WorldWideScience

Sample records for leber des menschen

  1. Darwin, Engels und die Rolle der Arbeit in der biologischen und kulturellen Evolution des Menschen

    Science.gov (United States)

    Reichholf, Josef H.

    Im Jahre 1876, 5 Jahre nach Erscheinen von Darwins Buch über die Evolution des Menschen und die sexuelle Selektion (Darwin 1871), veröffentlichte Friedrich Engels den berühmt gewordenen Essay "Anteil der Arbeit an der Menschwerdung des Affen“ (Engels 1876). Die Kernfrage darin lautet in Kurzform: Warum hat der Mensch eigentlich ein Bedürfnis nach Arbeit? Engels Antwort wird nachfolgend näher betrachtet und vom gegenwärtigen Kenntnisstand aus beurteilt. Wie sich zeigen wird, beantworten seine Überlegungen die Frage nicht wirklich. Sie ist weiterhin offen. Es können lediglich einige zusätzliche Anhaltspunkte zur Diskussion gestellt werden. Angesichts des drängenden Problems millionenfacher Arbeitslosigkeit und der Forderungen nach einem "Grundrecht auf Arbeit“ kommt den Überlegungen zum möglichen Ursprung des Bedürfnisses nach Arbeit mehr als nur akademisches Interesse zu.

  2. La obra póstuma de Blumenberg: Beschreibung des Menschen

    Directory of Open Access Journals (Sweden)

    Rincón Núñez, Antonio

    2008-12-01

    Full Text Available Beschreibund des Menschen is one of the posthumous works of Blumenberg. Two thirds of the book give an account of Husserl’s phenomenology and its critique. What brings face to face Blumenberg with phenomenology is the search for a philosophical anthropology in Husserl’s phenomenology. This defeat is because of his defence of a pure conscience, that means, never corrupted by psychologism and historicism. The second part of Beschreibung des Menschen is about the analysis in depth of categories, which are well – known in Blumenberg’s philosophical anthropology. He addresses the concepts of horizon, Lebenswelt, corporality, visibility, distance, gaining time, etc. There is no relevant news regarding to his earlier work, but what he gets deals with an increase of rigor and precision on his philosophical anthropology.

    Beschreibund des Menschen es una obra postuma de Blumeberg. Dos tercios del libro están dedicados a la exposición y crítica de la fenomenología de Husserl. Lo que enfrenta a Blumenberg con la fenomenología es la búsqueda de una antropología filosófica en la fenomenología que Husserl, que éste nunca quiso aceptar por su defensa de una conciencia pura que nunca fuera contaminada por el psicologismo y el historicismo. La segunda parte de Beschreibung des Menschen se ocupa del análisis y profundización de categorías ya familiares a la antropología filosófica de Blumenberg. Analiza los conceptos de horizonte, mundo de la vida, corporeidad, visibilidad, distancia, ganar tiempo, etc. No hay ninguna novedad importante respecto a sus libros anteriores, pero sí consigue que su antropología filosófica alcance un rigor y una precisión aun mayores en algunos aspectos de su obra.

  3. Untersuchungen zur Wirkung von Anthocyanen auf die mikrobielle Metabolisierung von Lactose-[13C]-Ureid und Lactose-[15N2]-Ureid im Colon des Menschen

    OpenAIRE

    2014-01-01

    Die vorliegende Arbeit wurde im Rahmen des Teilprojektes „Bioverfügbarkeits- und Interventionsstudien beim Menschen“ des BMBF-geförderten Verbundprojektes „Anthocyane in Fruchtsäften aus Beerenobst – In vivo Studien zu Bioverfügbarkeit und Wirkungen auf die Mikroflora“ (BMBF Az. 0315379A) angefertigt. Ziel dieser Arbeit war es, den Einfluss von Anthocyanen in Form von Fruchtsaftgetränken auf bakterielle Fermentationseigenschaften im Colon des Menschen mit 13C- und 15N-markiertem Lactoseur...

  4. Occupy als Jugendbewegung für Generationengerechtigkeit?: Mediatisierte Aushandlungen des ‚Politischen‘ durch junge Menschen

    Directory of Open Access Journals (Sweden)

    Stehling, Miriam

    2015-08-01

    Full Text Available Ausgehend von der Debatte um eine ‚Politikverdrossenheit‘ der Jugend diskutiert der Artikel, welche Bedeutung Generationengerechtigkeit bei den Occupy-Protesten zukommt. Vor dem Hintergrund eines erweiterten Begriffs des ‚Politischen‘ wird zum einen argumentiert, dass junge Menschen gegenwärtig in einen Bereich neuartiger Politikformen und Praktiken eingebunden sind, der eng mit der Omnipräsenz digitaler Medien verknüpft ist. Zum anderen wird herausgearbeitet, wie Medien bei den Occupy-Protesten genutzt werden, um Forderungen nach sozialer Gerechtigkeit zu artikulieren.

  5. Numerical simulation of spatial whole-body vibration behaviour of sitting man taking into account individual anthropometry and position; Numerische Simulation des raeumlichen Ganzkoerperschwingungsverhaltens des sitzenden Menschen unter Beruecksichtigung der individuellen Anthropometrie und Haltung

    Energy Technology Data Exchange (ETDEWEB)

    Pankoke, S.

    2003-07-01

    A dynamic FE model of the anatomy of humans in sitting position is presented for assessing the dynamic internal response of the human body to the effect of external vibrations. The model can be adapted to individual body measures, different positions and different spatial orientation. It was verified on the basis of extensive measured data. The problem of contact between the human body and the driver seat is solved by a simplified static description. The model comprises a sub-model of the lumbar vertebral column for assessing the spatial load distributions in this body region. [German] In der vorliegenden Arbeit wird ein dynamisches, an der menschlichen Anatomie orientiertes Finite-Elemente-Modell des sitzenden Menschen vorgestellt, das es gestaltet, dynamische innere Antworten des Koerpers auf von aussen auf den Menschen einwirkende Schwingungen zu ermitteln. Das Modell ist ueber eine Auswahl anthropometrischer Masse an das Schwingungsverhalten eines Individuums anpassbar und ermoeglicht zudem die Simulation von Schwingungseinwirkungen in unterschiedlichen Haltungen und in allen Raumrichtungen. Die Modellverifikation erfolgte an umfangreichen Messdatenbestaenden. Das Kontaktproblem des Menschen zum Fahrzeugsitz ist durch eine vereinfachte statische Beschreibung abgebildet. Ferner beinhaltet das Ganzkoerpermodell ein Submodell der Lendenwirbelsaeule, mit dessen Hilfe die aus den Ganzkoerperschwingungen folgenden raeumlichen Beanspruchungsverteilungen in der Lendenwirbelsaeule ermittelt werden koennen. (orig.)

  6. Charakterisierung von Sulfotransferasen im Gastrointestinaltrakt von Mensch und Ratte und Aktivierung von Promutagenen in V79-Zellen, die eine intestinale Form (1B1) des Menschen und der Ratte exprimieren

    Science.gov (United States)

    Teubner, Wera

    2001-05-01

    Die Ausstattung der gastrointestinalen Mukosa des Menschen und der Ratte mit Sulfotransferasen wurde mit Hilfe von Immunodetektion und Enzymaktivitätsmessungen untersucht. In Proben aus Colon und Rektum von 39 Personen wurden die Formen h1A1, h1A3 und h1B1 identifiziert, wobei in einer weiteren Probe, die als einzige von einem an Colitis Ulcerosa erkrankten Patienten stammte, keine Sulfotransferasen nachgewiesen werden konnten. Bei der Immunblot-Analyse war das Expressionsmuster der einzelnen Formen in allen Proben ähnlich. In wenigen Proben waren die relativen Signalintensitäten der h1A1 und der h1B1 um die Hälfte erniedrigt. Der Gehalt von SULT an zytosolischem Protein zeigte einen bis zu 8 - 10fachen Unterschied, er betrug jedoch bei zwei Dritteln der Proben zwischen 0,15 und 0,3 (h1A1 und h1A3) bzw. 0,6 und 0,8 Promille (h1B1). Die Variation konnte nicht auf Alter, Geschlecht oder Krankheitsbild der Patienten zurückgeführt werden. Auch der für die allelischen Varianten der h1A1 beschriebene Effekt auf die Enzymaktiviät bzw. Stabilität konnte in der Menge an immunreaktivem Protein nicht in diesem Ausma detektiert werden. Die Allelhäufigkeit von h1A1*R und h1A1*H war gegenüber der gesunden Bevölkerung nicht verändert. In den sieben Proben aus dem Dünndarm (Coecum, viermal Ileum, Jejunum) konnten zusätzlich die Formen h1E1 und h2A1 identifiziert werden. Ein möglicherweise der Form h1C1 entsprechendes Protein wurde im Magen detektiert. Im Vergleich zum Menschen war die Expression in der Ratte stärker auf die Leber konzentriert. Während beim Menschen in allen untersuchten Abschnitten Sulfotransferasen in Mengen detektiert wurden, die in zwei Fällen (h1B1 und h1A3) sogar den Gehalt in der Leber überstiegen, beschränkte sich die Expression in der Ratte auf im Vergleich zur Leber geringe Mengen im Magen und Dickdarm. Nachgewiesen wurden die r1B1, r1A1 sowie eine nicht identifizierte Form von 35kD, bei der es sich vermutlich um die r1C2 handelt. Im

  7. Zur Situation gehörloser Menschen im Alter (SIGMA)

    OpenAIRE

    Kaul, Thomas; Gelhardt, Anne; Klinner, Susanne; Menzel, Frank

    2009-01-01

    In dem Projekt SIGMA wurden im Auftrag des Bundesministeriums für Familie, Senioren, Frauen und Jugend erstmals aus der Perspektive gehörloser Menschen im Alter ihre individuellen Ressourcen sowie die Qualität und Quantität von Angeboten und Maßnahmen der Altenhilfe erforscht. Zwischen 2006 und 2009 wurden u.a. mehr als 200 gehörlose Menschen über 55 Jahre zu ihren spezifischen Lebensbedingungen und Lebensvorstellungen interviewt. Darüber hinaus wurden auch Experten zu der Versorgungssituatio...

  8. Menschen Technik Wissenschaft* : CERN 94

    CERN Multimedia

    Schweizer Fernsehen DRS

    1994-01-01

    Mit Felicitas Pauss and Peter Jenni * MTW, Menschen Technik Wissenschaft, Aktuelle und relevante Themen aus den Bereichen Wissenschaft, Industrie, Technik, Natur, Umwelt und Klima. Eine Sendung von Schweizer Fernsehen DRS.

  9. Governance, Behavioral Science und das Bild des Menschen im Verfassungsrecht: Konzeptive Überlegungen zur Inkorporierung von Behavioral-Science-Erkenntnissen in die Rechtswissenschaften am Beispiel einer Dogmatik staatlichen Informationshandelns

    Directory of Open Access Journals (Sweden)

    Stefan Storr

    2014-05-01

    Full Text Available ENGLISH: This paper discusses the connectivity of constitutional law doctrine on findings of governance research and behavioral science. Fundamental questions how to integrate "soft" instruments like "framing" and "nudging" in a constitutional law doctrine will be considered. The image of man in the constitutional order, as presupposed in the German and in the Austrian constitution, will be illuminated. For a doctrine of state communication accuracy, objectivity and due restraint are key postulates. DEUTSCH: Der Beitrag behandelt die Anschlussfähigkeit der Verfassungsrechtsdogmatik an Erkenntnisse der Governance-Forschung und Behavioral-Science. Es wird überlegt, welche grundlegenden Fragen sich für eine Integration „weicher“ Steuerungsformen wie „framing“ und „nudging“ in eine Verfassungsrechtsdogmatik stellen. Dabei dient das Bild des Menschen, wie es in der deutschen und in der österreichischen Verfassung vorausgesetzt wird, als Projektionsfläche. Daran ansetzend werden grundsätzliche Überlegungen an staatliches Kommunikationsverhalten angestellt. Richtigkeit, Sachlichkeit und angemessene Zurückhaltung sind zentrale Postulate.

  10. Pyrrole and 2,5-heptanedione in the urine of rats and 2,5-heptanedione in the urine of man: analytical determination of excretion upon exposure to n-heptane; Pyrrole und 2,5-Heptandion im Urin der Ratte und 2,5-Heptandion im Urin des Menschen: Analytische Bestimmung der Ausscheidung nach Exposition gegn n-Heptan

    Energy Technology Data Exchange (ETDEWEB)

    Stoermer, A.G.C.

    1997-09-01

    A method for quantifying levels of the neurotoxic metabolite 2,5-heptanedione in rats and man after experimental exposure to n-heptane was developed. It consisted in determining the quantity of 2,5-heptanedione excreted in urine and the relevant excretion kinetics. Moreover, the excretion of pyrrole in the urine of rats was measured. In the urine of non-exposed rats and man, a basic excretion of 2,5-heptanedione was measured, with the rates of excretion being 0.11 and 4.5 nmol per hour, respectively. This basic excretion of 2,5-heptanedione is assumed to have an endogenous cause. The quantitive investigation of the dose dependence of the excretion of 2,5-heptanedione and pyrrole in the urine of rats and of 2,5-heptanedione in the urine of man is a prerequisite for assessing the risk posed by n-heptane with a view to peripheral neuropathies. (orig./MG) [Deutsch] Ziel dieser Arbeit war die Entwicklung einer Methode zur Quantifizierung der Belastung von Ratte und Mensch mit dem neurotoxischen Metaboliten 2,5-Heptandion nach experimentellen Expositionen gegen n-Heptan. Dazu sollte jeweils die ausgeschiedene Menge und die zugehoerige Ausscheidungskinetik von 2,5-Heptandion im Urin bestimmt werden. Darueber hinaus sollte die Ausscheidung von Pyrrolen im Urin von Ratten gemessen werden. Im Urin von nicht exponierten Ratten und Menschen wurde eine Grundausscheidung von 2,5-Heptandion gefunden, wobei die Ausscheidungsraten jeweils 0,11 bzw. 4,5 nmol/h betrugen. Fuer die Grundausscheidung von 2,5-Heptandion wird ein endogener Ursprung angenommen. Die quantitativen Untersuchungen zur Dosisabhaengigkeit der Ausscheidung im Urin von 2,5-Heptandion und Pyrrolen bei der Ratte und von 2,5-Heptandion beim Menschen sind eine Grundvoraussetzung fuer eine Abschaetzung des Risikos von n-Heptan fuer periphere Neuropathien. (orig./MG)

  11. Magnetic resonance imaging (MRI) of liver and brain in haematologic-organic patients with fever of unknown origin; Magnetresonanztomographie (MRT) der Leber und des Gehirns bei haematologisch-onkologischen Patienten mit Fieber unbekannter Ursache

    Energy Technology Data Exchange (ETDEWEB)

    Heussel, C.P.; Kauczor, H.U.; Poguntke, M.; Schadmand-Fischer, S.; Mildenberger, P.; Thelen, M. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Radiologie; Heussel, G. [Mainz Univ. (Germany). 3. Medizinische Klinik und Poliklinik

    1998-08-01

    To examine the advantage of liver and brain MRI in clinically anomalous haematological patients with fever of unknown origin. Material and Methods: Twenty liver MRI (T{sub 2}-TSE, T{sub 2}-HASTE, T{sub 1}-FLASH{+-}Gd dynamic) and 16 brain MRI (T{sub 2}-TSE, FLAIR, T{sub 1}-TSE{+-}Gd) were performed searching for a focus of fever with a suspected organ system. Comparison with clinical follow-up. Results: suspected organ system. Comparison with clinical follow-up. Results: A focus was detected in 11/20 liver MRI. Candidiasis (n=3), mycobacteriosis (n=2), relapse of haematological disease (n=3), graft versus host disease (n=1), non-clarified (n=2). The remaining 9 cases with normal MRI were not suspicious of infectious hepatic disease during follo-wup. In brain MRI, 3/16 showed a focus (toxoplasmosis, aspergillosis, mastoiditis). Clinical indication for an infectious involvement of the brain was found in 4/16 cases 2--5 months after initially normal brain MRI. No suspicion of an infectious involvement of brain was present in the remaining 9/16 cases. Conclusion: In case of fever of unknown origin and suspicion of liver involvement, MRI of the liver should be performed due to data given in literature and its sensitivity of 100%. Because of the delayed detectability of cerebral manifestations, in cases of persisting suspicion even a previously normal MRI of the brain should be repeated. (orig.) [Deutsch] Untersuchung des Nutzens der MRT der Leber und des Gehirns bei klinisch auffaelligen haematologischen Patienten mit Fieber unbekannter Ursache. Material und Methoden: Es wurden 20 MRT der Leber (T{sub 2}-TSE, T{sub 2}-HASTE, T{sub 1}-FLASH{+-}Gd dynamisch) und 16 MRT des Gehirns (T{sub 2}-TSE, FLAIR, T{sub 1}-TSE{+-}Gd) zur Fokussuche bei Infektionsverdacht und Organhinweisen durchgefuehrt. Es erfolgte der Abgleich mit dem weiteren klinischen Verlauf. Ergebnisse: 11/20 MRT-Untersuchungen der Leber zeigten einen Herdbefund: Candidiasis (n=3), Mykobakteriose (n=2

  12. Endokrinologische Behandlung der Geschlechtsdysphorie bei Menschen mit Geschlechtsinkongruenz

    Directory of Open Access Journals (Sweden)

    Flütsch N

    2015-01-01

    Full Text Available Es gibt Menschen, die die innere Gewissheit besitzen, dass ihre Geschlechtsidentität nicht zu ihrem biologischen Ursprungsgeschlecht passt. Durch die Entwicklungen in der Medizin in den letzten hundert Jahren ist es möglich geworden, die körperlichen Geschlechtsmerkmale an das innerlich erlebte Geschlecht anzupassen. Die Zahl der Hilfesuchenden in den ärztlichen Ambulanzen und Privatpraxen hat in den vergangenen Jahren deutlich zugenommen. Das Vorgehen bei der Diagnostik und Therapieeinleitung erlebt zurzeit eine deutliche Veränderung hin zu mehr Patientenzentriertheit und Individualisierung des Transitionsprozesses. Dabei bildet die geschlechtsangleichende Hormontherapie ein wesentliches Standbein in der körperlichen Angleichung an das Gegengeschlecht. Unter Beachtung von bestimmten Sicherheitsaspekten ist eine Hormontherapie mit Sexualhormonen sicher und einfach durchzuführen. Regelmäßige Verlaufskontrollen sowie der offene und affirmative Umgang mit den Betroffenen tragen zudem wesentlich zur Sicherheit in der Behandlung bei.

  13. Lernen, sich auf Menschen einzulassen

    DEFF Research Database (Denmark)

    Mohr, Sebastian; Lindner, Rolf

    2017-01-01

    In his 1981 essay Die Angst des Forschers vor dem Feld, Rolf Lindner argues that the ethnographer’s first meeting with the field might cause anxieties that, when reflected upon as part of ethnographic knowledge production, might hold important insights into the field itself on the one hand...

  14. Prominente Menschen mit Angststörungen

    Directory of Open Access Journals (Sweden)

    Bandelow B

    2011-01-01

    Full Text Available In den Biographien prominenter Menschen wird häufig über Angsterkrankungen berichtet. Epidemiologische Untersuchungen bestätigen eine deutlich überzufällige Häufung von seelischen Störungen bei herausragenden Künstlern. Es scheint wahrscheinlich, dass Angststörungen, wie zum Beispiel die soziale Phobie, die Schaffenskraft eines Künstlers fördern. Auf der anderen Seite bevorzugt das Publikum Musik und Werke von sensiblen, empfindsamen Persönlichkeiten.

  15. Evaluation of the reliability concerning the identification of human factors as contributing factors by a computer supported event analysis (CEA); Einfluss des Menschen auf die Sicherheit von Kernkraftwerken - Bewertung der Zuverlaessigkeit einer computergestuetzten Ereignisanalyse (CEA) in der Kernindustrie

    Energy Technology Data Exchange (ETDEWEB)

    Wilpert, B.; Maimer, H.; Loroff, C.

    2000-05-01

    The project's objectives are the evaluation of the reliability concerning the identification of Human Factors as contributing factors by a computer supported event analysis (CEA). CEA is a computer version of SOL (Safety through Organizational Learning). Parts of the first step were interviews with experts from the nuclear power industry and the evaluation of existing computer supported event analysis methods. This information was combined to a requirement profile for the CEA software. The next step contained the implementation of the software in an iterative process of evaluation. The completion of this project was the testing of the CEA software. As a result the testing demonstrated that it is possible to identify contributing factors with CEA validly. In addition, CEA received a very positive feedback from the experts. (orig.) [German] Ziel des Vorhabens ist die Entwicklung und Bewertung der Zuverlaessigkeit einer computergestuetzten Ereignisanalyse (CEA) in der Kernindustrie. CEA stellt eine Umsetzung des Ursachenanalyseverfahrens SOL (Sicherheit durch Organisationales Lernen) in eine Computerversion dar. In diesem Zusammenhang wurde ein an der Praxis orientiertes Anforderungsprofil an die Software erstellt. Grundlage bildeten hierfuer Interviews mit Experten aus der Kerntechnik und die Betrachtung bereits vorhandener computergestuetzter Verfahren. In einem iterativen Verbesserungsprozess wurde die Software erstellt. Den Abschluss bildete die Erprobung der Software. Es liess sich feststellen, dass mit CEA valide kontribuierende Faktoren identifiziert werden. Auch das Feedback der Experten zu CEA war ausnahmslos positiv. (orig.)

  16. Study on the risk of late damage in humans after incorporation of the short-lived alpha emitter Ra-224; Studie zum Risiko von Spaetschaeden beim Menschen nach Inkorporation des kurzlebigen {alpha}-Strahlers Radium-224

    Energy Technology Data Exchange (ETDEWEB)

    Wick, R.R.; Nekolla, E.A.; Kellerer, A.M. [Muenchen Univ. (Germany). Strahlenbiologisches Inst.; Goessner, W. [Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg (Germany). Inst. fuer Pathologie

    2003-07-01

    besteht eine Kontrollgruppe von 1323 Bechterew-Patienten, die nicht mit radioaktiven Praeparaten und/oder Roentgenstrahlen behandelt worden sind. Zum Ende des Jahres 2002 liegen nunmehr gesicherte Todesursachen fuer 842 Patienten in der Expositionsgruppe vor, in der Kontrollgruppe belaeuft sich die Zahl der gesicherten Todesursachen auf 861 Faelle. In der Expositionsgruppe sind bisher insgesamt 219, in der Kontrollgruppe 206 Krebsfaelle registriert worden. Damit liegt die Anzahl der insgesamt beobachteten malignen Erkrankungen unterhalb der in einer Normalbevoelkerung zu erwartenden Anzahl. Unter anderem fanden wir in der Expositionsgruppe 15 Leukaemien (gegenueber 5,9 erwarteten Faellen). Dagegen wurden in der Kontrollgruppe bisher nur 8 Leukaemien beobachtet. Eine genauere Subklassifikation zeigt, dass in der Expositionsgruppe im Besonderen die myeloischen Leukaemien erhoeht sind (9 beobachtete Faelle gegenueber 2,5 erwartet), und davon wiederum die akuten myeloischen Leukaemien (6 Faelle gegenueber 1,6 erwartet), waehrend in der Kontrollgruppe die Anzahl der beobachteten Faelle im Rahmen der Erwartung liegt (3 myeloische Leukaemien vs. 2,6 erwartete Faelle). Von den 6 akuten myeloischen Leukaemien sind 3 Faelle bei einer Dosierung aufgetreten, wie sie auch bei der heutigen Therapie mit dem {sup 224}Ra-Praeparat SpondylAT {sup registered} ueblich ist; in einem Fall betrug die {sup 224}Ra-Dosis das 0,6fache, in einem weiteren Fall das 1,6fache, waehrend in einem Fall die Gesamtdosis nicht sicher verifiziert werden konnte. Die erhoehte Leukaemieinzidenz in der Expositionsgruppe unseres Patientenkollektivs stimmt mit tierexperimentellen Beobachtungen an Maeusen ueberein, die geringe Mengen des knochensuchenden {alpha}-Strahlers {sup 224}Ra erhalten hatten. (orig.)

  17. Über Leben : einige Szenarien zu einer Ethik des Überlebens nach Foucault, Agamben und Ridley Scotts 'Alien'

    OpenAIRE

    Zakravsky, Katherina

    2017-01-01

    Das Aufkommen der Biopolitik als Dispositiv der Moderne beschreibt Michel Foucault als Effekt einer Reihe von Transformationen, verbindet es allerdings an dieser Stelle nicht explizit mit den wissenschaftlichen Entdeckungen Darwins. Die Eingliederung des Menschen in das Kontinuum der lebenden Organismen ist aber eine der bedeutsamsten Konsequenzen von Darwins Theorie von der Abstammung des Menschen. Wenn parallel zu oder auch in Abhängigkeit von dieser Transformation des biologischen Wissens ...

  18. Soziales Funktionsniveau und dessen neuronale Korrelate bei gesunden Menschen und bei Menschen mit Schizophrenie

    OpenAIRE

    2015-01-01

    Defizite des sozialen Funktionsniveaus sind ein Hauptmerkmal schizophrener Erkrankungen. Diese Defizite sind gut beschrieben, aber ihre neurobiologischen Grundlagen sind bislang kaum verstanden. Übergeordnetes Ziel dieser Arbeit ist die Erweiterung des Wissens über neuronale Korrelate des sozialen Funktionsniveaus sowie ein besseres Verständnis sozialer Funktionsdefizite. Ein weiteres Ziel ist die Validierung und Etablierung einer deutschen Übersetzung der Social Functioning Scale (SFS), eine...

  19. [Leber's hereditary optic neuropathy].

    Science.gov (United States)

    Leo-Kottler, B; Wissinger, B

    2011-12-01

    Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today.

  20. Electromagnetic fields from the environment, or EMC for man. On the effect of electric, magnetic, and electromagnetic fields on man; EMVU, die EMV fuer den Menschen, ueber die Wirkungen elektrischer, magnetischer und elektromagnetischer Felder auf den Menschen

    Energy Technology Data Exchange (ETDEWEB)

    David, E. [Univ. Witten/Herdecke, Inst. fuer Normale und Pathologische Physiologie, Witten (Germany); Reissenweber, J. [Univ. Witten/Herdecke, Inst. fuer Normale und Pathologische Physiologie, Witten (Germany); Peier, D. [Univ. Dortmund, Inst. fuer Hochspannungstechnik (Germany)

    1994-12-31

    The increasing use of electrotechnical equipment causes enhanced exposure of the environment to electromagnetic fields. The impact of such fields on biological systems and on man is difficult to assess because of its complexity. In the first part the article gives an overview of the effect of electromagnetic fields on melatonin production in man, dealing specifically with the importance of melatonin for the night-and-day rhythm, sleep, the immune system, as a hormone antagonist, and for the development and growth of tumors. In a second part the authors discuss possible effects on electronic implants, especially cardiac pacemakers. (MG) [Deutsch] Die zunehmende Nutzung elektrotechnischer Einrichtungen fuehrt dazu, dass die Umwelt in steigendem Mass elektromagnetischen Feldern ausgesetzt ist. Die Ermittlung der Auswirkungen dieser Felder auf biologische System und auf den Menschen erweist sich aufgrund ihrer Komplexitaet als schwierig. In einem ersten Teil gibt der Artikel einen Ueberblick ueber die Auswirkungen elektromagnetischer Felder auf die Melatoninproduktion beim Menschen, wobei naeher auf die Bedeutung des Melatonins beim Tag-Nacht-Rhythmus, dem Schlaf, auf das Immunsystem, als Hormonantagonist und bei Tumorentstehung und -wachstum diskutiert werden. In einem zweiten Teil diskutieren die Autoren moegliche Auswirkungen auf elektronische Implantate, v.a. auf Herzschrittmacher. (orig.)

  1. Genetics Home Reference: Leber congenital amaurosis

    Science.gov (United States)

    ... amaurosis, Leber congenital congenital amaurosis of retinal origin congenital retinal blindness CRB dysgenesis neuroepithelialis retinae hereditary epithelial dysplasia of retina hereditary retinal aplasia heredoretinopathia congenitalis LCA ...

  2. Kartierung der Bindungstasche des humanen Bittergeschmacksrezeptors hTAS2R10

    OpenAIRE

    Born, Stephan

    2012-01-01

    Die Bittergeschmacksrezeptoren stellen in der Superfamilie der G-Protein-gekoppelten Rezeptoren eine besondere Gruppe dar. Im Menschen können die 25 Rezeptoren eine große Anzahl unterschiedlichster Bittergeschmacksstoffe detektieren. Diese Substanzen können sowohl schädlich, wie etwa Strychnin, als auch der Gesundheit förderliche Arzneistoffe, wie etwa Chloramphenicol sein. Unter den Bittergeschmacksrezeptoren des Menschen gibt es eine Gruppe von drei Rezeptoren, die besonders viele Bittersto...

  3. [Sudden blindness: consider Leber's hereditary optic neuropathy

    NARCIS (Netherlands)

    Schieving, J.H.; Vries, L.B.A. de; Hol, F.A.; Stroink, H.

    2008-01-01

    In 3 young male patients, aged 10, 19 and 21 years respectively, sequential, severe, painless bilateral visual loss occurred. Ophthalmological examination revealed no other abnormalities and this delayed the diagnosis Leber's hereditary optic neuropathy (LHON). LHON is a mitochondrial genetic diseas

  4. Demyelinating polyneuropathy in Leber hereditary optic neuropathy.

    NARCIS (Netherlands)

    Gilhuis, H.J.; Schelhaas, H.J.; Cruysberg, J.R.M.; Zwarts, M.J.

    2006-01-01

    We report a patient with Leber hereditary optic neuropathy (G11778A mtDNA) and a severe demyelinating neuropathy, for which no other cause except his mitochondrial disorder could be found. The involvement of the peripheral nervous system of patients with LHON, in particular with a 11778 mtDNA, is di

  5. Contribution of occupational therapy for patients with depression / Beitrag der Ergotherapie in der Wahrnehmung von Menschen mit Depression

    Directory of Open Access Journals (Sweden)

    Treusch Yvonne

    2016-12-01

    Full Text Available In Bezug auf den professionellen Beitrag und die Wirkfaktoren der Ergotherapie bei Menschen mit Depression existieren bislang wenige Studien. Dies steht im Kontrast zum praktischen und quantitativen Beitrag dieser Therapieform.

  6. 31-P-Magnetresonanztomographie der menschlichen Leber

    OpenAIRE

    2006-01-01

    Die 31-P-Magnetresonanz-Spektroskopie (31-P-MRS) ist eine nicht-invasive Methode, welche einen direkten Einblick in den Phospholipid-Haushalt der menschlichen Leber erlaubt. Mit der 31-P-MR-Spektroskopie wurden Spektren von 10 Patienten mit Leberzirrhose sowie von 13 gesunden Probanden in Kombination mit dem Lokalisationsverfahren 3D-CSI und dem Nachbearbeitungsprogramm SLOOP (Spectral Localization with Optimal Pointspread Funktion) gewonnen. Die Ergebnisse dieser Studie ergaben signifikante ...

  7. Leber hereditary optic neuropathy mimicking neuromyelitis optica.

    Science.gov (United States)

    McClelland, Collin M; Van Stavern, Gregory P; Tselis, Alex C

    2011-09-01

    Leber hereditary optic neuropathy (LHON) is rarely associated with multiple sclerosis-like features. We present a case of a 65-year-old African American woman with LHON masquerading as neuromyelitis optica (NMO). We highlight the features of the clinical examination and MRI that were suggestive of an alternative diagnosis and review the literature regarding LHON and multiple sclerosis. The diagnosis of LHON should be considered in all cases of acute or subacute bilateral optic neuropathy, including presumed seronegative NMO.

  8. Die Wirksamkeit von Taurolidin auf das Harnblasenkarzinom des Menschen im Zellversuch und im Rattenmodell

    OpenAIRE

    Bueschges, Michael

    2010-01-01

    The effects of Taurolidine on bladder cancer was observed in cell cultures with human bladder (cancer-) cells (HCV-29, RT-4, Rt112, J-82), on bladder cancer cells of rats (AY-27) and in a rat model. In the cell-cultures, proliferation rate of the cells was measured with a XTT-Test. Taurolidine showed antiproliferative effects on all cell lines. In the rat model, bladder cancer was generated via injection of tumor cells (AY-27) in the bladder-muscularis of female fisher rats (F344). The rats w...

  9. Die lebensvision des semonides

    Directory of Open Access Journals (Sweden)

    Milivoj Sironić

    1980-12-01

    Full Text Available Der Autor analysiert die Weibersatire des Semonides und andere seiner kurzen Fragmente. Dabei kommt er zu der Schlussfolgerung, dass sich die Verse der Satire durch eine gute Technik auszeich­ nen, dass aber auch eine unnötige Weitschweifigkeit nicht zu Ubersehen ist. Trotzdem kann man jedoch dem Dichter nicht die künstlerische Überzeugungskraft absprechen, wie auch die Ten­ denz nach Detailschilderungen und die Feinheit geistreicher Charakterisierungen. Die Aussage beinhaltet manchmal eine be­ stimmte innere Ironie in der Einfachheit der Wörter.In kurzen Fragmenten wird die Fähigkeit des Semonides sichtbar, sich sehr präzise auszudrücken. Seine ironisch-epische Sprache ist sehr reich  und verdient vom linguistischen Standpunkt aus Auf­ merksamkeit wegen ihres reichhaltigen lexischen und termino­ logischen Materials, insbesondere was die Bereiche der Tier­ welt und des Essens anbelangt.Die Weltanschauung des Dichters ist in dem ersten Fragment recht deutlich erkennbar. Da sieht man, dass er düster und pessimistisch auf das Leben blickt. Das Fehlen jeglicher positiven Einstellung hat dann den Sar­ kasmus zur Folge, mit dem der Dichter die Darstellung der Weiber einkleidet, ihn aber auch auf die Menschen schlechthin ausweitet.

  10. Functional MR imaging of the liver; Funktionelle MR-Tomographie der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, A.; Nolz, R.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Allgemeines Krankenhaus der Stadt Wien, Universitaetsklinik fuer Radiodiagnostik und Nuklearmedizin, Wien (Austria); Trauner, M. [Medizinische Universitaet Wien, Universitaetsklinik fuer Innere Medizin III, Klinische Abteilung fuer Gastroenterologie und Hepatologie, Wien (Austria)

    2015-12-15

    The diagnostics of diffuse liver disease traditionally rely on liver biopsies and histopathological analysis of tissue specimens. However, a liver biopsy is invasive and carries some non-negligible risks, especially for patients with decreased liver function and those requiring repeated follow-up examinations. Over the last decades, magnetic resonance imaging (MRI) has developed into a valuable tool for the non-invasive characterization of focal liver lesions and diseases of the bile ducts. Recently, several MRI methods have been developed and clinically evaluated that also allow the diagnostics and staging of diffuse liver diseases, e. g. non-alcoholic fatty liver disease, hepatitis, hepatic fibrosis, liver cirrhosis, hemochromatosis and hemosiderosis. The sequelae of diffuse liver diseases, such as a decreased liver functional reserve or portal hypertension, can also be detected and quantified by modern MRI methods. This article provides the reader with the basic principles of functional MRI of the liver and discusses the importance in a clinical context. (orig.) [German] Die Diagnostik diffuser Lebererkrankungen stuetzt sich klassisch auf die Leberbiopsie und deren histopathologische Analyse. Dieses Verfahren ist allerdings fuer die Patienten unangenehm und schmerzhaft, birgt v. a. bei Patienten mit Lebererkrankungen ein gewisses Risiko und eignet sich daher nur sehr eingeschraenkt zur Verlaufskontrolle bei chronischen Erkrankungen. Die Magnetresonanztomographie (MRT) der Leber nimmt schon jetzt eine zentrale Stellung in der Diagnostik von Raumforderungen der Leber und von Erkrankungen der Gallenwege ein. Darueber hinaus bietet dieses nichtinvasive Verfahren Moeglichkeiten, diffuse Erkrankungen des Leberparenchyms zu diagnostizieren und ihren Schweregrad abzuschaetzen, z. B. bei nichtalkoholischer Leberverfettung, Hepatitis, Leberfibrose, Zirrhose, Haemochromatose und Siderose und anderen. Folgen einer parenchymatoesen Lebererkrankung, wie die portale

  11. 线粒体病--Leber's病

    Institute of Scientific and Technical Information of China (English)

    陆宏

    2001-01-01

    @@ Leber′s病也称遗传性视神经网膜病(Leber ′sherdeitary Optic Neuroretinopathy LHON).自Leber于1871年首次将此病作为1个独立的临床疾病以来,已有百余年历史,以后国内外陆续报道.其主要症状为视神经退行性变.故此病又称Leber′s视神经萎缩.

  12. Leber's Congenital Amaurosis and Gene Therapy.

    Science.gov (United States)

    Takkar, Brijesh; Bansal, Pooja; Venkatesh, Pradeep

    2017-07-07

    Retinal blindness is an important cause of pediatric visual loss. Leber's congenital amaurosis (LCA) is one of these causes, often wrongly included in the spectrum of retinitis pigmentosa. The disease has become the center of research after initial reports of success in management with gene therapy. This review discusses in brief the clinical presentation and investigative modalities used in LCA. Further, the road to gene discovery and details of currently applied gene therapy are presented. LCA is one of the first successfully managed human diseases and offers an entirely new dimension in ocular therapeutics.

  13. Leber hereditary optic neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Meyerson C

    2015-06-01

    Full Text Available Cherise Meyerson, Greg Van Stavern, Collin McClelland Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA Abstract: Leber hereditary optic neuropathy (LHON is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. Keywords: Leber hereditary optic neuropathy, mitochondria, neuro-ophthalmology, mitochondrial DNA

  14. Leber’s Inherited Optic Neuropathy: A Large Family

    Directory of Open Access Journals (Sweden)

    Taylan Pekoz

    2012-04-01

    Full Text Available Leber's hereditary optic neuropathy characterized by loss of central vision is often seen in men and a maternally inherited disease. Here, admitted to our clinic with complaints of unilateral visual loss was diagnosed as Leber's hereditary optic neuropathy which was confirmed by the presence of a mutation at 3460G>A position. [Cukurova Med J 2012; 37(2.000: 121-124

  15. Late-onset progressive visual loss in a man with unusual MRI findings: MS, Harding's, Leber's or Leber's Plus?

    LENUS (Irish Health Repository)

    Cawley, N

    2012-02-01

    Leber\\'s hereditary optic neuropathy (LHON) is a maternally inherited disorder, typically presenting in the second and third decade. We report the case of an elderly gentleman with significant vascular risk factors, presenting with slowly progressive, bilateral, visual loss with high signal lesions in the pericallosal and periventricular deep white matter on MRI brain studies. Possible diagnoses included late-onset MS, ischaemic optic neuropathies, a mitochondrial disorder or an overlap syndrome such as Harding\\'s disease.

  16. [Research progress of Leber hereditary optic neuropathy].

    Science.gov (United States)

    Zhang, A-Mei; Yao, Yong-Gang

    2013-02-01

    Leber hereditary optic neuropathy (LHON; MIM 535000) is one of the most common mitochondrial diseases, with a clinical manifestation of painless, acute or sub-acute bilateral visual loss in young adults leading to blindness and central scotoma. Over 95% of LHON patients were caused by one of three primary mtDNA mutations (m.11778G>A, m.3460G>A and m.14484T>C). Incomplete penetrance and gender bias are two riddles of this disease. Here we summarized recent research progress of LHON, with a focus on the molecular pathogenic mechanisms, clinical features, in vitro experiments and animal models, and prevention and treatment of LHON. In particular, we presented the main findings and challenges in our recent efforts to decipher genetic susceptibility and mechanism of LHON in Chinese patients.

  17. Idebenone for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Gueven, N

    2016-03-01

    Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data.

  18. Foot steps of man, traces of thought. Vom Menschen of Werner Sombart - Footsteps of man, traces of thought. Vom Menschen of Werner Sombart

    Directory of Open Access Journals (Sweden)

    Roberta Iannone

    2015-03-01

    Full Text Available In his work – Vom Menschen – Sombart wonders “Who is man?”. This article tries to answer this timeless question, by revisiting some of the key points of the work. Sombart, as well as the author of this present work, have a similar objective: to deal in scientific terms, not only with the human being but also with his body language, soul and spirit. The purpose is to portray “a human science with a critical edge”, a “science of rational comprehension”. A question arises in relation to the bond between body, soul, and spirit: do they harmoniously constitute man? Or, do they lead to de-humanization? (a certain deprivation of the constitutive essence of man. These key questions are addressed to the following subjects: a ancestors, in view of which centuries of theoretical elaborations of fundamental anthropology are reviewed; b Erfahrungswissen, which is the experience that leads to knowledge of facts and Evidenzswissen, or known evidence, which is the a priori knowledge; c actions and reasons; d the spirit.

  19. Identifizierung und Charakterisierung von Genen mit Einfluss auf Entwicklung und Erhalt des Knorpel-/Knochen-Systems

    OpenAIRE

    Tagariello, Andreas

    2006-01-01

    Defekte bei Bildung, Wachstum und Homöostase des Skeletts sind verantwortlich für eine Reihe menschlicher Erkrankungen, zu denen neben zahlreichen Skelettdysplasien und Kraniosynostosen auch Osteoarthrose und rheumatoide Arthritis gehören. Da die diesen Erkrankungen zugrunde liegenden molekularen Prozesse nur in Ansätzen aufgeklärt sind, war es Ziel der Arbeit, neue Gene, die in die komplexen Prozesse der Knorpel-/Knochenbildung, -differenzierung und -homöostase beim Menschen involviert sind,...

  20. Wie die Medienberichterstattung über die Wirtschaft das Bild der Menschen von der Wirtschaft prägt. Eine Analyse zur Rezeption von Wirtschaftsnachrichten

    OpenAIRE

    Müller-Klier, Maike

    2012-01-01

    Was Menschen über die Welt wissen, hat im Prinzip drei Quellen: eigene Erfahrung, personale Kommunikation und mediale Information. Die Arbeit geht der Frage nach, was die Menschen über den Weltausschnitt wissen, der gemeinhin als „Wirtschaft“ bezeichnet wird, und inwieweit dieses Wissen seinen Ursprung in den Massenmedien hat. Da es zu dieser Frage kaum relevante Forschung gibt, aus der sich themaspezifische Annahmen ableiten ließen, basiert die Arbeit im Wesentlichen auf Theorien und Erkennt...

  1. Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's syndrome.

    Science.gov (United States)

    Parry-Jones, A R; Mitchell, J D; Gunarwardena, W J; Shaunak, S

    2008-04-01

    We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.

  2. Glaucoma progression associated with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Nucci, Carlo; Martucci, Alessio; Mancino, Raffaele; Cerulli, Luciano

    2013-02-01

    The purpose of this article is to describe a case of open-angle glaucoma progression associated with Leber's hereditary optic neuropathy. Single case analysis method is used. A 53-year-old woman with a previous diagnosis of glaucoma presented with progressive visual field loss. Complete ophthalmological examination and blood tests were negative for other concomitant diseases. Genetic counseling revealed mitochondrial DNA mutation compatible with the diagnosis of Leber's hereditary optic neuropathy. In conclusion, the case describes the concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We hypothesize that the two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the consequent rapid progression of visual impairment. Screening for mitochondrial DNA mutations may be requested in patients with glaucoma who, despite pharmacologically controlled intraocular pressure, show rapid progression of the disease.

  3. Leber hereditary optic neuropathy: current perspectives.

    Science.gov (United States)

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells.

  4. Leber hereditary optic neuropathy: current perspectives

    Science.gov (United States)

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609

  5. [Designation criteria for Leber's hereditary optic neuropathy].

    Science.gov (United States)

    Nakamura, Makoto; Mimura, Osamu; Wakakura, Masato; Inatani, Masaru; Nakazawa, Toru; Shiraga, Fumio

    2015-05-01

    Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan.

