, Western powers. Swedish eugenicists organized conferences, lecture tours, visits, scholarly exchanges, and transfers and translation of eugenic research. Herman Lundborg, the director of the world's first State Institute of Racial Biology, was an old-fashioned, deeply conservative, and anti-communist "scientific" racist, who somewhat paradoxically came to serve as something of a Western liaison for Soviet eugenicists. Whereas the contacts were disrupted in 1930, Swedish eugenicists had a lasting impact on Soviet physical anthropologists, who cited their works well into the 1970s, long after they had been discredited in Sweden.

  16. Border Gothic - history, violence and the border in the writings of Eugene McCabe

    Directory of Open Access Journals (Sweden)

    Éamonn Ó Ciardha

    2016-12-01

    Full Text Available As well as producing a rich body of novels, novellas, short-stories and plays spanning throughout seventy years of the century of partition, Eugene McCabe charts the broad trajectory of Irish history and politics from the Elizabethan Conquest and Ulster Plantation of the 16th and 17th centuries to the recent 'Troubles' which spanned the thirty years between the beginnings of the Civil Rights Movement (1968 and the signing of the Belfast/Good Friday Agreement (1998. They positively seethe with gruesome assassinations, indiscriminate bombings and deliberate shootings, while resonating with a veritable cacophony of deep-seeded ethnic rivalries and genocidal, religious hatreds, which are interlaced with poverty, social deprivation and dis-function, migration and emigration.

  17. "More than just boots! The eugenic and commercial concerns behind A. R. Kaufman's birth controlling activities".

    Science.gov (United States)

    Revie, Linda

    2006-01-01

    A. R. Kaufman (1885-1979), founder of the Kitchener-based Kaufman Rubber Company, was nicknamed "Canada's Mr. Birth Control" because he established the Parents' Information Bureau (PIB)-a birth control information centre that functioned out of his factory office. Besides creating mail order/home visiting services, Kaufman also funded birth control clinics. Because he was a rubber manufacturer, it was widely believed that commercial concerns were behind his activities. This article examines recently archived material, local newspaper accounts, and court transcripts to connect A. R. Kaufman and the PIB with the manufacture of contraceptive products. It also outlines Kaufman's involvement with the eugenics movement, especially his dealings with medical practitioners who carried out sterilization procedures for the PIB.

  18. Bogeria, eugenèsia i estadística amb Theodore M. Porter

    OpenAIRE

    Gil Farrero, Judit

    2014-01-01

    El Dr. Theodore M. Porter (University of California, Los Angeles) va impartir una xerrada titulada "Eugenic Madness: Asylums and the Data of Heredity" en el marc del cicle de col·loquis de la Societat Catalana d’Història de la Ciència i de la Tècnica (SCHCT) del curs 2013-2014, i amb la col·laboració del Centre d’Història de la Ciència (CEHIC-UAB). Porter és expert en la història de l’estadística i la quantificació en les ciències. En aquesta entrevista ens explica la relació entre els manico...

  19. Eugene Garfield and Algorithmic Historiography: Co-Words, Co-Authors, and Journal Names

    CERN Document Server

    Leydesdorff, Loet

    2010-01-01

    Algorithmic historiography was proposed by Eugene Garfield in collaboration with Irving Sher in the 1960s, but further developed only recently into HistCite^{TM} with Alexander Pudovkin. As in history writing, HistCite^{TM} reconstructs by drawing intellectual lineages. In addition to cited references, however, documents can be attributed a multitude of other variables such as title words, keywords, journal names, author names, and even full texts. New developments in multidimensional scaling (MDS) enable us not only to visualize these patterns at each moment of time, but also to animate them over time. Using title words, co-authors, and journal names in Garfield's oeuvre, the method is demonstrated and further developed in this paper (and in the animation at http://www.leydesdorff.net/garfield/animation). The variety and substantive content of the animation enables us to write, visualize, and animate the author's intellectual history.

  20. Eugene Onegin the Cold War Monument: How Edmund Wilson Quarreled with Vladimir Nabokov

    Directory of Open Access Journals (Sweden)

    Tim Conley

    2014-01-01

    Full Text Available The tale of how Edmund Wilson quarreled with Vladimir Nabokov over the latter’s 1964 translation of Eugene Onegin can be instructively read as a politically charged event, specifically a “high culture” allegory of the Cold War. Dissemination of anti-Communist ideals (often in liberal and literary guises was the mandate of the Congress for Cultural Freedom, whose funding and editorial initiatives included the publication of both pre-Revolution Russian literature and, more notoriously, the journal Encounter (1953-1990, where Nabokov’s fiery “Reply” to Wilson appeared. This essay outlines the propaganda value of the Onegin debate within and to Cold War mythology.

  1. [The early reception of the notion of schizophrenia of Eugen Bleuler in Austria].

    Science.gov (United States)

    Gabriel, Eberhard

    2012-01-01

    The 100th anniversary of Eugen Bleulers "Dementia praecox oder Gruppe der Schizophrenien" (Dementia praecox oder Gruppe der Schizophrenien. Leipzig: Deuticke; 1911) motivates a retrospective description of the early reception of the word and its meaning. It occurred in two phases: 1911-1914 (focus of that paper) and 1918-1929. The protagonists were Erwin Stransky (mainly in the first phase), Josef Berze (mainly in the second), Julius Wagner-Jauregg and Carl Meyer, leading motives criticisms of the further expansion of the earlier Kraepelinian notion of dementia praecox and of Bleulers' psychoanalytical interpreting of the disorder, but acceptance of the neologism 'schizophrenia' because of its meaning ("dissociative character") and the possibility to derive an adjective. The new word replaced the old denomination after world war I during the 1920s.

  2. Neuroscience in Nazi Europe part I: eugenics, human experimentation, and mass murder.

    Science.gov (United States)

    Zeidman, Lawrence A

    2011-09-01

    The Nazi regime in Germany from 1933 to 1945 waged a veritable war throughout Europe to eliminate neurologic disease from the gene pool. Fueled by eugenic policies on racial hygiene, the Nazis first undertook a sterilization campaign against "mental defectives," which included neurologic patients with epilepsy and other disorders, as well as psychiatric patients. From 1939-41 the Nazis instead resorted to "euthanasia" of many of the same patients. Some neuroscientists were collaborators in this program, using patients for research, or using extracted brains following their murder. Other reviews have focused on Hallervorden, Spatz, Schaltenbrand, Scherer, and Gross, but in this review the focus is on neuroscientists not well described in the neurology literature, including Scholz, Ostertag, Schneider, Nachtsheim, and von Weizsäcker. Only by understanding the actions of neuroscientists during this dark period can we learn from the slippery slope down which they traveled, and prevent history from repeating itself.

  3. Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles, Vermont

    Data.gov (United States)

    Vermont Center for Geographic Information — Digital Data from VG95-9A Thompson, PJ�and Thompson, TB, 1995, Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles,...

  4. Recent Trends in Detection of Huntingtin and Preclinical Models of Huntington's Disease.

    Science.gov (United States)

    Mantha, Neelima; Das, Nandita G; Das, Sudip K

    2014-01-01

    Huntington's disease is a genetically inherited neurodegenerative disease that is characterized by neuronal cell death in the brain. Molecular biology techniques to detect and quantify huntingtin protein in biological samples involve fluorescence imaging, western blotting, and PCR. Modified cell lines are widely used as models for Huntington's disease for preclinical screening of drugs to study their ability to suppress the expression of huntingtin. Although worm and fly species have been experimented on as models for Huntington's disease, the most successful animal models have been reported to be primates. This review critically analyses the molecular biology techniques for detection and quantitation of huntingtin and evaluates the various animal species for use as models for Huntington's disease.

  5. The Current Status of Neural Grafting in the Treatment of Huntington's Disease. A Review

    National Research Council Canada - National Science Library

    Wijeyekoon, Ruwani; Barker, Roger A

    2011-01-01

    Huntington's disease (HD) is a devastating, fatal, autosomal dominant condition in which the abnormal gene codes for a mutant form of huntingtin that causes widespread neuronal dysfunction and death...

  6. Hypothalamic Alterations in Huntington's Disease Patients : Comparison with Genetic Rodent Models

    NARCIS (Netherlands)

    Van Wamelen, D.J.; Aziz, N A; Roos, R A C; Swaab, D F

    2014-01-01

    Unintended weight loss, sleep and circadian disturbances and autonomic dysfunction are prevalent features of Huntington's disease (HD), an autosomal dominantly inherited neurodegenerative disorder caused by an expanded CAG repeat sequence in the HTT gene. These features form a substantial contributi

  7. 77 FR 51064 - Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application...

    Science.gov (United States)

    2012-08-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR Employment and Training Administration Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated May 21, 2012, the State...

  8. The role of tau in the pathological process and clinical expression of Huntington's disease

    DEFF Research Database (Denmark)

    Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan

    2015-01-01

    -mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report...... not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some...... instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington's disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau...

  9. Dynamics of the connectome in Huntington's disease : A longitudinal diffusion MRI study

    NARCIS (Netherlands)

    Odish, Omar F F; Caeyenberghs, Karen; Hosseini, Hadi; Van Den Bogaard, Simon J A; Roos, Raymund A C; Leemans, A

    2015-01-01

    Abstract Objectives To longitudinally investigate the connectome in different stages of Huntington's disease (HD) by applying graph theoretical analysis to diffusion MRI data. Experimental design We constructed weighted structural networks and calculated their topological properties. Twenty-two prem

  10. Evaluation of tetrathiomolybdate in the R6/2 model of Huntington disease.

    Science.gov (United States)

    Tallaksen-Greene, Sara J; Janiszewska, Anita; Benton, Kasha; Hou, Guoqing; Dick, Robert; Brewer, George J; Albin, Roger L

    2009-03-06

    Huntington disease is an uncommon autosomal dominant neurodegenerative disorder caused by expanded polyglutamine repeats in the huntingtin protein. The proximate mechanisms responsible for neurodegeneration are unknown. Copper ions may play a role in Huntington disease by promoting oligomerization of expanded polyglutamine repeat protein fragments. Ammonium tetrathiomolybdate is a copper complexing agent with demonstrated tolerability and efficacy in another neurodegenerative disorder, Wilson disease. We evaluated ammonium tetrathiomolybdate in the R6/2 transgenic mouse model of Huntington disease. Ammonium tetrathiomolybdate treatment delayed the onset of motor dysfunction in R6/2 mice. There was a trend towards reduced striatal degeneration, suggesting a neuroprotective effect of ammonium tetrathiomolybdate in this model. Given its known tolerability in humans with neurodegeneration, ammonium tetrathiomolybdate could be considered as a candidate for clinical trials in Huntington disease.

  11. The role of tau in the pathological process and clinical expression of Huntington's disease.

    Science.gov (United States)

    Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan; Cisbani, Giulia; Drouin-Ouellet, Janelle; Spillantini, Maria G; Cicchetti, Francesca; Barker, Roger A

    2015-07-01

    Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington's disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated in Huntington's disease. We explored this association in more detail at the neuropathological, genetic and clinical level. We first investigated tau pathology by looking for the presence of hyperphosphorylated tau aggregates, co-localization of tau with mutant HTT and its oligomeric intermediates in post-mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington's disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau entity) are present in the Huntington's disease brains. Finally we highlight the clinical significance of this pathology by demonstrating that the MAPT haplotypes affect the rate

  12. Increased brain tissue sodium concentration in Huntington's Disease - a sodium imaging study at 4 T.

    Science.gov (United States)

    Reetz, Kathrin; Romanzetti, Sandro; Dogan, Imis; Saß, Christian; Werner, Cornelius J; Schiefer, Johannes; Schulz, Jörg B; Shah, N Jon

    2012-10-15

    The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short "echo time". T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease-specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital

  13. [The life as a caregiver of a person affected by Chorea Huntington: multiple case study].

    Science.gov (United States)

    Winkler, Evi; Ausserhofer, Dietmar; Mantovan, Franco

    2012-10-01

    Chorea Huntington is an autosomal dominantly inherited, neurodegenerative brain disorder that leads to involuntary hyperkinesia, psychotic symptoms and dementia. The illness not only changes the life of the person itself but also the world of the caregivers. The challenges in the care of a person which is affected by Chorea Huntington have an effect on the daily living as an assemblage of natural and social conditions. a multiple case study was conducted. It included semi-structured interviews with three caregivers of people with Chorea Huntington in South Tyrol. The qualitative data was analyzed using the qualitative structured analysis of Mayring (2007). The objective of this study was to describe the phenomenon of change of life from family members that care people affected by Chorea Huntington in a specific cultural setting (South Tyrol, Italy). The caregivers reported that the diagnosis of Chorea Huntington leads to negative changes in "relationship and family". Particularly, frustration, aggression, impatience and apathy were perceived as stressful. At the same time they highlight the positive changes through home care. They report that the relationship became more intimate and integral and it was characterized by more cohesion. Family caregivers get valuable support from the home care service, however, they complain that there is no facility in South Tyrol, which is specialized to care people with Chorea Huntington. Therefore, the caregivers have to "give up a lot" and don't have any personal desires, dreams and expectations for the future. The caregivers have learned independently to deal with their changed life step by step, and to see also the positive effects of the caring role. The life of family caregivers of a person which is affected by Chorea Huntington is characterized by abandonment. A continuous and professional care would be important for the affected and his caregiver. A continuous and professional care is important for both, addressing the

  14. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia.

    OpenAIRE

    Quinn, N.; Marsden, C. D.

    1984-01-01

    Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause...

  15. It wasn't Witchcraft--It was Huntington Disease!

    Science.gov (United States)

    Penaranda, Eribeth; Garcia, Angel; Montgomery, Lisa

    2011-01-01

    Huntington disease (HD) is an autosomal-dominant, incurable, progressive disorder that manifests with chorea and behavioral and cognitive impairment. The disease usually occurs during the fourth or fifth decade of life; however, it may present at any age. Clinical suspicion is confirmed by genetic testing. Death occurs, on average, 15 to 20 years after the onset of symptoms. Here we report about a Hispanic woman and her family who were affected by the disease; this case illustrates the role of cultural values and beliefs in the decision-making process, as well as the importance of the physician's cultural competency in fostering a trusting relationship that may lessen the burden of catastrophic diseases on individuals, families, and society at-large.

  16. Huntington's disease impairs recognition of angry and instrumental body language.

    Science.gov (United States)

    de Gelder, Beatrice; Van den Stock, Jan; Balaguer, Ruth de Diego; Bachoud-Lévi, Anne-Catherine

    2008-01-15

    Patients with Huntington's disease (HD) exhibit motor impairments as well as cognitive and emotional deficits. So far impairments in the ability to recognize emotional stimuli have mostly been investigated by using facial expressions and emotional voices. Other important emotional signals are provided by the whole body. To investigate the impact of motor deficits on body recognition and the relation between motor disorders and emotion perception deficits, we tested recognition of emotional body language (instrumental, angry, fearful and sad) in 19 HD patients and their matched controls with a nonverbal whole body expression matching task. Results indicate that HD patients are impaired in recognizing both instrumental and angry whole body postures. Furthermore, the body language perception deficits are correlated with measures of motor deficit. Taken together the results suggest a close relationship between emotion recognition (specifically anger) and motor abilities.