  6. Leber congenital amaurosis: from darkness to spotlight.

    Science.gov (United States)

    Kaplan, Josseline

    2008-09-01

    Almost 150 years ago, Theodor Leber described a severe form of vision loss at or near birth which was later given his name. During the century that followed this description, ophthalmologists dedicated efforts to give an accurate definition of the disease but patients were neglected because of the inability of physicians to provide them with treatment. In the 90s, at the time of the Golden Age of Linkage, the first LCA locus was mapped to a human chromosome and shortly after identified as the gene for guanylate cyclase. This discovery was the spark that made the disease emerge from the shadows as illustrated by the flood of LCA genes identified in the following ten-year period. During the same time period, the clinical variability of the disease was rediscovered and an unexpected physiopathological heterogeneity demonstrated. In the beginning of the third millennium, LCA came out definitively from the tunnel to shine under the bright spotlights with the RPE65 gene therapy trial that succeeded to restore vision in a dog model and opened the door to gene therapy trials in humans.

  7. Grundlagen des Tissue Engineering

    Science.gov (United States)

    Mayer, Jörg; Blum, Janaki; Wintermantel, Erich

    Die Organtransplantation stellt eine verbreitete Therapie dar, um bei krankheitsoder unfallbedingter Schädigung eines Organs die Gesamtheit seiner Funktionen wieder herzustellen, indem es durch ein Spenderorgan ersetzt wird. Organtransplantationen werden für die Leber, die Niere, die Lunge, das Herz oder bei schweren grossflächigen Verbrennungen der Haut vorgenommen. Der grosse apparative, personelle und logistische Aufwand und die Risiken der Transplantationschirurgie (Abstossungsreaktionen) sowie die mangelnde Verfügbarkeit von immunologisch kompatiblen Spenderorganen führen jedoch dazu, dass der Bedarf an Organtransplantaten nur zu einem sehr geringen Teil gedeckt werden kann. Sind Spenderorgane nicht verfügbar, können in einzelnen Fällen lebenswichtige Teilfunktionen, wie beispielsweise die Filtrationsfunktion der Niere durch die Blutreinigung mittels Dialyse ersetzt oder, bei mangelnder Funktion der Bauchspeicheldrüse (Diabetes), durch die Verabreichung von Insulin ein normaler Zustand des Gesamtorganismus auch über Jahre hinweg erhalten werden. Bei der notwendigen lebenslangen Anwendung apparativer oder medikamentöser Therapie können für den Patienten jedoch häufig schwerwiegende, möglicherweise lebensverkürzende Nebenwirkungen entstehen. Daher werden in der Forschung Alternativen gesucht, um die Funktionen des ausgefallenen Organs durch die Implantation von Zellen oder in vitro gezüchteten Geweben möglichst umfassend wieder herzustellen. Dies erfordert biologisch aktive Implantate, welche die für den Stoffwechsel des Organs wichtigen Zellen enthalten und einen organtypischen Stoffwechsel entfalten.

  8. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    NARCIS (Netherlands)

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three pa

  9. Leber's hereditary optic neuropathy: case report and literature review

    Directory of Open Access Journals (Sweden)

    Hélio Afonso Ghizoni Teive

    Full Text Available CONTEXT: Leber's hereditary optic neuropathy is an important cause of progressive painless visual loss among young male patients. OBJECTIVE: To report on a case of a young patient with a clinical and neurophysiological condition suggestive of Leber's hereditary optic neuropathy, confirmed by genetic testing. CASE REPORT: We describe a 17-year-old male with progressive bilateral visual loss. Two maternal uncles had had similar patterns of visual loss. The patient had a history of smoking and alcohol abuse. Neuro-ophthalmological examination revealed visual acuity of 20/800 in both eyes, with decreased direct and consensual pupillary light reflexes. Fundus examination demonstrated pale optic discs. The visual evoked potential test showed signs of conduction disturbances in both optic nerves and campimetric study showed complete visual loss in all fields of both eyes. A diagnosis of bilateral optic neuropathy with a clinical suspicion of Leber's hereditary optic neuropathy was made. A blood sample was submitted to genetic analysis in relation to the principal mutations of this disorder, and homoplasmic mutation in 11778 was detected, thereby confirming the diagnosis of Leber's hereditary optic neuropathy.

  10. Gene-environment interactions in Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    M.A. Kirkman; P. Yu-Wai-Man (Patrick); A. Korsten (Alex); M. Leonhardt (Miriam); K. Dimitriadis (Konstantin); I.F.M. de Coo (René); T. Klopstock (Thomas); P.F. Chinnery

    2009-01-01

    textabstractLeber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to conf

  11. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    1997-01-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between t

  12. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

  13. Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Rudanko, S.-L.

    1995-01-01

    This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

  14. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    NARCIS (Netherlands)

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

  15. Leber congenital amaurosis: genes, proteins and disease mechanisms.

    NARCIS (Netherlands)

    Hollander, A.I. den; Roepman, R.; Koenekoop, R.K.; Cremers, F.P.M.

    2008-01-01

    Leber congenital amaurosis (LCA) is the most severe retinal dystrophy causing blindness or severe visual impairment before the age of 1 year. Linkage analysis, homozygosity mapping and candidate gene analysis facilitated the identification of 14 genes mutated in patients with LCA and juvenile retina

  16. The foundation of experimental ophthalmology by Theodor Leber.

    Science.gov (United States)

    Jaeger, W

    1988-01-01

    Theodor Leber grew up in Heidelberg as the son of a professor of Romance languages. Initially he planned to study natural sciences. Bunsen's advice led him to medicine. During his studies he succeeded in solving a competition problem posed by Helmholtz in the medical department. A short period of practical work in the eye hospital of Knapp was unsatisfactory. In Vienna with the physiologist Carl Ludwig, he was able in 1863/64, at the age of only 24 years, to demonstrate the blood circulation of the eye by color injections into the arteries and veins. Since that time the schematic drawings of his results can be found in every textbook of ophthalmology. On the occasion of the congress of the German Ophthalmological Society in Heidelberg in 1864, Theodor Leber reported on these findings and met with immense approval. In 1864-67 he followed an invitation as coworker of Liebreich to Paris; in 1867 he became A.v. Graefe's coworker in Berlin; in 1871 he moved to Göttingen, which became the first eye clinic with a laboratory for experimental investigations. The second epoch-making discovery accomplished by Leber was the detection of the fluid exchange in the eye. These results have also been confirmed by modern methods. Therefore, Theodor Leber can be called the father of experimental ophthalmology.

  17. Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial.

    Science.gov (United States)

    Cwerman-Thibault, Hélène; Augustin, Sébastien; Ellouze, Sami; Sahel, José-Alain; Corral-Debrinski, Marisol

    2014-03-01

    Mitochondrial disorders cannot be ignored anymore in most medical disciplines; indeed their minimum estimated prevalence is superior to 1 in 5000 births. Despite the progress made in the last 25 years on the identification of gene mutations causing mitochondrial pathologies, only slow progress was made towards their effective treatments. Ocular involvement is a frequent feature in mitochondrial diseases and corresponds to severe and irreversible visual handicap due to retinal neuron loss and optic atrophy. Interestingly, three clinical trials for Leber Congenital Amaurosis due to RPE65 mutations are ongoing since 2007. Overall, the feasibility and safety of ocular Adeno-Associated Virus delivery in adult and younger patients and consistent visual function improvements have been demonstrated. The success of gene-replacement therapy for RPE65 opens the way for the development of similar approaches for a broad range of eye disorders, including those with mitochondrial etiology such as Leber Hereditary Optic Neuropathy (LHON). Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  18. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Giordano, Carla; Montopoli, Monica; Perli, Elena; Orlandi, Maurizia; Fantin, Marianna; Ross-Cisneros, Fred N; Caparrotta, Laura; Martinuzzi, Andrea; Ragazzi, Eugenio; Ghelli, Anna; Sadun, Alfredo A; d'Amati, Giulia; Carelli, Valerio

    2011-01-01

    Leber's hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Leber's hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Leber's hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Leber's hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Leber's hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules.

  19. Natural and anthropogenic radiation exposure of humans in Germany; Natuerliche und zivilisatorische Strahlenexposition des Menschen in Deutschland

    Energy Technology Data Exchange (ETDEWEB)

    Koelzer, Winfried

    2016-12-15

    The contribution on natural and anthropogenic radiation exposure in Germany covers the following issues: (1) natural radiation exposure: external radiation exposure - cosmic and terrestric radiation, internal radiation exposure - primordial and cosmogenic radionuclides; radiation exposure due to sola neutrinos and geo-neutrinos. (2) Anthropogenic radiation exposure: radiation exposure in medicine, radioactivity in industrial products, radiation exposure during flights, radiation exposure due to nuclear facilities, radiation exposure due to fossil energy carriers in power generation, radiation exposure due to nuclear explosions, radiation exposure due to nuclear accidents. (3) Occupational radiation exposure in Germany: radiation monitoring with personal dosimeters in medicine and industry, dose surveillance of the aviation personal, working places with increases radiation exposure by natural radiation sources.

  20. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report

    Directory of Open Access Journals (Sweden)

    Luciano Mesquita Simão

    2012-08-01

    Full Text Available Neuromyelitis optica antibody (or aquaporin-4 antibody is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  1. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report.

    Science.gov (United States)

    Simão, Luciano Mesquita

    2012-01-01

    Neuromyelitis optica antibody (or aquaporin-4 antibody) is a well established serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  2. Die Entdeckung des Unteilbaren Quanten, Quarks und die Entdeckung des Higgs-Teilchens

    CERN Document Server

    Resag, Jörg

    2014-01-01

    Mitten in Europa ist eine der größten und komplexesten Maschinen in Betrieb gegangen, die wir Menschen je gebaut haben: der Large Hadron Collider (kurz LHC). Mit ihm öffnet sich ein Fenster in eine neue Welt, die viele Geheimnisse birgt: Was verleiht den Teilchen der Materie ihre Masse? Gibt es verborgene Raumdimensionen? Existiert ein tiefer Zusammenhang zwischen Teilchen mit verschiedenem Spin (Supersymmetrie)? Woraus besteht die dunkle Materie, die unser Universum durchdringt? Gibt es das Higgs-Teilchen? Mit diesem Buch taucht der Leser ein in diese wunderbare Welt, die wir Menschen in der Neuzeit entdeckt haben: Atome und ihre Substruktur aus Quarks und Leptonen, die rätselhafte Quantenmechanik, Teilchen des Lichts, Einsteins Gewebe aus Raum und Zeit, die vier Wechselwirkungen und schließlich die neue Welt, in die der LHC gerade vordringt und in der wir Higgs-Teilchen, Supersymmetrie und womöglich erste Anzeichen für die String-Theorie vermuten. Die erste Vermutung konnte mittlerweile bestätigt w...

  3. A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia.

    NARCIS (Netherlands)

    Spruijt, L.; Smeets, H.J.M.; Hendrickx, A.; Bettink-Remeijer, M.W.; Maat-Kievit, A.; Schoonderwoerd, K.C.; Sluiter, W.; Coo, I.F.M. de; Hintzen, R.Q.

    2007-01-01

    OBJECTIVE: To report a novel mutation that is associated with Leber hereditary optic neuropathy (LHON) within the same family affected by spastic dystonia. DESIGN: Leber hereditary optic neuropathy is a mitochondrial disorder characterized by isolated central visual loss. Of patients with LHON, 95%

  4. A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia.

    NARCIS (Netherlands)

    Spruijt, L.; Smeets, H.J.M.; Hendrickx, A.; Bettink-Remeijer, M.W.; Maat-Kievit, A.; Schoonderwoerd, K.C.; Sluiter, W.; Coo, I.F.M. de; Hintzen, R.Q.

    2007-01-01

    OBJECTIVE: To report a novel mutation that is associated with Leber hereditary optic neuropathy (LHON) within the same family affected by spastic dystonia. DESIGN: Leber hereditary optic neuropathy is a mitochondrial disorder characterized by isolated central visual loss. Of patients with LHON, 95%

  5. Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy

    Science.gov (United States)

    Wallace, Douglas C.; Singh, Gurparkash; Lott, Marie T.; Hodge, Judy A.; Schurr, Theodore G.; Lezza, Angela M. S.; Elsas, Louis J.; Nikoskelainen, Eeva K.

    1988-12-01

    Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

  6. Atypical Leber Hereditary Optic Neuropathy: 18 Year Interval Between Eyes.

    Science.gov (United States)

    Ohden, Kaitlyn L; Tang, Peter H; Lilley, Chrystia C; Lee, Michael S

    2016-09-01

    A 5-year-old boy developed profound loss of vision in his right eye and was found to have a 11778 mitochondrial point mutation consistent with Leber hereditary optic neuropathy (LHON). He maintained 20/20 vision in the left eye for 18 years until age 23, when he experienced loss of vision in that eye. This 18 year interval between eye involvement in LHON is the longest reported to date and reinforces the variability in presentation and progression seen in this disease.

  7. Late-onset Leber hereditary optic neuropathy mimicking Susac's syndrome.

    Science.gov (United States)

    Zoccolella, Stefano; Petruzzella, Vittoria; Prascina, Francesco; Artuso, Lucia; Pacillo, Francesca; Dell'Aglio, Rosa; Avolio, Carlo; Delle Noci, Nicola; Attimonelli, Marcella; Specchio, Luigi Maria

    2010-12-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by bilateral painless optic atrophy and blindness. It usually occurs in young men in association with three major mutations in the mitochondrial genome (mtDNA). We report a patient with a history of alcohol abuse who developed at age 63 years visual impairment, sensorineural hearing loss, and memory dysfunction, suggestive of Susac's syndrome. The patient carried the heteroplasmic mt. 11778G>A mutation on the T2e mtDNA haplogroup. It remains unclear if chronic alcohol abuse combined with the mitochondrial genetic background prompted an aged-related neurodegeneration or deferred the onset of the LHON disease.

  8. Leber Hereditary Optic Neuropathy: Bringing the Lab to the Clinic.

    Science.gov (United States)

    Rasool, Nailyn; Lessell, Simmons; Cestari, Dean M

    2016-01-01

    Leber hereditary optic neuropathy (LHON) was the first clinically characterized mitochondrial disorder. Since its first description in 1871, much has been discovered regarding the genetics and pathophysiology of the disease. This has enabled the development of in vitro cell and animal models that can be used to try to determine not only the effects of the genetic mutation upon the clinical phenotype but to also test potential novel therapies. Treatments for LHON have ranged from vitamins and minerals to immunosuppressants and, more recently, targeted gene therapy. This article reviews the pathophysiology and clinical features of LHON with a focus on translational research.

  9. Leber Hereditary Optic Neuropathy Associated with Bilateral Macular Holes

    Science.gov (United States)

    Shimada, Yoshiaki; Horiguchi, Masayuki

    2016-01-01

    ABSTRACT Leber hereditary optic neuropathy (LHON) causes visual loss, predominantly in healthy young men. We recently examined a patient who previously had bilateral macular holes and subsequently developed LHON at 74 years of age. Although his central scotomas were initially attributed to the macular holes, his visual acuity declined following an initial improvement after operative closure of the macular holes; thus, other diagnoses, including LHON, were considered. Furthermore, macular optical coherence tomography (OCT) images remained unchanged in this time. A mitochondrial genetic analysis identified a 11778G→A mutation. From this case, we propose that LHON remains in the differential diagnosis even in older patients, as has previously been reported. PMID:27335507

  10. [Progress in gene therapy study of Leber congenital amaurosis].

    Science.gov (United States)

    Pan, Shan-Shan; Zheng, Qin-Xiang; Li, Wen-Sheng; Pang, Ji-Jing

    2011-01-01

    Leber congenital amaurosis (LCA) is an early onset retinal dystrophy that causes severe visual impairment. With the development of molecular genetics and the therapeutic gene replacement technology, the adeno-associated viral (AAV) vector-mediated gene therapy for LCA achieved encouraging progress in the past decade. The success of the Phase I clinical trials of human RPE65 gene therapy for LCA II patients makes it a pioneer in the field of retinal gene therapy and brings light to the cure of other hereditary retinopathy. This article briefly reviews the recent developments in the preclinical animal experiments and Phase I clinical trials for LCA.

  11. Available Evidence on Leber Congenital Amaurosis and Gene Therapy.

    Science.gov (United States)

    Alkharashi, Maan; Fulton, Anne B

    2017-01-01

    Leber congenital amaurosis (LCA) is a group of severe inherited retinal dystrophies that lead to early childhood blindness. In the last decade, interest in LCA has increased as advances in genetics have been applied to better identify, classify, and treat LCA. To date, 23 LCA genes have been identified. Gene replacement in the RPE65 form of LCA represents a major advance in treatment, although limitations have been recognized. In this article, we review the clinical and genetic features of LCA and evaluate the evidence available for gene therapy in RPE65 disease.

  12. Leber hereditary optic neuropathy - historical report in comparison with the current knowledge.

    Science.gov (United States)

    Piotrowska, Agnieszka; Korwin, Magdalena; Bartnik, Ewa; Tońska, Katarzyna

    2015-01-15

    Leber hereditary optic neuropathy (LHON) is a genetic, maternally inherited disease caused by point mutations in the mitochondrial genome. LHON patients present with sudden, painless and usually bilateral loss of vision caused by optic nerve atrophy. The first clinical description of the disease was made by Theodor Leber, a German ophthalmologist, in 1871. Here we present his thorough notes about members of four families and their pedigrees. We also provide insights into the current knowledge about LHON pathology, genetics and treatment in comparison with Leber's findings.

  13. Die Kehre als völlige Umwendung des Menschen. Von der Verwirklichung des „mystischen” Antriebs der Phänomenologie im Denken Martin Heideggers

    Directory of Open Access Journals (Sweden)

    Eckard WOLZ-GOTTWALD

    2016-12-01

    Full Text Available The article first outlines Edmund Husserl’s idea of “complete transformation” (völlige Umwendung and the philosophy of “the turn” (Kehre of Martin Heidegger. In the following chapter it is shown that you can understand both Husserl as well as Heidegger in the light of “the essential turn” in the German mysticism of the fourteenth century. In this way it becomes clear that Husserl’s idea of a “complete transformation” seems to be a forgotten “mystical” impetus of phenomenology, which was much more realized by Martin Heidegger than by Husserl. In this way Heidegger’s philosophy of “the turn” appears as an important modern approach of the mystical philosophy of transformation.

  14. Gene therapy for Leber congenital amaurosis: advances and future directions.

    Science.gov (United States)

    Hufnagel, Robert B; Ahmed, Zubair M; Corrêa, Zélia M; Sisk, Robert A

    2012-08-01

    Leber congenital amaurosis (LCA) is a congenital retinal dystrophy that results in significant and often severe vision loss at an early age. Comprehensive analysis of the genetic mutations and phenotypic correlations in LCA patients has allowed for significant improvements in understanding molecular pathways of photoreceptor degeneration and dysfunction. The purpose of this article is to review the literature on the subject of retinal gene therapy for LCA, including historical descriptions, preclinical animal studies, and human clinical trials. A literature search of peer-reviewed and indexed publications from 1996-2011 using the PubMed search engine was performed. Key terms included "Leber congenital amaurosis", LCA, RPE65, "cone-rod dystrophy", "gene therapy", and "human trials" in various combinations. Seminal articles prior to 1996 were selected from primary sources and reviews from the initial search. Articles were chosen based on pertinence to clinical, genetic, and therapeutic topics reviewed in this manuscript. Fundus photographs from LCA patients were obtained retrospectively from the clinical practice of one of the authors (R.A.S). Herein, we reviewed the literature on LCA as a genetic disease, the results of human gene therapy trials to date, and possible future directions towards treating inherited retinal diseases at the genetic level. Original descriptions of LCA by Theodor Leber and subsequent research demonstrate the severity of this disease with early-onset blindness. Discoveries of the causative heritable mutations revealed genes and protein products involved in photoreceptor development and visual transduction. Animal models have provided a means to test novel therapeutic strategies, namely gene therapy. Stemming from these experiments, three independent clinical trials tested the safety of subretinal delivery of viral gene therapy to patients with mutations in the RPE65 gene. More recently, efficacy studies have been conducted with encouraging

  15. Multiple sclerosis associated with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Palace, Jacqueline

    2009-11-15

    The cause of multiple sclerosis is unknown although it is recognised to involve an inflammatory process associated with demyelinating plaques and more widespread neurodegeneration. It appears to have become progressively more common in females which is further discussed in this issue, and genetic factors, as identified to date, appear to play only a moderate role. One curious observation is that Leber's Hereditary Optic Neuropathy (LHON), a rare genetic syndrome, presents clinically overwhelmingly in males, but can be associated with an MS-like illness and when it does it occurs mainly in females. It is interesting to examine this further to assess if this could give us any clues as to the pathogenesis of MS.

  16. Therapeutic strategies for Leber's hereditary optic neuropathy: A current update.

    Science.gov (United States)

    Gueven, Nuri; Faldu, Dharmesh

    2013-11-01

    Leber's hereditary optic neuropathy (LHON) is a rare mitochondrial retinopathy, caused by mutations in subunits of complex I of the respiratory chain, which leads to elevated levels of oxidative stress and an insufficient energy supply. This molecular pathology is thought to be responsible for the dysfunction and eventual apoptotic loss of retinal ganglion cells in the eye, which ultimately results in blindness. Many strategies, ranging from neuroprotectants, antioxidants, anti-apoptotic- and anti-inflammatory compounds have been tested with mixed results. Currently, the most promising compounds are short-chain quinones that have been shown to protect the vision of LHON patients during the early stages of the disease. This commentary gives a brief overview on the current status of tested therapeutics and also addresses future developments such as the use of gene therapy that hopefully will provide safe and efficient therapy options for all LHON patients.

  17. Neuropatía óptica hereditaria de Leber Leber´s hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Yannara Elina Columbié Garbey

    2012-06-01

    Full Text Available La neuropatía óptica hereditaria de Leber es una enfermedad de herencia materna que se caracteriza por la pérdida subaguda, indolora y bilateral, aunque por lo general no siempre al unísono de la visión central. Predomina en hombres jóvenes y es causada por mutaciones puntuales del ADN mitocondrial. Esta es una de las neuropatías ópticas hereditarias más frecuentes y altamente invalidante, cuyo diagnóstico de certeza lo constituyen los estudios moleculares. El propósito de esta revisión es alertar en cuanto a su diagnóstico y posible incremento en condiciones ambientales favorecedoras. Se realizó una búsqueda automatizada de artículos científicos relacionados con el tema, en PUBMED e Hinari, que resultó en 37 publicaciones realizadas durante los años 1988-2010. Se estudiaron y discutieron aspectos de la enfermedad tales como antecedentes históricos, factores de riesgo, epidemiología, genética, características clínicas, diagnóstico y tratamiento; además de profundizar en su estado actual en nuestro contexto. En Cuba actualmente se conoce de la existencia de varias familias que padecen la neuropatía óptica hereditaria de Leber. El alza de la incidencia probablemente se debió a las condiciones medioambientales que favorecen o son factores de riesgo de esta entidad, como ocurrió durante la pasada epidemia de neuropatía óptica en Cuba. Cada día se producen más avances en el campo de la genética, que permiten identificar un número mayor de mutaciones asociadas a esta entidad. Esto unido al conocimiento de las características clínicas de la enfermedad ha permitido identificar las familias afectadas y actuar sobre los factores de riesgo.Leber´s hereditary optic neuropathy is a maternally inherited disease characterized by subacute, painless and bilateral loss of the central vision, although not always at the same time. It predominates in young men and is caused by mitochondrial DNA spot mutations. This is one of

  18. Die Charakteristik des kraniofazialen Wachstums beim FGFR3-assoziierten Koronarnahtsynostose-Syndrom (so genannte Muenke-Kraniosynostose)

    OpenAIRE

    Phan The, Phuoc Long

    2007-01-01

    Das Muenke-Syndom, das auch als FGFR3-Koronarnahtsynostose-Syndrom oder als Muenke-Typ-Kraniosynostose bezeichnet wird (BELLUS et al. 1996, MUENKE et al. 1997, WILKIE 1997, GRAHAM et al. 1998) ist eine seit Mitte der Neunziger Jahre bekannte Mutation des Menschen, die familiär oder sporadisch auftritt. Diese Kraniosynostoseform zeichnet sich durch einen variablen Phänotypus aus, sodass Verwechslungen mit einem Saethre-Chotzen-, Pfeiffer- oder auch Crouzon-Syndrom auftreten können (ADÈS et al....

  19. Den öffentlichen Raum „hacken“ und die Menschen beeinflussen

    Directory of Open Access Journals (Sweden)

    Irwan Ahmett

    2014-05-01

    Full Text Available 65 Jahre nach der Unabhängigkeitserklärung Indonesiens kletterte ein Mann mittleren Alters in Jakarta verbotenerweise auf das Dach des indonesischen Parlamentsgebäudes. Seine Botschaft waren drei Wörter, die sehr gut die Stimmung im Land zum Ausdruck brachten. Seine „Waffe“ war eine Farbspraydose für zwei US-Dollar. Pong Harjatmos Aktion stieß auf öffentliche Resonanz, weil klar war, dass es nicht mehr ausreicht, sich von der Politik abzuwenden und diesem ruhmreichen Gebäude lediglich den Mittelfinger zu zeigen. Die zahllosen Korruptionsaffären sind nur die Spitze eines Eisbergs. Harjatmo, ein einfacher Mann, überbrachte den Volks vertreter_innen eine Botschaft, die aus der Tiefe seines Gewissens kam: „Honest, Fair, Firm“. (... Waffen und Kämpfe sind untrennbar. Ich war immer überzeugt davon, dass die Effizienz einer Waffe vor allem davon abhängt, wie sie eingesetzt wird und nicht von der Kraft der sie nutzenden Person.

  20. Die Kunst des Scheiterns

    DEFF Research Database (Denmark)

    Juul, Jesper

    2014-01-01

    Menschen haben von Kindesbeinen an das Verlangen, Erfolge zu erzielen und Kompetenz zu erreichen. Computerspieler entscheiden sich jedoch fortlaufend für eine Aktivität, die oft und wiederholt zum Verlieren führen muss und ein taubes Gefühl der Unfähigkeit erzeugt. Im Kino, im Theatersaal und bei...

  1. Die Kunst des Scheiterns

    DEFF Research Database (Denmark)

    Juul, Jesper

    2014-01-01

    Menschen haben von Kindesbeinen an das Verlangen, Erfolge zu erzielen und Kompetenz zu erreichen. Computerspieler entscheiden sich jedoch fortlaufend für eine Aktivität, die oft und wiederholt zum Verlieren führen muss und ein taubes Gefühl der Unfähigkeit erzeugt. Im Kino, im Theatersaal und bei...

  2. Neustart des LHC CERN und die Beschleuniger : die Weltmaschine anschaulish erklärt

    CERN Document Server

    Hauschild, Michael

    2016-01-01

    Michael Hauschild führt den Leser dieses essentials zurück zu den Anfängen des CERN, des Europäischen Forschungszentrums für Teilchenphysik bei Genf; einem der faszinierendsten Forschungszentren überhaupt, zu seiner Geschichte, zu seinen Menschen und seinen Beschleunigern. Der Autor erläutert die Funktionsweise von Teilchenbeschleunigern und wie ausgehend von den ersten Ideen schließlich der Large Hadron Collider LHC gebaut wurde, der größte Teilchenbeschleuniger der Welt und die heutige Weltmaschine. Nach einer Pause von mehr als zwei Jahren wurde der LHC im Frühjahr 2015 wieder in Betrieb genommen, um mit höherer Energie als je zuvor die Geheimnisse der Natur zu enträtseln.

  3. Gene-environment interactions in Leber hereditary optic neuropathy.

    Science.gov (United States)

    Kirkman, Matthew Anthony; Yu-Wai-Man, Patrick; Korsten, Alex; Leonhardt, Miriam; Dimitriadis, Konstantin; De Coo, Ireneaus F; Klopstock, Thomas; Chinnery, Patrick Francis

    2009-09-01

    Leber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to confirm this to be the case. LHON has no treatment, so identifying environmental triggers is the key to disease prevention, whilst potentially revealing new mechanisms amenable to therapeutic manipulation. To address this issue, we conducted a large, multicentre epidemiological study of 196 affected and 206 unaffected carriers from 125 LHON pedigrees known to harbour one of the three primary pathogenic mtDNA mutations: m.3460G>A, m.11778G>A and m.14484T>C. A comprehensive history of exposure to smoking, alcohol and other putative environmental insults was collected using a structured questionnaire. We identified a strong and consistent association between visual loss and smoking, independent of gender and alcohol intake, leading to a clinical penetrance of 93% in men who smoked. There was a trend towards increased visual failure with alcohol, but only with a heavy intake. Based on these findings, asymptomatic carriers of a LHON mtDNA mutation should be strongly advised not to smoke and to moderate their alcohol intake.

  4. Genotype-phenotype correlations in Leber hereditary optic neuropathy.

    Science.gov (United States)

    Tońska, Katarzyna; Kodroń, Agata; Bartnik, Ewa

    2010-01-01

    Leber hereditary optic neuropathy (LHON), acute or subacute vision loss due to retinal ganglion cell death which in the long run leads to optic nerve atrophy is one of the most widely studied maternally inherited diseases caused by mutations in mitochondrial DNA. Although three common mutations, 11778G>A, 14484T>C or 3460G>A are responsible for over 90% of cases and affect genes encoding complex I subunits of the respiratory chain, their influence on bioenergetic properties of the cell is marginal and cannot fully explain the pathology of the disease. The following chain of events was proposed, based on biochemical and anatomical properties of retinal ganglion cells whose axons form the optic nerve: mitochondrial DNA mutations increase reactive oxygen species production in these sensitive cells, leading to caspase-independent apoptosis. As LHON is characterized by low penetrance and sex bias (men are affected about 5 times more frequently than women) the participation of the other factors-genetic and environmental-beside mtDNA mutations was studied. Mitochondrial haplogroups and smoking are some of the factors involved in the complex etiology of this disease.

  5. Leber's Hereditary Optic Neuropathy: The Mitochondrial Connection Revisited.

    Science.gov (United States)

    Abu-Amero, Khaled K

    2011-01-01

    Our current understanding of Leber's hereditary optic neuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.

  6. Idebenone: A Review in Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A

    2016-05-01

    Idebenone (Raxone(®)), a short-chain benzoquinone, is the only disease-specific drug approved to treat visual impairment in adolescents and adults with Leber's hereditary optic neuropathy (LHON), a rare genetic mitochondrial disease that causes rapid and progressive bilateral vision loss. The mechanism of action of idebenone involves its antioxidant properties and ability to act as a mitochondrial electron carrier. Idebenone overcomes mitochondrial complex I respiratory chain deficiency in patients with LHON by transferring electrons directly to mitochondrial complex III (by-passing complex I), thereby restoring cellular energy (ATP) production and re-activating inactive-but-viable retinal ganglion cells, which ultimately prevents further vision loss and promotes vision recovery. The approval of idebenone in the treatment of LHON was based on the overall data from a randomized clinical trial, a follow-up study and real-world data. Taken together, these studies provide convincing evidence that oral idebenone 900 mg/day for 24 weeks has persistent beneficial effects in preventing further vision impairment and promoting vision recovery in patients with LHON relative to the natural course of the disease. Therefore, idebenone is a valuable agent to treat visual impairment in adolescents and adults with LHON.

  7. Secondary post-geniculate involvement in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Rizzo, Giovanni; Tozer, Kevin R; Tonon, Caterina; Manners, David; Testa, Claudia; Malucelli, Emil; Valentino, Maria Lucia; La Morgia, Chiara; Barboni, Piero; Randhawa, Ruvdeep S; Ross-Cisneros, Fred N; Sadun, Alfredo A; Carelli, Valerio; Lodi, Raffaele

    2012-01-01

    Leber's hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (Poptic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.

  8. [Leber's hereditary optic neuropathy - phenotype, genetics, therapeutic options].

    Science.gov (United States)

    Gallenmüller, C; Klopstock, T

    2014-03-01

    Leber's hereditary optic neuropathy is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent severe bilateral loss of visual acuity within weeks or months. Males are much more likely to be affected than females, disease onset in most cases takes place between age 15 and 35 years. The disease is caused by point mutations in the mitochondrial DNA. The penetrance of the disease is incomplete, i.e., not all mutation carriers develop clinical symptoms. The phenotype is relatively uniform, but age at onset, severity and prognosis may vary even within the same family. Environmental and endocrine factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors are discussed to influence penetrance as well as interindividual and intrafamilial variability. However, only cigarette smoking and excessive alcohol consumption have been shown to trigger disease onset. The disease is characterised by a central visual field defect, impaired colour vision and fundoscopically a peripapillary microangiopathy in the acute phase. Most patients end up after some months with a severe visual loss below 0.1 and in most cases there is no significant improvement of visual acuity in the course. In rare cases patients experience a mostly partial visual recovery which depends on the type of mutation. For confirmation of the diagnosis a detailed ophthalmological examination with fundoscopy, family history and genetic analysis of the mitochondrial DNA is needed. To date, there is no proven causal therapy, but at early disease stages treatment with idebenone can be tried.

  9. Auditory function in individuals within Leber's hereditary optic neuropathy pedigrees.

    Science.gov (United States)

    Rance, Gary; Kearns, Lisa S; Tan, Johanna; Gravina, Anthony; Rosenfeld, Lisa; Henley, Lauren; Carew, Peter; Graydon, Kelley; O'Hare, Fleur; Mackey, David A

    2012-03-01

    The aims of this study are to investigate whether auditory dysfunction is part of the spectrum of neurological abnormalities associated with Leber's hereditary optic neuropathy (LHON) and to determine the perceptual consequences of auditory neuropathy (AN) in affected listeners. Forty-eight subjects confirmed by genetic testing as having one of four mitochondrial mutations associated with LHON (mt11778, mtDNA14484, mtDNA14482 and mtDNA3460) participated. Thirty-two of these had lost vision, and 16 were asymptomatic at the point of data collection. While the majority of individuals showed normal sound detection, >25% (of both symptomatic and asymptomatic participants) showed electrophysiological evidence of AN with either absent or severely delayed auditory brainstem potentials. Abnormalities were observed for each of the mutations, but subjects with the mtDNA11778 type were the most affected. Auditory perception was also abnormal in both symptomatic and asymptomatic subjects, with >20% of cases showing impaired detection of auditory temporal (timing) cues and >30% showing abnormal speech perception both in quiet and in the presence of background noise. The findings of this study indicate that a relatively high proportion of individuals with the LHON genetic profile may suffer functional hearing difficulties due to neural abnormality in the central auditory pathways.

  10. [Leber's hereditary optic neuropathy after head trauma: a case report].

    Science.gov (United States)

    Hayashi, Shintaro; Okamoto, Koichi

    2011-10-01

    A previously healthy 34-year-old man sustained multiple skull fractures in a traffic accident. Radiological findings and visual field examination did not detect any abnormality. Shortly after the accident, he noticed blurred vision in both eyes. Six months after the accident, he gradually developed disturbance of visual acuity in the right eye. His best corrected visual acuity (BCVA) was 0.8 OD and 1.2 OS and brain MRI did not show any abnormality, while Humphrey visual field analysis demonstrated right homonymous hemianopsia. Two months after the initial presentation, his BCVA showed 0.1 OD and 0.08 OS. Visual field examination suggested that both right homonymous hemianopsia and left blind spot had become enlarged. Mitochondrial DNA analysis demonstrated G11,778A mutation and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. A few reports have documented mild acute insult to the head or blunt optic trauma as triggers of optic neuropathy in subjects with LHON. Although, the precise mechanism of LHON following trauma remains unknown, it appears that an acute insult may be sufficient to precipitate neuropathy in the optic nerve already compromised by mitochondrial dysfunction. Asymptomatic carriers should be advised to avoid possible precipitating factors such as head trauma.

  11. Novel therapeutic approaches for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Iyer, Shilpa

    2013-03-01

    Many human childhood mitochondrial disorders result from abnormal mitochondrial DNA (mtDNA) and altered bioenergetics. These abnormalities span most of the mtDNA, demonstrating that there are no "unique" positions on the mitochondrial genome that when deleted or mutated produce a disease phenotype. This diversity implies that the relationship between mitochondrial genotype and clinical phenotype is very complex. The origins of clinical phenotypes are thus unclear, fundamentally difficult-to-treat, and are usually clinically devastating. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and mortality. Vitamin supplements and pharmacological agents have been used in isolated cases and clinical trials, but the efficacy of these interventions is unclear. In spite of recent advances in the understanding of the pathogenesis of mitochondrial diseases, a cure remains elusive. An optimal cure would be gene therapy, which involves introducing the missing gene(s) into the mitochondria to complement the defect. Our recent research results indicate the feasibility of an innovative protein-transduction ("protofection") technology, consisting of a recombinant mitochondrial transcription factor A (TFAM) that avidly binds mtDNA and permits efficient targeting into mitochondria in situ and in vivo. Thus, the development of gene therapy for treating mitochondrial disease offers promise, because it may circumvent the clinical abnormalities and the current inability to treat individual disorders in affected individuals. This review aims to focus on current treatment options and future therapeutics in mitochondrial disease treatment with a special emphasis on Leber's hereditary optic neuropathy.

  12. Evidence for retrochiasmatic tissue loss in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Barcella, Valeria; Rocca, Maria A; Bianchi-Marzoli, Stefania; Milesi, Jacopo; Melzi, Lisa; Falini, Andrea; Pierro, Luisa; Filippi, Massimo

    2010-12-01

    Patients with Leber's hereditary optic neuropathy (LHON) have loss of central vision with severe damage of small-caliber fibers of the papillomacular bundle and optic nerve atrophy. The aim of this study was to define the presence and topographical distribution of brain grey matter (GM) and white matter (WM) injury in LHON patients using voxel-based morphometry (VBM). The correlation of such changes with neuro-ophthalmologic findings and measurements of peripapillary retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) was also assessed. Dual-echo and fast-field echo scans were acquired from 12 LHON patients and 12 matched controls. VBM analysis was performed using SPM5 and an ANCOVA model. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary RNFL thickness measurements were obtained in all the patients. Compared with controls, average peripapillary RNFL thickness was significantly decreased in LHON patients. LHON patients also had significant reduced GM volume in the bilateral primary visual cortex, and reduced WM volume in the optic chiasm, optic tract, and several areas located in the optic radiations (OR), bilaterally. Visual cortex and OR atrophy were significantly correlated with average and temporal peripapillary RNFL thickness (P optic nerve or to local mitochondrial dysfunction.

  13. Safety and efficacy of gene transfer for Leber's congenital amaurosis.

    Science.gov (United States)

    Maguire, Albert M; Simonelli, Francesca; Pierce, Eric A; Pugh, Edward N; Mingozzi, Federico; Bennicelli, Jeannette; Banfi, Sandro; Marshall, Kathleen A; Testa, Francesco; Surace, Enrico M; Rossi, Settimio; Lyubarsky, Arkady; Arruda, Valder R; Konkle, Barbara; Stone, Edwin; Sun, Junwei; Jacobs, Jonathan; Dell'Osso, Lou; Hertle, Richard; Ma, Jian-xing; Redmond, T Michael; Zhu, Xiaosong; Hauck, Bernd; Zelenaia, Olga; Shindler, Kenneth S; Maguire, Maureen G; Wright, J Fraser; Volpe, Nicholas J; McDonnell, Jennifer Wellman; Auricchio, Alberto; High, Katherine A; Bennett, Jean

    2008-05-22

    Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA. Copyright 2008 Massachusetts Medical Society.

  14. CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype.

    Science.gov (United States)

    Burnight, E R; Wiley, L A; Drack, A V; Braun, T A; Anfinson, K R; Kaalberg, E E; Halder, J A; Affatigato, L M; Mullins, R F; Stone, E M; Tucker, B A

    2014-07-01

    Mutations in CEP290 are the most common cause of Leber congenital amaurosis (LCA), a severe inherited retinal degenerative disease for which there is currently no cure. Autosomal recessive CEP290-associated LCA is a good candidate for gene replacement therapy, and cells derived from affected individuals give researchers the ability to study human disease and therapeutic gene correction in vitro. Here we report the development of lentiviral vectors carrying full-length CEP290 for the purpose of correcting the CEP290 disease-specific phenotype in human cells. A lentiviral vector containing CMV-driven human full-length CEP290 was constructed. Following transduction of patient-specific, iPSC-derived, photoreceptor precursor cells, reverse transcriptase-PCR analysis and western blotting revealed vector-derived expression. As CEP290 is important in ciliogenesis, the ability of fibroblast cultures from CEP290-associated LCA patients to form cilia was investigated. In cultures derived from these patients, fewer cells formed cilia compared with unaffected controls. Cilia that were formed were shorter in patient-derived cells than in cells from unaffected individuals. Importantly, lentiviral delivery of CEP290 rescued the ciliogenesis defect. The successful construction and viral transfer of full-length CEP290 brings us closer to the goal of providing gene- and cell-based therapies for patients affected with this common form of LCA.

  15. The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Amati-Bonneau, Patrizia; Safiedeen, Zainab; Prunier-Mirebeau, Delphine; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Gueguen, Naïg; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Ferré, Marc; Bris, Céline; Kouassi Nzoughet, Judith; Bocca, Cinzia; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Lenaers, Guy; Martinez, M Carmen; Procaccio, Vincent; Reynier, Pascal

    2016-09-15

    Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q(2)cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as

  16. Vision improvement in a Taiwanese (Han Chinese) family with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Lin, Hong-Zin; Pang, Cheng-Yoong; Chen, Shee-Ping; Tsai, Rong-Kung

    2012-12-01

    In this report, we describe a Taiwanese (Han Chinese) family with Leber's hereditary optic neuropathy. The family carried a mitochondrial DNA mutation (mtDNA m.14484T>C) associated with spontaneous visual improvement. A 15-year-old boy from this family was diagnosed with Leber's hereditary optic neuropathy 6 months after losing his vision. His vision recovered after 8 months of supportive treatment. His mother, older brother, and two sisters also had the same mutation and had previously experienced vision loss. In this family, there was no male predominance.

  17. Novel use of idebenone in Leber's hereditary optic neuropathy in Hong Kong.

    Science.gov (United States)

    Cheng, S W; Ko, C H; Yau, S K; Mak, Chloe; Yuen, Y F; Lee, C Y

    2014-10-01

    We report a case of a young Chinese male presenting with sequential, painless, bilateral visual loss in Hong Kong. He was diagnosed to have Leber's hereditary optic neuropathy with genetic workup showing G11778A mutation with over 80% heteroplasmy. He was started on idebenone treatment 11 months after onset of the binocular disease. To our best knowledge, this is the first case of Leber's hereditary optic neuropathy treated with idebenone in Hong Kong. The recent evidence of the diagnosis and treatment of this devastating disease is reviewed.

  18. "Are you human?" Plädoyer für eine kommunikationstheoretische Fundierung interpretativer Forschung an den Grenzen des Sozialen

    Directory of Open Access Journals (Sweden)

    Florian Muhle

    2016-01-01

    Full Text Available Im Zentrum von Soziologie im Allgemeinen und interpretativer Sozialforschung im Besonderen stehen in der Regel unhinterfragt Menschen und ihre Weltdeutungen. In aktuellen sozialtheoretischen Debatten und empirischen Forschungen wird die Zentralstellung des Menschen in soziologischen Analysen jedoch zunehmend infrage gestellt. Vor diesem Hintergrund geht der vorliegende Beitrag der Frage nach, wie Sozialität jenseits der Fixierung auf menschliche Akteur/innen konzipiert werden kann und wie sich Grenzziehungen zwischen Sozialem und Nicht-Sozialem in gegenstandsangemessener Perspektive untersuchen lassen. Hierzu werden in Auseinandersetzung mit konkurrierenden Überlegungen (insbesondere der Akteur-Netzwerk-Theorie und Ansätzen, die subjektive Sichtweisen von Akteuren und Akteurinnen fokussieren, eine kommunikationstheoretische Perspektive auf die Grenzen des Sozialen und eine darauf aufbauende Methodologie entwickelt, die ergebnisoffene Forschung an und zu den Grenzen des Sozialen anleiten können. Wie sich entsprechende empirische Analysen konkret umsetzen lassen, wird exemplarisch an einem Fall der Mensch-Maschine-Kommunikation in einer virtuellen Welt gezeigt. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1601183

  19. Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?

    NARCIS (Netherlands)

    Nemes, A.; Coo, I.F.M. de; Spruijt, L.; Smeets, H.J.; Chinnery, P.F.; Soliman, O.I.; Geleijnse, M.L.; Cate, FJ Ten

    2008-01-01

    PURPOSE: Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties

  20. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background.

    NARCIS (Netherlands)

    Hudson, G.; Carelli, V.; Spruijt, L.; Gerards, M.; Mowbray, C.; Achilli, A.; Pyle, A.; Elson, J.; Howell, N.; Morgia, C. La; Valentino, M.L.; Huoponen, K.; Savontaus, M.L.; Nikoskelainen, E.; Sadun, A.A.; Salomao, S.R.; Belfort Jr, R.; Griffiths, P.; Man, P.Y.; Coo, R.F. de; Horvath, R.; Zeviani, M.; Smeets, H.J.M.; Torroni, A.; Chinnery, P.F.

    2007-01-01

    Leber hereditary optic neuropathy (LHON) is due primarily to one of three common point mutations of mitochondrial DNA (mtDNA), but the incomplete penetrance implicates additional genetic or environmental factors in the pathophysiology of the disorder. Both the 11778G-->A and 14484T-->C LHON mutation

  1. Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation.

    NARCIS (Netherlands)

    Korsten, A.; Coo, I.F.M. de; Spruijt, L.; Wit, L.E. de; Smeets, H.J.M.; Sluiter, W.

    2010-01-01

    Ninety-five percent of Leber hereditary optic neuropathy (LHON) patients carry a mutation in one out of three mtDNA-encoded ND subunits of complex I. Penetrance is reduced and more male than female carriers are affected. To assess if a consistent biochemical phenotype is associated with LHON express

  2. LEBERS HEREDITARY OPTIC NEUROPATHY - CORRELATIONS BETWEEN MITOCHONDRIAL GENOTYPE AND VISUAL OUTCOME

    NARCIS (Netherlands)

    OOSTRA, RJ; BOLHUIS, PA; WIJBURG, FA; ZORNENDE, G; BLEEKERWAGEMAKERS, EM

    1994-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with mitochondrial DNA (mtDNA) mutations. We describe the distribution of seven different mtDNA mutations and the clinical findings in 334 LHON patients belonging to 29 families. Mutations described only in LHON

  3. Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?

    NARCIS (Netherlands)

    Nemes, A.; Coo, I.F.M. de; Spruijt, L.; Smeets, H.J.; Chinnery, P.F.; Soliman, O.I.; Geleijnse, M.L.; Cate, FJ Ten

    2008-01-01

    PURPOSE: Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties du

  4. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.

    NARCIS (Netherlands)

    Hollander, A.I. den; Koenekoop, R.K.; Mohamed, M.D.; Arts, H.H.; Boldt, K.; Towns, K.V.; Sedmak, T.; Beer, M. de; Nagel-Wolfrum, K.; McKibbin, M.; Dharmaraj, S.; Lopez, I.; Ivings, L.; Williams, G.A.; Springell, K.; Woods, C.G.; Jafri, H.; Rashid, Y.; Strom, T.M.; Zwaag, B. van der; Gosens, I.; Kersten, F.F.J.; Wijk, E. van; Veltman, J.A.; Zonneveld, M.N.; Beersum, S.E.C. van; Maumenee, I.H.; Wolfrum, U.; Cheetham, M.E.; Ueffing, M.; Cremers, F.P.M.; Inglehearn, C.F.; Roepman, R.

    2007-01-01

    Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We dete

  5. Influence of mutation type on clinical expression of Leber hereditary optic neuropathy.

    NARCIS (Netherlands)

    Spruijt, L.; Kolbach, D.; Coo, R.F. de; Plomp, A.S.; Bauer, N.J.; Smeets, H.J.M.; Die-Smulders, C.E.M. de

    2006-01-01

    PURPOSE: The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. The prevalence of LHON in the Dutch population was determined. DESIGN: Observational

  6. Involvement of LCA5 in Leber congenital amaurosis and retinitis pigmentosa in the Spanish population

    NARCIS (Netherlands)

    Corton, M.; Avila-Fernandez, A.; Vallespin, E.; Lopez-Molina, M.I.; Almoguera, B.; Martin-Garrido, E.; Tatu, S.D.; Khan, M.I.; Blanco-Kelly, F.; Riveiro-Alvarez, R.; Brion, M.; Garcia-Sandoval, B.; Cremers, F.P.M.; Carracedo, A.; Ayuso, C.

    2014-01-01

    OBJECTIVE: We aimed to identify novel genetic defects in the LCA5 gene underlying Leber congenital amaurosis (LCA) in the Spanish population and to describe the associated phenotype. DESIGN: Case series. PARTICIPANTS: A cohort of 217 unrelated Spanish families affected by autosomal recessive or isol

  7. Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa.

    NARCIS (Netherlands)

    Wang, H.; Hollander, A.I. den; Moayedi, Y.; Abulimiti, A.; Li, Yumei; Collin, R.W.J.; Hoyng, C.B.; Lopez, I.; Bray, M.; Lewis, R.A.; Lupski, J.R.; Mardon, G.; Koenekoop, R.K.; Chen, R.

    2009-01-01

    Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are the most common hereditary causes of visual impairment in infants and children. Using homozygosity mapping, we narrowed down the critical region of the LCA3 locus to 3.8 Mb between markers D14S1022 and D14S1005. By direct

  8. Secondary post-geniculate involvement in Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Giovanni Rizzo

    Full Text Available Leber's hereditary optic neuropathy (LHON is characterized by retinal ganglion cell (RGC degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR. Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05 and healthy subjects (P<0.01 in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05 and lack of recovery of visual acuity (B = 0.060; P<0.01. Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers in the LHON LGN associated with extremely severe axonal loss (99% in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons.

  9. Substancinė Dievo formos kaita kaip meninė Visybės reprezentacija (pagal Thomo Manno romaną Juozapas ir jo broliai | Substanziales Werden der Form Gottes als künstleriche Repräsentation des Ganzen (nach der Tetralogie Joseph und seine Brüder von Thomas Mann

    Directory of Open Access Journals (Sweden)

    Juldita Nagliuvienė

    2004-01-01

    Full Text Available Anhand der Polemik zwischen der Totalitätsphänomenologie von Emmanuel Lévinas und der Selbstphänomenologie von Ernst Bloch werden in diesem Artikel die Erscheinungen Gottes, mit denen sich das patriarchalische Subjekt in die Beziehung eingetreten ist, analysiert. Vor allem aktualisiert man den substanziellen Inhalt der künstlerichen Gottesform, deren Wurzeln in der primitiven archaischen Ikonographie der Babylonier und der Ägypter liegen. Das Bild Gottes verwandelt sich in der Situation der Begegnung aus der Substanz des unförmigen Steines, die pfallische Intentionen des Helden akzentuiert, in die symbiotische Form eines Menschentieres (oder Gottes-Tieres, das als Fremde Gott auf der Ebene der Erzählung funktioniert und den Numenaspekt durch die künstliche Form der animalischen Gottheit in sich trägt. Durch die Maske des Tieres strebt der göttliche Begegnungspartner, der das Werden Gottes aktualisiert, nach der Verwandlung in die Gestalt eines sterbenden und wieder auferstehenden Menschen-Gottes, der den sündigen Menschen erlösen kann. In der Tetralogie von Thomas Mann existiert diese Ebene des Nochnicht-gewordenen-Gottes als utopische Stufe der vollkommenen Beziehungen zwischen Mensch und Gott. Die Begegnung zwischen dem tierischen Gott und dem Helden geschieht im Roman in der Traumsphäre, die den Dialog zwischen dem Kunstding und dem Menschen möglich macht. Auf der Traumebene wird der Prozess der Metamorphose einer Gottheit dargestellt, aber sie erscheint als ein schon verwandeltes Wesen, das die Antropomorphie des Erlösungsprinzips aufnimmt, und dem Helden erst im bewussten Zustand begegnet.

  10. Irene Berkel (Hg.: Postsexualität. Zur Transformation des Begehrens. Gießen: Psychosozial-Verlag 2009.

    Directory of Open Access Journals (Sweden)

    Julia Jäckel

    2009-11-01

    Full Text Available Die Autor/-innen des vorliegenden Sammelbandes, die großteils aus psychologischen und kulturtheoretischen Kontexten stammen, befassen sich mit dem Wandel der Sexualität, der Sexualisierung des öffentlichen Raumes, mit neuen Reproduktionstechniken und dem Phänomen der Ent-Sexualisierung. Dabei liegt ein Schwerpunkt auf der Frage nach den Auswirkungen dieses Wandels auf Gesellschaftsstrukturen, Paarbeziehungen und den Menschen als begehrendes Subjekt.The authors, primarily working in the context of psychology and cultural studies, examine the transformation of sexuality, the sexualization of public space, new reproductive technologies, and the phenomenon of de-sexualization. Their emphasis is placed on the question as to the effect of this transformation on social structures, relationships between couples, and people as desiring subjects.

  11. Leber congenital amaurosis: genes, proteins and disease mechanisms.

    Science.gov (United States)

    den Hollander, Anneke I; Roepman, Ronald; Koenekoop, Robert K; Cremers, Frans P M

    2008-07-01

    Leber congenital amaurosis (LCA) is the most severe retinal dystrophy causing blindness or severe visual impairment before the age of 1 year. Linkage analysis, homozygosity mapping and candidate gene analysis facilitated the identification of 14 genes mutated in patients with LCA and juvenile retinal degeneration, which together explain approximately 70% of the cases. Several of these genes have also been implicated in other non-syndromic or syndromic retinal diseases, such as retinitis pigmentosa and Joubert syndrome, respectively. CEP290 (15%), GUCY2D (12%), and CRB1 (10%) are the most frequently mutated LCA genes; one intronic CEP290 mutation (p.Cys998X) is found in approximately 20% of all LCA patients from north-western Europe, although this frequency is lower in other populations. Despite the large degree of genetic and allelic heterogeneity, it is possible to identify the causative mutations in approximately 55% of LCA patients by employing a microarray-based, allele-specific primer extension analysis of all known DNA variants. The LCA genes encode proteins with a wide variety of retinal functions, such as photoreceptor morphogenesis (CRB1, CRX), phototransduction (AIPL1, GUCY2D), vitamin A cycling (LRAT, RDH12, RPE65), guanine synthesis (IMPDH1), and outer segment phagocytosis (MERTK). Recently, several defects were identified that are likely to affect intra-photoreceptor ciliary transport processes (CEP290, LCA5, RPGRIP1, TULP1). As the eye represents an accessible and immune-privileged organ, it appears to be uniquely suitable for human gene replacement therapy. Rodent (Crb1, Lrat, Mertk, Rpe65, Rpgrip1), avian (Gucy2D) and canine (Rpe65) models for LCA and profound visual impairment have been successfully corrected employing adeno-associated virus or lentivirus-based gene therapy. Moreover, phase 1 clinical trials have been carried out in humans with RPE65 deficiencies. Apart from ethical considerations inherently linked to treating children, major

  12. Gene-Based Therapies for Leber Hereditary Optic Neuropathy. Hype or Hope?

    Science.gov (United States)

    Mackey, David A; Kearns, Lisa S; Hewitt, Alex W

    2016-01-01

    Leber hereditary optic neuropathy has now joined Leber congenital amaurosis in the list of genetic eye diseases undergoing gene therapy clinical trials. Although a dramatic response to treatment would be welcome, a minor improvement in vision is a major challenge in efficacy assessment, given this may occur spontaneously as part of the natural history of minor recovery in some patients. Thus, we must await the outcome of adequately powered clinical trials to know if the treatment is effective, particularly given the likely high cost of such therapeutic interventions in the future. We need global cooperation to ensure that the most suitable patients are enrolled in these trials and that support is provided for participants who need to travel from the Asia-Pacific region to Europe or North America if there are no local arms of these trials.

  13. Leber's hereditary optic neuropathy mutations associated with infantile-onset myoclonic epilepsy.

    Science.gov (United States)

    Frye, Richard E

    2011-06-01

    Epilepsy syndromes with onset in the first year of life, especially when they include myoclonic features, have special significance since they are associated with long-term developmental and neurological abnormalities. Dravet's severe myoclonic epilepsy in infancy is especially interesting as it is associated with fever-provoked seizures and mutations in the alpha subunit of the sodium channel (SCN1A) in about one-third of the cases. Here, we report 2 children who had clinical features of severe myoclonic epilepsy of infancy without mutations in the SCN1A gene who were found to have mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy. These 2 children demonstrated markers of mitochondrial dysfunction, drug-resistant epilepsy, and dysfunction of nonneurological systems. These cases demonstrate that mitochondrial DNA mutations, especially those associated with Leber's hereditary optic neuropathy, should be considered in cases of myclonic epilepsy starting in infancy, especially when mutations in the SCN1A gene are not found.

  14. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

    DEFF Research Database (Denmark)

    Rosenberg, Niels Thomas; Nørby, Søren; Schwartz, Marianne

    2016-01-01

    PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from a nat...... of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines....

  15. Magnetic resonance findings in the pregeniculate visual pathways in Leber hereditary optic neuropathy.

    Science.gov (United States)

    van Westen, Danielle; Hammar, Björn; Bynke, Gunnel

    2011-03-01

    Two relatives, a 61-year-old man and the 21-year-old grandson of his sister, suffered from bilateral visual loss and were diagnosed with Leber hereditary optic neuropathy. In both cases, the diagnosis was molecularly confirmed with the 11778 mitochondrial mutation. MRI showed increased T2 signal not only in the optic nerves and chiasm but also in the optic tracts, extending to the lateral geniculate bodies. To our knowledge, the latter finding has not been described previously.

  16. Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation.

    Science.gov (United States)

    Rinalduzzi, Steno; Cipriani, Anna Maria; Accornero, Neri

    2012-04-01

    We describe a 43-year-old patient who experienced visual loss 4 years after beginning antiepileptic therapy with topiramate. Ophthalmological and neurological examinations led to a preliminary diagnosis of bilateral toxic optic neuritis. Mitochondrial genome sequence analysis detected a Leber hereditary optic neuropathy 11778G>A mutation. The possibility that topiramate might favor a conversion disease, alerts physicians to seek a history of blindness in patients undergoing chronic antiepileptic therapy.

  17. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Klopstock, Thomas; Yu-Wai-Man, Patrick; Dimitriadis, Konstantinos; Rouleau, Jacinthe; Heck, Suzette; Bailie, Maura; Atawan, Alaa; Chattopadhyay, Sandip; Schubert, Marion; Garip, Aylin; Kernt, Marcus; Petraki, Diana; Rummey, Christian; Leinonen, Mika; Metz, Günther; Griffiths, Philip G; Meier, Thomas; Chinnery, Patrick F

    2011-09-01

    Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

  18. Two pedigrees analysis of Leber disease%Leber病两家系分析

    Institute of Scientific and Technical Information of China (English)

    郑露; 胡可; 成进魁; 杨亚利; 胡维琨

    2013-01-01

    目的 探讨Leber病的临床特征和基因诊断方法.方法 采用聚合酶链反应,对两家系2例先证者目的DNA进行扩增,并基因测序,明确突变类型.结果 2例先证者均为Leber病患者,基因突变类型为G11778A.结论 基因检测明确两家系2例Leber病患者诊断.%Objective To investigate the clinical features of Lebefs hereditary optic neuropathy and its genetic diagnosis. Methods mtDNA was isolated from leukocyte of two probands. Gene was amplified by PCR. The type of gene mutation was determined by direct sequencing. Results Two pedigrees were the patients with Leber disease and the type of gene mutation was G11778A. Conclusion Leber disease was diagnosed as Leber disease by gene examination.

  19. X-inactivation patterns in female Leber`s hereditary optic neuropathy patients do not support a strong X-linked determinant

    Energy Technology Data Exchange (ETDEWEB)

    Pegoraro, E.; Hoffman, E.P. [Univ. of Pittsburgh School of Medicine, PA (United States); Carelli, V.; Cortelli, P. [Univ. of Bologna (Italy)] [and others

    1996-02-02

    Leber`s hereditary optic neuropathy (LHON) accounts for about 3% of the cases of blindness in young adult males. The underlying mitochondrial pathogenesis of LHON has been well studied, with specific mitochondrial DNA (mtDNA) mutations of structural genes described and well characterized. However, enigmatic aspects of the disease are not explained by mutation data, such as the higher proportion of affected males, the later onset of the disease in females, and the presence of unaffected individuals with a high proportion of mutant mtDNA. A hypothesis which has been put forward to explain the unusual disease expression is a dual model of mtDNA and X-linked nuclear gene inheritance. If a nuclear X-linked modifier gene influences the expression of the mitochondrial-linked mutant gene then the affected females should be either homozygous for the nuclear determinant, or if heterozygous, lyonization should favor the mutant X. In order to determine if an X-linked gene predisposes to LHON phenotype we studied X-inactivation patterns in 35 females with known mtDNA mutations from 10 LHON pedigrees. Our results do not support a strong X-linked determinant in LHON cause: 2 of the 10 (20%) manifesting carriers showed skewing of X-inactivation, as did 3 of the 25 (12%) nonmanifesting carriers. 39 refs., 2 figs., 1 tab.

  20. ’El Šaddaj kaip savimąstą paneigiantis ir gyvenimą transformuojantis principas. Kintančio Dievo idėja Thomo Manno tetralogijoje Juozapas ir jo broliai | ’El Shaddaj als das Selbst-Denken negierendes und Leben transformierendes Prinzip. Die Idee des sich-wandelnden Gottes in der Tetralogie von Thomas Mann Joseph und seine Brüder

    Directory of Open Access Journals (Sweden)

    Juldita Nagliuvienė

    2005-01-01

    Full Text Available Auf dem Hintergrund dieses Vortrags steht die theologische Kritik, die von Anfang an sich mit dem biblischen Werk von Thomas Mann beschäftigte und den modernen Roman als den Gegenstand der theologischen Untersuchung völlig negierte. Die Möglichkeit der theologischen Auslegung in einem Beispiel der polyphonischen schöngeistigen Literatur wird nicht nur mit der analogia entis Konzeption bestätigt, sondern auch in der Realisation des “Fremden Gottes”, der als das Schlüsselwort El Schaddaj im Roman auftrit und der in einer apriorischen Beziehung mit dem Menschen die Ebene des ganz Anderen konstituiert. Eben dadurch gewinnt das biblische Werk des deutschen Modernisten eine theologische Prägung, die durch die Gnadenwahl-Theorie (Die Verneinung einer Verneinung Karl Barths, durch die Idee der Offenbarung als einer Wandlung Gottes von Franz Rosenzweig und durch die Konzeption des Heiligen von Rudorf Otto analysieren werden kann.

  1. Des tuiles, des toits et des couleurs

    OpenAIRE

    Bonnot, Thierry

    2007-01-01

    La Bourgogne est une des régions françaises dont l’image de marque est le plus imprégnée par la notion de tradition. Elle est présentée comme un terroir où il fait bon vivre, où la gastronomie demeure à travers les siècles une valeur de base, où les paysages sont majestueux et où la gloire passée est sans cesse rappelée par de somptueux monuments. Parmi quelques emblèmes, l’hôtel-Dieu de Beaune et ses toitures de tuiles colorées sont très souvent mobilisés pour représenter ces valeurs « tradi...

  2. Analyses of functional brain connectivity; Untersuchungen zur funktionellen Konnektivitaet des Gehirns

    Energy Technology Data Exchange (ETDEWEB)

    Stephan, K.E.

    2003-03-01

    This dissertation includes two independent studies that investigate two complementary aspects of functional connectivity in the Macaque and the human brain. In the first study, a computational meta-analysis of published electrophysiological data on context-independent functional brain connectivity was conducted by means of three independent methods. The second study investigated the effects of the atypical antipsychotic substance olanzapine on the functional connectivity of the cerebellum during a simple motor task (self-paced finger tapping). Six schizophrenic patients and six control subjects matched for age and sex were investigated by functional magnetic resonance imaging (fMRI) twice. This study provided the first experimental data on the effects of atypical antipsychotic agents on functional brain connectivity and demonstrated pronounced olanzapine-dependent changes of functional couplings between cerebellum, thalamus, and prefrontal cortex. (orig.) [German] In der hier vorgelegten Arbeit werden zwei komplementaere Aspekte der funktionellen Konnektivitaet - im Gehirn des Makaken und Menschen anhand zweier separater Studien untersucht. In der ersten Studie wurde mittels dreier unabhaengiger Methoden eine Metaanalyse publizierter elektrophysiologischer Daten zur kontextunabhaengigen funktionellen Konnektivitaet des Makakenkortex durchgefuehrt. Diese Studie erbrachte damit zum ersten Mal den Nachweis einer funktionellen Small World-Netzwerkstruktur des Primatenkortex. In der zweiten Studie wurde der Effekt des atypischen Neuroleptikums Olanzapin auf die funktionelle Konnektivitaet des Zerebellums im Kontext einer einfachen motorischen Aufgabe (selbstgesteuertes Fingertrapping) untersucht. Sechs schizophrene Patienten, die Neuroleptika-naiv bzw. -entwoehnt waren, sowie sechs alters- und geschlechtsentprechende Kontrollprobanden wurden im Abstand von jeweils drei Wochen mit funktioneller Magnetresonanztomografie (fMRT) untersucht. Diese Studie lieferte die ersten

  3. Leber 遗传性视神经病变研究进展和挑战%Research progress of Leber hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    张阿梅; 姚永刚

    2013-01-01

    Leber hereditary optic neuropathy (LHON; MIM 535000) is one of the most common mitochondrial diseases, with a clinical manifestation of painless, acute or sub-acute bilateral visual loss in young adults leading to blindness and central scotoma. Over 95% of LHON patients were caused by one of three primary mtDNA mutations (m.H778G>A, m.3460G>A and m.14484T>C). Incomplete penetrance and gender bias are two riddles of this disease. Here we summarized recent research progress of LHON, with a focus on the molecular pathogenic mechanisms, clinical features, in vitro experiments and animal models, and prevention and treatment of LHON. In particular, we presented the main findings and challenges in our recent efforts to decipher genetic susceptibility and mechanism of LHON in Chinese patients.%Leber 遗传性视神经病变(Leber hereditary optic neuropathy,LHON; MIM535000)是最典型的线粒体遗传病之一,主要由线粒体DNA (Mitochondrial DNA,mtDNA)3 个原发突变(Primary mutation,m.11778G>A、m.3460G>A 和m.14484T>C)引起.患者表现为无痛性双侧视力下降或丧失,主要易感人群为青壮年男性.不完全外显(Incomplete penetrance)和性别偏好(Gender bias)是该病亟待解决的两大难题,目前尚无有效的预防及治疗措施.文章对近年来LHON 的分子发病机制、临床症状及特点、体外实验和动物模型研究、预防及治疗等方面的研究进展进行综述,并集中介绍了我们近期对于我国LHON 患者的研究结果.

  4. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Giordano, Carla; Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N; D'Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F; Zeviani, Massimo; Salomao, Solange R; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A; Tancredi, Andrea; Mancini, Massimiliano; d'Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro; Carelli, Valerio

    2014-02-01

    Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.

  5. Evaluation of Leber's hereditary optic neuropathy patients prior to a gene therapy clinical trial

    Science.gov (United States)

    Yang, Shuo; Yang, Hong; Ma, Si-qi; Wang, Shuai-shuai; He, Heng; Zhao, Min-jian; Li, Bin

    2016-01-01

    Abstract Gene therapy may be a promising approach for the treatment of Leber hereditary optic neuropathy. The aim of this study was to evaluate patients with this condition who were recruited into an upcoming gene therapy clinical trial and to assess any changes in the detection parameters to provide support for the clinical trial. Sixteen patients with Leber hereditary optic neuropathy were evaluated using visual function tests 12 months before the initiation of gene therapy. Then, the results of visual acuity (VA), visual field (VF), RNFL (retinal nerve fiber layer) thickness, and Pattern-reversal Visual evoked potential (PR-VEP) were compared and analyzed. A total of 32 eyes of 16 patients were evaluated. Based on the best-corrected visual acuity (BCVA), 24 eyes were relatively stable compared with the baseline evaluation, and 8 eyes had significant changes, including 5 eyes that showed improvement and 3 eyes that showed impairment. In all eyes, the changes in the best-corrected visual acuity were significantly correlated with the changes in the visual field index (VFI), mean defect (MD), and P100 of the visual evoked potential. In the eyes with relatively stable BCVA and those with an obvious improvement in the BCVA, only the visual mean defect showed a significant change; the other indicators were not significantly different. Aside from the patients showing a tendency of spontaneous improvement, the others were in accordance with the requirement. The effects of Leber hereditary optical neuropathy (LHON) gene therapy should be evaluated primarily based on visual acuity. Additionally, visual field, neural fiber thickness, and electrophysiology should be considered in the evaluation. PMID:27749593

  6. The Mitochondrial DNA Mutation at Position 11778 in Chinese Families with Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    We amplified the 340 bp of mitochondrial DMA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I . After amplification and digestion of SfaN I , two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I . We studied the mtDNAs of the patients with Leber's hereditary optic neur...

  7. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

    DEFF Research Database (Denmark)

    Rosenberg, Thomas; Nørby, Søren; Schwartz, Marianne

    2016-01-01

    PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from....... The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population. CONCLUSIONS: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those...

  8. Whole mitochondrial genome analysis in South Indian patients with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Saikia, Bibhuti Ballav; Dubey, Sushil Kumar; Shanmugam, Mahesh Kumar; Sundaresan, Periasamy

    2016-10-28

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) associated neurodegenerative disorder of retinal ganglion cells. In this study, whole mitochondrial genome sequencing of 75 LHON patients and 40 controls was performed to identify the mutation frequency and haplogroup background of South Indian population. Analysis of mtDNA revealed 559 different variants in LHON patients, including 7 pathogenic mutations, 30 private, and 22 other disease associated variants. A significantly higher (p=0.0008) overall variation load per individual was noted among LHON patients versus controls. We reported for the first time, the association of M haplogroup (p=0.028) with LHON in this cohort.

  9. Atypical presentation of Leigh syndrome associated with a Leber hereditary optic neuropathy primary mitochondrial DNA mutation.

    Science.gov (United States)

    Fruhman, Gary; Landsverk, Megan L; Lotze, Timothy E; Hunter, Jill V; Wangler, Michael F; Adesina, Adekunle M; Wong, Lee-Jun C; Scaglia, Fernando

    2011-06-01

    Leber hereditary optic neuropathy (LHON) is caused by point mutations in mitochondrial DNA (mtDNA), and is characterized by bilateral, painless sub-acute visual loss that develops during the second decade of life. Here we report the case of a five year old girl who presented with clinical and neuroradiological findings reminiscent of Leigh syndrome but carried a mtDNA mutation m.11778G>A (p.R340H) in the MTND4 gene usually observed in patients with LHON. This case is unusual for age of onset, gender, associated neurological findings and evolution, further expanding the clinical spectrum associated with primary LHON mtDNA mutations.

  10. Mouse mtDNA mutant model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Lin, Chun Shi; Sharpley, Mark S; Fan, Weiwei; Waymire, Katrina G; Sadun, Alfredo A; Carelli, Valerio; Ross-Cisneros, Fred N; Baciu, Peter; Sung, Eric; McManus, Meagan J; Pan, Billy X; Gil, Daniel W; Macgregor, Grant R; Wallace, Douglas C

    2012-12-04

    An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress.

  11. m.3635G>A mutation as a cause of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Kodroń, Agata; Krawczyński, Maciej R; Tońska, Katarzyna; Bartnik, Ewa

    2014-07-01

    Over 90% of Leber's hereditary optic neuropathy (LHON) is caused by one of three mtDNA mutations (m.11778A>G, m.3460G>A, m.14484T>C). The remaining cases are due to rare mutations in different genes encoding subunits of the respiratory chain. The proband is a 17-year-old male with symptoms of optic nerve atrophy. No common LHON mutations were found, but detailed sequencing identified a rare, homoplasmic mutation m.3635G>A in the ND1 gene.

  12. Identification of small molecules that improve ATP synthesis defects conferred by Leber's hereditary optic neuropathy mutations.

    Science.gov (United States)

    Datta, Sandipan; Tomilov, Alexey; Cortopassi, Gino

    2016-09-01

    Inherited mitochondrial complex I mutations cause blinding Leber's hereditary optic neuropathy (LHON), for which no curative therapy exists. A specific biochemical consequence of LHON mutations in the presence of trace rotenone was observed: deficient complex I-dependent ATP synthesis (CIDAS) and mitochondrial O2 consumption, proportional to the clinical severity of the three primary LHON mutations. We optimized a high-throughput assay of CIDAS to screen 1600 drugs to 2, papaverine and zolpidem, which protected CIDAS in LHON cells concentration-dependently. TSPO and cAMP were investigated as protective mechanisms, but a conclusive mechanism remains to be elucidated; next steps include testing in animal models.

  13. Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290

    NARCIS (Netherlands)

    Yzer, Suzanne; den Hollander, Anneke I.; Lopez, Irma; Pott, Jan-Willem R.; de Faber, Jan Tjeerd H. N.; Cremers, Frans P. M.; Koenekoop, Robert K.; van den Born, L. Ingeborgh

    2012-01-01

    Purpose: This study investigated the centrosomal protein, 290-KD (CEP290) associated genotype and ocular and extra-ocular phenotype in 18 patients with Leber congenital amaurosis (LCA). Methods: Eighteen patients with LCA from 14 families with mutations in the CEP290 gene were identified with sequen

  14. Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290

    NARCIS (Netherlands)

    Yzer, S.; Hollander, A.I. den; Lopez, I.; Pott, J.W.; Faber, J.T. de; Cremers, F.P.; Koenekoop, R.K.; Born, L.I. van den

    2012-01-01

    PURPOSE: This study investigated the centrosomal protein, 290-KD (CEP290) associated genotype and ocular and extra-ocular phenotype in 18 patients with Leber congenital amaurosis (LCA). METHODS: Eighteen patients with LCA from 14 families with mutations in the CEP290 gene were identified with sequen

  15. Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290

    NARCIS (Netherlands)

    Yzer, Suzanne; den Hollander, Anneke I.; Lopez, Irma; Pott, Jan-Willem R.; de Faber, Jan Tjeerd H. N.; Cremers, Frans P. M.; Koenekoop, Robert K.; van den Born, L. Ingeborgh

    2012-01-01

    Purpose: This study investigated the centrosomal protein, 290-KD (CEP290) associated genotype and ocular and extra-ocular phenotype in 18 patients with Leber congenital amaurosis (LCA). Methods: Eighteen patients with LCA from 14 families with mutations in the CEP290 gene were identified with sequen

  16. Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II.

    Science.gov (United States)

    Gerber, Sylvie; Hanein, Sylvain; Perrault, Isabelle; Delphin, Nathalie; Aboussair, Nisrine; Leowski, Corinne; Dufier, Jean-Louis; Roche, Olivier; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel

    2007-12-01

    Leber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophy responsible for blindness or severe visual impairment at birth or within the first months of life. Up to date, ten LCA genes have been identified. Three of them account for ca. 43% of families and are responsible for a congenital severe stationary cone-rod dystrophy (Type I, 60% of LCA) while the seven remaining genes account for 32% of patients and are responsible for a progressive yet severe rod-cone dystrophy (Type II, 40% of LCA ). Recently, mutations in LCA5, encoding the ciliary protein lebercilin, were reported to be a rare cause of leber congenital amaurosis. The purpose of this study was to evaluate the involvement of this novel gene and to look for genotype-phenotype correlations. Here we report the identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in our series (3/179; 1.7%). Besides, we suggest that the phenotype of these patients affected with a particularly severe form of LCA type II may represent a continuum with LCA type I.

  17. Leber's hereditary optic neuropathy masquerading as optic neuritis with spontaneous visual recovery.

    Science.gov (United States)

    Hsu, Tsui-Kang; Wang, An-Guor; Yen, May-Yung; Liu, Jorn-Hon

    2014-01-01

    We report a case of Leber's hereditary optic neuropathy (LHON) masquerading as optic neuritis with late visual recovery. A 28-year-old man had gradual visual loss in both eyes for two weeks. Visual acuity was 0.4 in the right eye and 0.7 in the left. Fundus examination revealed hyperaemic discs in each eye. Fluorescein angiography revealed dye leakage at both optic discs in the late phase. Static perimetry (Humphrey 30-2) revealed bilateral relative central scotomata. Magnetic resonance imaging of the optic nerves was normal and his lumbar puncture showed normal opening pressure. He received steroid pulse therapy for three days. Nevertheless, vision in his right eye deteriorated to 0.1 one month later and left vision worsened to 0.05 six months later. Fifteen months after onset, his vision began to improve. At 21 months, his vision recovered to 0.9 R and 1.0 L. Peripheral blood DNA sequencing revealed 14484 mutation of mitochondrial DNA (mtDNA). Visual recovery can occur in patients with Leber's hereditary optic neuropathy with mtDNA 14484 mutation. LHON could be misdiagnosed as optic neuritis in some cases. Molecular examination of mtDNA mutation can confirm the diagnosis of LHON in clinically controversial patients. We should keep in mind the diagnosis of LHON when optic neuritis shows poor response to pulse therapy.

  18. Oxidative phosphorylation differences between mitochondrial DNA haplogroups modify the risk of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Gómez-Durán, Aurora; Pacheu-Grau, David; Martínez-Romero, Iñigo; López-Gallardo, Ester; López-Pérez, Manuel J; Montoya, Julio; Ruiz-Pesini, Eduardo

    2012-08-01

    Leber's hereditary optic neuropathy is a maternally inherited optic atrophy caused by mitochondrial DNA point mutations. Previous epidemiological studies have shown that individuals from mitochondrial genetic backgrounds (haplogroups) J/Uk and H have a higher and a lower risk, respectively, of suffering this disorder. To analyze the bases of these associations at cellular and molecular levels, functional studies with cybrids provide high quality evidence. Cybrids from haplogroup J contain less mitochondrial deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and synthesize a smaller amount of mitochondrial DNA-encoded polypeptides than those from haplogroup H. Haplogroup J cybrids also display lower oxygen consumption, mitochondrial inner membrane potential and total adenosine-5'-triphosphate (ATP) levels. Moreover, mitochondrial DNA levels correlate with many parameters of the oxidative phosphorylation system. These results suggest that the mitochondrial DNA amount determines oxidative phosphorylation capacity and, along with other recently published observations, support the possibility that mitochondrial DNA levels may be responsible for the bias of the disorder toward males, for the incomplete penetrance of mutations causing Leber's hereditary optic neuropathy and for the association of the disease with particular mitochondrial DNA haplogroups.

  19. Thorotrast-induced liver cancer: results of the German thorotrast study; Thorotrast-induzierte Tumoren der Leber. Ergebnisse der Deutschen Thorotraststudie

    Energy Technology Data Exchange (ETDEWEB)

    Kaick, G. van; Bahner, M.L.; Liebermann, D.; Luehrs, H.; Wesch, H. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Forschungsschwerpunkt Radiologische Diagnostik und Therapie

    1999-08-01

    fuehrt zu einer chronischen Exposition durch {alpha}-Strahlung. Ziel der Deutschen Thorotraststudie sind die Erfassung der Strahlenspaetfolgen und die Berechnung des Strahlenrisikos. Patienten und Methoden: Die Deutsche Thorotraststudie laeuft seit 1968 im Sinn einer Kohortenstudie und umfasst 2326 Thorotrastpatienten und 1890 Patienten einer Kontrollgruppe. Bei den noch lebenden Thorotrastpatienten wurden Roentgenaufnahmen der Oberbauchorgane und der frueheren Injektionsstelle sowie Messungen mit dem Ganzkoerperzaehler durchgefuehrt. Zur fruehen Erkennung von Lebertumoren wurden den Patienten in regelmaessigen Abstaenden sonographische und spaeter computertomographische und magnetresonanztomographische Untersuchungen angeboten. Ergebnisse: In der Gruppe der Thorotrastpatienten traten bisher 454 primaere Lebertumoren auf, im Vergleich zu 3 Lebertumoren in der Kontrollgruppe. Bei einem Teil der Patienten konnten mit Hilfe moderner bildgebender Verfahren relativ kleine Lebertumoren nachgewiesen werden, die z.T. einer chirurgischen Therapie zugaenglich waren. Diskussion: Es besteht eine Korrelation zwischen der akkumulierten mittleren Dosis in der Leber und der Inzidenz von malignen Lebertumoren. Das kumulative Risiko fuer Lebermalignome liegt bei etwa 600 Erkrankungen pro 10{sup 4} Personen, deren Leber mit 1 Gy exponiert wurde. Auch fuer Leberzirrhosen besteht eine Korrelation zwischen akkumulierter Dosis und Inzidenz der Erkrankung. (orig.)

  20. Loin des sciences sociales.

    Directory of Open Access Journals (Sweden)

    René-Éric Dagorn

    2002-05-01

    Full Text Available Plusieurs numéros de Livres Hebdo et du Monde des Livres des mois de janvier-février 2002 permettent de proposer un rapide survol des grandes ventes de l’année 2001 et de quelques tendances éditoriales de l’année 2002. Quelques points ressortent particulièrement de la lecture des articles de ces deux sources : l’intérêt de la nouvelle méthode d’estimation des ventes proposée par l’institut Ipsos et Livres Hebdo , le tableau des grandes ventes en 2001 (et ...

  1. La metamorphose des cypris femelles des Rhizocephales

    NARCIS (Netherlands)

    Veillet, A.

    1964-01-01

    Depuis la découverte de la métamorphose des cypris de Sacculina carcini Thompson par Delage, peu de biologistes se sont intéressés au développement des Rhizocéphales. On admet aujourd'hui que tous les Cirripèdes parasites ont, comme Sacculina carcini, une forme kentrogone qui inocule le parasite au

  2. Die Entdeckung des Higgs-Teilchens oder wie das Universum seine Masse bekam

    CERN Document Server

    2013-01-01

    Im Oktober 2013 setzte der Nobelpreis für Peter Higgs und François Englert den vorläufigen Höhepunkt in der verrückten Geschichte um das sogenannte Gottesteilchen, das Higgs-Boson. Schon im Juli des Vorjahres hatten die Physiker weltweit gejubelt: Mehr als fünfzig Jahre nachdem Peter Higgs und andere Wissenschaftler die Existenz des Teilchens theoretisch begründet hatten, war es im gigantischen Teilchenbeschleuniger CERN gefunden worden. Jetzt erzählen Harald Lesch und seine Co-Autoren, warum sich rund um das Higgs-Teilchen so viele skurrile Missverständnisse und mediale Sensationen ranken. Gewohnt kurzweilig und gut verständlich enthüllen sie, wie aus dem verzweifelt gesuchten „gottverdammten Teilchen“ das Gottesteilchen wurde, dass der Urknall nicht simuliert werden kann und dass Schwarze Löcher nicht unbedingt alles verschlingende Monster sind. Dabei wird deutlich, dass die Suche nach den geheimnisvollen Kräften, die das Universum, unsere Erde und letztlich auch uns Menschen zusammenhalten...

  3. Analysis of Mitochondrial Gene Mutations in Chinese Pedigrees of Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    Ling Lin; Yikai Chen; Yi Tong; Zhihong Zheng; Jianyin Lin

    2002-01-01

    Purpose: To investigate the frequency of common pathogenic primary mitochondrial DNA mutations in Leber's hereditary optic neuropathy (LHON) families.Methods: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing were used to detect mitochondrial DNA mutations.Sixty-six Chinese examiners from 15 families, including 22 visual affected and their 44 unaffected maternal relatives, underwent molecular genetic evaluation. Eleven normal individuals underwent evaluation as contrl.Results: Of the 15 families with suspicion of LHON, 13 had nucleotide position (nt) Gl1778A mutations, 2 had nt T14484C mutations. All examiners had nt G11719A mutations.Conclusions: The mutations at nucleotides 11778 and 14484 are primary LHON mutations. Molecular genetic findings suggest that the silent mutation at nt G11719A may be a common genetic polymorphism in Chinese.

  4. Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy.

    Directory of Open Access Journals (Sweden)

    Anais Thouin

    Full Text Available Leber Hereditary Optic Neuropathy (LHON is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers.

  5. Abnormalities of the five serum ions in patients with Leber congenital amaurosis

    Directory of Open Access Journals (Sweden)

    Zhi-Zhong Wu

    2017-03-01

    Full Text Available AIM:To study the concentration changes of the serum magnesium, calcium, potassium, sodium and chloride ions of the patients of Leber congenital amaurosis(LCA.METHODS:Based on the retrospective study and the simple size in the statistics, 50 cases of LCA patients and 99 cases of normal people were tested the serum ions by professionals in hospital according to the single blind study. Data were analyzed statistically between LCA and normal groups. RESULTS: In the clinical serum ions test of LCA group, the concentration of calcium and potassium were 2.338±0.090mmol/L and 4.164±0.356mmol/L respectively, which were significantly higher than those of the normal group(all PPP>0.05. CONCLUSION: In the patients with LCA, abnormal concentration changes of magnesium, calcium and potassium will be needed to concern of the ophthalmologist, which is probably related with the occurrence of LCA.

  6. Clinical Analysis of Leber's Hereditary Optic Neuropathy Harboring mtDNA Mutation at nt11778

    Institute of Scientific and Technical Information of China (English)

    Xinyu Zhang; Qiang Yu; Qingjiong Zhang; Changxian Yi

    2001-01-01

    Purpose: To improve our diagnostic technique through the analysis of clinical features ofLeber's heredita'y optic neuropathy (LHON) harboring mtDNA point mutation at nt11778. Methods: Detection of nt11778 mutation was performed on 38 patients clinically diagnosed as LHON in our ophthalmic center from year 1998 to 2000. Circumstances of onset and family history were obtained and ophthalmoscopy, fundus fluorescein angiography, visual field and visual evoked potential were performed on all 38 patients. Result: 30 In 38 patients (78.95 % ) harbor nt11778 mutation, including 28 male (93.33%) and 2 female (6.67%). The ratio of affected male to female is 14: 1. Patients harboring nt11778 mutation display typical clinical nanifestations. Ccnclusion: Identification of one of the three LHON specifically associated ntDNA mutations is essential to confirm the diagnosis. Eye Science 2001: 17:31 ~ 34.

  7. Single-cell analysis of intercellular heteroplasmy of mtDNA in Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Y.; Sharpe, H.; Brown, N.

    1994-07-01

    The authors have investigated the distribution of mutant mtDNA molecules in single cells from a patient with Leber hereditary optic neuropathy (LHON). LHON is a maternally inherited disease that is characterized by a sudden-onset bilateral loss of central vision, which typically occurs in early adulthood. More than 50% of all LHON patients carry an mtDNA mutation at nucleotide position 11778. This nucleotide change converts a highly conserved arginine residue to histidine at codon 340 in the NADH-ubiquinone oxidoreductase subunit 4 (ND4) gene of mtDNA. In the present study, the authors used PCR amplification of mtDNA from lymphocytes to investigate mtDNA heteroplasmy at the single-cell level in a LHON patient. They found that most cells were either homoplasmic normal or homoplasmic mutant at nucleotide position 11778. Some (16%) cells contained both mutant and normal mtDNA.

  8. Raised intraocular pressure as a potential risk factor for visual loss in Leber Hereditary Optic Neuropathy.

    Science.gov (United States)

    Thouin, Anais; Griffiths, Philip G; Hudson, Gavin; Chinnery, Patrick F; Yu-Wai-Man, Patrick

    2013-01-01

    Leber Hereditary Optic Neuropathy (LHON) is an important cause of inherited mitochondrial blindness among young adults. The majority of patients carry one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A and m.14484T>C, all of which affect critical complex I subunits of the mitochondrial respiratory chain. LHON is characterised by marked incomplete penetrance, clearly implying that the mtDNA mutation is insufficient on its own to trigger retinal ganglion cell dysfunction and visual loss. In this case series of three affected patients harbouring the m.11778G>A mutation, we provide evidence suggesting that raised intraocular pressure could be a risk factor triggering visual loss in at-risk LHON carriers.