  17. Rapid eye movement sleep disturbances in Huntington disease

    DEFF Research Database (Denmark)

    Arnulf, I.; Nielsen, J.; Lohmann, E.

    2008-01-01

    with very mild HD and worsened with disease severity. In contrast to narcoleptic patients, HD patients had no cataplexy, hypnagogic hallucinations, or sleep paralysis. Four HD patients had abnormally low (sleep latencies, but none had multiple sleep-onset REM periods. Conclusions......Background: Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). Objective: To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages...... interview, nighttime video and sleep monitoring, and daytime multiple sleep latency tests. Their results were compared with those of patients with narcolepsy and control patients. Results: The HD patients had frequent insomnia, earlier sleep onset, lower sleep efficiency, increased stage I sleep, delayed...

  18. Nucleic Acid-Based Therapy Approaches for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Tatyana Vagner

    2012-01-01

    Full Text Available Huntington's disease (HD is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to date.

  19. Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease.

    Science.gov (United States)

    Khakh, Baljit S; Beaumont, Vahri; Cachope, Roger; Munoz-Sanjuan, Ignacio; Goldman, Steven A; Grantyn, Rosemarie

    2017-07-01

    Astrocytes are abundant within mature neural circuits and are involved in brain disorders. Here, we summarize our current understanding of astrocytes and Huntington's disease (HD), with a focus on correlative and causative dysfunctions of ion homeostasis, calcium signaling, and neurotransmitter clearance, as well as on the use of transplanted astrocytes to produce therapeutic benefit in mouse models of HD. Overall, the data suggest that astrocyte dysfunction is an important contributor to the onset and progression of some HD symptoms in mice. Additional exploration of astrocytes in HD mouse models and humans is needed and may provide new therapeutic opportunities to explore in conjunction with neuronal rescue and repair strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Genetic counseling and testing for Huntington's disease: A historical review.

    Science.gov (United States)

    Nance, Martha A

    2017-01-01

    This manuscript describes the ways in which genetic counseling has evolved since John Pearson and Sheldon Reed first promoted "a genetic education" in the 1950s as a voluntary, non-directive clinical tool for permitting individual decision making. It reviews how the emergence of Huntington's disease (HD) registries and patient support organizations, genetic testing, and the discovery of a disease-causing CAG repeat expansion changed the contours of genetic counseling for families with HD. It also reviews the guidelines, outcomes, ethical and laboratory challenges, and uptake of predictive, prenatal, and preimplantation testing, and it casts a vision for how clinicians can better make use of genetic counseling to reach a broader pool of families that may be affected by HD and to ensure that genetic counseling is associated with the best levels of care. © 2016 Wiley Periodicals, Inc.

  1. Modern Genome Editing Technologies in Huntington's Disease Research.

    Science.gov (United States)

    Malankhanova, Tuyana B; Malakhova, Anastasia A; Medvedev, Sergey P; Zakian, Suren M

    2017-01-01

    The development of new revolutionary technologies for directed gene editing has made it possible to thoroughly model and study NgAgo human diseases at the cellular and molecular levels. Gene editing tools like ZFN, TALEN, CRISPR-based systems, NgAgo and SGN can introduce different modifications. In gene sequences and regulate gene expression in different types of cells including induced pluripotent stem cells (iPSCs). These tools can be successfully used for Huntington's disease (HD) modeling, for example, to generate isogenic cell lines bearing different numbers of CAG repeats or to correct the mutation causing the disease. This review presents common genome editing technologies and summarizes the progress made in using them in HD and other hereditary diseases. Furthermore, we will discuss prospects and limitations of genome editing in understanding HD pathology.

  2. Striatal Vulnerability in Huntington's Disease: Neuroprotection Versus Neurotoxicity.

    Science.gov (United States)

    Morigaki, Ryoma; Goto, Satoshi

    2017-06-07

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection.

  3. Genetic Mouse Models of Huntington's Disease: Focus on Electrophysiological Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlos Cepeda

    2010-03-01

    Full Text Available The discovery of the HD (Huntington's disease gene in 1993 led to the creation of genetic mouse models of the disease and opened the doors for mechanistic studies. In particular, the early changes and progression of the disease could be followed and examined systematically. The present review focuses on the contribution of these genetic mouse models to the understanding of functional changes in neurons as the HD phenotype progresses, and concentrates on two brain areas: the striatum, the site of most conspicuous pathology in HD, and the cortex, a site that is becoming increasingly important in understanding the widespread behavioural abnormalities. Mounting evidence points to synaptic abnormalities in communication between the cortex and striatum and cell-cell interactions as major determinants of HD symptoms, even in the absence of severe neuronal degeneration and death.

  4. High resolution impedance manometric findings in dysphagia of Huntington's disease

    Institute of Scientific and Technical Information of China (English)

    Tae Hee Lee; Joon Seong Lee; Wan Jung Kim

    2012-01-01

    Conventional manometry presents significant challenges,espedally in assessment of pharyngeal swallowing,because of the asymmetry and deglutitive movements of oropharyngeal structures.It only provides information about intraluminal pressure and thus it is difficult to study functional details of esophageal motility disorders.New technology of solid high resolution impedance manometry (HRIM),with 32 pressure sensors and 6 impedance sensors,is likely to provide better assessment of pharyngeal swallowing as well as more information about esophageal motility disorders.However,the clinical usefulness of application of HRIM in patients with oropharyngeal dysphagia or esophageal dysphagia is not known.We experienced a case of Huntington's disease presenting with both oropharyngeal and esophageal dysphagia,in which HRIM revealed the mechanism of oropharyngeal dysphagia and provided comprehensive information about esophageal dysphagia.

  5. Observation of the Wigner-Huntington transition to metallic hydrogen

    Science.gov (United States)

    Dias, Ranga P.; Silvera, Isaac F.

    2017-02-01

    Producing metallic hydrogen has been a great challenge in condensed matter physics. Metallic hydrogen may be a room-temperature superconductor and metastable when the pressure is released and could have an important impact on energy and rocketry. We have studied solid molecular hydrogen under pressure at low temperatures. At a pressure of 495 gigapascals, hydrogen becomes metallic, with reflectivity as high as 0.91. We fit the reflectance using a Drude free-electron model to determine the plasma frequency of 32.5 ± 2.1 electron volts at a temperature of 5.5 kelvin, with a corresponding electron carrier density of 7.7 ± 1.1 × 1023 particles per cubic centimeter, which is consistent with theoretical estimates of the atomic density. The properties are those of an atomic metal. We have produced the Wigner-Huntington dissociative transition to atomic metallic hydrogen in the laboratory.

  6. Westphal variant Huntington disease and refractory catatonia: a case report.

    Science.gov (United States)

    Merida-Puga, Jorge; Ramirez-Bermudez, Jesus; Aguilar-Venegas, Luis Carlos; Fricchione, Gregory L; Espinola-Nadurille, Mariana

    2011-12-01

    A young woman with Westphal variant (juvenile) Huntington disease (HD) also developed catatonia. Catatonia is an underdiagnosed psychomotor syndrome often associated with neurological and psychiatric disorders, but it has rarely been documented in patients with HD. Catatonia usually responds to standard treatment with benzodiazepines and electroconvulsive therapy; however, this patient's catatonic syndrome did not improve until we augmented the standard treatment with amantadine and levodopa. The underlying pathophysiology and a neurochemical hypothesis of HD and catatonia can explain their comorbidity and the refractoriness of catatonia to treatment. Both conditions are linked to dysregulation of neurotransmitters in the striatocortical and corticocortical pathways. This understanding may serve as a guide for the use of nonstandard treatments. Our evidence also suggests that electroconvulsive therapy can be useful and safe in the treatment of HD.

  7. Autophagy in Huntington disease and huntingtin in autophagy.

    Science.gov (United States)

    Martin, Dale D O; Ladha, Safia; Ehrnhoefer, Dagmar E; Hayden, Michael R

    2015-01-01

    Autophagy is an important biological process that is essential for the removal of damaged organelles and toxic or aggregated proteins by delivering them to the lysosome for degradation. Consequently, autophagy has become a primary target for the treatment of neurodegenerative diseases that involve aggregating proteins. In Huntington disease (HD), an expansion of the polyglutamine (polyQ) tract in the N-terminus of the huntingtin (HTT) protein leads to protein aggregation. However, HD is unique among the neurodegenerative proteinopathies in that autophagy is not only dysfunctional but wild type (wt) HTT also appears to play several roles in regulating the dynamics of autophagy. Herein, we attempt to integrate the recently described novel roles of wtHTT and altered autophagy in HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Diagnóstico molecular de la enfermedad de Huntington en Costa Rica Molecular diagnosis of Huntington´s disease in Costa Rica

    OpenAIRE

    Melissa Vásquez-Cerdas; Fernando Morales-Montero; Húbert Fernández-Morales; Gerardo el Valle-Carazo; Jaime Fornaguera-Trías; Patricia Cuenca-Berger

    2008-01-01

    Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 2008 Justificación y objetivo. Este estudio representa un esfuerzo para establecer por primera vez en Costa Rica el diagnóstico molecular de la enfermedad de Huntington; esto favorecerá un mejor manejo clínico de los pacientes y podrá ser traducido en un incremento de la calidad de vida de las familias. Se pretende determinar el número de repeticiones CAG en personas con la enfermedad de Huntington y f...

  9. Discrepancies in reporting the CAG repeat lengths for Huntington's disease.

    Science.gov (United States)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty; Dumoulin, Christine; Ramos-Arroyo, Maria; Biunno, Ida; Bauer, Peter; Kline, Margaret; Landwehrmeyer, G Bernhard

    2012-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.

  10. Orphan drugs in development for Huntington's disease: challenges and progress

    Directory of Open Access Journals (Sweden)

    Burgunder JM

    2015-02-01

    advanced strategies to develop novel treatments in Huntington's disease are examined. Keywords: Huntington's disease, symptomatic treatment, disease-modifying therapy

  11. Refrigerator Mothers and Sick Little Boys: Bruno Bettelheim, Eugenics and the De-Pathologization of Jewish Identity

    Directory of Open Access Journals (Sweden)

    griffin jaye epstein

    2014-06-01

    Full Text Available Child psychologist and Nazi concentration camp survivor Bruno Bettelheim’s influential theories of autism reveal a startling connection between Jewish identity, the medicalization of disability, colonial eugenics and race-making practices over the 20th century in North America. Using Bettelheim’s life and work as a case-study, this paper explores Ashkenazi Jewish immigrant complicity in a whitened colonial landscape through the lens of Disability Studies. It asks the question: can we be more accountable to our disabled identities – and to those disabled people who have come before us – if we learn how our families, our identities, our very selves have been complicit in medicalization and violence?  Keywords: madness, race, whiteness, Jewish identity, eugenics, psychiatry

  12. A New Translation Theory of“Correspondency”and Its Difference from“Functional Equivalence”by Eugene A. Nida

    Institute of Scientific and Technical Information of China (English)

    何欣

    2015-01-01

    This paper puts forward a new translation theory of“correspondency”, which is a more comprehensive and systematic translation theory that is especially effective in the translation criticism of“English-Chinese”or“Chinese-English”, absorbing some merits from Eugene A. Nida’s“functional equivalence”. A comparison of these two translation theories are offered in the paper, in hope of enlightening the readers in one aspect or another.

  13. The Souls’Journey into Light--On Eugene O’Neill’s Long Days Journey into Night

    Institute of Scientific and Technical Information of China (English)

    万红芳

    2013-01-01

    This paper aims to find a glimmer of light and hope from Eugene O’Neill’s tragedy: Long Days Journey into Night. The Tyrones’ periodic quarrel from dawn to dark is a journey into torture whereas it can also been seen as an indication of the unremitting hope for home. Behind the uneasy tensions of the characters who still cry for individual salvation, lies a world where the conflict between reality and fantasy can be resolved through love and reconciliation.

  14. The analysis of the eugenic culture in ancient China%中国古代优生文化辨析

    Institute of Scientific and Technical Information of China (English)

    蒋功成; 宗红

    2010-01-01

    There was a centuries-old culture of eugenics in ancient China. We should have comprehensive and objective cognition of this tradition. The ancient people did not generally advocate marrying at a mature age as do people of modern times. They not only considered the prepotency, but also were influenced by other complicated social factors on the problem of mate selection. Although advocates of coition techniques claimed the purpose of prepotency, the eugenic effect of coition techniques deserved to be suspect. Regarding the aspect of embryo conservation and care, the most significant thing was not so-called"prenatal education", but various antenatal care methods which were proposed by TCM scholars. By making a comparison with modern eugenics, the ancient eugenics had the characteristics of valuing the male child only, commiserating with deformity and being based on familial values.%中国古代具有非常悠久的优生传统,对这种传统应有全面客观的认识.古人并非如今人所认为的那样普遍提倡晚婚;在择偶问题上古人既有优生的考虑,更受到其他复杂社会因素的影响;房中术的提倡者虽声称以优生为目的,但房中术的优生效果是值得怀疑的;在胚胎保育方面,真正有意义的不是所谓的"胎教",而是中医学者们所建议的各种"胎养"方法.与近现代优生学相比较,中国古代优生学还体现出重男轻女、同情残疾者、一切以家族繁衍为本位的特点.

  15. Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

    Science.gov (United States)

    Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

    2012-04-01

    Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena

  16. "One of the Most Uniform Races of the Entire World": Creole Eugenics and the Myth of Chilean Racial Homogeneity.

    Science.gov (United States)

    Walsh, Sarah

    2015-11-01

    This article illuminates why Nicolás Palacios's 1904 monograph, Raza chilena: Libro escrito por un Chileno i para los Chilenos [Chilean Race: A Book Written by a Chilean for Chileans], is central to the creation of a myth of Chilean racial homogeneity at the turn of the twentieth century. Placing Palacios in the context of Latin American eugenic discourse, it demonstrates how he selected a specific racial origin story in order to accommodate his belief in racial hierarchy while also depicting race mixing in a positive light. Specifically, the article highlights how the myth of Chilean racial homogeneity elided the difference between the term "mestizo," which was applied to people of mixed racial heritage, and "white." I contend that Palacios sought to differentiate Chileans from other Latin Americans by emphasizing their racial distinctiveness. The article therefore highlights that Latin American eugenics was concerned with the creation of national narratives that historicized particular racial mixtures in order to reify and affirm national differences. As such, it connects to literature regarding the history of eugenics, race, nation, and the creation of whiteness.