  9. Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Chalmers, R.M.; Davis, M.B.; Sweeney, M.G.; Wood, N.W.; Harding, A.E. [Inst. of Neurology, London (United Kingdom)

    1996-07-01

    Pedigree analysis of British families with Leber hereditary optic neuropathy (LHON) closely fits a model in which a pathogenic mtDNA mutation interacts with an X-linked visual loss susceptibility locus (VLSL). This model predicts that 60% of affected females will show marked skewing of X inactivation. Linkage analysis in British and Italian families with genetically proven LHON has excluded the presence of such a VLSL over 169 cM of the X chromosome both when all families were analyzed together and when only families with the bp 11778 mutation were studied. Further, there was no excess skewing of X inactivation in affected females. There was no evidence for close linkage to three markers in the pseudoautosomal region of the sex chromosomes. The mechanism of incomplete penetrance and male predominance in LHON remains unclear. 27 refs., 1 fig., 3 tabs.

  10. Irreversible optic neuropathy in wernicke encephalopathy and leber hereditary optic neuropathy.

    Science.gov (United States)

    Li, John-Michael; Rucker, Janet C

    2010-03-01

    A 52-year-old woman with alcohol abuse presented with recent worsening of vision, imbalance, and confusion. Examination revealed counting fingers acuity in both eyes with central scotomas, color vision loss, horizontal nystagmus, and gait ataxia. Thiamine was initiated as treatment for a presumptive diagnosis of Wernicke encephalopathy (WE). Brain MRI revealed high T2 signal in the dorsal midbrain and thalami characteristic of WE. The lack of optic disc edema, usually present in patients with WE who have severe optic neuropathy, and lack of visual loss reversibility with thiamine treatment, led to the suspicion of coexisting Leber hereditary optic neuropathy (LHON), which was later confirmed when testing revealed the 14484 mitochondrial DNA mutation. Over the ensuing months, vision did not recover despite improvement of other neurologic findings. Irreversible optic neuropathy in WE should prompt consideration of a coexisting mitochondrial disorder such as LHON.

  11. Clinical and electrophysiological recovery in Leber hereditary optic neuropathy with G3460A mutation.

    Science.gov (United States)

    Sharkawi, Eamon; Oleszczuk, Justyna D; Holder, Graham E; Raina, Joyti

    2012-08-01

    To report a case of clinical and electrophysiological recovery in Leber hereditary optic neuropathy (LHON) with G3460A Mutation. A 10-year-old boy with a three-month history of painless bilateral sequential visual loss upon presentation underwent visual acuity (diminished), anterior and posterior segment examination (normal), fluorescein angiography (normal), Goldman kinetic perimetry (bilateral central scotomata), genetic (a point G3460A mutation) and electrophysiological investigation (undetectable pattern visual evoked potentials (VEP); low amplitude, broadened and reduced flash VEPs and loss of the N95 component in the pattern electroretinograms). Diagnosis of LHON was made. Eighteen months later vision and electrophysiological tests results began spontaneously improving. Kinetic perimetry revealed reduced density and size of scotomata. Two years later, there had been further electrophysiological improvement. This report describes both clinical and electrophysiological improvement in LHON with G3460A mutation.

  12. Successful chemotherapy in a male patient with malignant lymphoma and Leber's hereditary optic neuropathy (LHON).

    Science.gov (United States)

    Zanssen, Stefanie; Buse, Gerhard

    2003-04-01

    Leber's hereditary optic neuropathy (LHON) is a bilateral subacute optic neuropathy caused by hereditary missense mutations of the mitochondrial genome. Primary mutations are located at nucleotide positions 11778, 3460, and 14484 in genes encoding subunits of complex I of the respiratory chain. It has been suggested that degenerative changes in the optic nerve might be mediated by apoptosis. Therefore, we hypothesized that patients affected with LHON might show altered sensitivity to cytotoxic drugs. Here we report the case of a LHON patient carrying the 11778 mutation who required chemotherapy for malignant lymphoma. Using in vitro assays, we found that the patient's peripheral blood mononuclear cells did not show altered vulnerability to cytotoxic drugs. The patient was treated with combination chemotherapy and consolidating radiotherapy, leading to complete remission without inappropriately severe acute or chronic side effects. These data indicate that the 11778 mutation does not change cellular response to cytotoxic drugs in a clinically apparent manner.

  13. Differential cerebro spinal fluid proteome investigation of Leber hereditary optic neuropathy (LHON) and multiple sclerosis.

    Science.gov (United States)

    D'Aguanno, Simona; Barassi, Alessandra; Lupisella, Santina; d'eril, Gianlodovico Melzi; Del Boccio, Piero; Pieragostino, Damiana; Pallotti, Francesco; Carelli, Valerio; Valentino, Maria Lucia; Liguori, Rocco; Avoni, Patrizia; Bernardini, Sergio; Gambi, Domenico; Urbani, Andrea; Federici, Giorgio

    2008-01-01

    Leber's hereditary optic neuropathy (LHON) is a genetic disease leading to the loss of central vision and optic nerve atrophy. The existence of occasional cases of LHON patients developing a Multiple Sclerosis (MS)-like illness and the hypothesis that mtDNA variants may be involved in MS suggest the possibility of some common molecular mechanisms linking the two diseases. We have pursued a comparative proteomics approach on cerebrospinal fluid (CSF) samples from LHON and MS patients, as well as healthy donors by employing 2-DE gel separations coupled to MALDI-TOF-MS and nLC-MS/MS investigations. 7 protein spots showed significant differential distribution among the three groups. Both CSF of LHON or MS patients are characterized by lower level of transthyretin dimer adduct while a specific up regulation of Apo A-IV was detected in LHON CSF.

  14. Long-term evaluation of Leber's hereditary optic neuropathy-like symptoms in rotenone administered rats.

    Science.gov (United States)

    Zhang, Li; Liu, Laura; Philip, Ann L; Martinez, Juan C; Guttierez, Juan C; Marella, Mathieu; Patki, Gaurav; Matsuno-Yagi, Akemi; Yagi, Takao; Thomas, Biju B

    2015-01-12

    Leber's hereditary optic neuropathy (LHON) is an inherited disorder affecting the retinal ganglion cells (RGCs) and their axons that lead to the loss of central vision. This study is aimed at evaluating the LHON symptoms in rats administered with rotenone microspheres into the superior colliculus (SC). Optical coherence tomography (OCT) analysis showed substantial loss of retinal nerve fiber layer (RNFL) thickness in rotenone injected rats. Optokinetic testing in rotenone treated rats showed decrease in head-tracking response. Electrophysiological mapping of the SC surface demonstrated attenuation of visually evoked responses; however, no changes were observed in the ERG data. The progressive pattern of disease manifestation in rotenone administered rats demonstrated several similarities with human disease symptoms. These rats with LHON-like symptoms can serve as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease.

  15. Leber congenital amaurosis, from darkness to light: An ode to Irene Maumenee.

    Science.gov (United States)

    Coussa, Razek Georges; Lopez Solache, Irma; Koenekoop, Robert K

    2017-01-01

    This article is dedicated to Irene Hussels Maumenee, Professor of Human Genetics and Ophthalmology, Johns Hopkins' Wilmer Eye Institute, Ocular Genetics Fellowship director in 1994-1995. Leber congenital amaurosis (LCA) has almost come full circle, from a profound and molecularly uncharacterized form of congenital retinal blindness to one in which a large number of causative genes and disease pathways are known, and the world's first human retinal disease to be treated by gene therapy. Dr. Maumenee's insights, efforts, and leadership have contributed significantly to this remarkable scientific journey. In this manuscript, we present a short summary of the known LCA genes, LCA disease subtypes, and emerging treatment options. Our manuscript consolidates previous knowledge with current findings in an attempt to provide a more comprehensive understanding of LCA.

  16. Leber's congenital amaurosis as the retinal degenerative phenotype in thiamine responsive megaloblastic anemia: a case report.

    Science.gov (United States)

    Srikrupa, Natarajan N; Meenakshi, Swaminathan; Arokiasamy, Tharigopala; Murali, Kaushik; Soumittra, Nagasamy

    2014-06-01

    Thiamine responsive megaloblastic anemia syndrome (TRMA), an autosomal recessive disorder is caused by mutations in the SLC19A2 gene which encodes for thiamine transporter 1 (THTR1) protein. TRMA presents with a triad of clinical features that includes diabetes mellitus, megaloblastic anemia and sensorineural hearing loss. Apart from the triad, reported ophthalmic features include cone rod dystrophy, optic atropy and retinitis pigmentosa. A female child presented with Leber's congenital amaurosis at 10 months of age, later diagnosed with hearing impairment at 1 year, diabetes mellitus and megaloblastic anemia at 3 and a half years of age and hence as a case of thiamine responsive megaloblastic anemia. Six exons of the candidate gene SLC19A2 were screened by PCR and direct sequencing. SIFT and PolyPhen analysis was done to predict the probable effect of the mutation. Sequence analysis of the SLC19A2 coding region revealed a novel missense mutation in exon 2; c.314 G > A (p.G105E). Segregation analysis revealed parents heterozygous for the mutation and unaffected sib homozygous for wild type. SIFT and PolyPhen analyses predicted the mutation to be "damaging" (score-0.02) and "probably damaging" (score-0.994), respectively. SLC19A2, the high-affinity thiamine transporter, is the only gene known to be associated with TRMA. Here we describe for the first time Leber's congenital amaurosis as the retinal phenotype and also report a novel point mutation in the SLC19A2 gene that co-segregated with the disease in a TRMA patient.

  17. Leber's遗传性视神经病线粒体DNA突变二例的检测%Detection of mitochondrial DNA mutation in Leber's hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    郭锋; 夏蓓莉; 刘雯; 左伋

    2005-01-01

    目的检测两例Leber's遗传性视神经病的突变位点.方法常规酚-氯仿法提取2名LHON患者基因组DNA,PCR扩增后对mtDNA11778进行检测.结果mtDNA11778位点处存在G→A突变.

  18. ANALYSE DES MODES DE GESTION DES ENTREPRISES ...

    African Journals Online (AJOL)

    Administrateur

    L'étude de l'art et des biens culturels en général est longtemps restée en ... en économie et management), Université d'Angers / Chef de projet chez Arterial Network. ... culturelles publiques sont apparues à partir de la fin des années 1990.

  19. Des racines et des ailes

    Directory of Open Access Journals (Sweden)

    Stéphanie Vincent-Geslin

    2012-05-01

    Full Text Available Les mobilités pendulaires semblent être en augmentation en Europe depuis une dizaine d’années. Cette croissance du temps passé à se déplacer amène à remettre en question la conjecture de Zahavi et apparaît relativement inexplicable en regard du paradigme classique de l’acteur rationnel traditionnellement utilisé dans le champ des transports. Si, dans la littérature, les temps de déplacements sont principalement expliqués par le contexte résidentiel, la forme urbaine et le travail, ce cadre explicatif ne dit rien des processus de décision eux-mêmes qui amènent aux pendularités intensives.À partir d’une enquête qualitative menée auprès de pendulaires français, suisses et belges, cette contribution propose d’analyser les arbitrages et les éléments déterminants des processus de la grande pendularité. Les mobilités quotidiennes pendulaires apparaissent comme le résultat de compromis entre activité professionnelle, attachement résidentiel et choix de vie et prennent ainsi la forme de stratégies de conciliation entre vie privée et vie professionnelle. Ces mobilités spatiales permettent alors paradoxalement la préservation des ancrages résidentiels, sociaux et familiaux.Roots and wings. Long-distance commuting patterns, or how to conciliate professional and personal lifeLong-distance commuting patterns appear to be increasing in Europe over the last ten years. These raising mobility patterns lead to reappraise the Zahavi conjecture and appear largely inexplicable by the classical rational actor paradigm traditionally used in transportation research. In literature, commuting is mainly explained by residential contexts, urban forms and job. Nevertheless this theoretical frame says little about the decision-making processes themselves. Based on a qualitative survey conducted in three European countries - France, Belgium and Switzerland – among a population of high commuters, this paper proposes an analysis of

  20. Franz Baermann Steiner: Wegbereiter des Postkolonialismus

    Directory of Open Access Journals (Sweden)

    Isabella Parkhurst-Atger

    2010-12-01

    .Im folgenden Artikel wird das Werk von Franz Baermann Steiner, einem kaum bekannten deutsch-jüdischen Exilautor der dreißiger Jahre, vorgestellt. Im Rahmen des postcolonial turn der Exilforschung wird diesem Autor eine besondere Bedeutung zuteil. Als Prager Jude und überzeugter Kulturzionist hat Steiner in den vierziger Jahren innerhalb der britischen Sozialanthropologie einen Diskurs mit postkolonialen Akzenten entwickelt, der aus seiner Herkunft und aus seinen Forschungen am Oxforder Antrhopologieinstitut zu erklären ist. Tatsächlich besteht eine strukturelle Analogie zwischen den Prager Juden und den hybriden Beamten im britischen Kolonialreich, die einerseits auf den Alteritätsstatus und andererseits auf ihre liminale Stellung innerhalb ihrer Gesellschaften zurückzuführen ist. In Steiners vergleichenden, von Sprachkritik geprägten Schriften, wird der Eurozentrismus kritisiert und gewisse Gedanken entwickelt, die Steiners geistige Verwandtschaft mit Aimé Césaire, einem weiteren Wegbereiter des Postkolonialismus, bezeugen. Beide glauben eine Verbindung zwischen den Gewalttaten, die in den Kolonien gegen die Sklaven verübt wurden, und dem tragischen Schicksal der europäischen Juden im „Dritten Reich“ erkennen zu können. Außerdem entlarvt Steiner die epistemische Gewalt der anthropologischen Vergleichskategorien des 19. Jahrhunderts. Dabei befreit er das Konzept von jeglichem Primitivismus und definiert es neu als ein notwendiges, allen Menschen gemeines Meidungsverhalten in Gefahrensituationen. Steiner ist aufgrund seines hybriden Profils, seiner Kulturkritik und seiner theoretischen anthropologischen Schriften ein Wegbereiter des Postkolonialismus.

  1. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark

    DEFF Research Database (Denmark)

    Astuti, Galuh D N; Bertelsen, Mette; Preising, Markus N

    2016-01-01

    Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequenc...... therapies.European Journal of Human Genetics advance online publication, 2 December 2015; doi:10.1038/ejhg.2015.241....

  2. Molecular pathogenetic mechanism of Leber's hereditary optic neuropathy%Leber's遗传性视神经病变分子致病机制研究

    Institute of Scientific and Technical Information of China (English)

    瞿佳; 管敏鑫

    2006-01-01

    Leber's遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)是一种较常见的引起视神经萎缩的遗传性疾病.该病主要引起双侧中心视力丧失,造成永久性的严重视觉障碍,常常发生在一些即将或已工作或上学的年轻人身上,以及在对该病患者家系中其他成员进行遗传病检查时发现.在一些LHON家系中,视觉障碍的患者呈现母系遗传方式,这表明线粒体DNA(mitochondrial DNA,mtDNA)是该病的分子遗传基础.至今为止,在世界各地不同家系报道中已经发现大约有35个与LHON相关的灾变位点,其中ND1 G3460A、ND4 G11778A、ND6 T14484C为三个公认的原发突变位点,均参与呼吸链复合体I的亚基编码.在不同种族发病统计中,其中大约50%的LHON由三个原发致病突变中的一个所致,尤为G11778A突变为主.引人注意的是,LHON家系携带相同突变的母系成员表现出不同的外显率、表现度(如发病严重程度、发病年龄、视力丧失进展程度).不完全和不同的外显率以及轻度的生化影响说明mtDNA突变本身不足以产生临床表型,其他因素(如环境、核修饰基因、线粒体单体型等)可能影响LHON的外显率和表型表达.%Leber's hereditary optic neuropathy (LHON) is the most common hereditary optic atrophies. The disease causes the bilateral loss of central vision. The importance of LHON lies in it ability to cause such severe and usually permanent vision loss in young adults who are about to start or have recently begun employrent or higher education, and the ramification of diagnosing an inherited disease to other members of the patient's family. The maternal transmission of visual dysfunction in families with LHON suggested the mutations in mitochondrial DNA (mtDNA) are the molecular bases of this disorder. Up to date, 35 LHON-associated mtDNA mutations have been identified in many pedigrees worldwide. Of these, three primary mutations: ND1 G3460A, ND4 G11778A

  3. Screening of colorectal neoplasm; Screening des kolorektalen Karzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Layer, G. [Klinikum der Stadt Ludwigshafen gGmbH, Akademisches Lehrkrankenhaus der Johannes Gutenberg Universitaet Mainz, Zentralinstitut fuer Diagnostische und Interventionelle Radiologie, Ludwigshafen (Germany); Riemann, J.F. [Klinikum der Stadt Ludwigshafen gGmbH, Akademisches Lehrkrankenhaus der Johannes Gutenberg Universitaet Mainz, Medizinische Klinik C, Ludwigshafen (Germany)

    2008-01-15

    In Germany approximately 29,000 people died of colorectal carcinoma (CRC) in 2002; the risk of getting CRC is 4-6% in Germany, rising with age from the 50th year of life. About one third of all people over 50 years of age have polyps with the potential for malignant transformation in the colorectum, which is a sufficiently high prevalence rate to justify screening. In contrast to most other cancer diseases, in the case of CRC it is possible to prevent the cancer and not only to detect it at an early stage. Application of the test for occult blood in persons between their 45th and 80th years can reduce the mortality of CRC by 14%. We can assume that already regular sigmoidoscopies with consistent performance of polypectomy when needed could reduce the incidence of CRC by 50-70%. There is no doubt that coloscopy is the technique of choice for secondary prevention, as it unites the possibility of complete diagnosis and treatment with a justifiably low level of risk. The economic advantages of an avoidance strategy compared with the treatment of CRC, which is certainly expensive, have been documented. On the basis of all the data reported, in the case of CRC preventive strategies can be emphatically recommended. (orig.) [German] In Deutschland starben im Jahr 2002 ca. 29.000 Menschen an einem kolorektalen Karzinom (CRC); das Lebenszeitrisiko, an einem CRC zu erkranken, betraegt mit dem Alter steigend ab dem 50. Lebensjahr in Deutschland 4-6%. Etwa 1/3 aller ueber 50-Jaehrigen hat relevante Polypen im Kolorektum, ein ausreichend hoher Praevalenzwert fuer ein sinnvolles Screening. Im Gegensatz zu den meisten anderen Krebserkrankungen kann man beim CRC ausserdem die Krebserkrankung verhindern und nicht nur in einem fruehen Stadium erkennen. Die Mortalitaet des CRC kann durch die Anwendung des Tests auf okkultes Blut (FOBT) bei Personen zwischen dem 45. und 80. Lebensjahr um 14% gesenkt werden. Bereits durch regelmaessige Sigmoidoskopien mit einer konsequenten Polypektomie

  4. Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients.

    Science.gov (United States)

    Melillo, Paolo; Pecchia, Leandro; Testa, Francesco; Rossi, Settimio; Bennett, Jean; Simonelli, Francesca

    2012-07-19

    Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA). In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA) involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration. Pupillary light reflexes (PLR) were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate), and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison. The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye) compared to the left (untreated) eye at both follow-up time-points, showing stability of the improved PLR in the treated eye. Our method

  5. Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients

    Directory of Open Access Journals (Sweden)

    Melillo Paolo

    2012-07-01

    Full Text Available Abstract Background Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA. In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration. Methods Pupillary light reflexes (PLR were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate, and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison. Results The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye compared to the left (untreated eye at both follow-up time-points, showing stability of

  6. Liste des intrants 2015

    OpenAIRE

    Speiser, Bernhard; Tamm, Lucius; Maurer, Veronika; Berner, Alfred; Schneider, Claudia; Chevillat, Véronique

    2015-01-01

    La liste des intrants contient tous les produits phytosanitaires, les engrais, les substrats du commerce, les produits de lutte contre les mouches des étables, les agents d'ensilage, les aliments minéraux et complémentaires, les produits pour la désinfection des stabulations et les produits contre les maladies des abeilles autorisés pour l'agriculture biologique. Cette liste est contraignante pour les producteurs de Bio Suisse. Sur les fermes Bio Suisse, seuls les produits mentionnés sont aut...

  7. CCT2 Mutations Evoke Leber Congenital Amaurosis due to Chaperone Complex Instability

    Science.gov (United States)

    Minegishi, Yuriko; Sheng, XunLun; Yoshitake, Kazutoshi; Sergeev, Yuri; Iejima, Daisuke; Shibagaki, Yoshio; Monma, Norikazu; Ikeo, Kazuho; Furuno, Masaaki; Zhuang, Wenjun; Liu, Yani; Rong, Weining; Hattori, Seisuke; Iwata, Takeshi

    2016-01-01

    Leber congenital amaurosis (LCA) is a hereditary early-onset retinal dystrophy that is accompanied by severe macular degeneration. In this study, novel compound heterozygous mutations were identified as LCA-causative in chaperonin-containing TCP-1, subunit 2 (CCT2), a gene that encodes the molecular chaperone protein, CCTβ. The zebrafish mutants of CCTβ are known to exhibit the eye phenotype while its mutation and association with human disease have been unknown. The CCT proteins (CCT α-θ) forms ring complex for its chaperon function. The LCA mutants of CCTβ, T400P and R516H, are biochemically instable and the affinity for the adjacent subunit, CCTγ, was affected distinctly in both mutants. The patient-derived induced pluripotent stem cells (iPSCs), carrying these CCTβ mutants, were less proliferative than the control iPSCs. Decreased proliferation under Cct2 knockdown in 661W cells was significantly rescued by wild-type CCTβ expression. However, the expression of T400P and R516H didn’t exhibit the significant effect. In mouse retina, both CCTβ and CCTγ are expressed in the retinal ganglion cells and connecting cilium of photoreceptor cells. The Cct2 knockdown decreased its major client protein, transducing β1 (Gβ1). Here we report the novel LCA mutations in CCTβ and the impact of chaperon disability by these mutations in cellular biology. PMID:27645772

  8. Leber遗传性视神经病变%Hereditary Leber's optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    林玲; 郑志; 陈贻锴

    2001-01-01

    @@ Leber于1871年首次报道了一种遗传性视神经病变的临床症状、体征和遗传特性,该病以急性或亚急性双侧中心视力丧失为主要特征,可通过无临床症状的母亲传递给后代,似乎更好发于年轻男性[1~5],此后该病被称为莱贝视神经萎缩(Leber's hereditary optic neuropathy,LHON).1988年,Wallace等首次发现LHON存在线粒体DNA(mitochondrial DNA,mtDNA)的病理性突变,他们发现在许多LHON家族成员均有mtDNA 11778位点的点突变[6].此后,许多研究证实LHON为母系遗传性疾病, 其主要病因是线粒体基因组某些位点发生突变,是一种最为常见的线粒体遗传病[7].

  9. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions

    Science.gov (United States)

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-01-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70–80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. PMID:28689169

  10. Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia.

    Science.gov (United States)

    Wang, Kang; Takahashi, Yuji; Gao, Zong-Liang; Wang, Guo-Xiang; Chen, Xian-Wen; Goto, Jun; Lou, Jin-Ning; Tsuji, Shoji

    2009-10-01

    Leber hereditary optic neuropathy and dystonia (LDYT) is a mitochondrial disorder associated with variable combinations of vision loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial ND6 or ND4 gene. In this paper, we describe a Chinese family with 18 LDYT patients. The comprehensive nucleotide sequence analysis of the entire mitochondrial genome using resequencing microarray revealed a mutation (mtND3*10197A (m.10197G>A)) substituting a threonine for a highly conserved alanine at codon 47 of MTND3 on the background of haplogroup D4b. Quantitative analysis of the heteroplasmy of the mutation revealed a homoplasmy in the leukocytes of all the affected individuals on the maternal side. This is the first description of the ND3 mutation causing LDYT. The mtND3*10197A (m.10197G>A) mutation has recently been described in French and Korean patients with Leigh syndrome. These findings suggest that the clinical presentations associated with the mtND3*10197A (m.10197G>A) mutation (ND3) are much wider, encompassing those of LDYT and Leigh syndrome.

  11. Leber Hereditary Optic Neuropathy: Do Folate Pathway Gene Alterations Influence the Expression of Mitochondrial DNA Mutation?

    Directory of Open Access Journals (Sweden)

    A Aleyasin

    2010-09-01

    Full Text Available "nBackground: Leber hereditary optic neuropathy (LHON is an inherited form of bilateral optic atrophy leading to the loss of central vision.  The primary cause of vision loss is mutation in the mitochondrial DNA (mtDNA, however, unknown secon­dary genetic and/or epigenetic risk factors are suggested to influence its neuropathology.  In this study folate gene polymor­phisms were examined as a possible LHON secondary genetic risk factor in Iranian patients."nMethods: Common polymorphisms in the MTHFR (C677T and A1298C and MTRR (A66G genes were tested in 21 LHON patients and 150 normal controls."nResults:  Strong associations were observed between the LHON syndrome and C677T (P= 0.00 and A66G (P= 0.00 polymor­phisms.  However, no significant association was found between A1298C (P =0.69 and the LHON syndrome."nConclusion: This is the first study that shows MTHFR C677T and MTRR A66G polymorphisms play a role in the etiology of the LHON syndrome.  This finding may help in the better understanding of mechanisms involved in neural degeneration and vision loss by LHON and hence the better treatment of patients.

  12. Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON)

    Energy Technology Data Exchange (ETDEWEB)

    Johns, D.R. (Beth Israel Hospital, Boston, MA (United States)); Neufeld, M.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States))

    1993-10-01

    Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.

  13. Optic atrophy differentially diagnosed as spinocerebellar ataxia from Leber hereditary optic neuropathy by gene mutation analysis.

    Science.gov (United States)

    Song, Y P; Chen, Z S; Mo, G Y; Ding, Q; Zhu, L; Yan, M

    2012-01-01

    Optic atrophy describes a group of diseases of retinal ganglion cells and axons that eventually lead to loss of vision. Optic atrophy has both congenital and acquired causes, and its diagnosis (or differential diagnosis) is complicated. This case report describes a 20-year-old man who presented with a 1-year history of progressive vision loss in both eyes and no obvious systemic symptoms. Fundus examination revealed bilateral optic atrophy. Based on clinical characteristics, visual field analysis and pattern visual evoked potential examination, the presumptive diagnosis was Leber hereditary optic neuropathy (LHON). Analysis of mitochondrial DNA indicated the absence of all of three common mutations associated with LHON (m.3460G>A, m.11778G>A, m.14484T>C). Detailed questioning of the patient revealed a history of prolonged language development and poor balance. Neurological examination indicated abnormal co-ordination, suggesting the presence of inherited spinocerebellar ataxia (SCA). Analysis of the SCA7 gene revealed a high number of trinucleotide repeats [(CAG)(n), n > 64], confirming the diagnosis of SCA. The aetiology of optic atrophies is complicated and the molecular genetic detection approach provides the best information for diagnosing these diseases.

  14. Targeting estrogen receptor β as preventive therapeutic strategy for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Pisano, Annalinda; Preziuso, Carmela; Iommarini, Luisa; Perli, Elena; Grazioli, Paola; Campese, Antonio F; Maresca, Alessandra; Montopoli, Monica; Masuelli, Laura; Sadun, Alfredo A; d'Amati, Giulia; Carelli, Valerio; Ghelli, Anna; Giordano, Carla

    2015-12-15

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease characterized by degeneration of retinal ganglion cells (RGCs) and consequent optic nerve atrophy. Peculiar features of LHON are incomplete penetrance and gender bias, with a marked male prevalence. Based on the different hormonal metabolism between genders, we proposed that estrogens play a protective role in females and showed that these hormones ameliorate mitochondrial dysfunction in LHON through the estrogen receptors (ERs). We also showed that ERβ localize to the mitochondria of RGCs. Thus, targeting ERβ may become a therapeutic strategy for LHON specifically aimed at avoiding or delaying the onset of disease in mutation carriers. Here, we tested the effects of ERβ targeting on LHON mitochondrial defective metabolism by treating LHON cybrid cells carrying the m.11778G>A mutation with a combination of natural estrogen-like compounds that bind ERβ with high selectivity. We demonstrated that these molecules improve cell viability by reducing apoptosis, inducing mitochondrial biogenesis and strongly reducing the levels of reactive oxygen species in LHON cells. These effects were abolished in cells with ERβ knockdown by silencing receptor expression or by using specific receptor antagonists. Our observations support the hypothesis that estrogen-like molecules may be useful in LHON prophylactic therapy. This is particularly important for lifelong disease prevention in unaffected LHON mutation carriers. Current strategies attempting to combat degeneration of RGCs during the acute phase of LHON have not been very effective. Implementing a different and preemptive approach with a low risk profile may be very helpful.

  15. X-inactivation pattern in multiple tissues from two Leber's hereditary optic neuropathy (LHON) patients.

    Science.gov (United States)

    Pegoraro, Elena; Vettori, Andrea; Valentino, Maria L; Molon, Annamaria; Mostacciuolo, Maria L; Howell, Neil; Carelli, Valerio

    2003-05-15

    The more frequent manifestation of ophthalmological abnormalities in males, relative to females, is an unexplained feature of Leber's hereditary optic neuropathy (LHON) that suggests an X-linked modifying gene acting in concert with the pathogenic LHON mitochondrial DNA (mtDNA) mutation. In addition, segregation analysis of the optic neuropathy in LHON pedigrees was compatible with the presence of a recessive-modifying gene on chromosome X. According to this two-locus model, females would be affected only if homozygous or if they were susceptible to skewed X-inactivation. Attempts both to localize the putative LHON-modifying gene by linkage analysis and to find an excess of skewed X-inactivation in affected females were unsuccessful, although the inactivation pattern was only studied in DNA isolated from blood cells. We had the opportunity to analyze a wide range of tissues at autopsy, including the optic nerves and the retina, from two LHON female patients. We found no evidence of skewed X-inactivation in the affected tissues, thus weakening further the hypothesized involvement of a specific X chromosome locus in the pathophysiological expression of LHON.

  16. Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside

    Directory of Open Access Journals (Sweden)

    Rajeshwari D. Koilkonda

    2011-01-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally transmitted disorder caused by point mutations in mitochondrial DNA (mtDNA. Most cases are due to mutations in genes encoding subunits of the NADH-ubiquinone oxidoreductase that is Complex I of the electron transport chain (ETC. These mutations are located at nucleotide positions 3460, 11778, or 14484 in the mitochondrial genome. The disease is characterized by apoplectic, bilateral, and severe visual loss. While the mutated mtDNA impairs generation of ATP by all mitochondria, there is only a selective loss of retinal ganglion cells and degeneration of optic nerve axons. Thus, blindness is typically permanent. Half of the men and 10% of females who harbor the pathogenic mtDNA mutation actually develop the phenotype. This incomplete penetrance and gender bias is not fully understood. Additional mitochondrial and/or nuclear genetic factors may modulate the phenotypic expression of LHON. In a population-based study, the mtDNA background of haplogroup J was associated with an inverse relationship of low-ATP generation and increased production of reactive oxygen species (ROS. Effective therapy for LHON has been elusive. In this paper, we describe the findings of pertinent published studies and discuss the controversies of potential strategies to ameliorate the disease.

  17. A Female Patient with Down Syndrome and Low-Penetrance Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Frousiakis, Starleen E; Pouw, Andrew E; Karanjia, Rustum; Sadun, Alfredo A

    2014-09-01

    We present the case of a 19-year-old female with a history of Down syndrome (DS) who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON). The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS.

  18. Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Wan, Xing; Pei, Han; Zhao, Min-jian; Yang, Shuo; Hu, Wei-kun; He, Heng; Ma, Si-qi; Zhang, Ge; Dong, Xiao-yan; Chen, Chen; Wang, Dao-wen; Li, Bin

    2016-02-19

    Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON.

  19. White Matter Changes in Two Leber's Hereditary Optic Neuropathy Pedigrees: 12-Year Follow-Up.

    Science.gov (United States)

    Jančić, Jasna; Dejanović, Ivana; Radovanović, Saša; Ostojić, Jelena; Kozić, Duško; Đurić-Jovičić, Milica; Samardžić, Janko; Ćetković, Mila; Kostić, Vladimir

    2016-01-01

    We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression.

  20. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions.

    Science.gov (United States)

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-09-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Two novel CRX mutant proteins causing autosomal dominant Leber congenital amaurosis interact differently with NRL.

    Science.gov (United States)

    Nichols, Lorenzo L; Alur, Ramakrishna P; Boobalan, Elangovan; Sergeev, Yuri V; Caruso, Rafael C; Stone, Edwin M; Swaroop, Anand; Johnson, Mary A; Brooks, Brian P

    2010-06-01

    Leber congenital amaurosis (LCA) is a congenital retinal dystrophy characterized by severe visual loss in infancy and nystagmus. Although most often inherited in an autosomal recessive fashion, rare individuals with mutations in the cone-rod homeobox gene, CRX, have dominant disease. CRX is critical for photoreceptor development and acts synergistically with the leucine-zipper transcription factor, NRL. We report on the phenotype of two individuals with LCA due to novel, de novo CRX mutations, c.G264T(p.K74N) and c.413delT(p.I138fs48), that reduce transactivation in vitro to 10% and 30% of control values, respectively. Whereas the c.413delT(p.I138fs48) mutant allows co-expressed NRL to transactivate independently at its normal, baseline level, the c.G264T(p.K74N) mutant reduces co-expressed NRL transactivation and reduces steady state levels of both proteins. Although both mutant proteins predominantly localize normally to the nucleus, they also both show variable cytoplasmic localization. These observations suggest that some CRX-mediated LCA may result from effects beyond haploinsufficiency, such as the mutant protein interefering with other transcription factors' function. Such patients would therefore not likely benefit from a simple, gene-replacement strategy for their disease.

  2. Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis.

    Science.gov (United States)

    Zheng, Qinxiang; Ren, Yueping; Tzekov, Radouil; Zhang, Yuanping; Chen, Bo; Hou, Jiangping; Zhao, Chunhui; Zhu, Jiali; Zhang, Ying; Dai, Xufeng; Ma, Shan; Li, Jia; Pang, Jijing; Qu, Jia; Li, Wensheng

    2012-01-01

    Leber congenital amaurosis (LCA) is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65) in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG). Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6) were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process.

  3. Review and update on the molecular basis of Leber congenital amaurosis.

    Science.gov (United States)

    Chacon-Camacho, Oscar Francisco; Zenteno, Juan Carlos

    2015-02-16

    Inherited retinal diseases are uncommon pathologies and one of the most harmful causes of childhood and adult blindness. Leber congenital amaurosis (LCA) is the most severe kind of these diseases accounting for approximately 5% of the whole retinal dystrophies and 20% of the children that study on blind schools. Clinical ophthalmologic findings including severe vision loss, nystagmus and ERG abnormalities should be suspected through the first year of life in this group of patients. Phenotypic variability is found when LCA patients have a full ophthalmologic examination. However, a correct diagnosis may be carried out; the determination of ophthalmologic clues as light sensibility, night blindness, fundus pigmentation, among other, join with electroretinographics findings, optical coherence tomography, and new technologies as molecular gene testing may help to reach to a precise diagnosis. Several retinal clinical features in LCA may suggest a genetic or gene particular defect; thus genetic-molecular tools could directly corroborate the clinical diagnosis. Currently, approximately 20 genes have been associated to LCA. In this review, historical perspective, clinical ophthalmological findings, new molecular-genetics technologies, possible phenotype-genotypes correlations, and gene therapy for some LCA genes are described.

  4. Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential.

    Science.gov (United States)

    Jacobson, Samuel G; Cideciyan, Artur V; Aleman, Tomas S; Sumaroka, Alexander; Schwartz, Sharon B; Roman, Alejandro J; Stone, Edwin M

    2007-05-01

    To determine the treatment potential in Leber congenital amaurosis (LCA) resulting from an RPGRIP1 (retinitis pigmentosa GTPase regulating-interacting protein 1) mutation, a form of LCA with recent gene therapy success in an animal model. Case report of a rare genetic eye disease investigated for intervention potential. A 19-year-old man with LCA. We studied the retinal structure and function in an LCA patient with a novel homozygous Val1211Glu mutation in the RPGRIP1 gene using optical coherence tomography and colocalized dark-adapted thresholds. Optical coherence tomography results. Central retinal laminar architecture was preserved, and there was a measurable outer nuclear layer. The retained retinal structure corresponded to the region of visual sensitivity. With increasing eccentricity, there was no measurable visual function, and retinal laminar disorganization suggested a remodeling process. The RPGRIP1-LCA patient has treatment potential for a gene replacement strategy if targeted to central, but not pericentral or peripheral, retina. The results differ from similarly studied RPE65-LCA and CRB1-LCA patients. Preclinical progress toward therapy in LCA patients warrants detailed structure-function studies in humans to determine feasibility and candidacy for clinical trials.

  5. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy.

    Science.gov (United States)

    Cideciyan, Artur V

    2010-09-01

    Leber congenital amaurosis (LCA) is a rare hereditary retinal degeneration caused by mutations in more than a dozen genes. RPE65, one of these mutated genes, is highly expressed in the retinal pigment epithelium where it encodes the retinoid isomerase enzyme essential for the production of chromophore which forms the visual pigment in rod and cone photoreceptors of the retina. Congenital loss of chromophore production due to RPE65-deficiency together with progressive photoreceptor degeneration cause severe and progressive loss of vision. RPE65-associated LCA recently gained recognition outside of specialty ophthalmic circles due to early success achieved by three clinical trials of gene therapy using recombinant adeno-associated virus (AAV) vectors. The trials were built on multitude of basic, pre-clinical and clinical research defining the pathophysiology of the disease in human subjects and animal models, and demonstrating the proof-of-concept of gene (augmentation) therapy. Substantial gains in visual function of clinical trial participants provided evidence for physiologically relevant biological activity resulting from a newly introduced gene. This article reviews the current knowledge on retinal degeneration and visual dysfunction in animal models and human patients with RPE65 disease, and examines the consequences of gene therapy in terms of improvement of vision reported. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Massively parallel sequencing for early molecular diagnosis in Leber congenital amaurosis.

    Science.gov (United States)

    Coppieters, Frauke; De Wilde, Bram; Lefever, Steve; De Meester, Ellen; De Rocker, Nina; Van Cauwenbergh, Caroline; Pattyn, Filip; Meire, Françoise; Leroy, Bart P; Hellemans, Jan; Vandesompele, Jo; De Baere, Elfride

    2012-06-01

    Leber congenital amaurosis (LCA) is a rare congenital retinal dystrophy associated with 16 genes. Recent breakthroughs in LCA gene therapy offer the first prospect of treating inherited blindness, which requires an unequivocal and early molecular diagnosis. While present genetic tests do not address this due to a tremendous genetic heterogeneity, massively parallel sequencing (MPS) strategies might bring a solution. Here, we developed a comprehensive molecular test for LCA based on targeted MPS of all exons of 16 known LCA genes. We designed a unique and flexible workflow for targeted resequencing of all 236 exons from 16 LCA genes based on quantitative PCR (qPCR) amplicon ligation, shearing, and parallel sequencing of multiple patients on a single lane of a short-read sequencer. Twenty-two prescreened LCA patients were included, five of whom had a known molecular cause. Validation of 107 variations was performed as proof of concept. In addition, the causal genetic defect and a single heterozygous mutation were identified in 3 and 5, respectively, of 17 patients without previously identified mutations. We propose a novel targeted MPS-based approach that is suitable for accurate, fast, and cost-effective early molecular testing in LCA, and easily applicable in other genetic disorders.

  7. Clinical gene therapy for the treatment of RPE65-associated Leber congenital amaurosis.

    Science.gov (United States)

    Stein, Linda; Roy, Kamolika; Lei, Lei; Kaushal, Shalesh

    2011-03-01

    The positive results of pioneering clinical trials using gene therapy as treatment for patients with Leber congenital amaurosis (LCA) have ushered in a new era of molecular retinal therapeutics for LCA, other blinding retinal disorders and gene therapy applications. This review describes the role of retinal pigment epithelium-specific 65 kDa protein (RPE65) in the visual cycle and how RPE65 deficiency results in LCA; the extensive preclinical studies with recombinant adeno-associated virus (rAAV)-RPE65 gene vectors; and the human rAAV-RPE65 and related gene therapy clinical trials and studies. The literature search included a review of primary sources (e.g., journal articles) that reported study data results and key secondary sources such as meta-reviews available through PubMed, as well as reviews of clinical trial descriptions and results as reported in clinicaltrials.gov, conference publications and news releases. LCA-RPE65 gene therapy is an example of successful, innovative, translational research. Further research is needed regarding how retinal gene therapy can be improved.

  8. Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis.

    Directory of Open Access Journals (Sweden)

    Qinxiang Zheng

    Full Text Available Leber congenital amaurosis (LCA is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12 mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65 in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG. Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process.

  9. Leber's congenital amaurosis and the role of gene therapy in congenital retinal disorders.

    Science.gov (United States)

    Sharif, Walid; Sharif, Zuhair

    2017-01-01

    Leber's congenital amaurosis (LCA) and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE, PubMed and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium (RPE) derived retinoid isomerohydrolase (RPE65) to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine, porcine and rodent LCA2 models. The recombinant AAV2.hRPE65v2 adeno-associated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively, could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful, it will lead the way to additional gene therapy attempts to cure monogenic, inherited retinopathies.

  10. Variations in NPHP5 in Patients With Nonsyndromic Leber Congenital Amaurosis and Senior-Loken Syndrome

    Science.gov (United States)

    Stone, Edwin M.; Cideciyan, Artur V.; Aleman, Tomas S.; Scheetz, Todd E.; Sumaroka, Alexander; Ehlinger, Mary A.; Schwartz, Sharon B.; Fishman, Gerald A.; Traboulsi, Elias I.; Lam, Byron L.; Fulton, Anne B.; Mullins, Robert F.; Sheffield, Val C.; Jacobson, Samuel G.

    2014-01-01

    Objective To investigate whether mutations in NPHP5 can cause Leber congenital amaurosis (LCA) without early-onset renal disease. Methods DNA samples from 276 individuals with non-syndromic LCA were screened for variations in the NPHP5 gene. Each had been previously screened for mutations in 8 known LCA genes without identifying a disease-causing genotype. Results Nine of the 276 LCA probands (3.2%) harbored 2 plausible disease-causing mutations (7 different alleles) in NPHP5. Four of these have been previously reported in patients with Senior-Loken syndrome (F141del, R461X, H506del, and R489X) and 3 are novel (A111del, E346X, and R455X). All 9 patients had severe visual loss from early childhood but none had overt renal disease in the first decade of life. Two patients were diagnosed with nephronophthisis in the second decade. Retinal imaging studies showed retained photoreceptor nuclei and retinal pigment epithelium integrity mainly in the cone-rich central retina, a phenotype with strong similarities to that of NPHP6 disease. Conclusions Mutations in NPHP5 can cause LCA without early-onset renal disease. Abnormalities observed in the photoreceptor outer segments (a cilial structure) may explain the severe visual loss in NPHP5-associated LCA. Clinical Relevance The persistence of central photoreceptor nuclei despite severe visual loss in NPHP5 disease is encouraging for future therapeutic interventions. PMID:21220633

  11. Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

    Science.gov (United States)

    Ashtari, Manzar; Zhang, Hui; Cook, Philip A; Cyckowski, Laura L; Shindler, Kenneth S; Marshall, Kathleen A; Aravand, Puya; Vossough, Arastoo; Gee, James C; Maguire, Albert M; Baker, Chris I; Bennett, Jean

    2015-07-15

    Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy.