  17. Hope in Huntington's disease A survey in counseling patients with Huntington's disease,as well as the caregivers

    Institute of Scientific and Technical Information of China (English)

    Jerzy T Marcinkowski; Daniel Zielonka

    2009-01-01

    BACKGROUND: It is difficult to attract interest in non-compulsory, preventive, medical care, and persons diagnosed with certain diseases often ignore the existence of these diseases. However, Huntington's disease (HD) is an exception. OBJECTIVE: To qualitatively analyze factors motivating HD patients to participate in a study, namely the European Huntington's Disease Network (EHDN) REGISTRY. DESIGN, TIME AND SETTING: An observational survey was conducted in the EHDN Study Site in Pozna(n), Poland between 2007 and 2008.PARTICIPANTS: The study involved 22 persons affected with HD and 3 pre-symptomatic individuals, totaling 9 males and 16 females. The 24 participants in this study had 24 different caregivers. A total of 25 symptomatic or pre-symptomatic subjects participated in the initial REGISTRY visit, as well as 6 in the second, and 1 in the third. All subjects did not know each other prior to the visit. METHODS: A mutation in the IT15 gene was confirmed in each patient or pre-symptomatic mutation carrier. An in-depth interview produced detailed information on the HD patients, as well as the caregivers, for the REGISTRY study. MAIN OUTCOME MEASURES: A qualitative analysis of the factors motivating HD patients and the pre-symptomatic mutation carriers to participate in the REGISTRY longitudinal, observational, research project was performed. RESULTS: The primary motivating factor for involvement of HD patients and the caregivers in the REGISTRY study was the hope that an effective HD therapy would soon be discovered. In HD patients and the pre-symptomatic group, the response to participate in the REGISTRY project reached 100%, despite the fact that they knew the project was only an observational study. CONCLUSION: Patient hope is thought to be a factor for engaging in preventive, therapeutic activities. However, this is rarely mentioned in medical papers and clinical textbooks, and is usually overlooked in medical teaching. Clearly, efforts should be made to

  18. Rating scales for behavioral symptoms in Huntington's disease: Critique and recommendations.

    Science.gov (United States)

    Mestre, Tiago A; van Duijn, Erik; Davis, Aileen M; Bachoud-Lévi, Anne-Catherine; Busse, Monica; Anderson, Karen E; Ferreira, Joaquim J; Mahlknecht, Philipp; Tumas, Vitor; Sampaio, Cristina; Goetz, Chris G; Cubo, Esther; Stebbins, Glenn T; Martinez-Martin, Pablo

    2016-10-01

    Behavioral symptoms are an important feature of Huntington's disease and contribute to impairment in quality of life. The Movement Disorder Society commissioned the assessment of the clinimetric properties of rating scales in Huntington's disease to make recommendations regarding their use, following previously used standardized criteria. A systematic literature search was conducted to identify the scales used to assess behavioral symptoms in Huntington's disease. For the purpose of this review, 7 behavioral domains were deemed significant in Huntington's disease: irritability, anxiety, depression, apathy, obsessive-compulsive behaviors, psychosis, and suicidal ideation. We included a total of 27 behavioral rating scales, 19 of which were of a single behavioral domain and the remaining 8 scales included multiple behavioral domains. Three rating scales were classified as "recommended" exclusively for screening purposes: the Irritability Scale for irritability, the Beck Depression Inventory-II, and the Hospital Anxiety and Depression Scale for depression. There were no "recommended" scales for other purposes such as diagnosis, severity, or change in time or to treatment. The main challenges identified for assessment of behavioral symptoms in Huntington's disease are the co-occurrence of multiple behavioral symptoms, the particular features of a behavioral symptom in Huntington's disease, and the need to address stage- and disease-specific features, including cognitive impairment and lack of insight. The committee concluded that there is a need to further validate currently available behavioral rating scales in Huntington's disease to address gaps in scale validation for specific behavioral domains and purpose of use. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  19. A study of the CCG polymorphism in the IT15 cDNA in the Scottish Huntington`s disease and normal populations

    Energy Technology Data Exchange (ETDEWEB)

    Barron, L.H.; Rae, A.; Brock, D.J.H. [Univ. of Edinburgh (United Kingdom)] [and others

    1994-09-01

    The CCG rich sequence immediately 3{prime} to the CAG repeat that is expanded in Huntington`s disease (HD) has recently been shown to be polymorphic with at least 5 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 200 Scottish HD families and have found very strong evidence for almost complete disequilibrium in this population. For all the families phase was unambiguously determined and 196 were shown to have a CCG repeat allele of 176 bp cosegregating with the HD chromosome. This observation is significantly different to the normal population distribution where 31% of people have an allele of 185 bp. This overrepresentation of the 176 bp allele is also seen in the normal population on chromosomes with greater than 26 CAG repeats. The DNA sequence across the CAG and CCG repeats has been obtained for the four HD patients that do not have a 176 bp CCG repeat size and will be presented. We present strong evidence of genetic heterogeneity in the Scottish HD population making it very unlikely that there is a founder effect in the Scottish HD population. These data suggest that we may have identified a region of the IT15 gene that is critical in the mechanism of Huntington`s disease CAG expansion.

  20. More than a Mentor: Leonard Darwin's Contribution to the Assimilation of Mendelism into Eugenics and Darwinism.

    Science.gov (United States)

    Serpente, Norberto

    2016-08-01

    This article discusses the contribution to evolutionary theory of Leonard Darwin (1850-1943), the eighth child of Charles Darwin. By analysing the correspondence Leonard Darwin maintained with Ronald Aylmer Fisher in conjunction with an assessment of his books and other written works between the 1910s and 1930s, this article argues for a more prominent role played by him than the previously recognised in the literature as an informal mentor of Fisher. The paper discusses Leonard's efforts to amalgamate Mendelism with both Eugenics and Darwinism in order for the first to base their policies on new scientific developments and to help the second in finding a target for natural selection. Without a formal qualification in biological sciences and as such mistrusted by some "formal" scientists, Leonard Darwin engaged with key themes of Darwinism such as mimicry, the role of mutations on speciation and the process of genetic variability, arriving at important conclusions concerning the usefulness of Mendelian genetics for his father's theory.

  1. [The development of criminal psychology in the work of Eugen Bleuler].

    Science.gov (United States)

    Möller, A; Hell, D

    1997-11-01

    The study refers to Eugen Bleuler's first systematic publications on "the natural born criminal" (1896) and his subsequent forensic-psychiatric expertise, written by Bleuler as Director of the psychiatric Department of Psychiatry of the University of Zurich ("Burghölzli"). It could be clearly shown that Bleuler was influenced by a deterministic understanding of human behaviour. He referred to the Anglo-American concept of "moral insanity" as a circumscribed defect of altruistic feelings despite other psychic functions being normal and tended to include this psychopathic deviation in psychiatry. Although this theoretic position remained unchanged, the elderly E. Beuler--under pragmatic points of view--accepted the traditional differentiation between mental illness in a narrower sense and "moral insanity" as a personality feature of most delinquents, falling under the responsibility of law and penal institutions. In his publications as emeritus (after 1927). Bleuler was influenced by the natural philosophic and vitalistic concept of the so-called "Minemism", which, however, still made him reject the postulate of "freedom of will".

  2. 尤金·奥尼尔(Eugene O'Neill)

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    尤金·奥尼尔(Eugene O’Neill,1888~1953年)美国著名剧作家,表现主义文学的代表作家,美国民族戏剧的奠基人。他4次获普利策奖,并于1936年获诺贝尔文学奖。他一生创作了45个剧本,题材广泛,风格多样。由于他的努力,美国的戏剧事业得以在20世纪20年代发展起来,成为美国文化领域中堪与小说、绘画、音乐作品相提并论的艺术形式。因而被公认为美国最重要的戏剧作家。

  3. 尤金·奥尼尔(Eugene O'Neill)

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    尤金·奥尼尔(Eugene O’Neill,1888~1953年)美国著名剧作家,表现主义文学的代表作家,美国民族戏剧的奠基人。他4次获普利策奖,并于1936年获诺贝尔文学奖。他一生创作了45个剧本,题材广泛,风格多样。由于他的努力,美国的戏剧事业得以在20世纪20年代发展起来,成为美国文化领域中堪与小说、绘画、音乐作品相提并论的艺术形式,因而被公认为美国最重要的戏剧作家。

  4. Eugenics, environment, and acclimatizing to Manchukuo: psychiatric studies of Japanese colonists.

    Science.gov (United States)

    Matsumura, Janice

    2010-09-01

    Both the advocates and critics of what has been called "the new imperial history," which may be characterized by its focus on how colonies were not simply influenced by but also exercised an influence on a dominating foreign state, have inspired this article. The article addresses the production and dissemination of medical knowledge in its examination of psychiatric research conducted in the 1930s in Japan's unofficial colony of Manchukuo. It highlights the political dimension of studies of psychosomatic disorders, syphilis, and alcoholism among colonists by placing it in the context of contending theories of racial improvement and growing official support for mass migration, especially to northeast China. Moreover, it inquires into restrictions on the flow of ideas from the colonies by examining how these studies were received in Japan. While interest in the colonies ensured that psychiatrists in Manchukuo were able to publish their research in leading Japanese medical journals, their findings jeopardized too many political and professional interests to become more public. In much-publicized debates stimulated by the impeding establishment of eugenic sterilization legislation, their colleagues in Japan in the late 1930s who championed the argument of environment over heredity were conspicuously silent about conditions among Japanese colonists, using instead examples of European and North American colonists to make their case.

  5. In Genes We Trust: Germline Engineering, Eugenics, and the Future of the Human Genome.

    Science.gov (United States)

    Powell, Russell

    2015-12-01

    Liberal proponents of genetic engineering maintain that developing human germline modification technologies is morally desirable because it will result in a net improvement in human health and well-being. Skeptics of germline modification, in contrast, fear evolutionary harms that could flow from intervening in the human germline, and worry that such programs, even if well intentioned, could lead to a recapitulation of the scientifically and morally discredited projects of the old eugenics. Some bioconservatives have appealed as well to the value of retaining our "given" human biological nature as a reason for restraining the development and use of human genetic modification technologies even where they would tend to increase well-being. In this article, I argue that germline intervention will be necessary merely to sustain the levels of genetic health that we presently enjoy for future generations-a goal that should appeal to bioliberals and bioconservatives alike. This is due to the population-genetic consequences of relaxed selection pressures in human populations caused by the increasing efficacy and availability of conventional medicine. This heterodox conclusion, which I present as a problem of intergenerational justice, has been overlooked in medicine and bioethics due to certain misconceptions about human evolution, which I attempt to rectify, as well as the sordid history of Darwinian approaches to medicine and social policy, which I distinguish from the present argument.

  6. The Genomic Revolution and Beliefs about Essential Racial Differences: A Backdoor to Eugenics?

    Science.gov (United States)

    Phelan, Jo C; Link, Bruce G; Feldman, Naumi M

    2013-04-01

    Could the explosion of genetic research in recent decades affect our conceptions of race? In Backdoor to Eugenics, Duster argues that reports of specific racial differences in genetic bases of disease, in part because they are presented as objective facts whose social implications are not readily apparent, may heighten public belief in more pervasive racial differences. We tested this hypothesis with a multi-method study. A content analysis showed that news articles discussing racial differences in genetic bases of disease increased significantly between 1985 and 2008 and were significantly less likely than non-health-related articles about race and genetics to discuss social implications. A survey experiment conducted with a nationally representative sample of 559 adults found that a news-story vignette reporting a specific racial difference in genetic risk for heart attacks (the Backdoor Vignette) produced significantly greater belief in essential racial differences than did a vignette portraying race as a social construction or a no-vignette condition. The Backdoor Vignette produced beliefs in essential racial differences that were virtually identical to those produced by a vignette portraying race as a genetic reality. These results suggest that an unintended consequence of the genomic revolution may be the reinvigoration of age-old beliefs in essential racial differences.

  7. 76 FR 60492 - Adequacy Status of the Ohio Portion of the Huntington/Ashland Submitted Annual Fine Particulate...

    Science.gov (United States)

    2011-09-29

    ..., starting at 69 FR 40038, and we used the information in these resources in making our adequacy... AGENCY Adequacy Status of the Ohio Portion of the Huntington/Ashland Submitted Annual Fine Particulate... Ohio portion of the Huntington/Ashland WV-KY-OH area. Ohio submitted the insignificance findings...

  8. HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation.

    Science.gov (United States)

    Träger, Ulrike; Andre, Ralph; Lahiri, Nayana; Magnusson-Lind, Anna; Weiss, Andreas; Grueninger, Stephan; McKinnon, Chris; Sirinathsinghji, Eva; Kahlon, Shira; Pfister, Edith L; Moser, Roger; Hummerich, Holger; Antoniou, Michael; Bates, Gillian P; Luthi-Carter, Ruth; Lowdell, Mark W; Björkqvist, Maria; Ostroff, Gary R; Aronin, Neil; Tabrizi, Sarah J

    2014-03-01

    Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.

  9. Striatal and white matter predictors of estimated diagnosis for Huntington disease

    Science.gov (United States)

    Paulsen, Jane S.; Nopoulos, Peggy C.; Aylward, Elizabeth; Ross, Christopher A.; Johnson, Hans; Magnotta, Vincent A.; Juhl, Andrew; Pierson, Ronald K.; Mills, James; Langbehn, Douglas; Nance, Martha

    2010-01-01

    Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at one of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity. PMID:20385209

  10. Huntington disease skeletal muscle is hyperexcitable owing to chloride and potassium channel dysfunction.

    Science.gov (United States)

    Waters, Christopher W; Varuzhanyan, Grigor; Talmadge, Robert J; Voss, Andrew A

    2013-05-28

    Huntington disease is a progressive and fatal genetic disorder with debilitating motor and cognitive defects. Chorea, rigidity, dystonia, and muscle weakness are characteristic motor defects of the disease that are commonly attributed to central neurodegeneration. However, no previous study has examined the membrane properties that control contraction in Huntington disease muscle. We show primary defects in ex vivo adult skeletal muscle from the R6/2 transgenic mouse model of Huntington disease. Action potentials in diseased fibers are more easily triggered and prolonged than in fibers from WT littermates. Furthermore, some action potentials in the diseased fibers self-trigger. These defects occur because of decreases in the resting chloride and potassium conductances. Consistent with this, the expression of the muscle chloride channel, ClC-1, in Huntington disease muscle was compromised by improper splicing and a corresponding reduction in total Clcn1 (gene for ClC-1) mRNA. Additionally, the total Kcnj2 (gene for the Kir2.1 potassium channel) mRNA was reduced in disease muscle. The resulting muscle hyperexcitability causes involuntary and prolonged contractions that may contribute to the chorea, rigidity, and dystonia that characterize Huntington disease.

  11. Striatal and white matter predictors of estimated diagnosis for Huntington disease.

    Science.gov (United States)

    Paulsen, Jane S; Nopoulos, Peggy C; Aylward, Elizabeth; Ross, Christopher A; Johnson, Hans; Magnotta, Vincent A; Juhl, Andrew; Pierson, Ronald K; Mills, James; Langbehn, Douglas; Nance, Martha

    2010-05-31

    Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at 1 of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG-repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity.

  12. Factors associated with Mediterranean diet adherence in Huntington's disease.

    Science.gov (United States)

    Rivadeneyra, Jéssica; Cubo, Esther; Gil, Cecilia; Calvo, Sara; Mariscal, Natividad; Martínez, Asunción

    2016-04-01

    Little is known about the importance of the Mediterranean Diet (MeDi) and dietary intake as environmental neuroprotective factors in Huntington's disease (HD); so, we evaluated and analyzed the prevalence and factors associated with MeDi adherence, and dietary intake in HD. Spanish participants of the European Huntington Disease Network (EHDN) Registry study diagnosed with HD or premanifest HD gene carriers were included from June 2012 to August 2013. Self-reported dietary intake was collected by 3-day dietary record, MeDi adherence was assessed by 0-9 range (proposed by Trichopoulou et al.) and, other contributing factors related to nutrition were collected by telephone. Demographics and clinical variables were obtained from the EHDN Registry study database. Association of HD with MeDi adherence and nutritional characteristics were performed using logistic regression models. Ninety eight participants were included in the study, median age of 48 years (38-60 range), and median total functional capacity (TFC) 9 (5-13 range). HD severity was similar between participants with low vs moderate/high MeDi; however, quality of life (P = 0.009) was significantly higher among participants with moderate/high MeDi adherence. In terms of nutrients, higher MUFA/SFA intake was moderately correlated with better TFC and Unified HD Rating Scale (UHDRS) cognitive. Better TFC was associated with having a caregiver (OR = 11.86, P adherence to MeDi, was associated with older participants (OR = 1.19, P = 0.031), lower comorbidity (OR = 0.18, P = 0.018), lower UHDRS motor (OR = 0.90, P = 0.041), and lower risk for abdominal obesity (OR = 0.02, P = 0.011). In HD the moderate MeDi adherence is associated with better quality of life, lower comorbidity, lower motor impairment and lower risk for abdominal obesity compared to those participants with low MeDi adherence. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All

  13. ENFERMEDAD DE HUNTINGTON: MODELOS EXPERIMENTALES Y PERSPECTIVAS TERAPÉUTICAS Huntington'disease: Experimentals Models and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    TERESA SERRANO SÁNCHEZ

    Full Text Available La enfermedad de Huntington (EH es un trastorno degenerativo de Weiss de origen hereditario. Hasta el momento no existe un tratamiento efectivo para la enfermedad que inexorablemente después de transcurridos 15 a 20 años, evoluciona hacia incapacidad total o muerte. En este trabajo se revisan las características clínicas y morfológicas de la EH y los modelos experimentales más utilizados para su estudio tomando como fuente, artículos indexados en la base de datos Medline publicados en los últimos 20 años. Se valoran las ventajas y desventajas de estos modelos y su perspectiva para el desarrollo de ensayos clínicos. El consenso de lo reportado plantea que de los modelos tóxicos, los inducidos por neurotoxinas tales como ácido quinolínico parecen ser los más adecuados para reproducir las características neuropatológicas, y por otro lado los modelos genéticos contribuyen con más evidencias al conocimiento del origen etiológico de la enfermedad. Numerosos tratamientos han sido aplicados en el manejo de las manifestaciones clínicas que aparecen en EH, sin poder detener o disminuir las afectaciones que derivan de la pérdida neuronal. La sintomatología clínica ha sido posible reproducirla, al menos en parte, en animales de experimentación lo que ha permitido realizar ensayos terapéuticos. Desde el punto de vista de tratamiento, lo que más promisorio parece ser, la terapia celular con células provenientes de diferentes fuentes y dentro de ellas las no neurales, que implican menor censura ética y mayor factibilidad de obtención para la aplicación en los enfermos. Por otro lado el desarrollo de la tecnología del ARN de interferencia, emerge como una herramienta terapéutica potencial para el tratamiento de EH, así como para responder interrogantes básicas relacionadas con el desarrollo de la enfermedad.Huntington'disease (HD is a degenerative dysfunction of hereditary origin. Up to date there is not, an effective treatment

  14. [IT15 gene analysis in two pedigrees of Huntington's disease].

    Science.gov (United States)

    Zhang, Bao-Rong; Song, Fei; Yin, Xin-Zhen; Xia, Kun; Tian, Jun; Huang, Jian-Zheng; Xia, Jia-Hui

    2006-11-01

    To investigate the relationship between the clinical features and (CAG)n trinucleotide repeats in two pedigrees of Chinese Huntington's disease (HD). Clinical and neuroimaging features, the age of disease onset and pattern of transmission of the patients were studied in the two pedigrees of HD. Genomic DNA of 42 family members was used for amplification of the (CAG)n repeats of IT15 gene by PCR. The numbers of (CAG)n were determined by electrophoresis through a 6% polyacrylamide gel and direct sequence analysis. Results showed that patients in pedigree 1 were absent of the typical triad of HD symptoms or caudate atrophy. A total of 9 (5 patients and 4 asymptomatic) out of 18 family members had 40-50 (CAG)n repeats in the IT15 gene. In pedigree 2, all the patients were characterized by a triad of symptoms, including motor disturbance, cognitive impairment and psychiatric features. Three patients and two asymptomatic relatives had more than 50 (CAG)n repeats in the IT15 gene. In conclusion, the clinical symptoms are partly determined by (CAG)n repeats in the IT15 gene. The age of onset was correlated with (CAG)n repeats over 50, and the phenomenon called "anticipation" was found to have played a role.

  15. Familial aggregation of schizophrenia-like symptoms in Huntington's disease.

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    Tsuang, D; DiGiacomo, L; Lipe, H; Bird, T D

    1998-07-10

    An increased incidence of schizophrenia-like symptoms in Huntington's disease (HD) has been well-documented in the past. The reasons for this association, however, have never been explained. At the University of Washington Medical Genetics Clinic, we had the opportunity to evaluate a unique juvenile-onset HD proband who had schizophrenia-like symptoms. This patient was referred to our clinic because of new onset of somatic delusions and command auditory hallucinations early in the course of her illness. Since we had already evaluated other affected individuals in her family, we selected another family with a nonpsychotic juvenile-onset proband for comparison. Using these two families in a small case-control study, we investigated the following hypotheses which could explain the association between schizophrenia-like symptoms and HD: first, schizophrenia-like symptoms may be related to the number of CAG repeats in the HD gene; second, schizophrenia-like symptoms may segregate in certain HD families, for unknown reasons; and third, there may coincidentally be an unrelated gene for schizophrenia in certain HD families. Comparisons of clinical characteristics and the HD genotype showed that family history of schizophrenia-like symptoms segregated with the HD gene; however, age of onset of HD, size of CAG repeat, and sex of the transmitting parent were not associated with psychotic symptoms. Further genetic and neurobiological studies are necessary to investigate the potential mechanism underlying this association.

  16. The Role of Dopamine and Glutamate Modulation in Huntington Disease

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    Mittal, Sumeer K.; Eddy, Clare

    2013-01-01

    Background: Huntington disease (HD) is an inherited neuropsychiatric condition with progressive neurodegenerative changes, mainly affecting the striatum. Pathological processes within the striatum are likely to lead to alterations in dopamine and glutamate activity in frontostriatal circuitry, resulting in characteristic motor, behavioural and cognitive symptoms. Methods: We conducted a systematic literature search in order to identify and review randomised, double-blinded, placebo-controlled trials of anti-dopaminergic and anti-glutamatergic therapy in HD. Results: Ten studies satisfied our selection criteria. These studies investigated a range of agents which act to antagonise dopamine (tetrabenazine, typical and atypical antipsychotics) or glutamate (amantadine, riluzole) transmission. Discussion: Although most agents showed efficacy in terms of amelioration of chorea, the available evidence did not allow us to identify a universally effective treatment. One difficulty associated with analysing the available evidence was a high prevalence of side effects, which prevented the full therapeutic potential of the medications from being adequately investigated. A further limitation is that many studies evaluated treatment effectiveness only in relation to patients' motor symptoms, even though behavioural and cognitive changes may negatively impact patients' quality of life. There is a clear need for further higher-level evidence addressing the effects of dopaminergic and glutamatergic agents on global functioning in HD. PMID:22713410

  17. [Huntington disease: presymptomatic testing, prenatal diagnosis, preimplantation genetic diagnosis experience].

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    Durr, A; Viville, S

    2007-10-01

    Presymptomatic testing for Huntington disease has been available for 15 years. The possibility of determining the genetic status of an at-risk person for the disorder which runs in his or her family raises questions because of the absence of preventive treatments. In addition, being carrier does not allow to determine when the disease starts and how it will evolve, impairing the possibilities of planning the future. A pluridisciplinary approach to predictive testing with care before, during and after the test taking into account the medical, social and psychological aspects of the disease is good practice. At the present time, only a minority of at-risk individuals request presymptomatic testing and almost 50% do not pursue until the results. The consequences of the test may be harmful, more frequently after an unfavorable than after a favorable result. Motivations and the outcome in terms of request for prenatal testing after a carrier result are known today and the number or prenatal testing remains very limited. Preimplantation genetic testing is an alternative for couples who knows or do not their own genetic status. We report our experience in two French centres: Paris for presymptomatic and prenatal testing and Strasbourg for preimplantation diagnosis.

  18. Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease.

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    Analyne M Schroeder

    Full Text Available While Huntington's disease (HD is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3 months of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis and ultimately apoptosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol treatment; however, the medication exacerbated fibrotic lesions in the heart. Gene expression analysis indicated a strong tilt toward apoptosis in the young mutant heart as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the large changes occurring in the cardiovascular disease, cellular metabolism, and cellular transport clusters. The BACHD model of HD exhibits a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher cardiovascular risk in HD.

  19. Tractography of the corpus callosum in Huntington's disease.

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    Owen Phillips

    Full Text Available White matter abnormalities have been shown in presymptomatic and symptomatic Huntington's disease (HD subjects using Magnetic Resonance Imaging (MRI and Diffusion Tensor Imaging (DTI methods. The largest white matter tract, the corpus callosum (CC, has been shown to be particularly vulnerable; however, little work has been done to investigate the regional specificity of tract abnormalities in the CC. Thus, this study examined the major callosal tracts by applying DTI-based tractography. Using TrackVis, a previously defined region of interest tractography method parcellating CC into seven major tracts based on target region was applied to 30 direction DTI data collected from 100 subjects: presymptomatic HD (Pre-HD subjects (n=25, HD patients (n=25 and healthy control subjects (n=50. Tractography results showed decreased fractional anisotropy (FA and increased radial diffusivity (RD across broad regions of the CC in Pre-HD subjects. Similar though more severe deficits were seen in HD patients. In Pre-HD and HD, callosal FA and RD were correlated with Disease Burden/CAG repeat length as well as motor (UHDRSI and cognitive (URDRS2 assessments. These results add evidence that CC pathways are compromised prior to disease onset with possible demyelination occurring early in the disease and suggest that CAG repeat length is a contributing factor to connectivity deficits. Furthermore, disruption of these callosal pathways potentially contributes to the disturbances of motor and cognitive processing that characterize HD.

  20. The story of George Huntington and his disease

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    Kalyan B Bhattacharyya

    2016-01-01

    Full Text Available George Huntington described some families with choreiform movements in 1872 in the United States of America and since then many such families have been described in other parts of the world and works on the genetics of the disease have brought new vistas in the understanding of the disease. In 1958, Americo Negrette, a young Venezuelan physician observed similar subjects in the vicinity of Lake Maracaibo which was presented by his co-worker, Ramon Avilla Giron at New York in 1972 when United States of America had been commemorating the centenary year of Huntington′s disease. Nancy Wexler, a psychoanalyst, whose mother had been suffering from the disease attended the meeting and organized a research team to Venezuela and they systematically studied more than 18,000 individuals in order to work out a common pedigree. They identified the genetic locus of the disease in the short arm of chromosome 4 and observed that it was a trinucleotide repeat disorder.

  1. Therapeutic Effect of Berberine on Huntington's Disease Transgenic Mouse Model.

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    Wenxiao Jiang

    Full Text Available Huntington disease (HD represents a family of neurodegenerative diseases that are caused by misfolded proteins. The misfolded proteins accumulate in the affected brain regions in an age-dependent manner to cause late-onset neurodegeneration. Transgenic mouse models expressing the HD protein, huntingtin, have been widely used to identify therapeutics that may retard disease progression. Here we report that Berberine (BBR, an organic small molecule isolated from plants, has protective effects on transgenic HD (N171-82Q mice. We found that BBR can reduce the accumulation of mutant huntingtin in cultured cells. More importantly, when given orally, BBR could effectively alleviate motor dysfunction and prolong the survival of transgenic N171-82Q HD mice. We found that BBR could promote the degradation of mutant huntingtin by enhancing autophagic function. Since BBR is an orally-taken drug that has been safely used to treat a number of diseases, our findings suggest that BBR can be tested on different HD animal models and HD patients to further evaluate its therapeutic effects.

  2. Triplet repeat primed PCR simplifies testing for Huntington disease.

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    Jama, Mohamed; Millson, Alison; Miller, Christine E; Lyon, Elaine

    2013-03-01

    Diagnostic and predictive testing for Huntington disease (HD) requires an accurate determination of the number of CAG repeats in the Huntingtin (HHT) gene. Currently, when a sample appears to be homozygous for a normal allele, additional testing is required to confirm amplification from both alleles. If the sample still appears homozygous, Southern blot analysis is performed to rule out an undetected expanded HTT allele. Southern blot analysis is expensive, time-consuming, and labor intensive and requires high concentrations of DNA. We have developed a chimeric PCR process to help streamline workflow; true homozygous alleles are easily distinguished by this simplified method, and only very large expanded alleles still require Southern blot analysis. Two hundred forty-six HD samples, previously run with a different fragment analysis method, were analyzed with our new method. All samples were correctly genotyped, resulting in 100% concordance between the methods. The chimeric PCR assay was able to identify expanded alleles up to >150 CAG repeats. This method offers a simple strategy to differentiate normal from expanded CAG alleles, thereby reducing the number of samples reflexed to Southern blot analysis. It also provides assurance that expanded alleles are not routinely missed because of allele dropout.

  3. Advances in the pharmacological management of Huntington's disease.

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    Frank, Samuel; Jankovic, Joseph

    2010-03-26

    There is inevitable physical, cognitive and behavioural decline in Huntington's disease (HD), a dominantly inherited progressive neurological disorder. The hallmark of the disease is chorea, an involuntary brief movement that tends to flow between body regions. HD is diagnosed clinically with genetic confirmation. Predictive testing is available; however, it should be undertaken with caution in patients at risk for the disease but without clinical disease expression. Ongoing observational trials have identified not only early subtle motor signs, but also striatal volume, verbal memory and olfaction as possible early manifestations of clinical disease. Multiple areas of the brain degenerate, with dopamine, glutamate and GABA being the predominant neurotransmitters affected in HD. Although many pharmacotherapies have been evaluated targeting these neurotransmitters, few well conducted trials for symptomatic or neuroprotective interventions have yielded positive results. Tetrabenazine is one of the better studied and more effective agents for reducing chorea, although with a risk of potentially serious adverse effects. Newer antipsychotic agents such as olanzapine and aripiprazole may have adequate efficacy with a more favourable adverse-effect profile than older antipsychotics for treating chorea and psychosis. In this review, the pathogenesis, epidemiology and diagnosis of HD are discussed as background for understanding potential pharmacological treatment options. Potential strategies to delay the progression of HD that have been studied and are planned for the future are summarized. Although there is no current method to change the course of this devastating disease, education and symptomatic therapies are effective tools available to clinicians and the families affected by HD.