  12. A Female Patient with Down Syndrome and Low-Penetrance Leber's Hereditary Optic Neuropathy

    Directory of Open Access Journals (Sweden)

    Starleen E. Frousiakis

    2014-11-01

    Full Text Available We present the case of a 19-year-old female with a history of Down syndrome (DS who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON. The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS.

  13. Gestion des risques

    CERN Document Server

    Louisot, Jean-Paul

    2009-01-01

    Depuis le début du lie siècle, la gestion des risques connaît une véritable révolution culturelle. Jusqu'alors fonction technique, centrée autour de l'achat de couverture d'assurances, elle est devenue une discipline managériale et transversale : une valise d'instruments que chaque manager doit connaître et appliquer quels que soient son domaine de compétence et ses missions au sein de l'organisation. En effet, la gestion des risques est une culture qui doit être assimilée par chacun des acteurs. C'est précisément l'ambition des 101 questions rassemblées dans cet ouvrage : apporter à chaque manager d'entreprise, de collectivité, d'établissement de santé..., des réponses claires au " pourquoi " et au " comment " : Comment identifier les risques ? Comment analyser les risques ? Quels sont les objectifs de la gestion des risques ? Une carte des risques pour quoi faire ? Pourquoi faut-il financer les risques ? Les entreprises ont-elles des responsabilités pénales ? En quoi consiste la gestion...

  14. Le dialogisme intertextuel des contes des Grimm

    OpenAIRE

    2012-01-01

    « Le caractère le plus important de l’énoncé, ou en tous cas le plus ignoré, est son dialogisme, c’est-à-dire sa dimension intertextuelle », constate Todorov en référence à la conception dialogique du langage proposée par Bakthine. Cet article introductif postule que ce constat s’applique aussi aux contes des Grimm. En partant des recherches déjà menées sur Apulée, Straporola, Basile, Perrault, La Fontaine et Lhéritier, il présente des concepts (réponse intertextuelle, reconfiguration génériq...

  15. Is Leber hereditary optic neuropathy treatable? Encouraging results with idebenone in both prospective and retrospective trials and an illustrative case.

    Science.gov (United States)

    Sabet-Peyman, Esfandiar J; Khaderi, Khizer R; Sadun, Alfredo A

    2012-03-01

    A 31-year-old woman developed subacute bilateral visual loss over a 2-week period. Two months later, the diagnosis of Leber hereditary optic neuropathy (LHON) 11778/ND4 was established and the patient was treated with 900 mg of idebenone daily. Over the ensuing 9 months, visual acuity improved from 20/200 to 20/25 in each eye with near-total resolution in visual field abnormalities. Our case report is in agreement with 2 large published series of patients with LHON treated with idebenone, raising hope for treatment of this visually devastating mitochondrial disorder.

  16. Posterior reversible encephalopathy syndrome in a leber hereditary optic neuropathy patient with mitochondrial DNA 11778G>A point mutation.

    Science.gov (United States)

    Da, Yuwei; Zhang, Xuxiang; Li, Fang; Yang, Xiaoping; Zhang, Xinqing; Jia, Jianping

    2013-09-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder that primarily affects the optic nerve. We report a case of reduced visual acuity secondary to optic atrophy in a 13-year-old boy. Transient seizures developed subsequently. Serial magnetic resonance imaging of the brain showed posterior reversible encephalopathy syndrome. Ragged red fibers were not detected on skeletal muscle biopsy. A 11778G>A mitochondrial DNA point mutation was identified in the lymphocytes isolated from peripheral blood. His younger brother was a carrier with the same mutation. The presentation of this case is unusual documenting LHON in association with PRES.

  17. Leber's遗传性视神经病变3460A点突变及临床预后%Leber's hereditary optic neuropathy (LHON) pedigrees with G3460A mitochondrial mutation and its clinical prognosis

    Institute of Scientific and Technical Information of China (English)

    杜利平; 金学民; 孙大光; 马旭

    2006-01-01

    目的报道一个携带线粒体G3460A点突变的Leber's遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)家系及其临床预后.方法对一LHON家系10母系成员进行临床检查,应用聚合酶链反应扩增目的基因、琼脂糖凝胶电泳、切胶纯化并双向测序,对三个原发突变位点G3460A、G11778A、T14484C进行检测.结果所有母系成员均携带G3460A点突变,家系内对照未携带该突变;所有的家系成员未携带其他两个原发突变.结论携带G3460A点突变的患者有较好的视力预后.

  18. Analysis on the effect of secondary mutations on Leber's hereditary optic neuropathy%继发突变位点对Leber's遗传性视神经萎缩作用机制的研究

    Institute of Scientific and Technical Information of China (English)

    王影; 童绎; 胡世兴; 王剑勇; 邵俊斌; 张洪星

    2007-01-01

    目的 探讨继发突变位点在Leber's遗传性视神经萎缩(Leber's hereditary optic neuropathy, LHON)疾病发生发展中的作用.方法 对4个LHON家系患者及家系男性子代进行3个原发位点、24个继发位点及相邻片段检查. 结果 4家系均携带11778位点突变,所查患者无24个继发位点突变,但在这些位点的相邻片段上有5178、5108、3705、3721、13734等多个多态位点存在.结论 线粒体多态位点具有家族遗传性, 在LHON继发位点研究中应同时进行男性子代检查,以排查突变位点是否具有致病性."修复基因"的存在可能对LHON疾病发展有影响.

  19. Psychological analysis of patients with Leber's hereditary optic neuropathy%Leber's遗传性视神经病变患者的心理分析及护理对策

    Institute of Scientific and Technical Information of China (English)

    苏丽金; 许英; 林婉意; 刘荣娇

    2005-01-01

    目的探讨Leber's遗传性视神经病变(LHOW)患者的心理状况及护理对策.方法采用Zung焦虑自评量表(SAS)和抑郁自评量表(SDS)调查38例Leber's遗传性视神经病变患者的心理特点.结果LHON患者的焦虑、抑郁评分与常模比较,经统计学分析,均P<0.01,差异有统计学意义.结论LHON患者的焦虑、抑郁状态明显比常模高.保持病房的安静和舒适,做好生活护理,帮助患者宣泄情绪和发挥家庭、社会的支持作用对患者保持情绪稳定,提高治疗的效果具有重要的意义.

  20. Photonique des Morphos

    CERN Document Server

    Berthier, Serge

    2010-01-01

    La photonique est déjà présente dans notre vie quotidienne, et on attend maintenant que la manipulation des photons permette aussi le traitement logique des informations. Cependant, l’élément de base qui permet cette manipulation de la lumière, le cristal photonique, est d’une réalisation complexe et mal contrôlée. Dans la course à la maîtrise de la lumière, les structures photoniques naturelles ont beaucoup à nous apprendre. C’est ce que nous montre Serge Berthier qui étudie dans ce livre la structure des écailles des Morphos. Tenant compte de l’essor récent des approches biomimétiques, il présente de manière détaillée plus de dix-huit techniques expérimentales utilisées pour ses analyses, ainsi que les diverses approches théoriques développées pour la modélisation de structures multi-échelles complexes. Première étude quasi-exhaustive des structures fines d’un genre et des propriétés optiques ainsi que colorimétriques générées, ce livre fournit aux entomologiste...

  1. Droit des organisations internationales

    CERN Document Server

    Sorel, Jean-Marc; Ndior, Valère

    2013-01-01

    Cet ouvrage collectif offre aux enseignants et chercheurs en droit international, aux praticiens et aux étudiants, une analyse actualisée du droit des organisations internationales. Il dresse en cinq parties un tableau, illustré par des exemples variés, des problématiques que soulève le phénomène polymorphe d institutionnalisation de la société internationale. La première partie est consacrée au phénomène des « organisations internationales », sous l angle à la fois de l institutionnalisation progressive des relations internationales et de la difficulté à cerner une catégorie unifiée. La deuxième partie rend compte de la création, de la disparition et des mutations des organisations internationales, ici envisagées comme systèmes institutionnels et ordres juridiques dérivés. La troisième partie analyse l autonomie que l acquisition de la personnalité juridique et de privilèges et immunités, un organe administratif intégré, un personnel ou un budget propres confèrent aux organi...

  2. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    NARCIS (Netherlands)

    DeVries, DD; Went, LN; Bruyn, GW; Scholte, HR; Hofstra, RMW; Bolhuis, PA; vanOost, BA

    1996-01-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA

  3. Advantage of whole exome sequencing over allele-specific and targeted segment sequencing in detection of novel TULP1 mutation in leber congenital amaurosis

    DEFF Research Database (Denmark)

    Guo, Yiran; Prokudin, Ivan; Yu, Cong

    2015-01-01

    Background: Leber congenital amaurosis (LCA) is a severe form of retinal dystrophy with marked underlying genetic heterogeneity. Until recently, allele-specific assays and Sanger sequencing of targeted segments were the only available approaches for attempted genetic diagnosis in this condition. ...

  4. Sequence Analysis of the Mitochondrial Genomes from Dutch Pedigrees with Leber Hereditary Optic Neuropathy

    Science.gov (United States)

    Howell, Neil; Oostra, Roelof-Jan; Bolhuis, Piet A.; Spruijt, Liesbeth; Clarke, Lorne A.; Mackey, David A.; Preston, Gwen; Herrnstadt, Corinna

    2003-01-01

    The complete mitochondrial DNA (mtDNA) sequences for 63 Dutch pedigrees with Leber hereditary optic neuropathy (LHON) were determined, 56 of which carried one of the classic LHON mutations at nucleotide (nt) 3460, 11778, or 14484. Analysis of these sequences indicated that there were several instances in which the mtDNAs were either identical or related by descent. The most striking example was a haplogroup J mtDNA that carried the 14484 LHON mutation. Four different but related mitochondrial genotypes were identified in seven of the Dutch pedigrees with LHON, including six of those described by van Senus. The control region of the founder sequence for these Dutch pedigrees with LHON matches the control-region sequence that Macmillan and colleagues identified in the founder mtDNA of French Canadian pedigrees with LHON. In addition, we obtained a perfect match between the Dutch 14484 founder sequence and the complete mtDNA sequences of two Canadian pedigrees with LHON. Those results indicate that these Dutch and French Canadian 14484 pedigrees with LHON share a common ancestor, that the single origin of the 14484 mutation in this megalineage occurred before the year 1600, and that there is a 14484/haplogroup J founder effect. We estimate that this lineage—including the 14484 LHON mutation—arose 900–1,800 years ago. Overall, the phylogenetic analyses of these mtDNA sequences conservatively indicate that a LHON mutation has arisen at least 42 times in the Dutch population. Finally, analysis of the mtDNA sequences from those pedigrees that did not carry classic LHON mutations suggested candidate pathogenic mutations at nts 9804, 13051, and 14325. PMID:12736867

  5. Extra-visual functional and structural connection abnormalities in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Rocca, Maria A; Valsasina, Paola; Pagani, Elisabetta; Bianchi-Marzoli, Stefania; Milesi, Jacopo; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2011-02-10

    We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits.

  6. Extra-visual functional and structural connection abnormalities in Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Maria A Rocca

    Full Text Available We assessed abnormalities within the principal brain resting state networks (RSNs in patients with Leber's hereditary optic neuropathy (LHON to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits.

  7. Mitochondrial DNA variant associated with Leber hereditary optic neuropathy and high-altitude Tibetans.

    Science.gov (United States)

    Ji, Fuyun; Sharpley, Mark S; Derbeneva, Olga; Alves, Leonardo Scherer; Qian, Pin; Wang, Yaoli; Chalkia, Dimitra; Lvova, Maria; Xu, Jiancheng; Yao, Wei; Simon, Mariella; Platt, Julia; Xu, Shiqin; Angelin, Alessia; Davila, Antonio; Huang, Taosheng; Wang, Ping H; Chuang, Lee-Ming; Moore, Lorna G; Qian, Guisheng; Wallace, Douglas C

    2012-05-08

    The distinction between mild pathogenic mtDNA mutations and population polymorphisms can be ambiguous because both are homoplasmic, alter conserved functions, and correlate with disease. One possible explanation for this ambiguity is that the same variant may have different consequences in different contexts. The NADH dehydrogenase subunit 1 (ND1) nucleotide 3394 T > C (Y30H) variant is such a case. This variant has been associated with Leber hereditary optic neuropathy and it reduces complex I activity and cellular respiration between 7% and 28% on the Asian B4c and F1 haplogroup backgrounds. However, complex I activity between B4c and F1 mtDNAs, which harbor the common 3394T allele, can also differ by 30%. In Asia, the 3394C variant is most commonly associated with the M9 haplogroup, which is rare at low elevations but increases in frequency with elevation to an average of 25% of the Tibetan mtDNAs (odds ratio = 23.7). In high-altitude Tibetan and Indian populations, the 3394C variant occurs on five different macrohaplogroup M haplogroup backgrounds and is enriched on the M9 background in Tibet and the C4a4 background on the Indian Deccan Plateau (odds ratio = 21.9). When present on the M9 background, the 3394C variant is associated with a complex I activity that is equal to or higher than that of the 3394T variant on the B4c and F1 backgrounds. Hence, the 3394C variant can either be deleterious or beneficial depending on its haplogroup and environmental context. Thus, this mtDNA variant fulfills the criteria for a common variant that predisposes to a "complex" disease.

  8. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement.

    Science.gov (United States)

    Cideciyan, Artur V; Jacobson, Samuel G; Beltran, William A; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J; Olivares, Melani B; Schwartz, Sharon B; Komáromy, András M; Hauswirth, William W; Aguirre, Gustavo D

    2013-02-05

    Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5-11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term.

  9. Intervisit variability of visual parameters in Leber congenital amaurosis caused by RPE65 mutations.

    Science.gov (United States)

    Roman, Alejandro J; Cideciyan, Artur V; Schwartz, Sharon B; Olivares, Melani B; Heon, Elise; Jacobson, Samuel G

    2013-02-15

    To determine the intervisit variability of kinetic visual fields and visual acuity in patients with Leber congenital amaurosis (LCA) caused by mutations in the RPE65 (Retinal Pigment Epithelium-specific protein 65kDa) gene. RPE65-LCA patients (n = 20; ages 11-40 years) were studied on at least two visits separated by fewer than 120 days using Goldmann visual field (GVF) and ETDRS visual acuity (VA) in a retrospective review. GVFs were quantified by computing the spherical coordinates of their vertices and calculating the solid angle subtended, and reported in normalized solid-angle units (nsu) as a percentage of average normal field extent. Repeatability coefficients were calculated using 95% confidence intervals on log(10)-converted variables. Visual field extents in RPE65-LCA spanned a wide range from 4 to 95 nsu. The repeatability coefficient was 0.248 (log(10)nsu), suggesting cutoffs for significant change (in nsu) of +77% for improvement and -44% for worsening. VA in RPE65-LCA ranged from logMAR = 0.14 to 1.96 (20/40 to 20/1250). The repeatability coefficient was 0.170 (logMAR) (±8.5 ETDRS letters). Comparisons with published studies of ungenotyped retinitis pigmentosa showed that the RPE65-LCA patients had higher variability in kinetic field extent. VA variability in RPE65-LCA fell within reported results for retinitis pigmentosa. Variability data for GVF and VA are provided to permit interpretation of the significance of increases and decreases of these functional outcomes in ongoing and planned clinical trials of therapy for LCA caused by RPE65 mutations.

  10. Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP.

    Science.gov (United States)

    Pawlyk, Basil S; Smith, Alexander J; Buch, Prateek K; Adamian, Michael; Hong, Dong-Hyun; Sandberg, Michael A; Ali, Robin R; Li, Tiansen

    2005-09-01

    Retinitis pigmentosa GTPase regulator (RPGR) is a photoreceptor protein anchored in the connecting cilia by an RPGR-interacting protein (RPGRIP). Loss of RPGRIP causes Leber congenital amaurosis (LCA), a severe form of photoreceptor degeneration. The current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of LCA due to a defect in RPGRIP. An RPGRIP expression cassette, driven by a mouse opsin promoter, was packaged into recombinant adeno-associated virus (AAV). The AAV vector was delivered into the right eyes of RPGRIP(-/-) mice by a single subretinal injection into the superior hemisphere. The left eyes received a saline injection as a control. Full-field electroretinograms (ERGs) were recorded from both eyes at 2, 3, 4, and 5 months after injection. After the final follow-up, retinas were analyzed by immunostaining or by light and electron microscopy. Delivery of the AAV vector led to RPGRIP expression and restoration of normal RPGR localization at the connecting cilia. Photoreceptor preservation was evident by a thicker cell layer and well-developed outer segments in the treated eyes. Rescue was more pronounced in the superior hemisphere coincident with the site of delivery. Functional preservation was demonstrated by ERG. AAV-mediated RPGRIP gene replacement preserves photoreceptor structure and function in a mouse model of LCA, despite ongoing cell loss at the time of intervention. These results indicate that gene replacement therapy may be effective in patients with LCA due to a defect in RPGRIP and suggest that further preclinical development of gene therapy for this disorder is warranted.

  11. CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10.

    Science.gov (United States)

    Ruan, Guo-Xiang; Barry, Elizabeth; Yu, Dan; Lukason, Michael; Cheng, Seng H; Scaria, Abraham

    2017-02-01

    As the most common subtype of Leber congenital amaurosis (LCA), LCA10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. The most frequent mutation found in patients with LCA10 is a deep intronic mutation in CEP290 that generates a cryptic splice donor site. The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy. Here, we show that targeted genomic deletion using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system represents a promising therapeutic approach for the treatment of patients with LCA10 bearing the CEP290 splice mutation. We generated a cellular model of LCA10 by introducing the CEP290 splice mutation into 293FT cells and we showed that guide RNA pairs coupled with SpCas9 were highly efficient at removing the intronic splice mutation and restoring the expression of wild-type CEP290. In addition, we demonstrated that a dual AAV system could effectively delete an intronic fragment of the Cep290 gene in the mouse retina. To minimize the immune response to prolonged expression of SpCas9, we developed a self-limiting CRISPR/Cas9 system that minimizes the duration of SpCas9 expression. These results support further studies to determine the therapeutic potential of CRISPR/Cas9-based strategies for the treatment of patients with LCA10. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  12. Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy

    Science.gov (United States)

    Yee, Kenneth M.; Ross-Cisneros, Fred N.; Lee, Jeong Goo; Da Rosa, Arlon Bastos; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Chicani, Filipe; Moraes-Filho, Milton; Sebag, Jerry; Carelli, Valerio; Sadun, Alfredo A.

    2012-01-01

    Purpose. Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress. Methods. Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation “carriers,” 14/74 were “affected,” and 14/74 were “off-pedigree” controls. Serum NSE levels were determined by ELISA specific for the γ subunit of NSE. Results. Serum NSE concentrations in carriers (27.17 ± 39.82 μg/L) were significantly higher than affected (5.66 ± 4.19 μg/L; P = 0.050) and off-pedigree controls (6.20 ± 2.35 μg/L; P = 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean = 75.8 ± 42.3 μg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 ± 51.21 μg/L) than in asymptomatic female carriers (15.85 ± 22.27 μg/L; P = 0.034). Conclusions. Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress. PMID:22893673

  13. Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.

    Directory of Open Access Journals (Sweden)

    Sundaramurthy Srilekha

    Full Text Available Leber congenital amaurosis (LCA and retinitis pigmentosa (RP are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60% mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

  14. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy

    Science.gov (United States)

    Weiss, Jeffrey N.; Levy, Steven; Benes, Susan C.

    2016-01-01

    The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option. PMID:27904503

  15. Dental Encounter System (DES)

    Data.gov (United States)

    Department of Veterans Affairs — Dental Encounter System (DES) is an automated health care application designed to capture critical data about the operations of VA Dental Services. Information on...

  16. Table des illustrations

    OpenAIRE

    2016-01-01

    Tableaux Dates d’inauguration des grands hôtels japonais entre 1860 et 1945… 19 Histoire, tourisme et hôtellerie en Corée depuis les années 1870… 59-60 Dates d’inauguration des grands hôtels chinois depuis 1863… 84 Les hôtels de luxe et leurs capacités d’hébergement en Corée en 2000… 103 Les flux de personnes suscités par les hôtels « super luxe » de Séoul en 2000… 105 L’activité des grands hôtels à Séoul en 1999 (en wons)… 106 Propriété et gestion des grands hôtels à Séoul en 1999…. 110 La c...

  17. Chimie des processus biologiques

    OpenAIRE

    Fontecave, Marc

    2010-01-01

    La chimie du vivant : enzymes et métalloenzymes, des biocatalyseurs fascinants La catalyse enzymatique, ce pouvoir que possèdent certaines protéines d’accélérer de façon extraordinaire et d’orienter avec une précision fascinante les réactions chimiques de la cellule, reste, encore aujourd’hui, l’un des grands mystères des systèmes vivants. Les réactions dont il est question vont de la simple hydrolyse de liaisons peptidiques à des processus poly-électroniques d’une très grande complexité, com...

  18. Vom Ort des Philosophierens

    OpenAIRE

    Damir Barbaric

    2002-01-01

    Im Aufsatz wird versucht, den ursprünglichen Sinn der Platonischen Bestimmung vom Staunen als Anfang der Philosophie zu ermitteln, und zwar durch eine kritischen Abhebung von ihrer Umdeutung bei Aristoteles, und dann insbesondere in der Stoa wie auch bei Spinoza und Hegel. Dabei wird auf die frühgriechische Erfahrung vom Staunen als _______ aufmerksam gemacht, wo es vor allem die Grundstimmung des Dabeiseins des Göttlichen und der menschlichen Teilnahme am Göttlichen bedeutet. Dem entspricht ...

  19. Liste des auteurs

    OpenAIRE

    2015-01-01

    Fariba Adelkhah est chargée de recherche à la Fondation nationale des sciences politiques, Centre d’études et de recherches internationales (CERI) [] Jean-Marie Bouissou est chargé de recherche à la Fondation nationale des sciences politiques, Centre d’études et de recherches internationales (CERI) [] Jean-Louis Briquet est chargé de recherche au CNRS, Centre d’études et de recherches internationales (CERI) [...

  20. La revolution des savants

    CERN Document Server

    Chavanne, A

    1989-01-01

    Premiere cassette : - 1666 : impact de la creation de l'Academie des Sciences par Colbert, trente ans apres le proces de Galile, et au moment des disparitions de Pascal, Descartes et Fermat. Elle dirigee par le hollandais Huyggens jusqu'a sa fuite de France au moment de la revocation de l'Edit de Nantes. - 1750 : l'Encyclopedie (ou "Dictionnaire raisonne des Sciences, des Arts et des Metiers") de Diderot et d'Alembert, soutenus par Malherbes, Buffon, Condorcet et Rousseau. - 1789 : Revolution francaise. - 8 aout 1793 : l'Assemblee, par une declaration de Marat, dissout l'Academie des Sciences. Celle-ci continue cependant ses travaux pour les poids et mesures jusqu'en 1795. - la Terreur : la condamnation a mort, pas au nom d'une "Revolution qui n'a pas besoin de savants" mais pour d'autres raisons, de trois grands hommes de science : Lavoisier, Bailly et Condorcet. - 1793-1794 : Au printemps 93, le Comite de Salut Publique s'inquiete du demi-million de soldats etrangers de toutes les pays frontaliers qui essai...

  1. Le dialogisme intertextuel des contes des Grimm

    OpenAIRE

    2013-01-01

    Loin d'être « purement allemands », nombre de contes des Grimm réécrivent les contes français largement diffusés en Allemagne au XVIIIe siècle en les « reconfigurant » selon leurs propres paradigmes esthétiques et idéologiques. L'étude introductive de la comparatiste Ute Heidmann montre que ce dialogisme européen est resté peu exploré en raison d’une « scénographie en trompe-l’œil » qui les présente comme issus du « terroir » hessois. Toutefois, les notes des Grimm (constituées en volume auto...

  2. Maladie des vibrations

    Science.gov (United States)

    Shen, Shixin (Cindy); House, Ronald A.

    2017-01-01

    Résumé Objectif Permettre aux médecins de famille de comprendre l’épidémiologie, la pathogenèse, les symptômes, le diagnostic et la prise en charge de la maladie des vibrations, une maladie professionnelle importante et courante au Canada. Sources d’information Une recherche a été effectuée sur MEDLINE afin de relever les recherches et comptes rendus portant sur la maladie des vibrations. Une recherche a été effectuée sur Google dans le but d’obtenir la littérature grise qui convient au contexte canadien. D’autres références ont été tirées des articles relevés. Message principal La maladie des vibrations est une maladie professionnelle répandue touchant les travailleurs de diverses industries qui utilisent des outils vibrants. La maladie est cependant sous-diagnostiquée au Canada. Elle compte 3 éléments : vasculaire, sous la forme d’un phénomène de Raynaud secondaire; neurosensoriel; et musculosquelettique. Aux stades les plus avancés, la maladie des vibrations entraîne une invalidité importante et une piètre qualité de vie. Son diagnostic exige une anamnèse minutieuse, en particulier des antécédents professionnels, un examen physique, des analyses de laboratoire afin d’éliminer les autres diagnostics, et la recommandation en médecine du travail aux fins d’investigations plus poussées. La prise en charge consiste à réduire l’exposition aux vibrations, éviter les températures froides, abandonner le tabac et administrer des médicaments. Conclusion Pour assurer un diagnostic rapide de la maladie des vibrations et améliorer le pronostic et la qualité de vie, les médecins de famille devraient connaître cette maladie professionnelle courante, et pouvoir obtenir les détails pertinents durant l’anamnèse, recommander les patients aux cliniques de médecine du travail et débuter les demandes d’indemnisation de manière appropriée. PMID:28292812

  3. La convergence des rôles respectifs des relationnistes et des journalistes influence-t-elle la perception qu'ils ont les uns des autres?

    DEFF Research Database (Denmark)

    Valentini, Chiara

    2017-01-01

    la convergence des rôles respectifs des praticiens des relations publiques et des journalistes a un effet favorable sur la perception qu’ils ont les uns des autres. L’effet est plus marqué chez les praticiens des relations publiques, car leur vision de la profession en journalisme correspond à celle...

  4. À propos des occasionnalismes

    Directory of Open Access Journals (Sweden)

    Dal Georgette

    2016-01-01

    Full Text Available Les occasionnalismes (nonce formations ou contextual formations dans la terminologie anglo-saxonne, qu’on définira provisoirement comme de “new complex word[s] created by a speaker/writer on the spur of the moment to cover some immediate need” (Bauer, 1983 : 45 ont, à notre connaissance, peu retenu l’attention des morphologues du domaine francophone. Pourtant, toutes les conditions sont désormais réunies pour que cet objet, invisible lorsqu’il s’agissait de décrire le système morphologique du français (ou d’autres langues à partir de ressources dictionnairiques, émerge en tant qu’observable dans une morphologie puisant ses données dans le réel langagier des locuteurs. Par définition en effet, on s’attend à ce qu’un occasionalisme soit absent des dictionnaires (nous verrons que, dans les faits, la situation est plus complexe que cela, et que ces contextual formations ne puissent pas être étudiées en dehors du contexte dans lequel elles ont été produites. À cet égard, la Toile et les produits qui en dérivent constituent des ressources de choix. C’est particulièrement vrai des forums, dans lesquels les internautes s’expriment librement, laissant libre cours à leur potentiel créatif (ou ce qu’ils pensent tel. Dans la présente communication, après avoir défini la notion d’occasionalisme, nous utiliserons un corpus constitué au fil d’autres recherches pour dégager des motifs récurrents propices à leur apparition, autrement dit pour établir une grammaire des occasionnalismes.

  5. Rare primary mitochondrial DNA mutations and probable synergistic variants in Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Alessandro Achilli

    Full Text Available BACKGROUND: Leber's hereditary optic neuropathy (LHON is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes. However, the spectrum of mtDNA mutations causing the remaining 10% of cases is only partially and often poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: In order to improve such a list of pathological variants, we completely sequenced the mitochondrial genomes of suspected LHON patients from Italy, France and Germany, lacking the three primary common mutations. Phylogenetic and conservation analyses were performed. Sixteen mitochondrial genomes were found to harbor at least one of the following nine rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A-C/p.E143K-Q, m.4171C>A/p.L289M, MT-ND4L (m.10663T>C/p.V65A and MT-ND6 (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S. Phylogenetic analyses revealed that these substitutions were due to independent events on different haplogroups, whereas interspecies comparisons showed that they affected conserved amino acid residues or domains in the ND subunit genes of complex I. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that these nine substitutions are all primary LHON mutations. Therefore, despite their relative low frequency, they should be routinely tested for in all LHON patients lacking the three common mutations. Moreover, our sequence analysis confirms the major role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the general population of Western Europe and other putative synergistic mtDNA variants in LHON expression.

  6. Safety and Effects of the Vector for the Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial

    Science.gov (United States)

    Koilkonda, Rajeshwari D.; Yu, Hong; Chou, Tsung-Han; Feuer, William J.; Ruggeri, Marco; Porciatti, Vittorio; Tse, David; Hauswirth, William W.; Chiodo, Vince; Boye, Sanford L.; Lewin, Alfred S.; Neuringer, Martha; Renner, Lauren; Guy, John

    2014-01-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3

  7. Trial End Points and Natural History in Patients With G11778A Leber Hereditary Optic Neuropathy

    Science.gov (United States)

    Lam, Byron L.; Feuer, William J.; Schiffman, Joyce C.; Porciatti, Vittorio; Vandenbroucke, Ruth; Rosa, Potyra R.; Gregori, Giovanni; Guy, John

    2014-01-01

    IMPORTANCE Establishing the natural history of G11778A Leber hereditary optic neuropathy (LHON) is important to determine the optimal end points to assess the safety and efficacy of a planned gene therapy trial. OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study initiated in 2008 was conducted in primary and referral institutional practice settings. Participants included 44 individuals with G11778A LHON, recruited between September 2008 and March 2012, who were evaluated every 6 months and returned for 1 or more follow-up visits (6–36 months) as of August 2012. EXPOSURES Complete neuro-ophthalmic examination and main measures. MAIN OUTCOMES AND MEASURES Visual acuity, automated visual field testing, pattern electroretinogram, and spectral-domain optical coherence tomography. RESULTS Clinical measures were stable during the follow-up period, and visual acuity was as good as or better than the other visual factors used for monitoring patients. Based on a criterion of 15 or more letters from the Early Treatment Diabetic Retinopathy Study chart, 13 eyes of 8 patients (18%) improved, but 24 months after the onset of symptoms, any further improvements were to no better than 20/100. Acuity recovery occurred in some patients despite continued marked retinal nerve fiber layer thinning indistinguishable from that in patients who did not recover visual acuity. CONCLUSIONS AND RELEVANCE Spontaneous improvement of visual acuity in patients with G11778A LHON is not common and is partial and limited when it occurs, so improvements in vision with adeno-associated virus–mediated gene therapy of a synthetic wild-type ND4 subunit gene should be

  8. Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial.

    Science.gov (United States)

    Koilkonda, Rajeshwari D; Yu, Hong; Chou, Tsung-Han; Feuer, William J; Ruggeri, Marco; Porciatti, Vittorio; Tse, David; Hauswirth, William W; Chiodo, Vince; Boye, Sanford L; Lewin, Alfred S; Neuringer, Martha; Renner, Lauren; Guy, John

    2014-04-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3

  9. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Yang, Shuo; Ma, Si-Qi; Wan, Xing; He, Heng; Pei, Han; Zhao, Min-Jian; Chen, Chen; Wang, Dao-Wen; Dong, Xiao-Yan; Yuan, Jia-Jia; Li, Bin

    2016-08-01

    Leber's hereditary optic neuropathy (LHON) is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP), optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2-9) received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8) and untreated eyes (Patients 2, 3, 4, 6 and 8). Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1) who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains stable in the

  10. Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

    Science.gov (United States)

    Simonelli, Francesca; Ziviello, Carmela; Testa, Francesco; Rossi, Settimio; Fazzi, Elisa; Bianchi, Paolo Emilio; Fossarello, Maurizio; Signorini, Sabrina; Bertone, Chiara; Galantuomo, Silvana; Brancati, Francesco; Valente, Enza Maria; Ciccodicola, Alfredo; Rinaldi, Ernesto; Auricchio, Alberto; Banfi, Sandro

    2007-09-01

    To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis. DNA samples from 95 patients with LCA were analyzed by using a microarray chip containing disease-associated sequence variants in eight LCA genes. In addition, all patients in whom no mutations were identified by microarray were subjected to sequence analysis of the CEP290 gene. Patients with mutations identified underwent a detailed ophthalmic evaluation. Disease-causing mutations were identified in 28% of patients, and twelve novel variants were identified. Mutations occurred more frequently in the RPE65 (8.4%), CRB1 (7.4%), and GUCY2D (5.2%) genes. Mutations in CEP290 were found in only 4.2% of the patients analyzed. Clinical assessment of patients carrying RPE65 or CRB1 mutations revealed the presence of retained visual capabilities in the first decade of life. RPE65 mutations were almost always associated with normal macular thickness, as assessed by optical coherence tomography (OCT), whereas CRB1 mutations were associated with reduced retinal thickness and a coarsely laminated retina. Fundus autofluorescence was mostly observed in patients with RPE65 and GUCY2D mutations and was not elicitable in patients carrying CRB1. RPE65 gene mutations represented a significant cause of LCA in the Italian population, whereas GUCY2D and CEP290 mutations had a lower frequency than that found in other reports. This finding suggests that the genetic epidemiology of LCA in Italy is different from that reported in the United States and in northern European countries. Autofluorescence in patients with RPE65 mutations was more frequently associated with preserved retinal thickness, which suggests that these mutations are not associated with progression of retinal degeneration. Therefore, normal retinal thickness (identified with OCT) and fundus autofluorescence may be the means with which to identify patients with LCA who carry RPE65

  11. A retrospective analysis of characteristics of visual field damage in patients with Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Ran, Ruijin; Yang, Shuo; He, Heng; Ma, Shiqi; Chen, Zhiqi; Li, Bin

    2016-01-01

    The objective of this study is to investigate the characteristics and the evolution of visual field damage caused by Leber's hereditary optic neuropathy (LHON) and to provide clinical data for the diagnosis of LHON. Parameters of visual field in 32 consecutive patients (49 eyes) with LHON who were confirmed by genetic diagnostic tests were retrospectively measured within 1 week, between three to six months, and at six months after onset. Visual field defects revealed central scotoma in 26 eyes (53.1 %), paracentral scotoma in 12 eyes (24.5 %), ceco-central defects in 6 eyes (12.2 %), blind spot enlargenment in 3 eyes (6.1 %), quadrantanopia in 2 eyes (4.1 %) within 1 week after onset. After 3 to 6 months, ceco-central defects were detected in 22 eyes (44.9 %), central isopter constriction in 10 eyes (20.4 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), central scotoma in 4 eyes (8.2 %), and paracentral scotoma in 1 eye (2.0 %). After 6 months, central isopter constriction was observed in 18 eyes (36.7 %), diffuse defects in 21 eyes (42.9 %), ceco-central defects in 3 eyes (6.1 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), and central scotoma in 2 eyes (4.1 %). LHON at different stages was characterized by different focal visual field defects: visual field defects in LHON patients within 1 week after onset were mostly central or paracentral scotoma, which was enlarged around the ceco-central defect, or connected to form a blind spot after 3-6 months. Diffuse and central isopter constriction defects were usually developed after 6 months. Damages firstly appeared in papillomacular bundle and gradually expanded outward. These characteristics of visual field defects reported in this study might provide a clinical basis for better diagnosis of LHON.

  12. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Shuo Yang

    2016-08-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12 months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP, optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2–9 received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8 and untreated eyes (Patients 2, 3, 4, 6 and 8. Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1 who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3 months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains

  13. Bax-induced apoptosis in Leber's congenital amaurosis: a dual role in rod and cone degeneration.

    Directory of Open Access Journals (Sweden)

    Séverine Hamann

    Full Text Available Pathogenesis in the Rpe65(-/- mouse model of Leber's congenital amaurosis (LCA is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65(-/- mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65, was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe65(-/- mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors.Quantitative PCR analysis showed that increased expression of pro-apoptotic Bax and decreased level of anti-apoptotic Bcl-2 were restored in Rpe65(-/-/Gnat1(-/- mice lacking the Gnat1 gene encoding rod transducin. Moreover, photoreceptor apoptosis was prevented as assessed by TUNEL assay. These data indicate that abnormal activity of opsin apoprotein induces retinal cell apoptosis through the Bcl-2-mediated pathway. Following immunohistological and real-time PCR analyses, we further observed that decreased expression of rod genes in Rpe65-deficient mice was rescued in Rpe65(-/-/Bax(-/- mice. Histological and TUNEL studies confirmed that rod cell demise and apoptosis in diseased Rpe65(-/- mice were dependent on Bax-induced pathway. Surprisingly, early loss of cones was not prevented in Rpe65(-/-/Bax(-/- mice, indicating that pro-apoptotic Bax was not involved in the pathogenesis of cone cell death in Rpe65-deficient mice

  14. Des Vents et des Jets Astrophysiques

    Science.gov (United States)

    Sauty, C.

    well expected result from the theory. Although, collimation may be conical, paraboloidal or cylindrical (Part 4), cylindrical collimation is the more likely to occur. The shape of outflows may then be used as a tool to predict physical conditions on the flows or on their source. L'éjection continue de plasma autour d'objets massifs est un phénomène largement répandu en astrophysique, que ce soit sous la forme du vent solaire, de vents stellaires, de jets d'étoiles en formation, de jets stellaires autour d'objets compacts ou de jets extra-galactiques. Cette zoologie diversifiée fait pourtant l'objet d'un commun effort de modélisation. Le but de cette revue est d'abord de présenter qualitativement le développement, depuis leur origine, des diverses théories de vents (Partie 1) et l'inter disciplinarité dans ce domaine. Il s'agit d'une énumération, plus ou moins exhaustive, des idées proposées pour expliquer l'accélération et la morphologie des vents et des jets, accompagnée d'une présentation sommaire des aspects observationnels. Cette partie s'abstient de tout aspect faisant appel au formalisme mathématique. Ces écoulements peuvent être décrits, au moins partiellement, en résolvant les équations magnétohydrodynamiques, axisymétriques et stationnaires. Ce formalisme, à la base de la plupart des théories, est exposé dans la Partie 2. Il permet d'introduire quantitativement les intégrales premières qu'un tel système possède. Ces dernières sont amenées à jouer un rôle important dans la compréhension des phénomènes d'accélération ou de collimation, en particulier le taux de perte de masse, le taux de perte de moment angulaire ou l'énergie du rotateur magnétique. La difficulté de modélisation réside dans l'existence de points critiques, propres aux équations non linéaires, qu'il faut franchir. La nature physique et la localisation de ces points critiques fait l'objet d'un débat important car ils sont la clef de voute de la r

  15. Table des illustrations

    OpenAIRE

    2015-01-01

    Intégrer les Tsiganes Hongrie, 1970 (photo DR) 34 Discuter entretient la fraternité. (photo M. Stewart) 35 La veille du mariage (photo M. Stewart) 36 Le « salon » (photo M. Stewart) 37 Les activités économiques des Tsiganes sont conçues comme des jeux. (photo M. Stewart) 39 Lev cheval (photo I. Nemeth) 41 Le cortège d’un mariage (photo M. Stewart) 43 Avant le mariage (photo M. Stewart) 43 C’est par le chant (photo M. Stewart) 45 Des « frères » boivent en harmonie (photo M. Stewart) 46 Les che...

  16. Geschichte des SIN

    CERN Document Server

    Pritzker, Andreas

    2013-01-01

    Dieses Buch erzählt die Geschichte des Schweizerischen Instituts für Nuklearforschung (SIN). Das Institut wurde 1968 gegründet und ging 1988 ins Paul Scherrer Institut (PSI) über. Die Gründung des SIN erfolgte in einer Zeit, als die Physik weitherum als Schlüsseldisziplin für die technologische und gesellschaftliche Entwicklung galt. Der Schritt war für ein kleines Land wie die Schweiz ungewöhnliche und zeugte von Mut und Weitsicht. Ungewöhnlich waren der Folge die Leistungen des SIN im weltweiten Vergleich sowie sein Einfluss auf die schweizerische, teils auf die internationale Wissenschaftspolitik.

  17. Les lueurs des sables

    CERN Multimedia

    Les lueurs des sables

    2013-01-01

    Two CERN ladies are getting ready for the “Trophée Roses des Sables” rally adventure: Julie and Laetitia are finalizing the last details before setting off on Monday 7th October 2013. Julie from EN-MEF group and Laetitia from DGS-SEE group, met at the CERN Rugby club. This year, they are participating in the 100 % female rally which will take place in Morocco from 10 to 20 October. They will be carrying along 100 kg of humanitarian donation for children such as some clothes, books and medical material. Do not hesitate to show your support at their farewell party to be held on Monday 7 October, from 4 to 6 pm in front of the St Genis-Pouilly Mairie (city Hall). Follow their exciting adventure on the blog leslueursdessables.trophee-roses-des-sables.org and on their association’s Facebook page Les Lueurs des Sables.

  18. Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Carelli, Valerio; Vergani, Lodovica; Bernazzi, Barbara; Zampieron, Claudia; Bucchi, Laura; Valentino, Maria; Rengo, Chiara; Torroni, Antonio; Martinuzzi, Andrea

    2002-10-09

    The possibility that some combinations of mtDNA polymorphisms, previously associated with Leber's hereditary optic neuropathy (LHON), may affect mitochondrial respiratory function was tested in osteosarcoma-derived transmitochondrial cytoplasmic hybrids (cybrids). In this cellular system, in the presence of the same nuclear background, different exogenous mtDNAs are used to repopulate a parental cell line previously devoid of its original mtDNA. No detectable differences in multiple parameters exploring respiratory function were observed when mtDNAs belonging to European haplogroups X, H, T and J were used. Different possible explanations for the previously established association between haplogroup J and LHON 11778/ND4 and 14484/ND6 pathogenic mutations are discussed, including the unconventional proposal that mtDNA haplogroup J may exert a protective rather than detrimental effect.

  19. Mitochondrial dysfunction due to Leber's hereditary optic neuropathy as a cause of visual loss during assessment for epilepsy surgery.

    Science.gov (United States)

    Niehusmann, Pitt; Surges, Rainer; von Wrede, Randi D; Elger, Christian E; Wellmer, Jörg; Reimann, Jens; Urbach, Horst; Vielhaber, Stefan; Bien, Christian G; Kunz, Wolfram S

    2011-01-01

    Assessment for epilepsy surgery may require invasive measures such as implantation of intracranial electrodes or the Wada test. These investigations are commonly well tolerated. However, complications, including visual disturbances of various etiologies, have been reported. Here we describe two patients with pharmacoresistant temporal lobe epilepsy (TLE) who displayed loss of vision in the context of presurgical assessment and in whom mutations associated with Leber's hereditary optic neuropathy (LHON) were detected. Genetic analysis revealed in one patient the frequent mitochondrial G11778A LHON mutation in ND4. In the second patient, the mitochondrial C4640A mutation in ND2 was detected. This rare LHON mutation enhanced the sensitivity of the patient's muscle and brain tissue to amobarbital, a known blocker of the mitochondrial respiratory chain. Mitochondrial dysfunction has been reported in epilepsy. Thus, the presence of LHON mutations can be a rare cause of visual disturbances in patients with epilepsy and may have predisposed to development of epilepsy.

  20. Deep sequencing unearths nuclear mitochondrial sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants.

    Science.gov (United States)

    Petruzzella, Vittoria; Carrozzo, Rosalba; Calabrese, Claudia; Dell'Aglio, Rosa; Trentadue, Raffaella; Piredda, Roberta; Artuso, Lucia; Rizza, Teresa; Bianchi, Marzia; Porcelli, Anna Maria; Guerriero, Silvana; Gasparre, Giuseppe; Attimonelli, Marcella

    2012-09-01

    Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences.