  4. Genetic Testing for Huntington's Disease: How Is the Decision Taken?

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    Etchegary, Holly

    2006-01-01

    Research on genetic decision-making normally constructs the decision as an opportunity for choice. However, minimal research investigates how these decisions are taken and whether those who live with genetic risk perceive the test as an opportunity for choice. Employing semistructured interviews with at-risk persons, this study explored decisions about genetic testing for Huntington's disease (HD)--a fatal genetic disorder. A primary aim was to understand how test decisions were perceived. Qualitative data analysis revealed four decision pathways: (1) no decision to be made, (2) constrained decisions, (3) reevaluating the decision, and (4) indicators of HD. Contrary to the rational, "information-processor" approach to decision making, some test decisions were immediate and automatic. These stories challenged the conventional construction of a genetic-test decision as an opportunity for choice. Participant narratives suggested that this construction may be inadequate, at least for some people who live with genetic risk. Test decisions were sometimes constrained by perceived responsibility to other family members, notably offspring. For others at risk, the test decision was a dynamic process of critical thought and evaluation. Finally, behaviors that could be symptoms of HD were the catalyst for testing.

  5. Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia.

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    Dong, Y; Sun, Y-M; Liu, Z-J; Ni, W; Shi, S-S; Wu, Z-Y

    2013-04-01

    Recent studies have described Huntington's disease (HD) patients with atypical onset of ataxia. Symptoms in these patients can overlap with those of spinocerebellar ataxia (SCA). We retrospectively examined clinical data for 82 HD probands and found 7 had initially been clinically diagnosed as SCA cases. Clinical features in these patients were further investigated and the number of CAG repeats in the huntingtin (HTT) gene was determined by direct sequencing. Genetic screenings for SCAs in the 7 patients were all negative. By contrast, HTT was heterozygous in each patient. The distribution of CAG number in the 7 patients was statistically the same as that in the other 75 patients. Each of 7 HD patients had presented with atypical onset of ataxia. The mean time from onset to HTT genetic testing was 5.6 ± 5.52 years. Three of the patients developed chorea, but the others did not. Our observations confirm the clinical heterogeneity of HD in Han Chinese. Based on these findings, testing for HTT expansions should be considered for clinically diagnosed SCA patients who test negatively in genetic screening of SCA genes.

  6. Huntington's disease in Greece: the experience of 14 years.

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    Panas, M; Karadima, G; Vassos, E; Kalfakis, N; Kladi, A; Christodoulou, K; Vassilopoulos, D

    2011-12-01

    A large scale genetic and epidemiological study of Huntington's disease (HD) was carried out in Greece from January 1995 to December 2008. Diagnostic testing was carried out in 461 symptomatic individuals, while 256 were tested for presymptomatic purposes. The diagnosis of HD with a CAG expansion ≥ 36 was confirmed in 278 symptomatic individuals. The prevalence of HD in Greece was estimated at approximately 2.5 to 5.4:100,000, while the mean minimum incidence was estimated at 2.2 to 4.4 per million per year. The molecular diagnosis of HD was confirmed in the majority of patients (84.4%) sent for confirmation. The false-positive cases 15.6% were characterized by the absence of a family history of HD and the presence of an atypical clinical picture. The uptake of predictive testing for HD was 8.6%. A prenatal test was requested in six pregnancies. The findings of our study do not differ significantly from those of similar studies from other European countries despite the relative genetic isolation of Greece. Of interest is the identification of clusters of HD in Greece. The presence or absence of a family history of HD should be interpreted cautiously, during the diagnostic process.

  7. Impaired PGC-1alpha function in muscle in Huntington's disease.

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    Chaturvedi, Rajnish K; Adhihetty, Peter; Shukla, Shubha; Hennessy, Thomas; Calingasan, Noel; Yang, Lichuan; Starkov, Anatoly; Kiaei, Mahmoud; Cannella, Milena; Sassone, Jenny; Ciammola, Andrea; Squitieri, Fernando; Beal, M Flint

    2009-08-15

    We investigated the role of PPAR gamma coactivator 1alpha (PGC-1alpha) in muscle dysfunction in Huntington's disease (HD). We observed reduced PGC-1alpha and target genes expression in muscle of HD transgenic mice. We produced chronic energy deprivation in HD mice by administering the catabolic stressor beta-guanidinopropionic acid (GPA), a creatine analogue that reduces ATP levels, activates AMP-activated protein kinase (AMPK), which in turn activates PGC-1alpha. Treatment with GPA resulted in increased expression of AMPK, PGC-1alpha target genes, genes for oxidative phosphorylation, electron transport chain and mitochondrial biogenesis, increased oxidative muscle fibers, numbers of mitochondria and motor performance in wild-type, but not in HD mice. In muscle biopsies from HD patients, there was decreased PGC-1alpha, PGC-1beta and oxidative fibers. Oxygen consumption, PGC-1alpha, NRF1 and response to GPA were significantly reduced in myoblasts from HD patients. Knockdown of mutant huntingtin resulted in increased PGC-1alpha expression in HD myoblast. Lastly, adenoviral-mediated delivery of PGC-1alpha resulted increased expression of PGC-1alpha and markers for oxidative muscle fibers and reversal of blunted response for GPA in HD mice. These findings show that impaired function of PGC-1alpha plays a critical role in muscle dysfunction in HD, and that treatment with agents to enhance PGC-1alpha function could exert therapeutic benefits. Furthermore, muscle may provide a readily accessible tissue in which to monitor therapeutic interventions.

  8. Transcriptional dysregulation in Huntington's disease: The role of histone deacetylases.

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    Sharma, Sorabh; Taliyan, Rajeev

    2015-10-01

    Huntington's disease (HD) is a progressive neurological disorder for which there are no disease-modifying treatments. Although, the exact underlying mechanism(s) leading to the neural cell death in HD still remains elusive, the transcriptional dysregulation is a major molecular feature. Recently, the transcriptional activation and repression regulated by chromatin acetylation has been found to be impaired in HD pathology. The acetylation and deacetylation of histone proteins is carried out by opposing actions of histone acetyl-transferases and histone deacetylases (HDACs), respectively. Studies carried out in cell culture, yeast, Drosophila and rodent model(s) have indicated that HDAC inhibitors (HDACIs) might provide useful class of therapeutic agents for HD. Clinical trials have also reported the beneficial effects of HDACIs in patients suffering from HD. Therefore, the development of HDACIs as therapeutics for HD has been vigorously pursued. In this review, we highlight and summarize the putative role of HDACs in HD like pathology and further discuss the potential of HDACIs as new therapeutic avenues for the treatment of HD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Synaptopathic mechanisms of neurodegeneration and dementia: Insights from Huntington's disease.

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    Tyebji, Shiraz; Hannan, Anthony J

    2017-06-01

    Dementia encapsulates a set of symptoms that include loss of mental abilities such as memory, problem solving or language, and reduces a person's ability to perform daily activities. Alzheimer's disease is the most common form of dementia, however dementia can also occur in other neurological disorders such as Huntington's disease (HD). Many studies have demonstrated that loss of neuronal cell function manifests pre-symptomatically and thus is a relevant therapeutic target to alleviate symptoms. Synaptopathy, the physiological dysfunction of synapses, is now being approached as the target for many neurological and psychiatric disorders, including HD. HD is an autosomal dominant and progressive degenerative disorder, with clinical manifestations that encompass movement, cognition, mood and behaviour. HD is one of the most common tandem repeat disorders and is caused by a trinucleotide (CAG) repeat expansion, encoding an extended polyglutamine tract in the huntingtin protein. Animal models as well as human studies have provided detailed, although not exhaustive, evidence of synaptic dysfunction in HD. In this review, we discuss the neuropathology of HD and how the changes in synaptic signalling in the diseased brain lead to its symptoms, which include dementia. Here, we review and discuss the mechanisms by which the 'molecular orchestras' and their 'synaptic symphonies' are disrupted in neurodegeneration and dementia, focusing on HD as a model disease. We also explore the therapeutic strategies currently in pre-clinical and clinical testing that are targeted towards improving synaptic function in HD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Microglial Activation in the Pathogenesis of Huntington's Disease.

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    Yang, Hui-Ming; Yang, Su; Huang, Shan-Shan; Tang, Bei-Sha; Guo, Ji-Feng

    2017-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expanded CAG trinucleotide repeats (>36) in exon 1 of HTT gene that encodes huntingtin protein. Although HD is characterized by a predominant loss of neurons in the striatum and cortex, previous studies point to a critical role of aberrant accumulation of mutant huntingtin in microglia that contributes to the progressive neurodegeneration in HD, through both cell-autonomous and non-cell-autonomous mechanisms. Microglia are resident immune cells in the central nervous system (CNS), which function to surveil the microenvironment at a quiescent state. In response to various pro-inflammatory stimuli, microglia become activated and undergo two separate phases (M1 and M2 phenotype), which release pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), anti-inflammatory cytokines, and growth factors (TGF-β, CD206, and Arg1), respectively. Immunoregulation by microglial activation could be either neurotoxic or neuroprotective. In this review, we summarized current understanding about microglial activation in the pathogenesis and progression of HD, with a primary focus of M1 and M2 phenotype of activated microglia and their corresponding signaling pathways.

  11. Antidepressants for neuroprotection in Huntington's disease: A review.

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    Jamwal, Sumit; Kumar, Puneet

    2015-12-15

    Huntington Disease (HD), which is characterized by abnormal dance-like movements, is a neurodegenerative disorder caused by a genetic mutation that results in an expanded polyglutamine stretch in the NH2 terminus of huntingtin protein (HTT). The principal neuropathological hallmarks of disease include loss of striatal and cortical projection neurons. HTT is ubiquitously expressed and is implicated in several cellular functions including neurogenesis, cell trafficking and brain-derived neurotrophic factor (BDNF) production. Major depression is the most common symptom among pre-symptomatic HD carriers and numerous pieces of preclinical evidence have suggested the use of antidepressants in HD not only elevates mood but also slows down the disease progression by activating different neuroprotective mechanism like BDNF/TrkB pathway, MAPK/ERK signalling, neurogenesis and Wnt signalling. HTT plays major role in neurogenesis, a physiological phenomenon that is implicated in some of the behavioral effects of antidepressants. Currently, there is no clinically available treatment that can halt or slow down the progression of HD except tetrabenazine (the only FDA approved drug); however, this drug also induces depression and sedation in patients. In this review, a brief discussion has been made about the mutant HTT that induced various cellular and molecular mechanisms underlying behavioral disorders in HD. Further, an attempt has been made to understand the various cellular mechanisms involved in mediating the neuroprotective effects of antidepressants in HD. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Non-Verbal and Verbal Fluency in Prodromal Huntington's Disease

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    Tarja-Brita Robins Wahlin

    2015-12-01

    Full Text Available Background: This study examines non-verbal (design and verbal (phonemic and semantic fluency in prodromal Huntington's disease (HD. An accumulating body of research indicates subtle deficits in cognitive functioning among prodromal mutation carriers for HD. Methods: Performance was compared between 32 mutation carriers and 38 non-carriers in order to examine the magnitude of impairment across fluency tasks. The predicted years to onset (PYTO in mutation carriers was calculated by a regression equation and used to divide the group according to whether onset was predicted as less than 12.75 years (HD+CLOSE; n = 16 or greater than 12.75 years (HD+DISTANT; n = 16. Results: The results indicate that both non-verbal and verbal fluency is sensitive to subtle impairment in prodromal HD. HD+CLOSE group produced fewer items in all assessed fluency tasks compared to non-carriers. HD+DISTANT produced fewer drawings than non-carriers in the non-verbal task. PYTO correlated significantly with all measures of non-verbal and verbal fluency. Conclusion: The pattern of results indicates that subtle cognitive deficits exist in prodromal HD, and that less structured tasks with high executive demands are the most sensitive in detecting divergence from the normal range of functioning. These selective impairments can be attributed to the early involvement of frontostriatal circuitry and frontal lobes.

  13. Huntington disease: natural history, biomarkers and prospects for therapeutics.

    Science.gov (United States)

    Ross, Christopher A; Aylward, Elizabeth H; Wild, Edward J; Langbehn, Douglas R; Long, Jeffrey D; Warner, John H; Scahill, Rachael I; Leavitt, Blair R; Stout, Julie C; Paulsen, Jane S; Reilmann, Ralf; Unschuld, Paul G; Wexler, Alice; Margolis, Russell L; Tabrizi, Sarah J

    2014-04-01

    Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials.

  14. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease.

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    Naranjo, José R; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C; Arrabal, María D; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-02-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD.

  15. Wigner and Huntington: the long quest for metallic hydrogen

    Science.gov (United States)

    Nellis, W. J.

    2013-06-01

    In 1935, Wigner and Huntington (WH) predicted that at a density D Met=0.62 mole H/cm3, 'very low temperatures', and a pressure greater than 25 GPa, body-centered cubic H2 would undergo an isostructural phase transition directly to H with an associated insulator-metal transition (IMT). WH also predicted an H2 structure type that might occur if the simple H2/H dissociative IMT does not exist: 'It is possible … that a layer-like lattice … is obtainable under high pressure'. In 1991, Ashcroft predicted that the 'geometric and dynamic nature of the (H-H) pairing', possibly in a layered graphite-like structure, would substantially impede achieving metallic H2. In 1996, metallic fluid H was made under dynamic compression at 0.64 mole H/cm3, 140 GPa and T/T F≪1, where T F is Fermi temperature. In 2012, a layer-like lattice, called Phase IV, was discovered above ∼220 GPa static pressure. Phase IV is insulating and possibly semi-metallic up to ∼360 GPa, above which it has been predicted to become metallic. This paper is a historical perspective - a comparison of WH's predictions with recent dynamic, static and theoretical high pressure results. WH did extremely well.

  16. Making a measurable difference in advanced Huntington disease care.

    Science.gov (United States)

    Moskowitz, Carol Brown; Rao, Ashwini K

    2017-01-01

    Neurologists' role in the care of people with advanced Huntington disease (HD) (total functional capacity <7), often limited by a lack of clinical research to support good practice, includes the following: (1) provide comprehensive health records to an interdisciplinary care staff before admission to a more intense care setting (home health services, day program, assisted living, group home, long-term skilled nursing facility, palliative care); (2) consult with and refer to rehabilitation (occupational therapy, physical therapy, speech and language pathology), behavioral and psychiatric professionals for problem-solving strategies, which must be reviewed with direct care staff before implementation; (3) encourage and support qualitative and quantitative interdisciplinary research studies, and randomized controlled studies of nonpharmacologic interventions; and (4) assist in the development of meaningful measures to further document what works to provide a good quality of life for the patient and family and a comfortable thoughtful approach to a good death. Collaborative models of care depend on: (1) clear communication; (2) ongoing education and support programs; with (3) pharmacologic and rehabilitation interventions, always in the context of respect for the person with HD, a preservation of the individuals' dignity, autonomy, and individual preferences. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Cognitive and behavioral changes in Huntington disease before diagnosis.

    Science.gov (United States)

    Paulsen, Jane S; Miller, Amanda C; Hayes, Terry; Shaw, Emily

    2017-01-01

    Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The earliest detected cognitive changes are observed in the Symbol Digit Modalities Test, Stroop Interference, Stroop Color and Word Test-interference condition, and Trail Making Test. Cognitive changes in the middle and near motor diagnostic stages of prodromal HD involve nearly every cognitive test administered and the greatest changes over time (i.e., slopes) are found in those prodromal HD participants who are nearest to motor diagnosis. Psychiatric changes demonstrate significant worsening over time and remain elevated compared with healthy controls throughout the prodromal disease course. Psychiatric and behavior changes in prodromal HD are much lower than that obtained using cognitive assessment, although the psychiatric and behavioral changes represent symptoms most debilitating to independent capacity and wellness. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Founder mutation for Huntington disease in Caucasus Jews.

    Science.gov (United States)

    Melamed, O; Behar, D M; Bram, C; Magal, N; Pras, E; Reznik-Wolf, H; Borochowitz, Z U; Davidov, B; Mor-Cohen, R; Baris, H N

    2015-02-01

    Huntington disease (HD), an autosomal dominant disorder involving HTT, is characterized by chorea, psychiatric illness and cognitive decline. Diagnosis and age of onset depend on the degree of expansion of the trinucleotide CAG repeat within the gene. The prevalence of HD is known for Europeans but has not been studied in the Israeli population. Between 2006 and 2011 we diagnosed in our adult genetics clinic ten HD probands, nine of whom were Caucasus Jews (CJ) (Azerbaijani), and one Ashkenazi Jewish. We performed haplotype analysis to look for evidence of a founder mutation, and found that of the nine CJ, eight shared the same haplotype that was compatible with the A1 haplogroup. We calculated the coalescence age of the mutation to be between 80 and 150 years. Ninety percent of our HD patients are CJ, as are 27% of the HD patients in Israel, although the CJ comprise only 1.4% of the Israeli population. Our findings suggest a higher prevalence of HD among CJ compared to the general Israeli population and are consistent with a recent founder mutation. We recommend a higher degree of suspicion for HD in CJ with subtle clinical findings. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Metabolic disruption identified in the Huntington's disease transgenic sheep model.

    Science.gov (United States)

    Handley, Renee R; Reid, Suzanne J; Patassini, Stefano; Rudiger, Skye R; Obolonkin, Vladimir; McLaughlan, Clive J; Jacobsen, Jessie C; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2016-02-11

    Huntington's disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease.

  20. Cognitive and Brain Reserve in Prodromal Huntington Disease

    Science.gov (United States)

    Bonner-Jackson, Aaron; Long, Jeffrey D.; Westervelt, Holly; Tremont, Geoffrey; Aylward, Elizabeth; Paulsen, Jane S.

    2013-01-01

    Background Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Methods Participants were genetically-confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on 4 cognitive measures and 3 brain volumes over approximately 6 years. Results Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Conclusions Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals. PMID:23702309

  1. Rate of change in early Huntington's disease: a clinicometric analysis.

    Science.gov (United States)

    Meyer, Christina; Landwehrmeyer, Bernhard; Schwenke, Carsten; Doble, Adam; Orth, Michael; Ludolph, Albert C

    2012-01-01

    Sensitive outcome measures for patients with Huntington's disease (HD) are required for future clinical trials. Longitudinal data were collected from a 3-year study of 379 patients suffering from early HD who were not treated by antipsychotics. Progression of UHDRS item scores was evaluated by linear regression and slope, whereas correlation coefficient, standard error, and P values were estimated on the basis of the data of eight evaluations from screening to study end (36 months). For the functional assessment dimension, the proportion of "no" responses at baseline and at study end was determined. Linear progression was observed for the motor score and for all three functional measures (i.e., functional assessment score, independence assessment score, and total functional capacity score). In contrast, there was little evidence for progression of the behavioral assessment score over the study period, whereas the cognitive assessment score was intermediate. Twenty-two motor-score items showed linear progression, with a slope of >0.003. These included all chorea items, finger tapping and pronation/supination (left and right), gait, tongue protrusion, and tandem walking. Different symptom domains and individual items evolved at different rates in this group of patients suffering from early HD. It may be possible to select sensitive items to create a simplified version of the UHDRS, which would be more efficient and more sensitive for the assessment of disease progression in clinical trials and natural history studies.

  2. Did the “Woman in the Attic” in Jane Eyre Have Huntington Disease?

    Science.gov (United States)

    Coon, Elizabeth A.; Hassan, Anhar

    2015-01-01

    Background References to neurologic disorders are frequently found in fictional literature and may precede description in the medical literature. Aim Our aim was to compare Charlotte Brontë’s depiction of Bertha Mason in Jane Eyre to the tenets set forth in George Huntington’s original essay “On chorea” with the hypothesis that Mason was displaying features of Huntington disease. Results Charlotte Brontë’s 1847 Victorian novel Jane Eyre features the character Bertha Mason, who is portrayed with a progressive psychiatric illness, violent movements, and possible cognitive decline. Similar to Huntington’s tenets, Mason has a disorder with a strong family history suggestive of autosomal dominant inheritance with onset in adulthood, and culminating in suicide. Conclusion Brontë’s character had features of Huntington disease as originally described by Huntington. Brontë’s keen characterization may have increased awareness of treatment of neuropsychiatric patients in the Victorian era. PMID:26273542

  3. Results on single cell PCR for Huntington's gene and WAVE product analysis for preimplantation genetic diagnosis.

    Science.gov (United States)

    Drury, K C; Liu, M C; Lilleberg, S; Kipersztok, S; Williams, R S

    2001-10-22

    Triple repeat base pair amplification is the basis for a number of prevalent genetic diseases such as Huntington's, Fragile X, Myotonic Dystrophy and others. We have chosen to investigate the use of PCR to amplify a portion of the Huntington's gene in single cells in order to develop a clinical test system for preimplantation genetic diagnosis (PGD). Amplification of CAG triple repeat sequences poses difficulties due to resistance of GC melting for amplification. Special PCR modifications are necessary to carry out the amplification of GC rich areas found in most triple base pair expansions. We have used a modified polymerase chain reaction (PCR) protocol to amplify the expanded repeat sequence of the Huntington's gene with satisfactory efficiency. Detection of the amplified expanded CAG repeats is shown to be possible using both agarose gel electrophoresis and high definition denaturing high pressure liquid (DHPLC) chromatography. The incidence of allele dropout (ADO) is documented.

  4. Operant-based instrumental learning for analysis of genetically modified models of Huntington's disease.

    Science.gov (United States)

    Trueman, R C; Dunnett, S B; Brooks, S P

    2012-06-01

    Huntington's disease is the result of an expanded CAG repeat in the gene that codes for the protein huntingtin and results in a progressive sequelae of motor, cognitive and psychiatric symptoms. The development of genetically modified rodent models of Huntington's disease has led to the need for sensitive behavioural phenotyping. Operant tests for rodents have been developed that can determine the functional deficits in these genetically modified models, from motor, cognitive and emotional domains. The current review discusses tests that employ operant equipment, an automated and highly flexible method for testing rodents. Different operant paradigms are examined in relation to their relevance to Huntington's disease symptomology, as well as summarising research to date on genetic models with these tests.

  5. Acetylcholinesterase inhibitors in cognitive impairment in Huntington's disease: A brief review.

    Science.gov (United States)

    Vattakatuchery, Joe John; Kurien, Renjith

    2013-09-22

    Huntington's disease (HD) is a neurodegenerative disease associated with cognitive deficits. Cognitive dysfunction may be present in the early stages of the disease, even before the onset of motor symptoms. The cognitive dysfunction includes executive dysfunction, psychomotor symptoms, visuospatial deficits, perceptual deficits, memory loss and difficulty learning new skills. Acetylcholinesterase inhibitors have shown good effect in the treatment of other types of dementia and it is postulated that it might delay cognitive decline in HD. We reviewed the evidence for Acetylcholinesterase inhibitors in the treatment of cognitive decline and dementia associated with Huntington's disease. We identified 6 articles that investigated the role of Acetylcholinesterase inhibitors for treatment of cognitive deficits in Huntington's disease. Following the review, the authors concluded that there is limited evidence for the use of Acetylcholinesterase inhibitors for cognitive impairment in HD.

  6. An update on Huntington's disease: from the gene to the clinic.

    Science.gov (United States)

    Kim, Samuel D; Fung, Victor S C

    2014-08-01

    This review highlights the recent advances in Huntington's disease, with a particular focus on development of disease biomarkers for use in therapeutic trials in the premotor phase of the disease, as well as the growing literature regarding pathophysiological mechanisms and their relevance to potential therapeutic targets. There have been continued advances in the development of disease biomarkers, and promising neuroprotection trials are beginning to emerge in the premotor stage of Huntington's disease. Deeper understanding of the pathophysiological mechanisms is being translated into potential therapeutic strategies. The premotor stage of Huntington's disease provides an ideal time to trial disease-modifying therapy, but reliable biomarkers are required for monitoring disease progression, and this remains an area of intense research. Our understanding of the underlying pathophysiological mechanisms continues to expand, and a number of promising therapeutic strategies are emerging, including strategies to silence mutant huntingtin expression.

  7. [Fatty acid patterns and glucose tolerance in Huntington's chorea (author's transl)].

    Science.gov (United States)

    Schubotz, R; Hausmann, L; Kaffarnik, H; Zehner, J; Oepen, H

    1976-07-02

    Fatty acid patterns of plasma lipids and glucose-tolerance in Huntington's chorea. 25 patients with Huntington's chorea of various manifestation (9 predisposed symptomefree, 5 with light and 11 with severe manifestation) had studies of carbohydrate and lipid metabolism. These studies measured glucose-tolerance tests, insulin-, HGH-secretion, serum lipids and plasma fatty acid conposition of the cholesterylesters, triglycerides and phospholipids. The reactive insulin- but not HGH-levels were significantly raised, 32 % of the patients with Huntington's chorea had abnormal glucose-tolerance tests, compared with 3.2 % in a control group. Duration of symptoms correlated with higher cholesterol levels. Minor deviations were found in the fatty acid patterns in various lipid clases.

  8. Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease.

    Science.gov (United States)

    Nana, Alissa L; Kim, Eric H; Thu, Doris C V; Oorschot, Dorothy E; Tippett, Lynette J; Hogg, Virginia M; Synek, Beth J; Roxburgh, Richard; Waldvogel, Henry J; Faull, Richard L M

    2014-01-01

    Huntington's disease is an autosomal dominant neurodegenerative disease characterized by neuronal degeneration in the basal ganglia and cerebral cortex, and a variable symptom profile. Although progressive striatal degeneration is known to occur and is related to symptom profile, little is known about the cellular basis of symptom heterogeneity across the entire cerebral cortex. To investigate this, we have undertaken a double blind study using unbiased stereological cell counting techniques to determine the pattern of cell loss in six representative cortical regions from the frontal, parietal, temporal, and occipital lobes in the brains of 14 Huntington's disease cases and 15 controls. The results clearly demonstrate a widespread loss of total neurons and pyramidal cells across all cortical regions studied, except for the primary visual cortex. Importantly, the results show that cell loss is remarkably variable both within and between Huntington's disease cases. The results also show that neuronal loss in the primary sensory and secondary visual cortices relate to Huntington's disease motor symptom profiles, and neuronal loss across the associational cortices in the frontal, parietal and temporal lobes is related to both Huntington's disease motor and to mood symptom profiles. This finding considerably extends a previous study (Thu et al., Brain, 2010; 133:1094-1110) which showed that neuronal loss in the primary motor cortex was related specifically to the motor symptom profiles while neuronal loss in the anterior cingulate cortex was related specifically to mood symptom profiles. The extent of cortical cell loss in the current study was generally related to the striatal neuropathological grade, but not to CAG repeat length on the HTT gene. Overall our findings show that Huntington's disease is characterized by a heterogeneous pattern of neuronal cell loss across the entire cerebrum which varies with symptom profile.

  9. Characterisation of aggression in Huntington's disease: rates, types and antecedents in an inpatient rehabilitation setting.

    Science.gov (United States)

    Brown, Anahita; Sewell, Katherine; Fisher, Caroline A

    2016-10-12

    To systematically review aggression in an inpatient Huntington's cohort examining rates, types and antecedents. Although the prevalence of aggression in Huntington's disease is high, research into this problematic behaviour has been limited. Few studies have investigated the nature of aggressive behaviour in Huntington's disease or antecedents that contribute to its occurrence. A systematic, double-coded, electronic medical file audit. The electronic hospital medical records of 10 people with Huntington's disease admitted to a brain disorders unit were audited for a 90-day period using the Overt Aggression Scale-Modified for Neurorehabilitation framework, yielding 900 days of clinical data. Nine of 10 clients exhibited aggression during the audit period. Both verbal (37·1%) aggression and physical aggression were common (33·8%), along with episodes of mixed verbal and physical aggression (15·2%), while aggression to objects/furniture was less prevalent (5·5%). The most common antecedent was physical guidance with personal care, far exceeding any other documented antecedents, and acting as the most common trigger for four of the nine clients who exhibited aggression. For the remaining five clients, there was intraindividual heterogeneity in susceptibility to specific antecedents. In Huntington's sufferers at mid- to late stages following disease onset, particular care should be made with personal care assistance due to the propensity for these procedures to elicit an episode of aggression. However, given the degree of intraindividual heterogeneity in susceptibility to specific antecedents observed in the present study, individualised behaviour support plans and sensory modulation interventions may be the most useful in identifying triggers and managing aggressive episodes. Rates of aggression in Huntington's disease inpatients can be high. Knowledge of potential triggers, such as personal care, is important for nursing and care staff, so that attempts can be

  10. A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Eirini Kalliolia

    Full Text Available Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.We studied neuroendocrine profiles of corticotropic, somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour period in controlled environment in 15 healthy controls, 14 premanifest and 13 stage II/III Huntington's disease subjects. We also quantified fasting levels of vasopressin, oestradiol, testosterone, dehydroepiandrosterone sulphate, thyroid stimulating hormone, free triiodothyronine, free total thyroxine, prolactin, adrenaline and noradrenaline. Somatotropic axis hormones, growth hormone releasing hormone, insulin-like growth factor-1 and insulin-like factor binding protein-3 were quantified at 06:00 (fasting, 15:00 and 23:00. A battery of clinical tests, including neurological rating and function scales were performed.24-hour concentrations of adrenocorticotropic hormone, cortisol, luteinizing hormone and follicle-stimulating hormone did not differ significantly between the Huntington's disease group and controls. Daytime growth hormone secretion was similar in control and Huntington's disease subjects. Stage II/III Huntington's disease subjects had lower concentration of post-sleep growth hormone pulse and higher insulin-like growth factor-1:growth hormone ratio which did not reach significance. In Huntington's disease subjects, baseline levels of hypothalamo-pituitary axis hormones measured did not significantly differ from those of healthy controls.The relatively small subject group means that the study may not detect subtle perturbations in hormone concentrations. A targeted study of the somatotropic axis in larger cohorts may be warranted. However, the lack of significant results despite many

  11. NMDA receptor gene variations as modifiers in Huntington disease: a replication study

    OpenAIRE

    2011-01-01

    Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the ...