  1. Papilloedema and MRI enhancement of the prechiasmal optic nerve at the acute stage of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Lamirel, Cédric; Cassereau, Julien; Cochereau, Isabelle; Vignal-Clermont, Catherine; Pajot, Olivier; Tanguy, Jean-Yves; Zanlonghi, Xavier; Reynier, Pascal; Amati-Bonneau, Patrizia; Dubas, Frédéric; Bonneau, Dominique; Verny, Christophe

    2010-05-01

    The authors report a case of one patient from a family carrying the homoplasmic Leber hereditary optic neuropathy (LHON) G11778A mitochondrial DNA mutation with papilloedema 9 months prior to the acute stage of LHON and still present at the onset of visual loss. During the vision loss, the MRI demonstrated a T2 hyperintensity and an enhancement of the prechiasmal left optic nerve, suggesting the existence of an inflammatory mechanism. A retrospective review of the chart of two others members of the same family, with bilateral optic disc oedema at onset of the vision loss, suggests that the relationship of papilloedema and acute phase of LHON may not be just a coincidence, at least in this family. The visual loss related to LHON could have been triggered in the setting of the chronic papilloedema, associated with the intracranial hypertension.

  2. Features of mtDNA mutation patterns in European pedigrees and sporadic cases with leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Obermaier-Kusser, B.; Schubring, S.; Paprotta, A.; Meitinger, T.; Jaksch, M.; Gerbitz, K.D. [Univ. of Munich (Germany); Lorenz, B. [Univ. of Rogensburgh (Germany); Zerres, K. [Univ. of Bonn (Germany); Meire, F. [Univ. of Ghent (Belgium); Cochaux, P. [Univ. of Brussels (Belgium)] [and others

    1994-11-01

    Leber hereditary optic neuropathy (LHON) is maternally transmitted and is characterized by bilateral loss of central vision in young adults as a result of optic nerve degeneration. Fifteen transition mutations located in different genes for the mitochondrially encoded subunits of respiratory chain complexes have been associated thus far with the disease. Genetic studies have led to the classification of the pathogenic significance of these different mutations. However, more research is required to determine the causality of the mutations and the penetrance of the disease. The present study compares studies of populations of different ethnic origins, namely European LHON pedigrees and sporadic cases, in order to elucidate the pathogenic mechanisms involved. 21 refs., 2 figs., 1 tab.

  3. Language skills in a child with Leber hereditary optic neuropathy following intrathecal chemotherapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Lewis, Fiona M; Coman, David J; Murdoch, Bruce E

    2010-11-01

    The language skills of a male child with Leber hereditary optic neuropathy (LHON) and coincidentally treated for acute lymphoblastic leukemia (ALL) with intrathecal chemotherapy at the age of 3 years 8 months were comprehensively evaluated twice over a 6-month period approximately 5½ years after diagnosis of ALL. Despite marked chemotherapy-related leukoencephalopathic changes documented on magnetic resonance imaging, the child presented with stable language skills, which were generally average to above-average based on the normative data from a comprehensive language test battery. In light of the coincidental presentation in the child of a diagnosis of LHON, which may lead to serious vision impairment and increased vulnerability to drug neurotoxicity, coupled with a history of central nervous system (CNS)-directed treatment for ALL resulting in progressive white matter pathology, the study highlights the importance of ongoing monitoring of the child's language development throughout his adolescent years.

  4. Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells

    Science.gov (United States)

    Santini, Paolo

    2016-01-01

    Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment. PMID:26881022

  5. Previously Unclassified Mutation of mtDNA m.3472T>C: Evidence of Pathogenicity in Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Sheremet, N L; Nevinitsyna, T A; Zhorzholadze, N V; Ronzina, I A; Itkis, Y S; Krylova, T D; Tsygankova, P G; Malakhova, V A; Zakharova, E Y; Tokarchuk, A V; Panteleeva, A A; Karger, E M; Lyamzaev, K G; Avetisov, S E

    2016-07-01

    Leber's hereditary optic neuropathy (LHON) refers to a group of mitochondrial diseases and is characterized by defects of the mitochondrial electron transport chain and decreased level of oxidative phosphorylation. The list of LHON primary mtDNA mutations is regularly updated. In this study, we describe the homoplasmic nucleotide substitution m.3472T>C in the MT-ND1 (NADH-ubiquinone oxidoreductase chain 1) gene and specific changes in cell metabolism in a patient with LHON and his asymptomatic sister. To confirm the presence of mutation-related mitochondrial dysfunction, respiration of skin fibroblasts and platelets from the patient and his sister was studied, as well as the mitochondrial potential and production of reactive oxygen species in the skin fibroblasts. In addition, based on characteristics of the toxic effect of paraquat, a new approach was developed for detecting the functional activity of complex I of the mitochondrial respiratory chain.

  6. Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells.

    Science.gov (United States)

    Falabella, Micol; Forte, Elena; Magnifico, Maria Chiara; Santini, Paolo; Arese, Marzia; Giuffrè, Alessandro; Radić, Kristina; Chessa, Luciana; Coarelli, Giulia; Buscarinu, Maria Chiara; Mechelli, Rosella; Salvetti, Marco; Sarti, Paolo

    2016-01-01

    Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.

  7. AON-mediated Exon Skipping Restores Ciliation in Fibroblasts Harboring the Common Leber Congenital Amaurosis CEP290 Mutation

    Directory of Open Access Journals (Sweden)

    Xavier Gerard

    2012-01-01

    Full Text Available Leber congenital amaurosis (LCA is a severe hereditary retinal dystrophy responsible for congenital or early-onset blindness. The most common disease-causing mutation (>10% is located deep in intron 26 of the CEP290 gene (c.2991+1655A>G. It creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. In the present study, we show that the use of antisense oligonucleotides (AONs allow an efficient skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients. These data support the feasibility of an AON-mediated exon skipping strategy to correct the aberrant splicing.

  8. Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis.

    Science.gov (United States)

    Batten, Matthew L; Imanishi, Yoshikazu; Tu, Daniel C; Doan, Thuy; Zhu, Li; Pang, Jijing; Glushakova, Lyudmila; Moise, Alexander R; Baehr, Wolfgang; Van Gelder, Russell N; Hauswirth, William W; Rieke, Fred; Palczewski, Krzysztof

    2005-11-01

    Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. An animal model of LCA, the Lrat-/- mouse, recapitulates clinical features of the human disease. Here, we report that two interventions--intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds--each restore retinal function to Lrat-/- mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to approximately 50% of wild-type levels (p gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness.

  9. Stellenwert des Nativ-Spiral-CT in der Diagnostik von Ureterkonkrementen

    Directory of Open Access Journals (Sweden)

    Rau O

    2006-01-01

    Full Text Available Die differentialdiagnostische Vorgehensweise bei Pat. mit einer Urolithiasis, insbesondere bei Pat. mit nicht schattengebenden Konkrementen im konventionellen Röntgen, ist oftmals schwierig. Wir evaluierten den Einsatz des Nativ-Spiral-CT in dieser Patientengruppe. Die Sensitivität und Spezifität variiert in der Literatur zwischen 80 und 100 %. Zwischen 4/99 und 11/04 führten wir bei 103 Patienten (Pat. mit kolikartigen Flankenschmerzen, aber ohne Steinnachweis im konventionellen Röntgen, ein natives Spiral-CT durch. Zusätzlich verglichen wir mit dem korrespondierenden Ultraschall und der dazugehörigen Urinanalyse. Endpunkte unserer Untersuchung waren einerseits (A der makroskopische Steinnachweis, entweder als spontan abgegangenes Konkrement oder nach interventioneller Bergung des Konkrementes, bzw. (B kein Nachweis eines Konkrementes. Ein Steinnachweis ließ sich bei 55/103 Pat. führen. Bei 41/55 ließ sich mittels Spiral-CT das Konkrement bestätigen. Dies entspricht einer Spezifität von 75 %. 49 der 55 Pat. hatten zusätzlich eine Erythrozyturie und ebenfalls 49/55 zeigten im Ultraschall eine Dilatation des Nierenbeckenkelchsystems. Bei 48 Pat. von 103 wurden keine Konkremente gesichert. Bei 39 Pat. ließ sich in dieser Gruppe im Spiral-CT ebenfalls kein Konkrementnachweis führen, was einer Sensitivität von 82 % entspricht. Falsch positive Ergebnisse bei 9 Pat. ließen sich retrospektiv in der Auswertung der Spiral-CT’s auf Kalzifizierung benachbarter Strukturen zurückführen. Bei 34/48 wurde eine Erythrozyturie und bei 32/48 eine Dilatation des oberen Harntraktes diagnostiziert. Retrospektiv wurden diese Symptome auf eine infektiöse Mitbeteiligung des Retroperitonealraumes zurückgeführt. Zusätzlich ließ sich eine Raumforderung der Leber, eine Raumforderung im Bereich des proximalen Femur und drei Kolontumore sichern. Unsere Serie von Spiral-CT’s bei Pat. ohne Konkrementnachweis im konventionellen Röntgen zeigte eine

  10. [The mitochondrial ND5 T12338C mutation may be associated with Leber's hereditary optic neuropathy in two Chinese families].

    Science.gov (United States)

    Ji, Yan-Chun; Liu, Xiao-Ling; Zhao, Fu-Xin; Zhang, Juan-Juan; Zhang, Yu; Zhou, Xiang-Tian; Qu, Jia; Guan, Min-Xin

    2011-04-01

    Leber's hereditary optic neuropathy (LHON) associated with mitochondrial DNA mutation is a maternally inherited eye disease. We reported here the clinical, genetic and molecular characterization of two Han Chinese families with Leber's hereditary optic neuropathy. Ophthalmologic examinations revealed that the variable severity and age-of-onset in visual impairment among probands and other matrilineal relatives of these families. Strikingly, there were extremely low penetrances of visual impairment in these families. Sequence analysis of complete mitochondrial genomes in these pedigrees identified the homoplasmic ND4 G11696A and ND5 T12338C mutation and distinct sets of polymorphism belonging to haplogroups F2. It is well known that mitochondrial DNA ND4 G11696A is associated with LHON. The ND5 T12338C mutation resulted in replacement of the first amino acid, translation-initiating methionine with a threonine, and shortening two amino acids of ND5. This mutation also locates in two nucleotides adjacent to the 3' end of the tRNALeu(Cun). Thus, this mutation may alter structural formation and stabilization of functional tRNA, thereby leading to a failure in protein synthesis and mitochondrial dysfunction involved in visual impairment. Therefore, the ND4 G11696A and ND5 T12338C mutation is likely associated with LHON in these two Chinese families. But these families exhibited extremely low penetrances of visual impairment. It suggests that other factors, such as nuclear modifier gene(s) or environmental factor(s), may play a role in the phenotypic expression of the LHON-associated ND4 G11696A and ND5 T12338C mutation.

  11. Des Groupes et des Œuvres

    OpenAIRE

    Grojnowski, Daniel

    2015-01-01

    À la fin du xixe siècle, les groupes de bohèmes se multiplient et se diversifient, des salons privés aux tavernes ou cabarets. Une étude aussi attentive que possible de trois d’entre eux (les Zutiques, les Hydropathes, les Incohérents) montre la diversité de leurs configurations, ainsi que l’importance déterminante que leurs productions revêt au regard de la postérité.

  12. Differentialdiagnose des Ulcus cruris

    Directory of Open Access Journals (Sweden)

    Binder B

    2010-01-01

    Full Text Available Das Ulcus cruris ist eine Erkrankung vor allem des höheren Lebensalters. Ungefähr 1 % der Bevölkerung leidet an einer chronischen Wunde. An die 90 % der Ulzera sind vaskulärer Genese, doch gibt es vielfältige weitere Ursachen. Die Kenntnis der relevanten Differentialdiagnosen ist insbesondere bei therapierefraktären Verläufen von Bedeutung. Dazu gehören Neuropathien, myeloproliferative Erkrankungen, Infektionen, Medikamente oder Hauttumore. Für eine erfolgreiche Behandlung des Ulcus cruris ist die Identifikation der Genese von entscheidender Bedeutung, um eine kausale, interdisziplinäre Therapie zu ermöglichen.

  13. Liste des Auteurs

    OpenAIRE

    2014-01-01

    Amor Hakima, Université Cadi Ayyad, Faculté des sciences Semlalia, Département de biologie, Laboratoire d’écologie humaine, Marrakech, Maroc. Angeli Aurora, Universita degli studi di Bologna, Dipartimento di scienze statiche “Paolo Fortunati”, Bologne, Italie. Baali Abdellatif, Université Cadi Ayyad, Faculté des sciences Semlalia, Département de biologie, Laboratoire d’écologie humaine, Marrakech, Maroc. Bachtarzi T., Hôpital Ibn Sina, CHU Annaba, Algérie. Baudot Patrick, Université de Proven...

  14. Liste des Auteurs

    OpenAIRE

    2014-01-01

    Amor Hakima, Université Cadi Ayyad, Faculté des sciences Semlalia, Département de biologie, Laboratoire d’écologie humaine, Marrakech, Maroc. Angeli Aurora, Universita degli studi di Bologna, Dipartimento di scienze statiche “Paolo Fortunati”, Bologne, Italie. Baali Abdellatif, Université Cadi Ayyad, Faculté des sciences Semlalia, Département de biologie, Laboratoire d’écologie humaine, Marrakech, Maroc. Bachtarzi T., Hôpital Ibn Sina, CHU Annaba, Algérie. Baudot Patrick, Université de Proven...

  15. New possibilities for increasing marketability of combined traffic with semitrailers; Neue Wege zur Steigerung der Marktfaehigkeit des Kombinierten Verkehrs

    Energy Technology Data Exchange (ETDEWEB)

    Stumpe, F. [Technische Hochschule Aachen (DE). Hochschuldidaktisches Zentrum (HDZ)

    2001-05-01

    Combined cargo transport (KV) is one of numerous possibilities to move good transports from the street to rails. It offers environmentally friendly and sustainable transport through advantageous main rail segments between terminals combined with the flexibility of highway transport in pre- and post segments to the terminals. However, the technological advantage of highways in the area of the vehicles must be leveled. A solution to bridge the technological gap between rail and highway vehicles used in combined cargo transport is sought within the scopes of the project SAIL (semitrailers in advanced intermodal logistics), sponsored by the European Commission, in which all parties participating in the transport chain cooperate and introduce their specifications. This article reports on the process and the previous results of this project. (orig.) [German] Das stetig zusammenwachsende Europa stellt nach der Einfuehrung des gemeinsamen Wirtschaftsraumes und der einheitlichen Waehrung mit seinen mehr als 35 Staedten ueber 1. Mio. Einwohner und insgesamt mehr als 500 Mio. Menschen hohe Anforderungen an die Versorgung der Bevoelkerung. Logistische Konzepte muessen angepasst und erneuert werden, um die Versorgung mit den gewuenschten Guetern sicher zu stellen. Seitens der Technik muessen neue Transportkapazitaeten bereitgestellt werden, die den physikalischen Warentransport durchfuehren. Hierbei ist heute der Strassengueterverkehr der Innovationstraeger; er bringt mit seinen Standards andere Verkehrstraeger in Zugzwang. (orig.)

  16. Screening of a large cohort of Leber congenital amaurosis and retinitis pigmentosa patients identifies novel LCA5 mutations and new genotype-phenotype correlations

    OpenAIRE

    Mackay, Donna S.; Borman, Arundhati Dev; Sui, Ruifang; van den Born, L. Ingeborgh; Berson, Eliot L.; Ocaka, Louise A.; Davidson, Alice E.; Heckenlively, John R.; Branham, Kari; Ren, Huanan; Lopez, Irma; Maria, Maleeha; Azam, Maleeha; Henkes, Arjen; Blokland, Ellen

    2013-01-01

    To investigate the prevalence of sequence variants in LCA5 in patients with Leber congenital amaurosis (LCA), early onset rod-cone dystrophy (EORD) and autosomal recessive retinitis pigmentosa (RP), to delineate the ocular phenotypes, and to provide an overview of all published LCA5 variants in an online database._Patients underwent standard ophthalmic evaluations after providing informed consent. In selected patients, optical coherence tomography (OCT) and fundus autoflu...

  17. [A case or Leber hereditary optic neuropathy (LHON): differential diagnosis with post inflammatory atrophy of nerve II using the mtDNA analysis].

    Science.gov (United States)

    Lubos, Leszek; Wajgt, Andrzej; Maciejowski, Maciej; Mroczek-Tońska, Katarzyna; Bartnik, Ewa; Dziekanowska, Danuta

    2003-01-01

    The Leber hereditary optic neuropathy (LHON) is a disease due to a mtDNA mutation. The disorder results from enzymatic perturbations in the mitochondrial respiratory chain. Clinically the LHON may present as a progressive axonal atrophy of the optic nerves with or without other neurological symptoms. The process of reaching the diagnosis of the LHON by means of the molecular analysis of mtDNA is discussed.

  18. Pharmacological Amelioration of Cone Survival and Vision in a Mouse Model for Leber Congenital Amaurosis.

    Science.gov (United States)

    Li, Songhua; Samardzija, Marijana; Yang, Zhihui; Grimm, Christian; Jin, Minghao

    2016-05-25

    RPE65, an abundant membrane-associate protein in the retinal pigment epithelium (RPE), is a key retinoid isomerase of the visual cycle necessary for generating 11-cis-retinal that functions not only as a molecular switch for activating cone and rod visual pigments in response to light stimulation, but also as a chaperone for normal trafficking of cone opsins to the outer segments. Many mutations in RPE65 are associated with Leber congenital amaurosis (LCA). A R91W substitution, the most frequent LCA-associated mutation, results in a severe decrease in protein level and enzymatic activity of RPE65, causing cone opsin mislocalization and early cone degeneration in the mutation knock-in mouse model of LCA. Here we show that R91W RPE65 undergoes ubiquitination-dependent proteasomal degradation in the knock-in mouse RPE due to misfolding. The 26S proteasome non-ATPase regulatory subunit 13 mediated degradation specifically of misfolded R91W RPE65. The mutation disrupted membrane-association and colocalization of RPE65 with lecithin:retinol acyltransferase (LRAT) that provides the hydrophobic substrate for RPE65. Systemic administration of sodium 4-phenylbutyrate (PBA), a chemical chaperone, increased protein stability, enzymatic activity, membrane-association, and colocalization of R91W RPE65 with LRAT. This rescue effect increased synthesis of 11-cis-retinal and 9-cis-retinal, a functional iso-chromophore of the visual pigments, led to alleviation of S-opsin mislocalization and cone degeneration in the knock-in mice. Importantly, PBA-treatment also improved cone-mediated vision in the mutant mice. These results indicate that PBA, a U.S. Food and Drug Administration-approved safe oral medication, may provide a noninvasive therapeutic intervention that delays daylight vision loss in patients with RPE65 mutations. LCA is a severe early onset retinal dystrophy. Recent clinical trials of gene therapy have implicated the need of an alternative or combination therapy to

  19. La physique des infinis

    CERN Document Server

    Bernardeau, Francis; Laplace, Sandrine; Spiro, Michel

    2013-01-01

    Écrire l'histoire de l'Univers, tel est l'objectif commun des physiciens des particules et des astrophysiciens. Pour y parvenir, deux approches s'épaulent : la voie de l'infiniment petit, que l'on emprunte via de gigantesques accélérateurs de particules, et celle de l'infiniment grand, dont le laboratoire est l'Univers. Un Univers qui est bien loin d'avoir livré tous ses secrets. On connaît à peine 4,8 % de la matière qui le constitue, le reste étant composé de matière noire (25,8 %) et d'énergie noire (69,4 %), toutes deux de nature inconnue. Et si la récente découverte du boson de Higgs valide le Modèle standard de la physique des particules, celui-ci est toujours incomplet et doit être étendu à ou dépassé. Est-on arrivé au bout du jeu de poupées russes de la matière ? Quelles sont les particules manquantes ? Faut-il revoir les lois fondamentales ? Quels instruments faut-il mettre en œuvre pour accéder à cette « nouvelle physique » ? Comment parler de Super Big Science aux citoye...

  20. CHAINE DES ROTISSEUR @ HILTON

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The annual gala dinner of Chaine des Rotisseurs was hosted by Hilton Beijing. The “Ballet Dinner” - a great creation for both art and fine dining lovers was taken place in varies places within the hotel, including hotel lobby, 3rd floor and lobby lounge.

  1. REPRISE DES COURS - Yoga

    CERN Multimedia

    Club de Yoga

    2015-01-01

    REPRISE DES COURS – Venez nombreux ! Yoga, Sophrologie, Tai Chi La liste des cours pour le semestre allant du 1er septembre 2015 au 31 janvier 2016 est disponible sur notre site web : http://club-yoga.web.cern.ch Lieu Les cours ont lieu dans la salle des clubs, à l’entresol du restaurant No 2, Bât. 504 (dans la salle no 3 pour la Sophrologie). Prix des cours Le prix pour le semestre (environ 18 leçons) est fixé à 220 CHF plus 10 CHF d’adhésion annuelle au Club. Couple : 200 CHF par personne. 2 cours par semaine : 400 CHF. Inscriptions Les inscriptions aux cours seront prises directement auprès du professeur, lors de la 1ère séance. Avant de s’inscrire pour le semestre, il est possible d’essayer une séance gratuitement. Informations : http://club-yoga.web.cern.ch ----------------------------------------- cern.ch/club-yoga/

  2. Potenziale des Mobile Commerce

    OpenAIRE

    Turowski, Klaus

    2004-01-01

    Potenziale des Mobile Commerce / B. Bazijanec, K. Turowski. - In: Mobile economy : 4. Workshop Mobile Commerce, 02.-03. Februar 2004, Univ. Augsburg / Key Pousttchi ... (Hrsg.). - Bonn : Ges. für Informatik, 2004. - S. 7-11. - (GI-Edition : Proceedings ; 42)

  3. Vom Ort des Philosophierens

    Directory of Open Access Journals (Sweden)

    Damir Barbaric

    2002-12-01

    Full Text Available Im Aufsatz wird versucht, den ursprünglichen Sinn der Platonischen Bestimmung vom Staunen als Anfang der Philosophie zu ermitteln, und zwar durch eine kritischen Abhebung von ihrer Umdeutung bei Aristoteles, und dann insbesondere in der Stoa wie auch bei Spinoza und Hegel. Dabei wird auf die frühgriechische Erfahrung vom Staunen als _______ aufmerksam gemacht, wo es vor allem die Grundstimmung des Dabeiseins des Göttlichen und der menschlichen Teilnahme am Göttlichen bedeutet. Dem entspricht die bei Platon stark hervorgehobene Rolle des “Pathetischen” am Staunen, das in der nachkommenden Tradition grundsätzlich verlorengegangen ist. Für Platon entspringt das Staunen einem nie zu überwindenden Zustand der wesentlichen philosophischen “Weglosigkeit” (_____, welche schon bei Aristoteles nur noch im Sinne eines unbedingt zu verlassenden Ausgangspunkts der methodisch sicher fortfahrenden philosophischen Wissenschaft verstanden wird. Durch ein Zurückgreifen auf die Diotimas Lehre im Dialog Symposion wird dementgegen die Sokratisch-Platonische “Weglosigkeit” als der einzig angemessene “Ort” des echten Philosophierens bestimmt, welchen es, als das “Zwischen” für das Weltspiel der Unsterblichen und Sterblichen, um jeden Preis zu bewahren und offen zu halten gilt.

  4. Eine neue Alternative für die Prävention und Therapie postmenopausaler Erkrankungen, insbesondere des metabolischen Syndroms

    Directory of Open Access Journals (Sweden)

    Wuttke W

    2015-01-01

    Full Text Available Viele postmenopausale, aber in zunehmendem Maße auch junge Frauen und Männer werden übergewichtig. Heute werden 2 Fetttypen unterschieden: der gynoide Birnentyp mit großen glutealen Fettdepots und der androide Apfeltyp mit viel viszeralem Fett. Das metabolische Syndrom entwickelt sich bei übergewichtigen bzw. fettleibigen Menschen in erster Linie durch Bildung großer viszeraler Fettdepots. Diese Patienten gehören also zu den Apfeltypen mit großen androiden Fettdepots, oder platt ausgedrückt: Sie haben einen „Bierbauch“. Bei übergewichtigen Frauen liegt in der Regel ein Mischtyp vor. Die viszeralen Fettzellen dieser Menschen sezernieren große Mengen an proinflammatorischen Zytokinen, welche den gesamten Körper in einen chronisch entzündlichen Zustand versetzen. Der daraus resultierende hohe oxidative Stress und die Zytokine führen zu einer Hyperlipidämie und es folgen Hypertonie und Arteriosklerose. Auch Insulinrezeptoren werden desensibilisiert und es entwickelt sich ein Typ-2-Diabetes. Das metabolische Syndrom hat aber nicht nur negative Auswirkungen auf das Herz-Kreislaufsystem, sondern auch auf die Muskulatur, da auch hier schädliche Fettzellen akkumulieren und den Aufbau von Muskelfasern hemmen. Fettzellen im Knochenmark und Fettzotten in Gelenken schädigen durch die dort sezernierten Zytokine die knochen- und knorpelaufbauenden Osteo- und Chondroblasten, sodass sich eine Osteoporose entwickelt und die sich durch Übergewicht anbahnende Arthrose gefördert wird. Ecdyson unterbindet den Aufbau von Fettzellen. Deshalb ist Ecdyson in der Lage, den Anteil an Körperfett zu reduzieren und dabei gleichzeitig die Muskelmenge und -kraft zu steigern. Ecdyson kommt in Spinat vor. In Kombination mit Substanzen, welche bekanntermaßen Knochen, Knorpel oder Arterien schützen, wie Kalzium, Vitamin D oder Antioxidanzien, verhindert oder reduziert ein Ecdyson-haltiges Spinatpräparat die Entwicklung des metabolischen Syndroms, einer

  5. Neuropatía óptica hereditaria de Leber por mutación G11778A del ADN mitocondrial. Manejo de un caso

    Directory of Open Access Journals (Sweden)

    David Barreda Gago

    2016-11-01

    Full Text Available La neuropatía óptica hereditaria de Leber es una enfermedad genética mitocondrial que típicamente produce ceguera bilateral en adultos jóvenes varones. Además de la mutación del ADN mitocondrial son necesarios otros factores genéticos y ambientales para el desarrollo de la enfermedad. En la actualidad no existe un tratamiento eficaz para la neuropatía óptica hereditaria de Leber, pero el consejo genético en portadores asintomáticos es importante. Presentamos el caso clínico de un paciente de 23 años de edad que refiere pérdida de agudeza visual central aguda unilateral que se convierte en bilateral en semanas. La exploración del fondo de ojo (tortuosidad vascular peripapilar, telangiectasias e hiperemia papilar, la angiografía con fluoresceína (con ausencia de exudación y el engrosamiento de la capa de fibras nerviosas nos hacen sospechar la enfermedad. El test genético molecular confirma la neuropatía óptica hereditaria de Leber al encontrar la mutación G11778A en homoplasmia. A pesar del tratamiento con idebenona y suplementos vitamínicos la enfermedad evoluciona a atrofia papilar bilateral. El futuro parece estar en la terapia génica, actualmente en investigación.

  6. Injectabilite des coulis de ciment dans des milieux fissures

    Science.gov (United States)

    Mnif, Thameur

    Le travail presente ici est un bilan du travaux de recherche effectues sur l'injectabilite des coulis de ciment dans lu milieux fissures. Un certain nombre de coulis a base de ciment Portland et microfin ont ete selectionnes afin de caracteriser leur capacite a penetrer des milieux fissures. Une partie des essais a ete menee en laboratoire. L'etude rheologique des differents melanges a permis de tester l'influence de l'ajout de superplastifiant et/ou de fumee de silice sur la distribution granulometrique des coulis et par consequent sur leur capacite a injecter des colonnes de sable simulant un milieu fissure donne. La classe granulometrique d'un coulis, sa stabilite et sa fluidite sont apparus comme les trois facteurs principaux pour la reussite d'une injection. Un facteur de finesse a ete defini au cours de cette etude: base sur la classe granulometrique du ciment et sa stabilite, il peut entrer dans la formulation theorique du debit d'injection avant application sur chantier. La deuxieme et derniere partie de l'etude presente les resultats de deux projets de recherche sur l'injection realises sur chantier. L'injection de dalles de beton fissurees a permis le suivi de l'evolution des pressions avec la distance au point d'injection. L'injection de murs de maconnerie a caractere historique a montre l'importance de la definition de criteres de performance des coulis a utiliser pour traiter un milieu donne et pour un objectif donne. Plusieurs melanges peuvent ainsi etre predefinis et mis a disposition sur le chantier. La complementarite des ciments traditionnels et des ciments microfins devient alors un atout important. Le choix d'utilisation de ces melanges est fonction du terrain rencontre. En conclusion, cette recherche etablit une methodologie pour la selection des coulis a base de ciment et des pressions d'injection en fonction de l'ouverture des fissures ou joints de construction.

  7. Dopage et protection des jeunes sportifs : Loin des affaires

    OpenAIRE

    Guy, Daniel

    2002-01-01

    National audience; Loin des affaires et des révélations polémiques de la presse, les jeunes plébiscitent massivement les activités sportives. Sport compétition, sport participation, sport détente... Pourtant, quand la pratique devient intense, que les entraînements et les compétitions s'enchaînent à un rythme soutenu, l'ombre des conduites dopantes vient déchirer la quiétude des uns et des autres. Or, que savons-nous réellement de la pratique des jeunes sportifs ? Comment préparent-ils les co...

  8. Clinical and molecular genetic researches of a family with Leber's hereditary optic neuropathy%Leber's遗传性视神经病变一个双生子家系的研究

    Institute of Scientific and Technical Information of China (English)

    卢纯洁; 周翔天; 赵福星; 童绎; 陈洁; 吕帆; 管敏鑫; 瞿佳

    2006-01-01

    目的 探讨Leber's遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)一个双生子家系的临床和分子遗传学特征.方法 对LHON一个家系进行家系调查,分析其遗传特征和发病特点,并对家系成员(发病者、未发病者及对照者)进行眼科临床检查(包括视力、视野、眼底及电生理检查)和线粒体基因三个原发性突变位点的检测,即自全血提取线粒体DNA(mtDNA),应用聚合酶链反应技术,分别扩增mtDNA上相应片段检测G3460A、G11778A和T14484C位点突变.最后应用分子遗传学技术对该家系中的一对双生子(其中一人为先证者,另一个未患病)进行DNA多态性的比较分析以鉴定其卵性.结果 该家系显示为典型的母系遗传,先证者的临床表现为典型的LHON患者表现;母系亲属mtDNA的G11778A位点突变阳性,G3460A和T14484C位点突变阴性,而对照者三个位点检测结果均为阴性,双生子卵性鉴定结果为异卵双生.结论 该家系为典型的LHON家系,mtDNA上G11778A位点突变可导致LHON的发生,但并不是所有G11778A位点突变者均发生LHON.

  9. Le corps des anges

    OpenAIRE

    Margel,Serge

    2017-01-01

    Ce séminaire fait suite à un cycle de conférences données en 2014 sur la notion de corps de chair dans le premier christianisme. Cette année la recherche a porté sur le corps spécifique des anges dans la patristique grecque et latine. Sur la base d’un corpus de textes délimité, j’ai essayé de montrer deux choses principales : d’un côté, on ne peut pas comprendre la spécificité du corps des anges sans l’inscrire dans le champ de l’angélologie chrétienne, qui assimile l’ange et l’âme, et d’un a...

  10. Typologie des Accidents Cyclistes

    OpenAIRE

    Amoros, Emmanuelle; BILLOT-GRASSET, Alice; Hours, Martine

    2015-01-01

    L'usage du vélo est en hausse en ville ; cette pratique est encouragée dans le cadre du développement durable et de la lutte contre la sédentarité. Pour accompagner cela, il faut réduire les risques d'accident, et pour ce faire, mieux les connaître. Nous utilisons le Registre des victimes de la circulation routière du Rhône, basé sur les services hospitaliers (dont les urgences) ; il est quasi-exhaustif : env. 1100 blessés à vélo/an versus 120 dans les données officielles. L'ensemble des cycl...

  11. Table des tableaux

    OpenAIRE

    2014-01-01

    Présentation schématique de la production et de la transformation de l’acier 16 Chronologie des nationalisations en France 33 Importations de coke de la France 48 Comparaison entre les prix de l’acier en Allemagne et en France, août 1949 99 Prix du marché intérieur et du marché mondial pour les laminés marchands (qualité Thomas) 101 Évolution de la production allemande et française d’acier brut 119 Comparaison des coûts de l’extraction de charbon en Allemagne et en France, 1949 138 Évolution ...

  12. Table des illustrations

    OpenAIRE

    2017-01-01

    Illustration de couverture : Dolmen n° 2 des Géandes avec le Mont Ventoux en arrière-plan, octobre 2006 (cliché Wolfgang Pape). Illustration de la quatrième de couverture : René Gilles sur le dolmen n° 5 des Géandes en mars 1989 (cliché Wolfgang Pape). Fig. 1 - Gorges de l’Ardèche au niveau de la grotte de Saint-Marcel (cliché Bernard Gély) 21 Fig. 2 - Doline de Bidon (cliché Wolfgang Pape) 21 Fig. 3 - Paysage de garrigue (cliché Wolfgang Pape) 22 Fig. 4 - Données radio-chronométriques de l’A...

  13. Direction des Publications

    African Journals Online (AJOL)

    Synthese

    accroissement des pressions sur les écosystèmes et les espèces qu‟ils renferment. La pollution de ... Exacerbée par le changement climatique, cette anthropisation .... majeure partie de son aire de répartition. .... de cette région. .... savoir les impacts à plus grande échelle et ..... habitats et la totalité de l'aire géographique.

  14. Le vernis des apparences

    Directory of Open Access Journals (Sweden)

    Grazia Nicosia

    2010-04-01

    Full Text Available Le but de cet article est de comprendre l’incidence sémiotique du nettoyage d’un tableau ainsi que la résultante cognitive induite sur l’observateur. Cette étude confronte l’analyse des phénomènes visuels engendrés par le jaunissement du vernis et son retrait, à des entretiens réalisés à dessein. Le retrait d’un vernis jauni change considérablement l’image. L’heure, le climat, la saison et l’activité même des personnages s’en trouvent ainsi modifié. La patine peut être perçue, soit comme un obstacle à l’exploration, soit pour ceux qui l’apprécient, comme le medium d’une relation plus intime entre l’œuvre et l’observateur.The purpose of this article is to understand the semiotic impact of the cleaning of a painting and the cognitive effects induced on the observer. This study analyses conjointly the visual phenomenon generated by yellowing varnish and its removal and controlled interviews of observers.The removal of yellowing varnish modifies considerably the perception of the picture. Daytime, climate, season and characters activities are modified. The patina may be perceived either as an obstacle to the painting exploration, or, for those who appreciate it, as a medium for a closer relationship between the painting and the observer.

  15. Dictionnaire des risques psychosociaux

    CERN Document Server

    Zawieja, Philippe

    2014-01-01

    Stress, suicide, harcèlement, épuisement professionnel, workaholism... Au-delà de la souffrance qu'elles désignent, ces notions souvent récentes constituent une approche inédite, et demandent à mieux être comprises, dans leur ensemble et isolément. C'est tout l'enjeu de ce dictionnaire, pionnier en son genre. Le lecteur y trouvera représentés, avec les 314 entrées (rédigées par 251 contributeurs) qui le composent, tous les champs disciplinaires s'intéressant à la souffrance au travail : psychologie du travail et des organisations, psychologie sociale et psychosociologie, psychanalyse, psychopathologie et psychiatrie, ergonomie, sociologie du travail et des organisations, médecine du travail, droit du travail et de la sécurité sociale, sciences de gestion, philosophie... Y sont détaillés les principaux concepts, notions, approches, méthodes, théories, outils, études, etc., ayant cours dans l'étude des risques psychosociaux, mais aussi certaines professions emblématiques (infirmières,...

  16. Accuracy of the CT-estimated weight of the right hepatic lobe prior to living related liver donation (LRLD) for predicting the intraoperatively measured weight of the graft; Vorraussagegenauigkeit der praeoperativen CT-gestuetzten Gewichtsbestimmung des rechten Leberlappens bezueglich des intraoperativen Transplantatgewichts bei Leberlappen-Lebendspendern

    Energy Technology Data Exchange (ETDEWEB)

    Lemke, A.-J.; Brinkmann, M.; Felix, R. [Universitaetsklinikum Charite, Berlin (Germany). Klinik fuer Strahlenheilkunde; Pascher, A.; Steinmueller, T.; Settmacher, U.; Neuhaus, P. [Universitaetsklinikum Charite, Berlin (Germany). Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie

    2003-09-01

    -Untersuchungen unter Zuhilfenahme der Volumetrie das Gewicht des rechten Leberlappens berechnet. Das Transplantatgewicht wurde als Produkt des Volumens und 1,00 g/ml (Dichte von gesundem Leberparenchym) berechnet und mit dem intraoperativ bestimmten Gewicht des transplantierten rechten Leberlappens verglichen. Aus der Abweichung wurde ein Korrekturfaktor zur naeherungsweisen Bestimmung des tatsaechlich zu erwartenden Transplantatgewichts abgeleitet. Ergebnisse: Unter der Annahme einer physikalischen Dichte der Leber von 1,00 g/ml betrug die mittlere Abweichung der praeoperativen Gewichte des rechten Leberlappens (Mittelwert 980 g {+-} 168 g) von den intraoperativ ermittelten Gewichten (Mittelwert 749 g {+-} 170 g) + 33%. Das tatsaechliche Transplantatgewicht kann durch Reduktion des praeoperativen Gewichtes um einen Korrekturfaktor von 0,75 naeherungsweise abgeschaetzt werden. (orig.)

  17. Leber先天黑矇的临床研究%Clinical study on Leber congenital amaurosis

    Institute of Scientific and Technical Information of China (English)

    睢瑞芳; 赵潺; 姜茹欣; 周崎; 于伟泓; 董方田

    2009-01-01

    Objectives To observe the clinical characteristics of Leber congenital amaurosis (LCA)and analyze the features to differentiate LCA from other similar disorders.Methods Prospective study of 15LCA patients which include 10 males and 5 females,aged from 2 to 31 years with the mean age 13.6 years.Medical history,family history,perinatal conditions,as well as complete ocular evaluations were well documented.Among the subjects,12 patients underwent optometry check,10 patients underwent ERG and 8 patients had OCT testing.Results All of the patients had nystagmus and sluggish pupillary reflex.The visual acuity distributed from light perception to 0.1.Fivepatients (33.3%) were presented with photophobia,while 7 patients (46.7%) had nyctalopia.Among 12 cases underwent refraction examination,6 patients (50% ) had spherical equivalent of≥ + 5D;1 patient(8.3 % )had spherical equivalent of≥+5D;2patients (16.7%) had bilateral mild to moderate hyperopia;1 patient (8.3%) had one emmertropic eye and one mild myopic eye;2 patients (16.7%) had moderate to high myopia.Eight patients (53.3%) had enophthalmus,4 patients (26.7%) had oculo-digital sign.All of the 10 patients underwent ERG showed extinguished waveform.Under OCT assesement,7 patients had decreased fovea thickness;1 patient had increased fovea thickness,complicated by epiretinal membrane;mild abnormality of microstrueture of the retina with diminished and disrupted IS/OS hyperreflectivity were found in 2 cases;while more pronounced disarrangement of the retinal layers were found in 6 cases,inner layers were better reserved in all patients.Conclusions Severe visual impairment or blindness,nystagmus,pupillary reflex,extinguished ERG and hyperopia are main clinical characteristics of LCA.%目的 观察中国Leber先天黑嚎(LCA)患者的临床特征.方法 前瞻性临床研究,分析15例LCA患者的临床资料.其中,男性10例,女性5例,年龄2~31岁,平均13.6岁.所有患者就诊时详细记录病史、家族

  18. Analysis of Mitochondrial Gene Mutations in Pedigrees of Leber's Hereditary Optic Neuropathy%Leber 遗传性视神经病变家系的线粒体基因突变分析

    Institute of Scientific and Technical Information of China (English)

    林玲; 陈贻锴; 童绎; 郑志竑; 林建银; 朱进伟

    2003-01-01

    为探讨Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)家系线粒体DNA(mtDNA)常见致病原发突变的频谱,用聚合酶链反应(polymerase chin reaction,PCR)和单链构象多态性(single-strandedconformational polymorphism,SSCP)以及DNA测序的方法,对13个家系22位临床诊断为LHON的患者及其母系亲属21人的线粒体DNA进行检测,同时检测71例正常人作为对照.临床拟诊为LHON的13个家系中,11个家系存在mtDNA位点11778 G→A突变,另2个家系存在14484位点T→C突变.说明中国LHON病人存在线粒体DNA11778或14484位点突变,其中14484位点突变在国内尚未见报道.

  19. Relationship between Leber hereditary optic neuropathy and 14484 mutation in mtDNA in Chinese%中国人mtDNA14484位点突变与Leber's视神经遗传性疾病

    Institute of Scientific and Technical Information of China (English)

    隋桂芹; 左玲; 刘红; 王桂云; 张晓光

    2004-01-01

    目的探讨mtDNA14484位点突变与中国人Leber's视神经遗传性疾病的关系.方法从4例LHON先证者及其母系亲属8例和正常对照8例外周血白细胞中提取DNA,对从线粒体基因组中获得的PCR产物进行Sau3AI限制性内切酶酶切分析,并进行单链构象分析.结果4例LHON先证者均失去了Sau3AI限制性内切酶酶切位点,在聚丙烯酰胺凝胶电泳中,PCR产物的迁移率增加.结论中国人群中存在14484突变位点的LHON家系.

  20. Reticulation des fibres lignocellulosiques

    Science.gov (United States)

    Landrevy, Christel

    Pour faire face à la crise économique la conception de papier à valeur ajoutée est développée par les industries papetières. Le but de se projet est l'amélioration des techniques actuelles de réticulation des fibres lignocellulosiques de la pâte à papier visant à produire un papier plus résistant. En effet, lors des réactions de réticulation traditionnelles, de nombreuses liaisons intra-fibres se forment ce qui affecte négativement l'amélioration anticipée des propriétés physiques du papier ou du matériau produit. Pour éviter la formation de ces liaisons intra-fibres, un greffage sur les fibres de groupements ne pouvant pas réagir entre eux est nécessaire. La réticulation des fibres par une réaction de « click chemistry » appelée cycloaddition de Huisgen entre un azide et un alcyne vrai, catalysée par du cuivre (CuAAC) a été l'une des solutions trouvée pour remédier à ce problème. De plus, une adaptation de cette réaction en milieux aqueux pourrait favoriser son utilisation en milieu industriel. L'étude que nous désirons entreprendre lors de ce projet vise à optimiser la réaction de CuAAC et les réactions intermédiaires (propargylation, tosylation et azidation) sur la pâte kraft, en milieu aqueux. Pour cela, les réactions ont été adaptées en milieu aqueux sur la cellulose microcristalline afin de vérifier sa faisabilité, puis transférée à la pâte kraft et l'influence de différents paramètres comme le temps de réaction ou la quantité de réactifs utilisée a été étudiée. Dans un second temps, une étude des différentes propriétés conférées au papier par les réactions a été réalisée à partir d'une série de tests papetiers optiques et physiques. Mots Clés Click chemistry, Huisgen, CuAAC, propargylation, tosylation, azidation, cellulose, pâte kraft, milieu aqueux, papier.

  1. Etude des cas: Gestion alternatîves des conflits

    OpenAIRE

    Lo, H.