  12. Guidelines for presymptomatic testing for Huntington's disease: past, present and future in France.

    Science.gov (United States)

    Clément, S; Gargiulo, M; Feingold, J; Durr, A

    2015-01-01

    Huntington's disease was the first adult onset neurological disease for which presymptomatic genetic testing became possible. It served as a model for the approach which constituted a radical change in medical practice and provided an important framework for multi-step, multidisciplinary, counselling for at risk persons. We will review the historical context of guidelines and good clinical practices, the experiences of our team which covers more than 20 years of presymptomatic testing for Huntington's disease in France, and explore the impact of the new French legislation for the future of presymptomatic testing of diseases for which neither preventive measures nor curative treatments are yet available.

  13. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

    DEFF Research Database (Denmark)

    Aziz, N A; Jurgens, C K; Landwehrmeyer, G B;

    2009-01-01

    OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

  14. Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

    Science.gov (United States)

    Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

    1980-12-01

    Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

  15. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia.

    Science.gov (United States)

    Quinn, N; Marsden, C D

    1984-08-01

    Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause tardive dyskinesia. Among currently available treatments, it may therefore be considered a drug of choice for treatment of tardive dyskinesia.

  16. An Evil Hitherto Unchecked: Eugenics and the 1917 Ontario Royal Commission on the Care and Control of the Mentally Defective and Feeble-Minded.

    Science.gov (United States)

    Koester, C Elizabeth

    2016-01-01

    In 1917, the Ontario government appointed the Royal Commission on the Care and Control of the Mentally Defective and Feeble-Minded, headed by Justice Frank Hodgins. Its final report made wide-ranging recommendations regarding the segregation of feeble-minded individuals, restrictions on marriage, the improvement of psychiatric facilities, and the reform of the court system, all matters of great concern to the eugenics movement. At the same time, however, it refrained from using explicitly eugenic vocabulary and ignored the question of sterilization. This article explores the role the commission played in the trajectory of eugenics in Ontario (including the province's failure to pass sterilization legislation) and considers why its recommendations were disregarded.

  17. Leaders in Cardiovascular Medicine. Eugene Braunwald MD: an icon of the 20th century still going strong.

    Science.gov (United States)

    Braunwald, Eugene; Nicholls, Mark

    2015-06-07

    Considered one of the pre-eminent cardiologists of our time, Dr Eugene Braunwald, MD, has extended knowledge of congestive heart failure, coronary artery disease, and valvular heart disease. Having published hundreds of papers and medical articles, with his textbook Braunwald’s Heart Disease cited worldwide, Dr Braunwald has received numerous honours and awards. Born in Austria in 1929, his family emigrated to the USA during World War II and after his studies he began a long, successful and hugely-influential career as a cardiologist. Now well into his 80s, he still practices medicine and continues to contribute to the field of cardiology.

  18. Expanded CAG repeats in the murine Huntington's disease gene increases neuronal differentiation of embryonic and neural stem cells.

    Science.gov (United States)

    Lorincz, Matthew T; Zawistowski, Virginia A

    2009-01-01

    Huntington's disease is an uncommon autosomal dominant neurodegenerative disorder caused by expanded polyglutamine repeats. Increased neurogenesis was demonstrated recently in Huntington's disease post-mortem samples. In this manuscript, neuronally differentiated embryonic stem cells with expanded CAG repeats in the murine Huntington's disease homologue and neural progenitors isolated from the subventricular zone of an accurate mouse Huntington's disease were examined for increased neurogenesis. Embryonic stem cells with expanded CAG repeats in the murine Huntington's disease homologue were demonstrated to undergo facilitated differentiation first into neural progenitors, then into more mature neurons. Neural progenitor cells isolated from the subventricular zone of a Huntington's disease knock-in animal displayed increased production of neural progenitors and increased neurogenesis. These findings suggested that neuronally differentiating embryonic stem cells with expanded CAG repeats is a reasonable system to identify factors responsible for increased neurogenesis in Huntington's disease. Expression profiling analysis comparing neuronally differentiating embryonic stem cells with expanded CAG repeats to neuronally differentiating embryonic stem cells without expanded CAG repeats identified transcripts involved in development and transcriptional regulation as factors possibly mediating increased neurogenesis in response to expanded CAG repeats.

  19. Prefrontal cortex white matter tracts in prodromal Huntington disease

    Science.gov (United States)

    Matsui, Joy T.; Vaidya, Jatin G.; Wassermann, Demian; Kim, Regina Eunyoung; Magnotta, Vincent A.; Johnson, Hans J.; Paulsen, Jane S.

    2015-01-01

    Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e. prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATR), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. PMID:26179962

  20. Awareness of memory deficits in early stage Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Laurent Cleret de Langavant

    Full Text Available Patients with Huntington's disease (HD are often described as unaware of their motor symptoms, their behavioral disorders or their cognitive deficits, including memory. Nevertheless, because patients with Parkinson's disease (PD remain aware of their memory deficits despite striatal dysfunction, we hypothesize that early stage HD patients in whom degeneration predominates in the striatum can accurately judge their own memory disorders whereas more advanced patients cannot. In order to test our hypothesis, we compared subjective questionnaires of memory deficits (in HD patients and in their proxies and objective measures of memory dysfunction in patients. Forty-six patients with manifest HD attending the out-patient department of the French National Reference Center for HD and thirty-three proxies were enrolled. We found that HD patients at an early stage of the disease (Stage 1 were more accurate than their proxies at evaluating their own memory deficits, independently from their depression level. The proxies were more influenced by patients' functional decline rather than by patients' memory deficits. Patients with moderate disease (Stage 2 misestimated their memory deficits compared to their proxies, whose judgment was nonetheless influenced by the severity of both functional decline and depression. Contrasting subjective memory ratings from the patients and their objective memory performance, we demonstrate that although HD patients are often reported to be unaware of their neurological, cognitive and behavioral symptoms, it is not the case for memory deficits at an early stage. Loss of awareness of memory deficits in HD is associated with the severity of the disease in terms of CAG repeats, functional decline, motor dysfunction and cognitive impairment, including memory deficits and executive dysfunction.

  1. Prospects for neuroprotective therapies in prodromal Huntington's disease.

    Science.gov (United States)

    Chandra, Abhishek; Johri, Ashu; Beal, M Flint

    2014-03-01

    Huntington's disease (HD) is a prototypical dominantly inherited neurodegenerative disorder characterized by progressive cognitive deterioration, psychiatric disturbances, and a movement disorder. The genetic cause of the illness is a CAG repeat expansion in the huntingtin gene, which leads to a polyglutamine expansion in the huntingtin protein. The exact mechanism by which mutant huntingtin causes HD is unknown, but it causes abnormalities in gene transcription as well as both mitochondrial dysfunction and oxidative damage. Because the penetrance of HD is complete with CAG repeats greater than 39, patients can be diagnosed well before disease onset with genetic testing. Longitudinal studies of HD patients before disease onset have shown that subtle cognitive and motor deficits occur as much as 10 years before onset, as do reductions in glucose utilization and striatal atrophy. An increase in inflammation, as shown by elevated interleukin-6, occurs approximately 15 years before onset. Detection of these abnormalities may be useful in defining an optimal time for disease intervention to try to slow or halt the degenerative process. Although reducing gene expression with small interfering RNA or short hairpin RNA is an attractive approach, other approaches targeting energy metabolism, inflammation, and oxidative damage may be more easily and rapidly moved into the clinic. The recent PREQUEL study of coenzyme Q10 in presymptomatic gene carriers showed the feasibility of carrying out clinical trials to slow or halt onset of HD. We review both the earliest detectable clinical and laboratory manifestations of HD, as well as potential neuroprotective therapies that could be utilized in presymptomatic HD.

  2. Chromosome substitution strain assessment of a Huntington's disease modifier locus.

    Science.gov (United States)

    Ramos, Eliana Marisa; Kovalenko, Marina; Guide, Jolene R; St Claire, Jason; Gillis, Tammy; Mysore, Jayalakshmi S; Sequeiros, Jorge; Wheeler, Vanessa C; Alonso, Isabel; MacDonald, Marcy E

    2015-04-01

    Huntington's disease (HD) is a dominant neurodegenerative disorder that is due to expansion of an unstable HTT CAG repeat for which genome-wide genetic scans are now revealing chromosome regions that contain disease-modifying genes. We have explored a novel human-mouse cross-species functional prioritisation approach, by evaluating the HD modifier 6q23-24 linkage interval. This unbiased strategy employs C57BL/6J (B6J) Hdh(Q111) knock-in mice, replicates of the HD mutation, and the C57BL/6J-chr10(A/J)/NaJ chromosome substitution strain (CSS10), in which only chromosome 10 (chr10), in synteny with the human 6q23-24 region, is derived from the A/J (AJ) strain. Crosses were performed to assess the possibility of dominantly acting chr10 AJ-B6J variants of strong effect that may modulate CAG-dependent Hdh(Q111/+) phenotypes. Testing of F1 progeny confirmed that a single AJ chromosome had a significant effect on the rate of body weight gain and in Hdh(Q111) mice the AJ chromosome was associated subtle alterations in somatic CAG instability in the liver and the formation of intra-nuclear inclusions, as well as DARPP-32 levels, in the striatum. These findings in relatively small cohorts are suggestive of dominant chr10 AJ-B6 variants that may modify effects of the CAG expansion, and encourage a larger study with CSS10 and sub-strains. This cross-species approach may therefore be suited to functional in vivo prioritisation of genomic regions harbouring genes that can modify the early effects of the HD mutation.

  3. Impaired brain creatine kinase activity in Huntington's disease.

    Science.gov (United States)

    Zhang, S F; Hennessey, T; Yang, L; Starkova, N N; Beal, M F; Starkov, A A

    2011-01-01

    Huntington's disease (HD) is associated with impaired energy metabolism in the brain. Creatine kinase (CK) catalyzes ATP-dependent phosphorylation of creatine (Cr) into phosphocreatine (PCr), thereby serving as readily available high-capacity spatial and temporal ATP buffering. Substantial evidence supports a specific role of the Cr/PCr system in neurodegenerative diseases. In the brain, the Cr/PCr ATP-buffering system is established by a concerted operation of the brain-specific cytosolic enzyme BB-CK and ubiquitous mitochondrial uMt-CK. It is not yet established whether the activity of these CK isoenzymes is impaired in HD. We measured PCr, Cr, ATP and ADP in brain extracts of 3 mouse models of HD - R6/2 mice, N171-82Q and HdhQ(111) mice - and the activity of CK in cytosolic and mitochondrial brain fractions from the same mice. The PCr was significantly increased in mouse HD brain extracts as compared to nontransgenic littermates. We also found an approximately 27% decrease in CK activity in both cytosolic and mitochondrial fractions of R6/2 and N171-82Q mice, and an approximately 25% decrease in the mitochondria from HdhQ(111) mice. Moreover, uMt-CK and BB-CK activities were approximately 63% lower in HD human brain samples as compared to nondiseased controls. Our findings lend strong support to the role of impaired energy metabolism in HD, and point out the potential importance of impairment of the CK-catalyzed ATP-buffering system in the etiology of HD. Copyright © 2010 S. Karger AG, Basel.

  4. What do we know about Late Onset Huntington's Disease?

    Science.gov (United States)

    Chaganti, Sai S; McCusker, Elizabeth A; Loy, Clement T

    2017-01-01

    Although the typical age of onset for Huntington's disease (HD) is in the fourth decade, between 4.4-11.5% of individuals with HD have a late onset (over 60 years of age). Diagnosis of Late onset HD (LoHD) can be missed, due to the perceived low likelihood of HD in the over 60-year-olds. To review the epidemiology, genotype and phenotype of LoHD. We systematically searched MEDLINE, EMBASE and Web of Science (inception-November 2016). Web of Science was then used to search for papers citing identified studies. Content experts were consulted for any additional studies. We included all studies reporting the clinical phenotype of LoHD for more than one participant. 20 studies were identified from a potential list of 1243. Among Caucasian HD cohorts, 4.4-11.5% of individuals have LoHD, and this proportion may be increasing. Proportion of LoHD without a positive family history ranges from 3-68%. 94.4% of reported cases of LoHD had CAG repeat lengths of ≤44. Motor manifestations are the commonest initial presentation, although 29.2% presented with non-motor manifestations as the first clinical feature in one case series. Individuals with LoHD may have slower progression of illness. Cognitive impairment rather than chorea may be the major source of disability in this group. LoHD represents a substantial proportion of new diagnoses of HD and has some unique features. Further characterization of this population will aid clinicians in diagnosis.

  5. Prefrontal cortex white matter tracts in prodromal Huntington disease.

    Science.gov (United States)

    Matsui, Joy T; Vaidya, Jatin G; Wassermann, Demian; Kim, Regina Eunyoung; Magnotta, Vincent A; Johnson, Hans J; Paulsen, Jane S

    2015-10-01

    Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e., prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717-3732, 2015. © 2015 Wiley Periodicals, Inc.

  6. Prenatal testing in Huntington disease: after the test, choices recommence.

    Science.gov (United States)

    Bouchghoul, Hanane; Clément, Stéphane-Françoise; Vauthier, Danièle; Cazeneuve, Cécile; Noel, Sandrine; Dommergues, Marc; Héron, Delphine; Nizard, Jacky; Gargiulo, Marcela; Durr, Alexandra

    2016-11-01

    The objective of this study was (1) to determine the impact of prenatal diagnosis (PND) for Huntington disease (HD) on subsequent reproductive choices and family structure; and (2) to assess whether children born after PND were informed of their genetic status. Out of 354 presymptomatic carriers of HD gene mutation, aged 18-45 years, 61 couples requested 101 PNDs. Fifty-four women, 29 female carriers and 25 spouses of male carriers, accepted to be interviewed (0.6-16.3 years after the last PND, median 6.5 years) on their obstetrical history and information given to children born after PND. Women were willing to undergo two or more PNDs with a final success rate of 75%. Reproductive decisions differed depending on the outcome of the first PND. If favourable, 62% couples decided against another pregnancy and 10% chose to have an untested child. If unfavourable, 83% decided for another pregnancy (P<0.01), and the majority (87%) re-entered the PND procedure. In contrast, after a second PND, only 37% asked for a PND and 30% chose to have an untested child. Thirty-three percent had both, tested and untested children. Among children born after PND, 10 years and older, 75% were informed of their genetic status. The decision to prevent transmission of the HD mutation is made anew with each pregnancy. Couples may need more psychological support after PND and pre-counselling sessions should take into account the effect of the outcome of a first PND on subsequent reproductive choices.