    2006-01-01

    Metadata only record Pour mieux consolider les acquis consensuels pour la gestion alternative des conflits, il nous paraît essentiel de maîtriser un certain nombre de facteurs ayant trait au "partage" des gommeraies entre autres: Available in SANREM office, FS

  2. Antisense Oligonucleotide (AON-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290

    Directory of Open Access Journals (Sweden)

    Rob WJ Collin

    2012-01-01

    Full Text Available Leber congenital amaurosis (LCA is the most severe form of inherited retinal degeneration, with an onset in the first year of life. The most frequent mutation that causes LCA, present in at least 10% of individuals with LCA from North-American and Northern-European descent, is an intronic mutation in CEP290 that results in the inclusion of an aberrant exon in the CEP290 mRNA. Here, we describe a genetic therapy approach that is based on antisense oligonucleotides (AONs, small RNA molecules that are able to redirect normal splicing of aberrantly processed pre-mRNA. Immortalized lymphoblastoid cells of individuals with LCA homozygously carrying the intronic CEP290 mutation were transfected with several AONs that target the aberrant exon that is incorporated in the mutant CEP290 mRNA. Subsequent RNA isolation and reverse transcription-PCR analysis revealed that a number of AONs were capable of almost fully redirecting normal CEP290 splicing, in a dose-dependent manner. Other AONs however, displayed no effect on CEP290 splicing at all, indicating that the rescue of aberrant CEP290 splicing shows a high degree of sequence specificity. Together, our data show that AON-based therapy is a promising therapeutic approach for CEP290-associated LCA that warrants future research in animal models to develop a cure for this blinding disease.

  3. Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation

    Institute of Scientific and Technical Information of China (English)

    Wanshi Cai; Qun Fu; Xiangtian Zhou; Jia Qu; Yi Tong; Min-Xin Guan

    2008-01-01

    We report here the characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strik-ingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen (11 males/8 females) of 29 matrilineal relatives in this family developed visual loss with a wide range of severity,ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G11778A mutation is present at homoplasmy in matri-lineal relatives of this Chinese family. Of other variants, the CO1 G6480A, ND5 T12811C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated Gl1778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T12811C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.

  4. Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fuxin [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Guan, Minqiang [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhou, Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yuan, Meixia; Liang, Ming [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Qi [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Yan; Zhang, Yongmei [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yang, Li [Division of Human Genetics, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH 45229 (United States); Tong, Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 (China); Wei, Qi-Ping; Sun, Yan-Hong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Qu, Jia, E-mail: jqu@wzmc.net [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); and others

    2009-11-20

    We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.

  5. Leber's hereditary optic neuropathy is associated with mitochondrial ND1 T3394C mutation

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Min [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Guan, Minqiang [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhao, Fuxing; Zhou, Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yuan, Meixia [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Tong, Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 (China); Yang, Li [Division of Human Genetics, Cincinnati Children' s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States); Wei, Qi-Ping; Sun, Yan-Hong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Lu, Fan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Qu, Jia, E-mail: jqu@wzmc.net [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); and others

    2009-06-05

    We report here the clinical, genetic and molecular characterization of four Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age-of-onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T3394C (Y30H) mutation, which localized at a highly conserved tyrosine at position 30 of ND1, and distinct sets of mtDNA polymorphisms belonging to haplogroups D4b and M9a. The occurrence of T3394C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. However, there was the absence of functionally significant mtDNA mutations in these four Chinese pedigrees carrying the T3394C mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated T3394C mutation.

  6. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Fabrice D Heitz

    Full Text Available Leber's hereditary optic neuropathy (LHON is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients.

  7. Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Chadderton, Naomi; Palfi, Arpad; Millington-Ward, Sophia; Gobbo, Oliverio; Overlack, Nora; Carrigan, Matthew; O'Reilly, Mary; Campbell, Matthew; Ehrhardt, Carsten; Wolfrum, Uwe; Humphries, Peter; Kenna, Paul F; Farrar, G Jane

    2013-01-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies.

  8. Leber氏病的线粒体研究%Research on Leber's Hereditary Optic Neuropathy in Two Strips

    Institute of Scientific and Technical Information of China (English)

    肖文玮; 郭锋; 李春霞; 王颖; 陈良君; 于晓莉

    2005-01-01

    目的了解Leber氏遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)相关的线粒体DNA原发性突变基因检测结果,探讨该项检查的临床意义.方法采用聚合酶链反应(polymerase chain reaction,PCR),检测先证者及其母系血缘亲属外周血DNA中提取的线粒体DNA的3 460位点,11778位点.结果本组临床确诊患者的DNA均表现为11 778位点突变,未发现3 460位点突变.结论Leber病发病机制为mtDNA点突变,线粒体DNA的检测分析为确立LHON提供了诊断依据,尤其对无家族史或原因不明的双侧性视神经炎的患者更具有诊断价值.并为其它神经性遗传病的研究提供了技术支撑.

  9. Insights into the role of RD3 in guanylate cyclase trafficking, photoreceptor degeneration and Leber Congenital Amaurosis

    Directory of Open Access Journals (Sweden)

    Robert S. Molday

    2014-05-01

    Full Text Available RD3 is an evolutionarily conserved 23 kDa protein expressed in rod and cone photoreceptor cells. Mutations in the gene encoding RD3 resulting in unstable non-functional C-terminal truncated proteins are responsible for early onset photoreceptor degeneration in Leber Congenital Amaurosis 12 (LCA12 patients, the rd3 mice, and the rcd2 collies. Recent studies have shown that RD3 interacts with guanylate cyclases GC1 and GC2 in retinal cell extracts and HEK293 cells co-expressing GC and RD3. This interaction inhibits GC catalytic activity and promotes the exit of GC1 and GC2 from the endoplasmic reticulum and their trafficking to photoreceptor outer segments. Adeno-associated viral vector delivery of the normal RD3 gene to photoreceptors of the Rd3 mouse restores GC1 and GC2 expression and outer segment localization and leads to the long-term recovery of visual function and photoreceptor cell survival. This review focuses on the genetic and biochemical studies that have provided insight into the role of RD3 in photoreceptor function and survival.

  10. Leber's hereditary optic neuropathy (LHON) pathogenic mutations induce mitochondrial-dependent apoptotic death in transmitochondrial cells incubated with galactose medium.

    Science.gov (United States)

    Ghelli, Anna; Zanna, Claudia; Porcelli, Anna Maria; Schapira, Anthony H V; Martinuzzi, Andrea; Carelli, Valerio; Rugolo, Michela

    2003-02-01

    Leber's hereditary optic neuropathy (LHON), a maternally inherited form of central vision loss, is associated with mitochondrial DNA pathogenic point mutations affecting different subunits of complex I. We here report that osteosarcoma-derived cytoplasmic hybrids (cybrid) cell lines harboring one of the three most frequent LHON pathogenic mutations, at positions 11778/ND4, 3460/ND1, and 14484/ND6, undergo cell death when galactose replaces glucose in the medium, contrary to control cybrids that maintain some growth capabilities. This is a well known way to produce a metabolic stress, forcing the cells to rely on the mitochondrial respiratory chain to produce ATP. We demonstrate that LHON cybrid cell death is apoptotic, showing chromatin condensation and nuclear DNA laddering. Moreover, we also document the mitochondrial involvement in the activation of the apoptotic cascade, as shown by the increased release of cytochrome c into the cytosol in LHON cybrid cells as compared with controls. Cybrids bearing the 3460/ND1 and 14484/ND6 mutations seemed more readily prone to undergo apoptosis as compared with the 11778/ND4 mutation. In conclusion, LHON cybrid cells forced by the reduced rate of glycolytic flux to utilize oxidative metabolism are sensitized to an apoptotic death through a mechanism involving mitochondria.

  11. 干血斑滤纸片检测Leber's视神经萎缩线粒体突变

    Institute of Scientific and Technical Information of China (English)

    贾小云; 郭向明; 郭莉; 申煌煊; 黎仕强; 肖学珊; 张清炯

    2003-01-01

    目的建立干血斑滤纸片分析Leber's遗传性视神经萎缩(LHON)线粒体DNA(mtDNA)的方法,为更加广泛开展LHON的基因诊断和为进一步研究LHON积累资料.方法收集了81例视神经炎、视神经萎缩或临床怀疑LHON患者的干血斑滤纸片,提取DNA,用突变特异性引物PCR(MSP-PCR)和异源双链-单链构象多态性(HA-SSCP)检测其mtDNA的三个常见原发致病突变位点.结果81例受检者中,检出51例11778位点突变阳性;1例3460位点突变阳性;14484位点突变全部阴性.结论应用干血滤纸片检测LHON的mtDNA,具有微量、准确、有效、邮寄方便的特点,值得推广.

  12. Inner retinal contributions to the multifocal electroretinogram: patients with Leber's hereditary optic neuropathy (LHON). Multifocal ERG in patients with LHON.

    Science.gov (United States)

    Kurtenbach, Anne; Leo-Kottler, Beate; Zrenner, Eberhart

    2004-05-01

    In this study we examine the multifocal electroretinogram (mfERG) recorded from patients suffering from Leber's hereditary optic neuropathy (LHON), a degeneration of the ganglion cell and nerve fibre layers of the retina. We compared the mfERGs recorded from 11 patients with LHON, to those from 11 control subjects. The pattern ERG (PERG) was additionally performed with 9 of the patients. MfERGs were recorded and analysed using the VERIS 3.01 system with a stimulus of 103 equal-sized hexagons. For analysis, hexagons were grouped according to distance from the optic nerve head (ONH) and according to distance from the fovea. Two significant differences were found between the waveforms of the two groups: In the first order kernel, the control group showed a component around 34 ms that decreased with distance from the ONH. This component was reduced in the LHON group of subjects. In the second order (first slice) kernel, the patient group was missing features that decrease with distance from the fovea in the control group. PERG amplitudes showed a significant correlation with the amplitude of the second order mfERG kernel. The results show that the damage to ganglion cells and nerve fibres caused by LHON can be detected in mfERG recordings and indicate that activity from the inner retina can contribute significantly to first and second order waveforms.

  13. Leber's hereditary optic neuroretinopathy (LHON) associated with mitochondrial DNA point mutation G11778A in two Croatian families.

    Science.gov (United States)

    Martin-Kleiner, Irena; Gabrilovac, Jelka; Bradvica, Mario; Vidović, Tomislav; Cerovski, Branimir; Fumić, Ksenija; Boranić, Milivoj

    2006-03-01

    Leber's hereditary optic neuroretinopathy (LHON) is manifested as a bilateral acute or subacute loss of central vision due to optic atrophy. It is linked to point mutations of mitochondrial DNA, which is inherited maternally. The most common mitochondrial DNA point mutations associated with LHON are G3460A, G11778A and T14484C. These mutations are linked with the defects of subunits of the complex I (NADH-dehydrogenase-ubiquinone reductase) in mitochondria. The G11778A mitochondrial DNA point mutation is manifested by a severe visual impairment. In this paper two Croatian families with the LHON G11778A mutation are presented. Three LHON patients from two families were younger males which had the visual acuity of 0.1 or below, the ophthalmoscopy revealed telangiectatic microangiopathy and papilloedema, while Goldmann kinetic perimetry showed a central scotoma. The mothers and female relatives were LHON mutants without symptoms, whereas their sons suffered from a severe visual impairment. Molecular diagnosis helps to explain the cause of LHON disease.

  14. Minocycline, a possible neuroprotective agent in Leber's hereditary optic neuropathy (LHON): studies of cybrid cells bearing 11,778 mutation.

    Science.gov (United States)

    Haroon, Mohammad Fahad; Fatima, Ambrin; Schöler, Susanne; Gieseler, Anne; Horn, Thomas F W; Kirches, Elmar; Wolf, Gerald; Kreutzmann, Peter

    2007-12-01

    Leber's hereditary optic neuropathy (LHON) is a retinal neurodegenerative disorder caused by mitochondrial DNA point mutations. Complex I of the respiratory chain affected by the mutation results in a decrease in ATP and an increase of reactive oxygen species production. Evaluating the efficacy of minocycline in LHON, the drug increased the survival of cybrid cells in contrast to the parental cells after thapsigargin-induced calcium overload. Similar protection was observed by treatment with cyclosporine A, a blocker of the mitochondrial permeability transition pore (mPTP). Ratiometric Ca(2+) imaging reveals that acetylcholine/thapsigargin triggered elevation of the cytosolic calcium concentration is alleviated by minocycline and cyclosporine A. The mitochondrial membrane potential of LHON cybrids was significantly conserved and the active-caspase-3/procaspase-3 ratio was decreased in both treatments. Our observations show that minocycline inhibits permeability transition induced by thapsigargin in addition to its antioxidant effects. In relation with its high safety profile, these results would suggest minocycline as a promising neuroprotective agent in LHON.

  15. Mitochondrial tRNA(Thr) A15951G mutation may not be associated with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Zhang, Xi; Yu, Shuaishuai; Tu, Yunhai; Huang, Wenjie

    2016-07-01

    Mutation in mitochondrial DNA (mtDNA) has been found to play an important role in the pathogenesis of Leber's Hereditary Optic Neuropathy (LHON). Three primary mutations, the ND4 G11778A, ND6 T14484C, and ND1 G3460A, have been found to account more than 90% of LHON patients in many families worldwide. In addition to the mutations in genes encoding the respiratory chain complex I, reports concerning the mt-tRNA gene mutations associated with LHON have increased, some pathogenic mutations caused the failure in mt-tRNA metabolism, thereby worsened the mitochondrial dysfunction that is responsible for LHON. Recently, the A15951G mutation in mt-tRNA(Thr) gene has been reported to be a "modified" factor in increasing the penetrance and expressivity of LHON-associated ND4 G11778A mutation in three Chinese families. However, evolutionary conservation analysis of this mutation suggested a poor conservation index and the pathogenicity scoring system showed that this mutation was a neutral polymorphism.

  16. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Heitz, Fabrice D; Erb, Michael; Anklin, Corinne; Robay, Dimitri; Pernet, Vincent; Gueven, Nuri

    2012-01-01

    Leber's hereditary optic neuropathy (LHON) is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC) dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients.

  17. Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused by NPHP5 mutation.

    Science.gov (United States)

    Downs, Louise M; Scott, Erin M; Cideciyan, Artur V; Iwabe, Simone; Dufour, Valerie; Gardiner, Kristin L; Genini, Sem; Marinho, Luis Felipe; Sumaroka, Alexander; Kosyk, Mychajlo S; Swider, Malgorzata; Aguirre, Geoffrey K; Jacobson, Samuel G; Beltran, William A; Aguirre, Gustavo D

    2016-10-01

    Ciliary defects can result in severe disorders called ciliopathies. Mutations in NPHP5 cause a ciliopathy characterized by severe childhood onset retinal blindness, Leber congenital amaurosis (LCA), and renal disease. Using the canine NPHP5-LCA model we compared human and canine retinal phenotypes, and examined the early stages of photoreceptor development and degeneration, the kinetics of photoreceptor loss, the progression of degeneration and the expression profiles of selected genes. NPHP5-mutant dogs recapitulate the human phenotype of very early loss of rods, and relative retention of the central retinal cone photoreceptors that lack function. In mutant dogs, rod and cone photoreceptors have a sensory cilium, but develop and function abnormally and then rapidly degenerate; L/M cones are more severely affected than S-cones. The lack of outer segments in mutant cones indicates a ciliary dysfunction. Genes expressed in mutant rod or both rod and cone photoreceptors show significant downregulation, while those expressed only in cones are unchanged. Many genes in cell-death and -survival pathways also are downregulated. The canine disease is a non-syndromic LCA-ciliopathy, with normal renal structures and no CNS abnormalities. Our results identify the critical time points in the pathogenesis of the photoreceptor disease, and bring us closer to defining a potential time window for testing novel therapies for translation to patients.

  18. Gene Therapy Using a miniCEP290 Fragment Delays Photoreceptor Degeneration in a Mouse Model of Leber Congenital Amaurosis.

    Science.gov (United States)

    Zhang, Wei; Li, Linjing; Su, Qin; Gao, Guangping; Khanna, Hemant

    2017-07-05

    Mutations in the cilia-centrosomal protein CEP290 are frequently observed in autosomal recessive childhood blindness disorder Leber congenital amaurosis (LCA). No treatment or cure currently exists for this disorder. The Cep290(rd16) (retinal degeneration 16) mouse (a model of LCA) carries a mutation in the Cep290 gene. This mutation leads to shorter cilia formation and defective photoreceptor structure and function. A roadblock to developing a gene replacement strategy for CEP290 using conventional adeno-associated virus (AAV) vectors is its large size. The identification and characterization is reported of a miniCEP290 gene that is amenable to AAV2/8-mediated delivery and delaying retinal degeneration in the Cep290(rd16) mice. Using the ability of Cep290(rd16) mouse embryonic fibroblasts to from shorter cilia as a platform, a human CEP290 domain encoded by amino acids 580-1180 (miniCEP290(580-1180)) was identified that can recover the cilia length in vitro. Furthermore, subretinal injection of AAV particles carrying the cDNA expressing miniCEP290(580-1180) into neonatal Cep290(rd16) mice resulted in significantly improved photoreceptor survival, morphology, and function compared to control injected mice. These studies show the potential of using a truncated CEP290 to treat this fast progressing and devastating disease.

  19. Replacement gene therapy with a human RPGRIP1 sequence slows photoreceptor degeneration in a murine model of Leber congenital amaurosis.

    Science.gov (United States)

    Pawlyk, Basil S; Bulgakov, Oleg V; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Khani, Shahrokh C; Berson, Eliot L; Sandberg, Michael A; Li, Tiansen

    2010-08-01

    RPGR-interacting protein-1 (RPGRIP1) is localized in the photoreceptor-connecting cilium, where it anchors the RPGR (retinitis pigmentosa GTPase regulator) protein, and its function is essential for photoreceptor maintenance. Genetic defect in RPGRIP1 is a known cause of Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. We evaluated the efficacy of replacement gene therapy in a murine model of LCA carrying a targeted disruption of RPGRIP1. The replacement construct, packaged in an adeno-associated virus serotype 8 (AAV8) vector, used a rhodopsin kinase gene promoter to drive RPGRIP1 expression. Both promoter and transgene were of human origin. After subretinal delivery of the replacement gene in the mutant mice, human RPGRIP1 was expressed specifically in photoreceptors, localized correctly in the connecting cilia, and restored the normal localization of RPGR. Electroretinogram and histological examinations showed better preservation of rod and cone photoreceptor function and improved photoreceptor survival in the treated eyes. This study demonstrates the efficacy of human gene replacement therapy and validates a gene therapy design for future clinical trials in patients afflicted with this condition. Our results also have therapeutic implications for other forms of retinal degenerations attributable to a ciliary defect.

  20. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark

    Science.gov (United States)

    Astuti, Galuh D N; Bertelsen, Mette; Preising, Markus N; Ajmal, Muhammad; Lorenz, Birgit; Faradz, Sultana M H; Qamar, Raheel; Collin, Rob W J; Rosenberg, Thomas; Cremers, Frans P M

    2016-01-01

    Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequence analysis of LRAT and RPE65 may be important in view of treatments that are emerging for patients carrying variants in these genes. Screening of the aforementioned variants and genes was performed in 64 Danish LCA probands. Upon the identification of heterozygous variants, Sanger sequencing was performed of the relevant genes to identify the second allele. In combination with prior arrayed primer extension analysis, this led to the identification of two variants in 42 of 86 cases (49%). Remarkably, biallelic RPE65 variants were identified in 16% of the cases, and one novel variant, p.(D110G), was found in seven RPE65 alleles. We also collected all previously published RPE65 variants, identified in 914 alleles of 539 patients with LCA or early-onset retinitis pigmentosa, and deposited them in the RPE65 Leiden Open Variation Database (LOVD). The in silico pathogenicity assessment of the missense and noncanonical splice site variants, as well as an analysis of their frequency in ~60 000 control individuals, rendered 864 of the alleles to affect function or probably affect function. This comprehensive database can now be used to select patients eligible for gene augmentation or retinoid supplementation therapies. PMID:26626312

  1. Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration.

    Science.gov (United States)

    Simonelli, Francesca; Maguire, Albert M; Testa, Francesco; Pierce, Eric A; Mingozzi, Federico; Bennicelli, Jeannette L; Rossi, Settimio; Marshall, Kathleen; Banfi, Sandro; Surace, Enrico M; Sun, Junwei; Redmond, T Michael; Zhu, Xiaosong; Shindler, Kenneth S; Ying, Gui-Shuang; Ziviello, Carmela; Acerra, Carmela; Wright, J Fraser; McDonnell, Jennifer Wellman; High, Katherine A; Bennett, Jean; Auricchio, Alberto

    2010-03-01

    The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies have provided evidence that the subretinal administration of adeno-associated viral (AAV) vectors encoding RPE65 in patients affected with LCA2 due to mutations in the RPE65 gene, is safe and, in some cases, results in efficacy. We evaluated the long-term safety and efficacy (global effects on retinal/visual function) resulting from subretinal administration of AAV2-hRPE65v2. Both the safety and the efficacy noted at early timepoints persist through at least 1.5 years after injection in the three LCA2 patients enrolled in the low dose cohort of our trial. A transient rise in neutralizing antibodies to AAV capsid was observed but there was no humoral response to RPE65 protein. The persistence of functional amelioration suggests that AAV-mediated gene transfer to the human retina does not elicit immunological responses which cause significant loss of transduced cells. The persistence of physiologic effect supports the possibility that gene therapy may influence LCA2 disease progression. The safety of the intervention and the stability of the improvement in visual and retinal function in these subjects support the use of AAV-mediated gene augmentation therapy for treatment of inherited retinal diseases.

  2. Targeted Multifunctional Lipid ECO Plasmid DNA Nanoparticles as Efficient Non-viral Gene Therapy for Leber's Congenital Amaurosis.

    Science.gov (United States)

    Sun, Da; Sahu, Bhubanananda; Gao, Songqi; Schur, Rebecca M; Vaidya, Amita M; Maeda, Akiko; Palczewski, Krzysztof; Lu, Zheng-Rong

    2017-06-16

    Development of a gene delivery system with high efficiency and a good safety profile is essential for successful gene therapy. Here we developed a targeted non-viral delivery system using a multifunctional lipid ECO for treating Leber's congenital amaurosis type 2 (LCA2) and tested this in a mouse model. ECO formed stable nanoparticles with plasmid DNA (pDNA) at a low amine to phosphate (N/P) ratio and mediated high gene transfection efficiency in ARPE-19 cells because of their intrinsic properties of pH-sensitive amphiphilic endosomal escape and reductive cytosolic release (PERC). All-trans-retinylamine, which binds to interphotoreceptor retinoid-binding protein (IRBP), was incorporated into the nanoparticles via a polyethylene glycol (PEG) spacer for targeted delivery of pDNA into the retinal pigmented epithelium. The targeted ECO/pDNA nanoparticles provided high GFP expression in the RPE of 1-month-old Rpe65(-/-) mice after subretinal injection. Such mice also exhibited a significant increase in electroretinographic activity, and this therapeutic effect continued for at least 120 days. A safety study in wild-type BALB/c mice indicated no irreversible retinal damage following subretinal injection of these targeted nanoparticles. All-trans-retinylamine-modified ECO/pDNA nanoparticles provide a promising non-viral platform for safe and effective treatment of RPE-specific monogenic eye diseases such as LCA2. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Missile Aerodynamics (Aerodynamique des Missiles)

    Science.gov (United States)

    1998-11-01

    guerre froide la production des missiles a baisse’, avec pour consequence une diminution des budgets de d6veloppement. Les nouveaux types de conflits ...Roma) Directeur - Gestion de l’information LUXEMBOURG (Recherche et developpement) - DRDGI 3 Voir Belgique Ministbre de la Difense nationale NORVEGE

  4. Therapie des Status epilepticus

    Directory of Open Access Journals (Sweden)

    Trinka E

    2009-01-01

    Full Text Available Der Status epilepticus (SE ist nach dem Schlaganfall der häufigste neurologische Notfall. Er stellt als generaliserter konvulsiver SE (GKSE die schwerste Ausprägung eines epileptischen Anfalls dar, der mit einer signifikanten Morbidität und einer ca. 20%igen Letalität verbunden ist. Nur bei der Hälfte der Patienten mit SE besteht zuvor eine Epilepsie; die meisten Fälle sind symptomatisch, wobei Schädel- Hirn-Traumata, zerebrovaskuläre Erkrankungen, ZNS-Infektionen und metabolische Ursachen führend sind. Bei Patienten mit vorbestehender Epilepsie lässt sich eine frühe Phase des GKSE erkennen, in der die Anfälle crescendoartig zunehmen, bis sie in kontinuierliche Anfallsaktivität münden (etablierte Phase. Das Management eines GKSE verlangt rasches und beherztes Vorgehen. Neben der sofort einzuleitenden Therapie muss gleichzeitig die artdiagnostische Zuordnung des SE und die Ursache erkannt und behandelt werden. Als Therapie der ersten Wahl sind Benzodiazepine etabliert, wobei intravenösem (i.v. Lorazepam gegenüber Diazepam der Vorzug zu geben ist. Versagt die Therapie mit Benzodiazepinen, muss rasch und konsequent nach einem Stufenschema vorgegangen werden. Phenytoin/Fosphenytoin, Valproinsäure, Levetiracetam und Lacosamid sind als i.v. Formulierung erhältliche Antiepileptika. Obwohl Vergleichsstudien hier fehlen, wird Phenytoin bevorzugt. Valproat und Levetiracetam sind nicht sedierend und kardiovaskulär gut verträglich, sodass hier Alternativen zu Phenytoin vorhanden sind. Lacosamid ist eine neue Therapieoption, deren Stellenwert erst bestimmt werden muss. Versagt auch die zweite Therapiestufe, so muss der Patient intubiert und in Allgemeinanästhesie intensivmedizinisch behandelt werden. Dafür stehen Thiopental, Propofol oder hoch dosiertes Midazolam zu Verfügung. Durch den eklatanten Mangel an randomisierten Studien bleibt die Therapie des GKSE empirisch und durch den Off-label-Einsatz gekennzeichnet.

  5. Mécanique des fluides

    CERN Document Server

    Cengel, Y A

    2017-01-01

    La mécanique des fluides est un outil performant qui permet d'expliquer les phénomènes qui nous entourent de l'échelle microscopique à l'échelle macroscopique. Elle est aussi à la base du développement de nombreuses technologies. Cet ouvrage à destination des étudiants donne une vision complète de la mécanique des fluides. Bien que la mécanique des fluides puisse souvent paraître rébarbative aux yeux des étudiants, cet ouvrage valorise ce domaine d'enseignement en l'illustrant de nombreux exemples issus de l'ingénierie navale, l'aéronautique, la météorologie, etc.

  6. Computertomographie- und Magnetresonanztomographie-Diagnostik in der Gastroenterologie: Leber, Gallenblase, Gallenwege und Pankreas

    Directory of Open Access Journals (Sweden)

    Schima W

    2012-01-01

    Full Text Available Die Multidetektor-Computertomographie (MDCT und die Magnetresonanztomographie (MRT haben ihren festen Platz in der Diagnostik gastroenterologischer Erkrankungen. Neueste Techniken in der MRT mit leberspezifischen Kontrastmitteln und diffusionsgewichteter Bildgebung erzielen eine exzellente Sensitivität und Spezifität im Nachweis von Lebertumoren. Die MRT ist der MDCT im Nachweis des hepatozellulären Karzinoms und von Lebermetastasen überlegen. Die Kombination einer MRCP mit kontrastmittelverstärkter MRT („one-stop shopping“ erlaubt eine genaue Beurteilung der Ausdehnung von hilären Cholangiokarzinomen (Klatskin-Tumoren und ist entscheidend für das weitere Management. Die MRCP ist mittlerweise Standard für die nicht-invasive Abklärung von Gallenwegserkrankungen, sie besitzen eine Sensitivität 90 % im Nachweis von Gallengangskonkrementen 3 mm. Für die Diagnose einer Cholezystolithiasis oder unkomplizierten Cholezystitis ist die Sonographie unverändert Standard, MDCT oder MRT kommen lediglich bei Komplikationen zur Anwendung. Die kontrastmittelverstärkte MDCT ist heutzutage Methode der Wahl in der Diagnostik einer Pankreatitis oder eines Pankreastumors (Sensitivität 95 %. In Problemfällen (unklare CT, kleine Tumoren oder Ausschluss von Lebermetastasen kommt die MRT zur Anwendung.

  7. Molekulare Formen des PSA in der Diagnostik des Prostatakarzinoms

    Directory of Open Access Journals (Sweden)

    Lein M

    2003-01-01

    Full Text Available Das prostataspezifische Antigen ist die wichtigste Kenngröße in der Diagnostik und Therapieüberwachung des Prostatakarzinoms. Zur besseren Abgrenzung zwischen Männern mit und ohne Prostatakarzinom, aber auch zur Früherkennung, haben sich die molekularen Formen des PSA als wertvolle Entscheidungshilfen erwiesen. Es wird eine Übersicht über bisher vorliegende Informationen zur Aussagekraft des freien PSA, des an alpha 1-Antichymotrypsin gebundenen PSA und des komplexierten PSA (cPSA zusammen mit eigenen Resultaten gegeben. Der Quotient aus freiem und Gesamt-PSA hat sich als eine wichtige Entscheidungsgröße in der urologischen Praxis etabliert, mit der Sensitivität und Spezifität der Prostatakarzinomdiagnostik verbessert werden. Die Zahl von Prostatastanzbiopsien im Gesamt-PSA-Bereich von 4–10 ng/ml kann damit reduziert werden. Ein diagnostischer Vorteil der alleinigen Bestimmung des komplexierten PSA bzw. der entsprechenden Quotienten im Vergleich zum Gesamt-PSA und des Quotienten freies PSA zu Gesamt-PSA konnte bisher nicht sicher nachgewiesen werden.

  8. Mécanique des sols et des roches

    CERN Document Server

    Vullier, Laurent; Zhao, Jian

    2016-01-01

    La mécanique des sols et la mécanique des roches sont des disciplines généralement traitées séparément dans la littérature. Pour la première fois, un traité réunit ces deux spécialités, en intégrant également les connaissances en lien avec les écoulements souterrains et les transferts thermiques. A la fois théorique et pratique, cet ouvrage propose tout d'abord une description détaillée de la nature et de la composition des sols et des roches, puis s'attache à la modélisation de problèmes aux conditions limites et présente les essais permettant de caractériser les sols et les roches, tant d'un point de vue mécanique qu'hydraulique et thermique. La problématique des sols non saturés et des écoulements multiphasiques est également abordée. Une attention particulière est portée aux lois de comportement mécanique et à la détermination de leurs paramètres par des essais in situ et en laboratoire, et l'ouvrage offre également une présentation détaillée des systèmes de classi...

  9. [Gene therapy for vision restoration in patients with Leber congenital amaurosis (LCA) due to RPE65 gene mutations: beginning the phase IV trial].

    Science.gov (United States)

    Chacón-Camacho, Óscar Francisco; Zenteno, Juan Carlos

    This is a significant time moment in the field of gene therapy in humans. Recently, results from a phase III clinical trial were published, demonstrating the first gene therapy success for a genetic disease. A clinical trial was carried out in patients suffering a hereditary blindness disease named Leber congenital amaurosis, caused by mutations in the RPE65 gene. Participating subjects received a subretinal injection of the normal RPE65 gene and one year after exhibited a significant improvement in visual acuity. It is expected that this gene therapy treatment will be approved by the FDA and commercialized in the USA in 2017.

  10. Le silence des agneaux

    Directory of Open Access Journals (Sweden)

    BERNARD ROY

    2012-01-01

    Full Text Available Ce texte est avant tout une réflexion sur la notion d'obéissance, initiée à partir de deux évènements impliquant étroitement des membres de la profession infirmière. L'auteur se réjouit de la prise de parole et de l'implication directe d'infirmières dans le contexte du printemps érable. Il estime que la posture de ces infirmières s'inscrit dans ce que l'éthicien Guy Durand, appelle une obéissance autonome qui peut, du coup, mener à la désobéissance civile, à l'objection de conscience. En prenant exemple sur le silence des infirmières dans le contexte de la fermeture de postes d'infirmières en Minganie, l'auteur estime que cette posture est marginale chez les infirmières qui, majoritairement, adoptent une position de soumission et d'obéissance hétéronome.

  11. La médicalisation des humeurs des enfants

    OpenAIRE

    Monzée, Joël

    2015-01-01

    Les enfants qui ont des comportements dérangeants ou qui souffrent de problèmes neurologiques, comme le trouble déficitaire de l’attention avec ou sans hyperactivité (TDAH), remettent en question nos moyens d’intervention pour les aider. Alors que le contexte européen tend à privilégier une intervention psychoéducative, les milieux nord-américains recourent davantage aux psychostimulants pour réduire les effets des problèmes comportementaux des enfants. Cet article aborde quelques problématiq...

  12. EXTREMISMUS IM KLASSENZIMMER - THEORETISCHE CHANCEN UND MÖGLICHKEITEN DES POLITIKUNTERRICHTES.

    Directory of Open Access Journals (Sweden)

    Amelie Zuschke

    2015-06-01

    Full Text Available Durch Phänomene wie PEGIDA wird eine Unsicherheit in der Bevölkerung ausgedrückt, die auch vor den Schultüren nicht Halt macht. Ein Querschnitt der Gesellschaft sitzt im Klassenraum und auf diesen muss sich eingestellt werden. Ob Kinder zuhause oder in ihrer Freizeit mit Populismus konfrontiert werden, die Schule hat als immer größerer Teil im Leben von Schülern in Deutschland (im Zuge der nach und nach fortschreitenden Einführung eines Ganztages-Prinzips auch eine Verantwortung mit diesen Eindrücken und Einflüssen bedacht umzugehen. Deutschland sollte aus der eigenen Geschichte heraus zudem die aufmerksame und sensible Handhabung mit extremem Gedankengut im Allgemeinen und mit rechtsextremistischem Gedankengut im Besonderen haben. Die Tendenz zu den politischen Extremen in wirtschaftlich und sozial herausfordernden Zeiten ist ein mit jedem wirtschaftlichen Abschwung auftretendes Phänomen, aber stark nationalistisches Gedankengut ist mit der heutigen Idealvorstellung von einem offenen Europa nicht vereinbar. In der Bundesrepublik Deutschland fußt die politische Bildung, geschichtlich begründet, auf demokratievermittelnden Prinzipien. Diese eignen sich vielseitig für die Auseinandersetzung mit Extremismus und den hierzu unumstrittenen Grundlagen und Werte der pluralistischen Gesellschaft in einer Demokratie. Das Kontroversitätsgebot des Beutelsbacher Konsenses aus dem Jahr 1977 (vgl Breit/Massig, 1993 bietet einen Ansatz zur Behandlung von Extremismus in der politischen Bildung auf der Grundlage der gegenseitigen Akzeptanz. Hier wird das Kontroversitätsgebot aufgeschlüsselt und anschließend auf Extremismus in der Schule bezogen. Die Fragestellung, wie der Politikunterricht trotz des Kontroversitätsgebotes mit Extremismus umgehen sollte, ist auf den Umgang mit dem gegenwärtigen Rechtsextremismus ausgelegt, welcher einen großen Teil politisch motivierter Straftaten begründet, sich in radikalisierter Form am stärksten gegen

  13. Habilitations à diriger des recherches

    Directory of Open Access Journals (Sweden)

    2007-04-01

    Full Text Available Pierre Corbin, Avec des dictionnaires pour compagnons.Habilitation à diriger des recherches soutenue le 24 novembre 2006.Composition du juryHenri Béjoint (Lyon 2Franz Josef Hausmann (Erlangen-NürnbergBenoît Habert (Paris 10Pierre Rézeau (CNRSMichel Roché (Toulouse 2Danièle Van de Velde (Lille 3, UMR STL, Directrice d'habilitation.Philippe Sabot, La philosophie, entre pratiques de lecture et pratiques d'écritureHabilitation à diriger des recherches soutenue le 24 novembre 2006.Compositio...

  14. Des cartes dans la classe…

    Directory of Open Access Journals (Sweden)

    R. Gimeno

    1990-09-01

    Full Text Available La majorité des enseignants qui veulent faire des cartes — et les faire réaliser aux élèves — pour répondre aux exigences des instructions officielles, doivent surmonter leur manque de compétences en cartographie et en didactique ainsi que les difficultés propres aux logiciels de cartographie encore peu performants. Ces compétences et la réflexion qui les accompagne sont pourtant accessibles aux enfants de l’école élémentaire…

  15. Wider die Verherrlichung des Weiblichen : Kritik des Ökofeminismus

    OpenAIRE

    Attia, Iman

    1991-01-01

    Die Studie ist eine Kritik am Frauen- und Gesellschaftsbild des Ökofeminismus. Nach der Darstellung wesentlicher theoretischer Kategorien des Ökofeminismus, die sich zentrieren im Ideal der Hausarbeit als wichtigste Form von Subsistenzarbeit, stellt die Autorin zusammenfassend fest, daß der Ökofeminismus die gesellschaftlichen Unterschiede und historischen Veränderungen ignoriert, indem er den Weiblichkeitsbegriff aus der Gebärfähigkeit ableitet. Jede Ausbeutungsform wird reduziert auf biolog...

  16. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy.

    Directory of Open Access Journals (Sweden)

    Nicole J Van Bergen

    Full Text Available Primary Open Angle Glaucoma (POAG is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs. Aging and increased intraocular pressure (IOP are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower. Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.

  17. Mitochondrial DNA mutation m.10680G > A is associated with Leber hereditary optic neuropathy in Chinese patients

    Directory of Open Access Journals (Sweden)

    Zhang A-Mei

    2012-03-01

    Full Text Available Abstract Background Leber hereditary optic neuropathy (LHON is a mitochondrial disorder with gender biased and incomplete penetrance. The majority of LHON patients are caused by one of the three primary mutations (m.3460G > A, m.11778G > A and m.14484T > C. Rare pathogenic mutations have been occasionally reported in LHON patients. Methods We screened mutation m.10680G > A in the MT-ND4L gene in 774 Chinese patients with clinical features of LHON but lacked the three primary mutations by using allele specific PCR (AS-PCR. Patients with m.10680G > A were further determined entire mtDNA genome sequence. Results The optimal AS-PCR could detect as low as 10% heteroplasmy of mutation m.10680G > A. Two patients (Le1263 and Le1330 were identified to harbor m.10680G > A. Analysis of the complete mtDNA sequences of the probands suggested that they belonged to haplogroups B4a1 and D6a1. There was no other potentially pathogenic mutation, except for a few private yet reported variants in the MT-ND1 and MT-ND5 genes, in the two lineages. A search in reported mtDNA genome data set (n = 9277; excluding Chinese LHON patients identified no individual with m.10680G > A. Frequency of m.10680G > A in Chinese LHON patients analyzed in this study and our previous studies (3/784 was significantly higher than that of the general populations (0/9277 (P = 0.0005. Conclusion Taken together, we speculated that m.10680G > A may be a rare pathogenic mutation for LHON in Chinese. This mutation should be included in future clinical diagnosis.

  18. Longitudinal study of a heteroplasmic 3460 Leber hereditary optic neuropathy family by multiplexed primer-extension analysis and nucleotide sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, S.S.; Fahy, E. [Applied Genetics, San Diego, CA (United States); Bodis-Wollner, I. [State Univ. of New York College of Optometry, New York, NY (United States)] [and others

    1996-02-01

    Nucleotide-sequencing and multiplexed primer-extension assays have been used to quantitate the mutant-allele frequency in 14 maternal relatives, spanning three generations, from a family that is heteroplasmic for the primary Leber hereditary optic neuropathy (LHON) mutation at nucleotide 3460 of the mitochondrial genome. There was excellent agreement between the values that were obtained with the two different methods. The longitudinal study shows that the mutant-allele frequency was constant within individual family members over a sampling period of 3.5 years. Second, although there was an overall increase in the mutant-allele frequency in successive generations, segregation in the direction of the mutant allele was not invariant, and there was one instance in which there was a significant decrease in the frequency from parent to offspring. From these two sets of results, and from previous studies of heteroplasmic LHON families, we conclude that there is no evidence for a marked selective pressure that determines the replication, segregation, or transmission of primary LHON mutations to white blood cells and platelets. Instead, the mtDNA molecules are most likely to replicate and segregate under conditions of random drift at the cellular level. Finally, the pattern of transmission in this maternal lineage is compatible with a developmental bottleneck model in which the number of mitochondrial units of segregation in the female germ line is relatively small in relation to the number of mtDNA molecules within a cell. However, this is not an invariant pattern for humans, and simple models of mitochondrial gene transmission are inappropriate at the present time. 37 refs., 4 figs., 1 tab.

  19. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy.

    Science.gov (United States)

    Van Bergen, Nicole J; Crowston, Jonathan G; Craig, Jamie E; Burdon, Kathryn P; Kearns, Lisa S; Sharma, Shiwani; Hewitt, Alex W; Mackey, David A; Trounce, Ian A

    2015-01-01

    Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.

  20. A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology

    Energy Technology Data Exchange (ETDEWEB)

    Mackey, D. (Royal Children' s Hospital, Melbourne (Australia)); Howell, N. (Univ. of Texas, Galveston (United States))

    1992-12-01

    The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary optic neuropathy (LHON). The risk of developing the optic neuropathy shows strict maternal inheritance, and the opthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences. 29 refs., 3 figs., 3 tabs.

  1. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.D.; Sun, F.; Wallace, D.C. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1997-02-01

    Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.

  2. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways

    Science.gov (United States)

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-01-01

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that

  3. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways.

    Science.gov (United States)

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-12-17

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that

  4. Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy

    Science.gov (United States)

    Van Bergen, Nicole J; Crowston, Jonathan G.; Craig, Jamie E.; Burdon, Kathryn P.; Kearns, Lisa S.; Sharma, Shiwani; Hewitt, Alex W.; Mackey, David A.; Trounce, Ian A.

    2015-01-01

    Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function. PMID:26496696

  5. Characterization of retinal nerve fiber layer thickness changes associated with Leber's hereditary optic neuropathy by optical coherence tomography.

    Science.gov (United States)

    Zhang, Yixin; Huang, Houbin; Wei, Shihui; Qiu, Huaiyu; Gong, Yan; Li, Hongyang; Dai, Yanli; Jiang, Zhaocai; Liu, Zihao

    2014-02-01

    In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber's hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ≤3 months; group 2, 4-6 months; group 3, 7-9 months; group 4, 10-12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P<0.05), the RNFL was observed to be thinner in the temporal quadrant in groups 1 and 2. The eyes in groups 3 and 4 showed a thinner RNFL in the temporal (P=0.001), superior and inferior (both P<0.05) quadrants, and a lower 360°-average RNFL thickness as compared with controls (P=0.001). No significant correlation was identified between BCVA and RNFL thickness. RNFL thickness was observed to undergo a unique process from thickening to thinning in the patients with LHON. Changes in different quadrants occurred at different time periods and the BCVA was not found to be correlated with RNFL thickness.

  6. Patterns of white matter diffusivity abnormalities in Leber's hereditary optic neuropathy: a tract-based spatial statistics study.

    Science.gov (United States)

    Milesi, Jacopo; Rocca, Maria A; Bianchi-Marzoli, Stefania; Petrolini, Melissa; Pagani, Elisabetta; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2012-09-01

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by retinal ganglion cell degeneration and optic nerve atrophy, leading to a loss of central vision. The aim of this study was to explore the topographical pattern of damage to the brain white matter (WM) tracts from patients with chronic LHON using diffusion tensor (DT) MRI and tract-based spatial statistics (TBSS). Brain dual-echo and DT MRI scans were acquired from 13 patients with chronic LHON and 25 matched controls using a 3.0 T scanner. TBSS analysis was performed using the FMRIB's Diffusion Toolbox. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary retinal nerve fiber layer thickness (PRNFL) measurements, was obtained in all patients. Mean average and temporal PRNFL thicknesses were decreased significantly in LHON patients. Compared to controls, TBSS analysis revealed significant diffusivity abnormalities in these patients, which were characterized by a decreased fractional anisotropy (FA) and an increased mean diffusivity and radial diffusivity, affecting exclusively the optic tracts and optic radiations (OR). In patients, a significant correlation was found between optic tract average FA and mean visual acuity (r = 0.57, p = 0.04). In LHON patients, DT MRI reveals a microstructural alteration of the WM along the entire visual pathways, with a sparing of the other main WM tracts of the brain. Damage to the OR may be secondary either to trans-synaptic degeneration, which in turn is due to neuroaxonal loss in the retina and optic nerve, or to local mitochondrial dysfunction.

  7. Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration.

    Science.gov (United States)

    den Hollander, Anneke I

    2016-03-01

    The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs.