  7. Phonatory Dysfunction as a Preclinical Symptom of Huntington Disease

    Science.gov (United States)

    Schlegel, Uwe; Hoffman, Rainer; Skodda, Sabine

    2014-01-01

    Purpose Although dysphonia has been shown to be a common sign of Huntington disease (HD), the extent of phonatory dysfunction in gene positive premanifest HD individuals remains unknown. The aim of the current study was to explore the possible occurrence of phonatory abnormalities in prodromal HD. Method Sustained vowel phonations were acquired from 28 premanifest HD individuals and 28 healthy controls of comparable age. Data were analysed acoustically for measures of several phonatory dimensions including airflow insufficiency, aperiodicity, irregular vibration of vocal folds, signal perturbations, increased noise, vocal tremor and articulation deficiency. A predictive model was built to find the best combination of acoustic features and estimate sensitivity/specificity for differentiation between premanifest HD subjects and controls. The extent of voice deficits according to a specific phonatory dimension was determined using statistical decision making theory. The results were correlated to global motor function, cognitive score, disease burden score and estimated years to disease onset. Results Measures of aperiodicity and increased noise were able to significantly differentiate between premanifest HD individuals and controls (p<0.01). The combination of these aspects of dysphonia led to a sensitivity of 91.5% and specificity of 79.2% to correctly distinguish speakers with premanifest HD from healthy individuals. Some form of disrupted phonatory function was revealed in 68% of our premanifest HD subjects, where 18% had one affected phonatory dimension and 50% showed impairment of two or more dimensions. A relationship between pitch control and cognitive score was also observed (r = −0.50, p = 0.007). Conclusions Phonatory abnormalities are detectable even the in premotor stages of HD. Speech investigation may have the potential to provide functional biomarkers of HD and could be included in future clinical trials and therapeutic interventions. PMID

  8. Neuroanatomical correlates of cognitive functioning in prodromal Huntington disease.

    Science.gov (United States)

    Harrington, Deborah L; Liu, Dawei; Smith, Megan M; Mills, James A; Long, Jeffrey D; Aylward, Elizabeth H; Paulsen, Jane S

    2014-01-01

    The brain mechanisms of cognitive impairment in prodromal Huntington disease (prHD) are not well understood. Although striatal atrophy correlates with some cognitive abilities, few studies of prHD have investigated whether cortical gray matter morphometry correlates in a regionally specific manner with functioning in different cognitive domains. This knowledge would inform the selection of cognitive measures for clinical trials that would be most sensitive to the target of a treatment intervention. In this study, random forest analysis was used to identify neuroanatomical correlates of functioning in five cognitive domains including attention and information processing speed, working memory, verbal learning and memory, negative emotion recognition, and temporal processing. Participants included 325 prHD individuals with varying levels of disease progression and 119 gene-negative controls with a family history of HD. In intermediate analyses, we identified brain regions that showed significant differences between the prHD and the control groups in cortical thickness and striatal volume. Brain morphometry in these regions was then correlated with cognitive functioning in each of the domains in the prHD group using random forest methods. We hypothesized that different regional patterns of brain morphometry would be associated with performances in distinct cognitive domains. The results showed that performances in different cognitive domains that are vulnerable to decline in prHD were correlated with regionally specific patterns of cortical and striatal morphometry. Putamen and/or caudate volumes were top-ranked correlates of performance across all cognitive domains, as was cortical thickness in regions related to the processing demands of each domain. The results underscore the importance of identifying structural magnetic resonance imaging (sMRI) markers of functioning in different cognitive domains, as their relative sensitivity depends on the extent to which

  9. Role of brain-derived neurotrophic factor in Huntington's disease.

    Science.gov (United States)

    Zuccato, Chiara; Cattaneo, Elena

    2007-04-01

    Neurotrophic factors are essential contributors to the survival of peripheral and central nervous system (CNS) neurons, and demonstration of their reduced availability in diseased brains indicates that they play a role in various neurological disorders. This paper will concentrate on the role of brain-derived neurotrophic factor (BDNF) in the survival and activity of the neurons that die in Huntington's disease (HD) by reviewing the evidence indicating that it involves profound changes in BDNF levels and that attempts to restore these levels are therapeutically interesting. BDNF is a small dimeric protein that is widely expressed in adult mammalian brain and has been shown to promote the survival of all major neuronal types affected in Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, cortical BDNF production is required for the correct activity of the corticostriatal synapse and the survival of the GABA-ergic medium-sized spiny striatal neurons that die in HD. We will highlight the available data concerning changes in BDNF levels in HD cells, mice and human postmortem samples, describe the molecular evidence underlying this alteration, and review the data concerning the impact of the experimental manipulation of BDNF levels on HD progression. Such studies have revealed a major loss of BDNF protein in the striatum of HD patients which may contribute to the clinical manifestations of the disease. They have also opened up a molecular window into the underlying pathogenic mechanism and new therapeutic perspectives by raising the possibility that one of the mechanisms triggering the reduction in BDNF in HD may also affect the activity of many other neuronal proteins.

  10. Iron accumulates in Huntington's disease neurons: protection by deferoxamine.

    Directory of Open Access Journals (Sweden)

    Jianfang Chen

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine-encoding CAG expansion in the huntingtin gene. Iron accumulates in the brains of HD patients and mouse disease models. However, the cellular and subcellular sites of iron accumulation, as well as significance to disease progression are not well understood. We used independent approaches to investigate the location of brain iron accumulation. In R6/2 HD mouse brain, synchotron x-ray fluorescence analysis revealed iron accumulation as discrete puncta in the perinuclear cytoplasm of striatal neurons. Further, perfusion Turnbull's staining for ferrous iron (II combined with transmission electron microscope ultra-structural analysis revealed increased staining in membrane bound peri-nuclear vesicles in R6/2 HD striatal neurons. Analysis of iron homeostatic proteins in R6/2 HD mice revealed decreased levels of the iron response proteins (IRPs 1 and 2 and accordingly decreased expression of iron uptake transferrin receptor (TfR and increased levels of neuronal iron export protein ferroportin (FPN. Finally, we show that intra-ventricular delivery of the iron chelator deferoxamine results in an improvement of the motor phenotype in R6/2 HD mice. Our data supports accumulation of redox-active ferrous iron in the endocytic / lysosomal compartment in mouse HD neurons. Expression changes of IRPs, TfR and FPN are consistent with a compensatory response to an increased intra-neuronal labile iron pool leading to increased susceptibility to iron-associated oxidative stress. These findings, together with protection by deferoxamine, support a potentiating role of neuronal iron accumulation in HD.

  11. Cerebral neurotransmission in huntington's disease and wilson's disease; Zerebrale Neurotransmission bei Chorea Huntington und Morbus Wilson

    Energy Technology Data Exchange (ETDEWEB)

    Barthel, H.; Sabri, O. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Leipzig (Germany)

    2002-09-01

    Huntington's disease and Wilson's disease are hereditary disorders with different neuropsychiatric symptoms. In both cases, these symptoms are mainly attributed to functional alterations of neurons, which are located in the basal ganglia. According deficits have been found by investigating the dopaminergic neurotransmission with different PET and SPECT tracers. For both diseases, these deficits revealed to concordantly involve the pre- and postsynaptic compartment. Apart from the dopaminergic system, more recent studies showed alterations of other neurotransmitter systems, like the serotonergic, GABA-ergic and opioide system. Except for scientific studies, nuclear medicine imaging is not regularly required for primary diagnosis of both disorders. In the case of Huntington's disease, however, imaging can be helpful for differential diagnosis to other diseases with similar initial symptoms and to determine the organic manifestation of the gene defect. In addition, neurotransmitter imaging with radiortracers could gain more relevance in the future in supporting decisions on specific treatments or for therapy monitoring in both diseases. (orig.) [German] Bei der Chorea Huntington und dem Morbus Wilson handelt es sich um erbliche Erkrankungen mit unterschiedlicher neuropsychiatrischer Symptomatik, welche im Wesentlichen auf Funktionsstoerungen von im Basalganglienbereich lokalisierten Neuronen zurueckgefuehrt werden. Untersuchungen der dopaminergen Neurotransmission mit verschiedenen PET- und SPECT-Radiopharmaka ergaben dementsprechende Defizite, welche fuer beide Erkrankungen konkordant das prae- und postsynaptische Kompartment betrafen. Juengere Studien deuten darueber hinaus auf Stoerungen anderer Neurotransmitter-Systeme, wie z.B. des serotonergen, GABAergen und Opioid-Systems, hin. Ausserhalb von wissenschaftlichen Fragestellungen ist die nuklearmedizinische Bildgebung bei beiden Erkrankungen in der Primaerdiagnostik eher selten erforderlich. Im

  12. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.

    Science.gov (United States)

    Krause, Amanda; Mitchell, Claire; Essop, Fahmida; Tager, Susan; Temlett, James; Stevanin, Giovanni; Ross, Christopher; Rudnicki, Dobrila; Margolis, Russell

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations.

  13. Nasty Nazis and Extreme Americans: Cloning, Eugenics, and the Exchange of National Signifiers in Contemporary Science Fiction

    Directory of Open Access Journals (Sweden)

    Elizabeth Bridges

    2014-01-01

    Full Text Available This article addresses German science fiction novels from the last ten to fifteen years, specifically those that thematize cloning and/or eugenics. The main novels under discussion include Die verbesserte Frau by Barbara Kirchner , Duplik Jonas 7 by Birgit Rabisch, and Blueprint/Blaupause by Charlotte Kerner, (which was released as a film adaptation starring Franka Potente in 2004. This discussion shows how these and similar novels do or do not contend with the legacy of Nazi eugenics and reproductive experimentation, and second, how the existent historical awareness in the novels relates to the content of debates on current issues of biotechnology, including those by Jürgen Habermas, Slavoj Zizek, and Peter Sloterdijk. The article concludes by bringing these debates to bear on cultural cross-referencing in comparative examples of American texts ( Gattaca [1997] , The Island [2005] , to name two, which tend to imbue frightening aspects of reproductive technologies with signifiers of Nazism, while the German texts tend to implicate America as the future source of nightmarish reproductive possibilities.

  14. Avoiding genetic genocide: understanding good intentions and eugenics in the complex dialogue between the medical and disability communities.

    Science.gov (United States)

    Miller, Paul Steven; Levine, Rebecca Leah

    2013-02-01

    The relationship between the medical and disability communities is complex and is influenced by historical, social, and cultural factors. Although clinicians, health-care researchers, and people with disabilities all work from the standpoint of the best interest of disabled individuals, the notion of what actually is "best" is often understood quite differently among these constituencies. Eugenics campaigns, legal restrictions on reproductive and other freedoms, and prenatal testing recommendations predicated on the lesser worth of persons with disabilities have all contributed toward the historic trauma experienced by the disability community, particularly with respect to medical genetics. One premise of personalized medicine is that different individuals require different solutions. Disabled persons' experiences are a reminder that these solutions can be best realized by maintaining awareness and sensitivity in a complex ethical and moral terrain. Geneticists should recognize that their research may have implications for those with disabilities; they should recognize the impact of the historical trauma of the eugenics movement, and seek to involve people with disabilities in discussions about policies that affect them. Dialogue can be messy and uncomfortable, but it is the only way to avoid the mistakes of the past and to ensure a more equitable, and healthful, future.

  15. [Familial amyotrophic lateral sclerosis associated with Huntington chorea with increased aspartate level in the cerebrospinal fluid].

    Science.gov (United States)

    Blin, O; Samuel, D; Guieu, R; Pouget, J; Nieoullon, A; Serratrice, G

    1992-01-01

    We report the case of a patient who presented with both amyotrophic lateral sclerosis and Huntington's disease. Interestingly, aspartate level was increased in the lumbar CSF. In vitro and in vivo studies have convincingly suggested that these two neurodegenerative diseases could be related to an excitotoxic mechanism.

  16. Not on the Face Alone: Perception of Contextualized Face Expressions in Huntington's Disease

    Science.gov (United States)

    Aviezer, Hillel; Bentin, Shlomo; Hassin, Ran R.; Meschino, Wendy S.; Kennedy, Jeanne; Grewal, Sonya; Esmail, Sherali; Cohen, Sharon; Moscovitch, Morris

    2009-01-01

    Numerous studies have demonstrated that Huntington's disease mutation-carriers have deficient explicit recognition of isolated facial expressions. There are no studies, however, which have investigated the recognition of facial expressions embedded within an emotional body and scene context. Real life facial expressions are typically embedded in…

  17. Wishes for the end of life in Huntington's Disease. Observations and reflections, initiated in The Netherlands

    NARCIS (Netherlands)

    Booij, Suzanne José

    2014-01-01

    Euthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding physician-patient relationship. Secondly a thorough knowlegde of the requirements of due care is necessa

  18. The use of stem cells in regenerative medicine for Parkinson's and Huntington's Diseases.

    Science.gov (United States)

    Lescaudron, L; Naveilhan, P; Neveu, I

    2012-01-01

    Cell transplantation has been proposed as a means of replacing specific cell populations lost through neurodegenerative processes such as that seen in Parkinson's or Huntington's diseases. Improvement of the clinical symptoms has been observed in a number of Parkinson and Huntington's patients transplanted with freshly isolated fetal brain tissue but such restorative approach is greatly hampered by logistic and ethical concerns relative to the use of fetal tissue, in addition to potential side effects that remain to be controlled. In this context, stem cells that are capable of self-renewal and can differentiate into neurons, have received a great deal of interest, as demonstrated by the numerous studies based on the transplantation of neural stem/progenitor cells, embryonic stem cells or mesenchymal stem cells into animal models of Parkinson's or Huntington's diseases. More recently, the induction of pluripotent stem cells from somatic adult cells has raised a new hope for the treatment of neurodegenerative diseases. In the present article, we review the main experimental approaches to assess the efficiency of cell-based therapy for Parkinson's or Huntington's diseases, and discuss the recent advances in using stem cells to replace lost dopaminergic mesencephalic or striatal neurons. Characteristics of the different stem cells are extensively examined with a special attention to their ability of producing neurotrophic or immunosuppressive factors, as these may provide a favourable environment for brain tissue repair and long-term survival of transplanted cells in the central nervous system. Thus, stem cell therapy can be a valuable tool in regenerative medicine.

  19. Language Deficits in Pre-Symptomatic Huntington's Disease: Evidence from Hungarian

    Science.gov (United States)

    Nemeth, Dezso; Dye, Cristina D.; Sefcsik, Tamas; Janacsek, Karolina; Turi, Zsolt; Londe, Zsuzsa; Klivenyi, Peter; Kincses, Zsigmond Tamas; Szabo, Nikoletta; Vecsei, Laszlo; Ullman, Michael T.

    2012-01-01

    A limited number of studies have investigated language in Huntington's disease (HD). These have generally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and morphology. Several studies of verbal inflectional morphology in English and French have reported evidence of over-active rule processing, such as…

  20. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease

    DEFF Research Database (Denmark)

    Fennema-Notestine, C; Archibald, S.L.; Jacobsen, M.W.;

    2004-01-01

    OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in a...