  8. Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis.

    Directory of Open Access Journals (Sweden)

    Matthew L Batten

    2005-11-01

    Full Text Available BACKGROUND: Leber congenital amaurosis (LCA, a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT, which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat-/- mouse, recapitulates clinical features of the human disease. Here, we report that two interventions--intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds--each restore retinal function to Lrat-/- mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to approximately 50% of wild-type levels (p < 0.05 versus wild-type and knockout controls, and pupillary light responses (PLRs of Lrat-/- mice increased approximately 2.5 log units (p < 0.05. Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from approximately 5% of wild-type levels in Lrat-/- mice to approximately 50% of wild-type levels in treated Lrat-/- mice (p < 0.05 versus wild-type and knockout controls. The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and approximately 1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision

  9. Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy.

    Science.gov (United States)

    Tan, Mei Hong; Mackay, Donna S; Cowing, Jill; Tran, Hoai Viet; Smith, Alexander J; Wright, Genevieve A; Dev-Borman, Arundhati; Henderson, Robert H; Moradi, Phillip; Russell-Eggitt, Isabelle; MacLaren, Robert E; Robson, Anthony G; Cheetham, Michael E; Thompson, Dorothy A; Webster, Andrew R; Michaelides, Michel; Ali, Robin R; Moore, Anthony T

    2012-01-01

    Leber Congenital Amaurosis (LCA) and Early Childhood Onset Severe Retinal Dystrophy are clinically and genetically heterogeneous retinal disorders characterised by visual impairment and nystagmus from birth or early infancy. We investigated the prevalence of sequence variants in AIPL1 in a large cohort of such patients (n = 392) and probed the likelihood of disease-causation of the identified variants, subsequently undertaking a detailed assessment of the phenotype of patients with disease-causing mutations. Genomic DNA samples were screened for known variants in the AIPL1 gene using a microarray LCA chip, with 153 of these cases then being directly sequenced. The assessment of disease-causation of identified AIPL1 variants included segregation testing, assessing evolutionary conservation and in silico predictions of pathogenicity. The chip identified AIPL1 variants in 12 patients. Sequencing of AIPL1 in 153 patients and 96 controls found a total of 46 variants, with 29 being novel. In silico analysis suggested that only 6 of these variants are likely to be disease-causing, indicating a previously unrecognized high degree of polymorphism. Seven patients were identified with biallelic changes in AIPL1 likely to be disease-causing. In the youngest subject, electroretinography revealed reduced cone photoreceptor function, but rod responses were within normal limits, with no measurable ERG in other patients. An increasing degree and extent of peripheral retinal pigmentation and degree of maculopathy was noted with increasing age in our series. AIPL1 is significantly polymorphic in both controls and patients, thereby complicating the establishment of disease-causation of identified variants. Despite the associated phenotype being characterised by early-onset severe visual loss in our patient series, there was some evidence of a degree of retinal structural and functional preservation, which was most marked in the youngest patient in our cohort. This data suggests

  10. Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy.

    Directory of Open Access Journals (Sweden)

    Mei Hong Tan

    Full Text Available Leber Congenital Amaurosis (LCA and Early Childhood Onset Severe Retinal Dystrophy are clinically and genetically heterogeneous retinal disorders characterised by visual impairment and nystagmus from birth or early infancy. We investigated the prevalence of sequence variants in AIPL1 in a large cohort of such patients (n = 392 and probed the likelihood of disease-causation of the identified variants, subsequently undertaking a detailed assessment of the phenotype of patients with disease-causing mutations. Genomic DNA samples were screened for known variants in the AIPL1 gene using a microarray LCA chip, with 153 of these cases then being directly sequenced. The assessment of disease-causation of identified AIPL1 variants included segregation testing, assessing evolutionary conservation and in silico predictions of pathogenicity. The chip identified AIPL1 variants in 12 patients. Sequencing of AIPL1 in 153 patients and 96 controls found a total of 46 variants, with 29 being novel. In silico analysis suggested that only 6 of these variants are likely to be disease-causing, indicating a previously unrecognized high degree of polymorphism. Seven patients were identified with biallelic changes in AIPL1 likely to be disease-causing. In the youngest subject, electroretinography revealed reduced cone photoreceptor function, but rod responses were within normal limits, with no measurable ERG in other patients. An increasing degree and extent of peripheral retinal pigmentation and degree of maculopathy was noted with increasing age in our series. AIPL1 is significantly polymorphic in both controls and patients, thereby complicating the establishment of disease-causation of identified variants. Despite the associated phenotype being characterised by early-onset severe visual loss in our patient series, there was some evidence of a degree of retinal structural and functional preservation, which was most marked in the youngest patient in our cohort

  11. La fabrique des extraterrestres

    OpenAIRE

    Poulain, Sébastien

    2012-01-01

    Grâce à différentes stratégies discursives et médiatiques, Radio Ici et Maintenant joue un rôle dans la fabrication de la rumeur de l’existence des extraterrestres. Cette rumeur, teintée de complot, doit servir à légitimer l’utopie messianique et millénariste de cette radio New Age qui dispose de 5 000 auditeurs au quotidien. Cette radio prophétique et thérapeutique participe donc, jusqu’à un certain degré, au renouvellement de l’espace du politico-religieux. Thanks to various media and di...

  12. Therapie des Harnwegsinfekts

    Directory of Open Access Journals (Sweden)

    Stoiser B

    2010-01-01

    Full Text Available Harnwegsinfektionen gehören zu den häufigsten entzündlichen Erkrankungen im niedergelassenen Bereich. Eine intelligente Therapiestrategie stellt damit nicht nur eine klinische Herausforderung dar, sondern ermöglicht rasche Heilung, Vermeidung von Resistenzbildungen sowie oft unnötiger, teurer diagnostischer Schritte. Der erste entscheidende Schritt ist die genaue Klassifizierung des Harnweginfektes – asymptomatische Bakteriurie bis zur komplizierten Pyelonephritis. Hier entscheiden sich bereits Aggressivität der Behandlung sowie diagnostischer Aufwand. Für die Entwicklung einer empirischen antimikrobiellen Therapie ist die Kenntnis der häufigsten Erreger sowie lokaler Resistenzmuster wichtig. Bei gezieltem Vorgehen können die meisten Harnwegsinfekte ohne erhöhten diagnostischen Aufwand therapiert werden.

  13. Biologie des Geruchs: Die Bedeutung von Pheromonen für Verhalten und Reproduktion

    Directory of Open Access Journals (Sweden)

    Atzmüller M

    2000-01-01

    Full Text Available Dieser Artikel geht der Frage nach dem Vorkommen und der Wirkung von Pheromonen beim Menschen nach. Es wird der Status quo der Geruchsforschung aufgezeigt und ein Überblick über die Voraussetzungen der Geruchskommunikation geboten. Über Beispiele aus dem Tierreich wird zu ihrem Vorkommen und ihrer Bedeutung beim Menschen geführt. So hat sich in den letzten Jahren gezeigt, daß besonders die Geruchsstoffe aus dem Schweiß das Potential besitzen, menschliches Verhalten nachweislich zu beeinflussen. Darüber hinaus zeigt sich, daß auch die menschliche Reproduktion dem Einfluß von Pheromonen zu unterliegen scheint. Die Bedeutung der Geruchskommunikation beim Menschen wird größtenteils noch immer unterschätzt, obwohl sie durchaus das Potential für zukünftigen medizinischen Einsatz zu bergen scheint.

  14. Der Gesundheitsbegriff des Jedermanns: Studien zum Wandel des Gesundheitsbegriffs anhand der deutschen Literatur vom Mittelalter bis heute

    OpenAIRE

    Franck, Annette

    2007-01-01

    Diese Arbeit entstand im Rahmen eines von der Deutschen Forschungsgemeinschaft geförderten Studienprojekts zur Frage „Gesundheit als Determinante von Lebensqualität“. Es galt heraus¬zu¬arbeiten, was Gesundheit nicht für Medizinphilosophen und Soziologen, sondern für denjenigen bedeutet, den sie unmittelbar, an Leib und Seele spürbar betrifft, den Menschen. In den einleitenden Kapiteln wurde vorerst der Begriff „Gesundheit“ unter e...

  15. LA TRADUCTION DES PREPOSITIONS

    Directory of Open Access Journals (Sweden)

    Samira MOUTAKIL

    2013-05-01

    Full Text Available L’idée de cet article nous est venue d’un cours qu’on assure pour les futurs guides touristiques en Jordanie. En traduisant des textes - français-arabe ou arabe-français, les étudiants se heurtent à certains problèmes pour rendre le texte vers la langue cible et qui soit convenable syntaxiquement et sémantiquement. On a remarqué donc que la traduction des prépositions vers l’une ou l’autre langue présente un dilemme pour les apprenants. On a décidé de composer un corpus de phrases contenant les propositions en français, « à » avec toutes ses formes, « dans et sur » et de l'arabe "على", "في" . Dans un premier temps, on a constitué le corpus avec 25 phrases dans les deux langues et on les a soumises aux étudiants, la liste en français aux étudiants du niveau A2 et la liste ne arabe aux étudiants du niveau A1. Par la suite, on a dégagé ce qui ressort de leurs traductions ce qui nous a permis de faire une analyse sémantico-syntaxique assez détaillée. En conclusion de cet article, on présente les résultats de cette expérience très intéressante.

  16. Marais Des Cygnes Wildlife Area

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This brochure is for the Marais des Cygnes Wildlife Area, managed by Kansas Department of Wildlife, Parks and Tourism, and located in the floodplain of the Marais...

  17. Digitalisierung des Kulturellen Erbes (Europas)

    NARCIS (Netherlands)

    Gruber, Marion

    2011-01-01

    Gruber, M. R. (2011, 13 December). Digitalisierung des Kulturellen Erbes (Europas). Guest lecture at the IPMZ - Institute of Mass Communication and Media Research, Devision Media Change & Innovation, University of Zurich, Switzerland.

  18. Des enjeux éthiques et politiques dans l’œuvre d’Hermann Broch (1886-1951

    Directory of Open Access Journals (Sweden)

    Djéhanne Gani

    2009-12-01

    Full Text Available L’œuvre de Hermann Broch (1886-1951 est polymorphe, comportant romans, essais, correspondances, mêlant philosophie, histoire, psychanalyse et littérature. Cette diversité n’est pas, cependant, synonyme de dispersion puisque tous les écrits revêtent des enjeux éthiques et politiques. Broch, auteur engagé, concentre sa pensée sur l’homme, sa situation dans le monde moderne. L’absence d’ « un » sens et le sentiment de solitude forment la toile de fond de ses romans et de sa pensée. Son concept d’ « état crépusculaire » est à la fois symptôme et révélateur de la crise de l’homme et il montre le lien étroit entre théorie et création littéraire dans son œuvre. Dans un contexte marqué par l’expérience de l’antisémitisme et du totalitarisme, Broch développe une anthropologie de la responsabilité qui dénonce l’individualisme et l’indifférence. L’écriture relève pour lui de la « responsabilité sociale » et engage des enjeux éthiques et politiques. Hermann Broch croit à la « conversion » de ceux qui sont dans l’ « état crépusculaire » et qui somnolent. Il décrit la crise du monde moderne qu’il met en valeur, mais au-delà de l’analyse, sa réflexion a peut-être avant tout une visée pratique, comme son idée de la « conversion » en atteste. La dimension politique va de pair avec son engagement éthique. Il propose une éthique de l’humanité.Hermann Brochs (1886-1951 Werk ist äußerst vielseitig, es umfasst Romane, Essays, einen umfangreichen Briefwechsel und vermischt Philosophie, Geschichte, Psychoanalyse und Literatur. Diese Vielseitigkeit ist jedoch nicht gleichbedeutend mit Zerstreuung – Brochs Schriften vereint, dass sie sich alle mit Fragen von Politik und Ethik beschäftigen. Die Gedanken des engagierten Autors Broch sind auf den Menschen gerichtet, auf dessen Platz in der modernen Welt. Das Fehlen „eines“ Sinnes und das Gefühl der Einsamkeit bilden

  19. The research progress of leber's hereditary optic neuropathy%Leber遗传性视神经病变的研究进展

    Institute of Scientific and Technical Information of China (English)

    张娟娟; 冀延春; 周翔天; 瞿佳; 管敏鑫

    2016-01-01

    Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)是一种主要累及青壮年男性,导致视神经退行性变的母系遗传病.线粒体DNA(mitochondrial DNA,mtDNA)突变为LHON发病的主要分子基础.LHON不完全外显和男性好发的特征表明,其他因素(如mtDNA单体型、核修饰基因和/或环境因素等)在LHON发病中起着重要作用.%Leber's hereditary optic neuropathy (LHON) is a maternally-inherited eye disease that generally affects young adults.Mutations in mtDNA are the molecular bases for this disorder.The incomplete penetrancc and male bias of LHON indicate that other factors,including mitochondrial haplogroup,nuclear modified genes and/or environmental factors,play an important role in the incidence of LHON.

  20. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    Energy Technology Data Exchange (ETDEWEB)

    De Vries, D.D.; Oost, B.A. van [Univ. Hospital Nijmegen (Netherlands); Went, L.N.; Bruyn, G.W. [Univ. of Leiden (Netherlands)] [and others

    1996-04-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A{yields}G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T{yields}A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. 80 refs., 2 figs., 3 tabs.

  1. Leber遗传性视神经病变分子遗传学研究进展%Molecule Genetic Research Advances of Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    赵福新; 管敏鑫

    2008-01-01

    Leber hereditary optic neuropathy(LHON)is a maternally inherited disorder leading to rapid,painless,bilateral loss of central vision.Point mutation of mitochondrial DNA(mtDNA)results in LHON.This paper makes a brief introduction of primary,secondary mutations and other mutations,and elucidates the role of nuclear modified gene;haplogroup and surroundings factor(smoking,alcohol,etc.)in the penetrance and phenotypic expression of the LHON,respectively.%Leber遗传性视神经病变(Leber hereditary optic neuropathy,LHON)是一种导致双眼快速的、无痛性的中心视力丧失的母系遗传性疾病.主要是由线粒体DNA(mitochondrial DNA,mtDNA)发生点突变所致.本文主要介绍LHON原发性、继发性和其他相关位点突变,阐述核修饰基因、mtDNA单体型及环境因素(吸烟、饮酒等)对LHON外显率和发病严重程度的影响.

  2. Rational imaging of hepatocellular carcinoma. The challenge of multimodal diagnostic criteria; Rationale Schnittbildgebung des hepatozellulaeren Karzinoms. Die Herausforderung multimodaler Diagnosekriterien

    Energy Technology Data Exchange (ETDEWEB)

    Kircher, A.; Bongartz, G.; Merkle, E.M.; Zech, C.J. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland)

    2014-07-15

    specificity. For daily clinical routine, CT offers a fast, reliable and easy available modality with benefits for patients in reduced general state of health and restricted compliance. (orig.) [German] CT und MRT bilden den Goldstandard in der bildgebenden Diagnostik des hepatozellulaeren Karzinoms (HCC). Beide Verfahren erlauben als alleinige Untersuchung bei entsprechendem Kontrastmittelverhalten die Diagnose eines HCC. Eine radiologische Herausforderung stellen immer noch die Detektion von HCC-Laesionen < 2 cm, die Abgrenzung praemaligner und maligner Laesionen von anderen benignen Vorstufen der Hepatokarzinogenese sowie die Dignitaetseinschaetzung hypovaskulaerer Leberlaesionen in der zirrhotischen Leber dar. Beide Untersuchungsmodalitaeten erreichen inzwischen fuer Laesionen > 2 cm sehr hohe Detektionsraten zwischen 90 und 100 %. Fuer Laesionen zwischen 1 und 2 cm bestehen Vorteile der MRT mit Sensitivitaeten zwischen 80 und 90 % gegenueber 60-75 % der CT. Die MRT-Diagnostik profitiert neben den multimodalen Diagnosekriterien zusaetzlich vom Einsatz leberspezifischer Kontrastmittel, insbesondere in Kombination mit der Diffusionsbildgebung, wobei sowohl eine Erhoehung der Sensitivaet als auch der diagnostischen Genauigkeit fuer Laesionen < 2 cm nachgewiesen werden konnte. Bezueglich der Abgrenzung des HCC von anderen nodulaeren Herdlaesionen der zirrhotischen Leber hat sich gezeigt, dass die gleichzeitig vorliegende arterielle Hypervaskularisation und Hypointensitaet in der hepatobiliaeren Phase als spezifisch fuer das Vorliegen eines HCC einzustufen ist. Zudem ist ein hypointenses Signal in der hepatobiliaeren Phase mit einem hohen Vorhersagewert von bis zu 100 % fuer das Vorliegen eines High-grade-dysplastischen Knotens oder HCC assoziiert. Die MRT unter Beruecksichtigung von hepatobiliaerer und diffusionsgewichteter Bildgebung (''diffusion-weighted imaging'', DWI) stellt heutzutage die beste nichtinvasive Bilddiagnostik fuer die Detektion des HCC

  3. Terre des hommes

    CERN Multimedia

    Staff Association

    2012-01-01

    Transformez votre téléphone portable en geste de solidarité ! Collecte du 12 au 23 novembre 2012   Faites un geste simple et utile en déposant vos téléphones portables inutilisés dans les urnes installées dans les trois restaurants du CERN. En Suisse, une personne change tous les 12 à 18 mois de téléphone portable. La plupart de nos vieux appareils sont simplement laissés à l’abandon avec comme seule fonction de parer une éventuelle panne à venir. On  estime ainsi que 8 millions de portables sont inutilisés, alors qu'entre 30 et 50% peuvent être réutilisés. L'action Solidarcomm leur offre une deuxième vie ! Terre des Hommes Suisse, dans le cadre de la campagne Solidarcomm, collecte et valorise vos téléphones inutilis&...

  4. Onlinespieler abseits des Mainstreams

    Directory of Open Access Journals (Sweden)

    Harald Baumgartlinger

    2012-12-01

    Full Text Available MMO(RPGs „Massively Multiplayer Online (Role-Playing Games“ nehmen einen Sonderstatus unter den Onlinespielen ein, welcher durch den wachsenden wirtschaftlichen Erfolg, insbesondere durch den „breakthrough hit“ (Duchenaut et al. 2006: 407 World of Warcraft (WoW, auch an Bedeutung für die Medien- und Kommunikationswissenschaft gewinnt (vgl. Inderst 2009: 15; vgl. Seifert/Jöckel 2008: 297. Der Primus des Genres, WoW, repräsentiert gemeinsam mit einigen nahezu identen Titeln insgesamt 85 Prozent der gespielten MMOGs (vgl. Williams et al. 2008: 999. Daher befasst sich auch die Mehrheit der vorliegenden Studien mit eben diesen Spielen. Neue Formen von MMO(Gs können jedoch zu ebenso neuartigen Spielerfahrungen führen und damit unterschiedliche Nutzungsmotive befriedigen (vgl. Seifert/Jöckel 2008: 309 und folglich zu einem gänzlich anderen Spielerleben führen. Während im Mainstream die kooperativen Spielerbeziehungen überwiegen, dominiert in Darkfall Online der soziale Wettbewerb. Der von Williams et al. 2008 verwendete Fragebogen diente als Rohling für die Kreation eines für die speziellen Anforderungen adaptierten Erhebungstools zur Erforschung der Spielertypologie und der Motive der Darkfall-Online-SpielerInnen. Die in der Onlinebefragung (N = 506 gesammelten Daten belegen, dass sich sowohl die Spielerdemographie, als auch die Motive der Spieler von den Mainstream MMOs unterscheiden. Zudem konnten realweltliche Eigenschaften der Spieler als signifikante Einflussfaktoren für die Spielzuwendung identifiziert werden.

  5. Peste des petits ruminants.

    Science.gov (United States)

    Parida, S; Muniraju, M; Mahapatra, M; Muthuchelvan, D; Buczkowski, H; Banyard, A C

    2015-12-14

    Peste des petits ruminants virus causes a highly infectious disease of small ruminants that is endemic across Africa, the Middle East and large regions of Asia. The virus is considered to be a major obstacle to the development of sustainable agriculture across the developing world and has recently been targeted by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation (FAO) for eradication with the aim of global elimination of the disease by 2030. Fundamentally, the vaccines required to successfully achieve this goal are currently available, but the availability of novel vaccine preparations to also fulfill the requisite for differentiation between infected and vaccinated animals (DIVA) may reduce the time taken and the financial costs of serological surveillance in the later stages of any eradication campaign. Here, we overview what is currently known about the virus, with reference to its origin, updated global circulation, molecular evolution, diagnostic tools and vaccines currently available to combat the disease. Further, we comment on recent developments in our knowledge of various recombinant vaccines and on the potential for the development of novel multivalent vaccines for small ruminants. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Leber's hereditary optic neuropathy and limbs abnormity claudication may be associated with the mitochondrial ND1 T3866C mutation%线粒体ND1基因T3866C突变可能是Leber's遗传性视神经病和四肢畸形跛行相关的突变

    Institute of Scientific and Technical Information of China (English)

    刘燕; 管敏鑫; 庄淑流; 童绎; 瞿佳; 周翔天; 赵福新; 张娟娟; 张永梅; 章豫

    2010-01-01

    线粒体DNA(Mitochondrial DNA,mtDNA)突变与人类许多疾病的发病机制相关.现报道1个具有典型母系遗传特征的中国人Leber's遗传性视神经病和四肢畸形跛行的家系.该家系共5代60人,共27名母系成员,其中4人只有Leber's遗传性视神经病症状,1人呈现四肢畸形跛行症状,4人同时具有上述两种临床症状,而其他成员无临床症状.对先证者的mtDNA全序列进行分析,发现ND1基因T3866C突变位点和43个多态位点,经系统进化树分析属于东亚单体型D4a3.MtDNA ND1 3866位点T-C碱基的改变使ND1亚基第187位进化高度保守的异亮氨酸转变为苏氨酸,从而改变该蛋白的结构,进而影响其功能.在135名正常对照中未发现该突变.因此,线粒体ND1 T3866C可能是与Leber's遗传性视神经病和四肢畸形跛行相关的线粒体基因突变.

  7. Schritt fur Schritt: Die Durschsetzung der Rechte geistig behinderter Menschen; Pas a Pas: La mise en application des droits des personnes handicapees mentales; Paso a Paso: Puesta en practica de los derechos de los deficientes mentales (Step by Step: Implementation of the Rights of Mentally Retarded Persons).

    Science.gov (United States)

    International League of Societies for the Mentally Handicapped, Brussels (Belgium).

    The booklet presents the proceedings (in English, French, Spanish, and German) of Session 62 of the Seventh World Congress of the International League of Societies for the Mentally Handicapped, detailing some analytical guidelines for national societies on the implementation of the rights of mentally retarded persons. Rights discussed include…

  8. Schritt fur Schritt: Die Durschsetzung der Rechte geistig behinderter Menschen; Pas a Pas: La mise en application des droits des personnes handicapees mentales; Paso a Paso: Puesta en practica de los derechos de los deficientes mentales (Step by Step: Implementation of the Rights of Mentally Retarded Persons).

    Science.gov (United States)

    International League of Societies for the Mentally Handicapped, Brussels (Belgium).

    The booklet presents the proceedings (in English, French, Spanish, and German) of Session 62 of the Seventh World Congress of the International League of Societies for the Mentally Handicapped, detailing some analytical guidelines for national societies on the implementation of the rights of mentally retarded persons. Rights discussed include…

  9. CCC/WPA study : Des Lacs NWR

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Summary of the Civilian Conservation Corps (CCC) camp at Des Lacs National Wildlife Refuge from July 1935-May 1942 to carry on restoration and development of Des...

  10. Current algebra; Algebre des courants

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, M. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The first three chapters of these lecture notes are devoted to generalities concerning current algebra. The weak currents are defined, and their main properties given (V-A hypothesis, conserved vector current, selection rules, partially conserved axial current,...). The SU (3) x SU (3) algebra of Gell-Mann is introduced, and the general properties of the non-leptonic weak Hamiltonian are discussed. Chapters 4 to 9 are devoted to some important applications of the algebra. First one proves the Adler- Weisberger formula, in two different ways, by either the infinite momentum frame, or the near-by singularities method. In the others chapters, the latter method is the only one used. The following topics are successively dealt with: semi leptonic decays of K mesons and hyperons, Kroll- Ruderman theorem, non leptonic decays of K mesons and hyperons ( {delta}I = 1/2 rule), low energy theorems concerning processes with emission (or absorption) of a pion or a photon, super-convergence sum rules, and finally, neutrino reactions. (author) [French] La premiere partie de ce cours (trois premiers chapitres), traite des generalites concernant l'algebre de courants. Apres une definition rapide des courants faibles et un rappel de leurs proprietes (hypothese V-A, conservation du courant vecteur, regles de selection, courant axial partiellement conserve,...), l'on introduit l'algebre de Gell-Mann SU (3) x SU (3), et discute les proprietes generales de l'Hamiltonien faible non leptonique. Les chapitres IV a IX sont consacres a des applications importantes de l'algebre des courants. En premier lieu l'on demontre la formule de Adler et Weisberger, par deux methodes differentes, celle dite du repere de moment infini et celle des singularites proches. Cette derniere est seule utilisee dans la suite. Puis, l'on traite successivement les problemes suivants: desintegrations semi-leptoniques des mesons K et des hyperons, theoreme de Kroll

  11. La théorie des industries culturelles (et informationnelles, composante des SIC

    Directory of Open Access Journals (Sweden)

    Bernard Miège

    2012-09-01

    Full Text Available Inaugurer le Cahier central de la Revue des SIC est certes une forme de reconnaissance, mais cela comporte des obligations, au premier rang desquelles la nécessité d’intéresser des lecteurs a priori pas immédiatement concernés par la thématique.Si la théorie des industries culturelles est devenue progressivement une approche marquante des SIC, en France, en Europe et plus largement encore (avec des dénominations variables et des modalités spécifiques, ce n’est en effet ni en le proclamant ha...

  12. Leber遗传性视神经病变研究进展%Research progress of Leber hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    张阳阳

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common maternally transmitted hereditary retinal diseases,which is mainly caused by one of the three point mutations in mitochondrial DNA(mt DNA) (G11778A,G3460A and G14484C).LHON is characterized by painless,acute or sub-acute bilateral visual loss in young men with central scotoma.Incomplete dominance and gender bias are two puzzles of this disease.Although currently there is no effective therapy to prevent or cure the LHON,the ongoing clinical trials of gene therapy have showed initial success in some LHON patients with G11778A mutation.Here we summarized recent research progress of LHON,focusing on the clinical features,molecular and pathogenic mechanisms,animal models,and gene therapy of it.%Leber遗传性视神经病变(LHON)是临床上常见的遗传性视神经病变,是一种以母系遗传为特征的线粒体疾病,主要由线粒体DNA (mtDNA)3个原发突变G11778A、G3460A和G14484C引起.LHON多见于青壮年男性,主要临床表现为无痛性双侧视力下降或丧失和中心盲点.不完全外显和性别偏好是该病亟待解决的两大难题.虽然目前尚无有效的预防及治疗措施,但在美国进行的LHON基因治疗临床试验已取得初步成功.本文就LHON的临床表现、发病机制、分子遗传学特点、动物模型、基因治疗等进行介绍,进一步加强对本病的认识.

  13. The Leber congenital amaurosis protein AIPL1 and EB proteins co-localize at the photoreceptor cilium.

    Directory of Open Access Journals (Sweden)

    Juan Hidalgo-de-Quintana

    Full Text Available The aim of this study was to investigate the interaction and co-localization of novel interacting proteins with the Leber congenital amaurosis (LCA associated protein aryl hydrocarbon receptor interacting protein-like 1 (AIPL1.The CytoTrapXR yeast two-hybrid system was used to screen a bovine retinal cDNA library. A novel interaction between AIPL1 and members of the family of EB proteins was confirmed by directed yeast two-hybrid analysis and co-immunoprecipitation assays. The localization of AIPL1 and the EB proteins in cultured cells and in retinal cryosections was examined by immunofluorescence microscopy and cryo-immunogold electron microscopy.Yeast two-hybrid (Y2H analysis identified the interaction between AIPL1 and the EB proteins, EB1 and EB3. EB1 and EB3 were specifically co-immunoprecipitated with AIPL1 from SK-N-SH neuroblastoma cells. In directed 1:1 Y2H analysis, the interaction of EB1 with AIPL1 harbouring the LCA-causing mutations A197P, C239R and W278X was severely compromised. Immunofluorescent confocal microscopy revealed that AIPL1 did not co-localize with endogenous EB1 at the tips of microtubules, endogenous EB1 at the microtubule organising centre following disruption of the microtubule network, or with endogenous β-tubulin. Moreover, AIPL1 did not localize to primary cilia in ARPE-19 cells, whereas EB1 co-localized with the centrosomal marker pericentrin at the base of primary cilia. However, both AIPL1 and the EB proteins, EB1 and EB3, co-localized with centrin-3 in the connecting cilium of photoreceptor cells. Cryo-immunogold electron microscopy confirmed the co-localization of AIPL1 and EB1 in the connecting cilia in human retinal photoreceptors.AIPL1 and the EB proteins, EB1 and EB3, localize at the connecting cilia of retinal photoreceptor cells, but do not co-localize in the cellular microtubule network or in primary cilia in non-retinal cells. These findings suggest that AIPL1 function in these cells is not related

  14. Novel GUCY2D mutation causes phenotypic variability of Leber congenital amaurosis in a large kindred.

    Science.gov (United States)

    Gradstein, Libe; Zolotushko, Jenny; Sergeev, Yuri V; Lavy, Itay; Narkis, Ginat; Perez, Yonatan; Guigui, Sarah; Sharon, Dror; Banin, Eyal; Walter, Eyal; Lifshitz, Tova; Birk, Ohad S

    2016-07-30

    Leber congenital amaurosis (LCA) is a severe retinal degenerative disease that manifests as blindness or poor vision in infancy. The purpose of this study was to clinically characterize and identify the cause of disease in a large inbred Bedouin Israeli tribe with LCA. Thirty individuals of a single kindred, including eight affected with LCA, were recruited for this study. Patients' clinical data and electroretinography (ERG) findings were collected. Molecular analysis included homozygosity mapping with polymorphic markers and Sanger sequencing of candidate genes. Of the eight affected individuals of the kindred, nystagmus was documented in five subjects and keratoconus in three. Cataract was found in 5 of 16 eyes. Photopic and scotopic ERG performed in 5 patients were extinguished. All affected subjects were nearly blind, their visual acuity ranged between finger counting and uncertain light perception. Assuming autosomal recessive heredity of a founder mutation, studies using polymorphic markers excluded homozygosity of affected individuals at the genomic loci of all previously known genes associated with LCA, except GUCY2D. Sequencing of GUCY2D identified a novel missense mutation (c.2129C>T; p.Ala710Val) resulting in substitution of alanine by valine at position 710 within the protein kinase domain of the retina-specific enzyme guanylate cyclase 1 (GC1) encoded by GUCY2D. Molecular modeling implied that the mutation changes the conformation of the regulatory segment within the kinase styk-domain of GC1 and causes loss of its helical structure, likely inhibiting phosphorylation of threonine residue within this segment, which is needed to activate the catalytic domain of the protein. This is the first documentation of the p.Ala710Val mutation in GC1 and the second ever described mutation in its protein kinase domain. Our findings enlarge the scope of genetic variability of LCA, highlight the phenotypic heterogeneity found amongst individuals harboring an

  15. Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture.

    Science.gov (United States)

    Stone, Edwin M

    2007-12-01

    To critically evaluate our experience in molecular testing of Leber congenital amaurosis (LCA) and to use this information to devise a general approach to heterogeneous recessive disorders. Careful clinical and molecular characterization of large cohorts of patients affected with inherited eye diseases will be an essential step in the development of effective therapy for these diseases, especially when the therapy involves gene replacement. A molecular genetic case-control study. Six hundred forty-two unrelated individuals with the clinical diagnosis of LCA and 200 unrelated control individuals were screened for disease-causing sequence variations in eight genes using various combinations of single-strand conformational polymorphism analysis (SSCP), automated DNA sequencing, multiplex allele-specific ligation analysis (SNPlex), and high-density solid-phase single nucleotide polymorphism genotyping. Four hundred forty instances of 189 different disease-causing sequence variations were observed in this study, 98 of which have not been previously reported. One hundred forty-six of the 189 variations (77%) were observed in only a single individual. The observed variations were not evenly distributed among the LCA patients or among the eight genes. Empirical analysis of this uneven distribution was used to devise a multi-platform mutation detection strategy that is four times more efficient than a more conventional strategy of completely sequencing all of the coding regions of all LCA genes in all subjects. Hardy-Weinberg analysis of the observed mutations suggests that these eight genes are collectively responsible for about 70% of the cases of LCA in North America. The carrier frequency of the most common LCA allele (an intron 26 variation in CEP290) was found to be 2/3,248, which suggests that the overall prevalence of LCA in this population is about 1/81,000. An allele-specific ligation assay (SNPlex) was designed to detect 68 of the most common LCA-causing alleles

  16. Neologismen des Lettischen anhand des schriftstellerischen Werkes von Zigmunds Skujins

    OpenAIRE

    Javojss, Skaidrite

    2010-01-01

    Untersuchung: Aus acht Werken des zeitgenössischen Schriftstellers Zigmunds Skujins wurden 500 lettische Wörter untersucht, die in den drei umfangreichsten lettischen Wörterbüchern nicht verzeichnet und somit möglicherweise Neologismen des Autors sind. Analysiert werden die Wortarten, die Komposita, die Herkunft der assimilierten Lehnwörter, orthographische und andere Varianten bereits lexikalisierter Wörter, die Arten der Diminutivbildung und der Präfigierung. Außerdem werden Aussagen über d...

  17. Evaluer des études de gestion des entreprises : combiner des éléments principales avec des éléments pratiques

    NARCIS (Netherlands)

    Pennink, B.J.W.

    2002-01-01

    Evaluer la recherche de gestion demande une combinaison des critères classiques et des critères pratiques. Par cette combinaison il est possible de trouver une réponse cerrecte concernant la validité et l'effet de la recherche. Dans cet article nous allons décrire comment une combinaison des

  18. Alimentation des tortues terrestres herbivores

    OpenAIRE

    Morin, Nicolas

    2015-01-01

    Chez les tortues, la plupart des affections rencontrées sont directement ou indirectement liées à un défaut dans les conditions d’entretien et notamment à une alimentation inadéquate. Les ouvrages de référence ne proposent généralement que des rations qualitatives déterminées empiriquement. Ce travail se veut une synthèse bibliographique des différents travaux qui ont été menés sur les tortues terrestres herbivores, dont le but est de dégager les paramètres physiologiques sous-jacents au ...

  19. LES APPROCHES PSYCHOSOCIOLOGIQUES DES ORGANISATIONS

    Directory of Open Access Journals (Sweden)

    Deaconu Alecxandrina

    2008-05-01

    Full Text Available Les préoccupations pour bien comprendre la complexité des organisations sont bien connues dans la théorie et la pratique du management. La motivation la plus fréquente pour toutes les recherches et les investigationes faites a été fondée sur le besoin de savoir gérer les situations diverses en vue de maximiser la performance organisationnelle. En ce qui nous concerne, pour enrichir les informations disponibles, nous voulons élargir, dans notre communication, les approches traditionelles, focaliser l’attention sur la dimension psychologiques des organisations et présenter les mécanismes qui favorisent l’implication des salariés.

  20. L’Internet des objets

    OpenAIRE

    Benghozi, Pierre-Jean; Bureau, Sylvain; Massit-Folléa, Françoise

    2012-01-01

    L’ « internet des objets » est une dimension majeure de l’internet du futur. Mais tout le monde ne s’accorde pas encore sur sa définition, ni sur la mesure de son importance économique ou des risques qu’il induit. L’étude de nombreux rapports prospectifs et l’observation des innovations d’ores et déjà engagées a permis de mettre en relief les incertitudes techniques, économiques et socio-politiques qui pèsent sur cette véritable mutation programmée de l’internet et de proposer une approche eu...

  1. L’Internet des objets

    OpenAIRE

    Benghozi, Pierre-Jean; Bureau, Sylvain; Massit-Folléa, Françoise

    2012-01-01

    L’ « internet des objets » est une dimension majeure de l’internet du futur. Mais tout le monde ne s’accorde pas encore sur sa définition, ni sur la mesure de son importance économique ou des risques qu’il induit. L’étude de nombreux rapports prospectifs et l’observation des innovations d’ores et déjà engagées a permis de mettre en relief les incertitudes techniques, économiques et socio-politiques qui pèsent sur cette véritable mutation programmée de l’internet et de proposer une approche eu...

  2. Géographie des cryptarchies

    Directory of Open Access Journals (Sweden)

    Gilles Fumey

    2002-06-01

    Full Text Available Si toute la surface du globe est appropriée, certains territoires sont encore revendiqués par des personnes ou petits groupes usurpateurs, conquérants ou aventuriers. Leur «conquête» porte sur des espaces physiques ou virtuels (internet. Elle traduit avec constance dans l'histoire le rôle considérable de l'ancrage territorial qui reste, pour l'homme, un antidote à toutes les formes d'organisation qui le dépassent.

  3. Cardiotoxicité des psychotropes

    OpenAIRE

    TAHIRI, Abdallah

    2013-01-01

    Même à dose thérapeutique, les médicaments psychotropes sont susceptibles d'engendrer des troubles du rythme cardiaque graves avec risque létal concourant à expliquer la pré valence de la mort subite dans la population psychiatrique. Les situations cliniques à risque telles que poly médication (des psychotropes entre eux ou d'un psychotrope avec un non psychotrope allongeur de QTc), interactions médicamenteuses aussi bien pharmacodynamiques que pharmacocinétiques, traitement pa...

  4. Physique statistique des Fluides Classiques

    OpenAIRE

    Aslangul, Claude

    2006-01-01

    0 - Préambule.Préambule, table des matières1 - Rappels sur la description d'un système à l'équilibre thermodynamiqueQuelques propriétés des systèmes macroscopiques. Nature statistique de l'entropie. Grandeurs internes et grandeurs externes. Relations thermodynamiques fondamentales. Potentiels thermodynamiques. Ensembles microcanonique, canonique, grand-canonique et isotherme - isobare. Exemple: fonction de partition d'un fluide classique. Principe variationnel pour l'énergie libre.2 - Stabili...

  5. Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, M.G.; Davis, M.B.; Lashwood, A.; Brockington, M.; Harding, A.E. (Institute of Neurology, Queen Square, London (United Kingdom)); Toscano, A. (Clinica Neurologica, Messina (Italy))

    1992-10-01

    Leber hereditary optic neuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0. 17 refs., 2 figs., 1 tab.

  6. Detection of the mtDNA 14484 mutation on an African-specific haplotype: Implications about its role in causing Leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Torroni, A.; Petrozzi, M.; Terracina, M. [Universita` di Roma (Italy)] [and others

    1996-07-01

    Leber hereditary optic neuropathy (LHON) is a maternally transmitted disease whose primary clinical manifestation is acute or subacute bilateral loss of central vision leading to central scotoma and blindness. To date, LHON has been associated with 18 mtDNA missense mutations, even though, for many of these mutations, it remains unclear whether they cause the disease, contribute to the pathology, or are nonpathogenic mtDNA polymorphisms. On the basis of numerous criteria, which include the specificity for LHON, the frequency in the general population, and the penetrance within affected pedigrees, the detection of associated defects in the respiratory chain, mutations at three nucleotide positions (nps), 11778 (G{r_arrow}A), 3460 (G{r_arrow}A), and 14484 (T{r_arrow}C) have been classified as high-risk and primary LHON mutations. Overall, these three mutations encompass {ge}90% of the LHON cases. 29 refs., 1 fig.

  7. Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber Hereditary Optic Neuropathy (LHON).

    Science.gov (United States)

    Beretta, Simone; Wood, John P M; Derham, Barry; Sala, Gessica; Tremolizzo, Lucio; Ferrarese, Carlo; Osborne, Neville N

    2006-11-01

    Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Müller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium-dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Müller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex I-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON.

  8. A mitochondrial mutation at nt 9101 in the ATP synthase 6 gene associated with deficient oxidative phosphorylation in a family with leber hereditary optic neuroretinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Lamninen, T.; Junoven, V.; Aula, P.; Savontaus, M.L. [Univ. of Turku (Finland); Majander, A.; Wikstroem, M. [Univ. of Helsinki (Finland)

    1995-05-01

    Leber hereditary optic neuroretinopathy (LHON) is a maternally inherited ocular disease resulting in bilateral optic atrophy in young adults. Several mtDNA point mutations have been proposed as being causative for LHON, all in complex I, III, or IV of the respiratory chain. The ND4/11778 mutation accounts for {approximately}50% of all LHON families, the ND1/3460 mutation is detected in {approximately}15% of cases, and {approximately}10% of LHON families have the ND6/14484 mutation. All these mutations are restricted to LHON families, and they change evolutionary conserved amino acids. Furthermore, these primary mutations have never been observed to occur simultaneously. Besides the primary mutations, several other replacement mutations have been found in LHON families. These mutations are also detected at low frequency in control individuals, and they change evolutionarily less conserved amino acids. 11 refs., 2 figs.

  9. Mitochondrial gene therapy improves respiration, biogenesis, and transcription in G11778A Leber's hereditary optic neuropathy and T8993G Leigh's syndrome cells.

    Science.gov (United States)

    Iyer, Shilpa; Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R; Bennett, James P

    2012-06-01

    Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ∼1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future.

  10. A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a pathogenic mitochondrial DNA mutation for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Shiraishi, Wataru; Hayashi, Shintaro; Kamada, Takashi; Isobe, Noriko; Yamasaki, Ryo; Murai, Hiroyuki; Ohyagi, Yasumasa; Kira, Jun-ichi

    2014-02-01

    We report the first case of definite neuromyelitis optica (NMO) with a pathogenic mitochondrial DNA (mtDNA) mutation for Leber's hereditary optic neuropathy (LHON) (G11778A point mutation). A 36-year-old Japanese woman had experienced recurrent neurological symptoms originating from involvements of the optic nerves and spinal cord. She finally lost her bilateral vision, and spastic paraparesis and sensory disturbances below the T6 level remained despite intensive immunotherapies. Brain and spinal magnetic resonance imaging (MRI) revealed T2-high-intensity lesions in the optic nerves and thoracic spinal cord, but no lesions in the brain. A blood examination revealed positivity for both anti-aquaproin-4 antibodies and an LHON mtDNA mutation.

  11. Searching the co-occurrence of pathogenic mutations for Leber's hereditary optic neuropathy and hearing loss in more than 26,000 whole mitochondrial genomes.

    Science.gov (United States)

    Yang, Haixin; Liu, Rui; Wang, Chuan-Chao

    2016-09-01

    The co-occurrence of pathogenic or candidate mutations for Leber's hereditary optic neuropathy (LHON) and hearing loss has long been suggested to be a rare incident. The "rare" is probably caused by inadequate database searches. In this study, we created and released a comprehensive database with detailed information of haplogroup, variants, coding sites, and potential pathogenic mutations for more than 26,000 whole mitochondrial genomes. We found the co-occurrence in more than 200 individuals including not only LHON or hearing loss patients but also individuals sampled from general populations with various haplogroup backgrounds. The results highlighted the significant importance of adequate database searching in the genetic analysis of mitochondrial disorders.

  12. Clinical features and the mutation of Leber's hereditary optic neuropathy in Chinese patients%中国人Leber 遗传性视神经病变的原发突变及临床特征

    Institute of Scientific and Technical Information of China (English)

    王燕; 郭向明; 贾小云; 黎仕强; 肖学珊; 郭莉; 张清炯

    2005-01-01

    目的分析中国人Leber遗传性视神经病变(Leber's hereditary optic neuropathy, LHON) 线粒体DNA 3个原发致病基因突变遗传及其临床特征. 方法分别用突变特异性引物聚合酶链反应,异源双链-单链构象多态性,限制性片段长度多态性和DNA测序方法,对110个家系的156例LHON患者进行11778A、3460A、14484C 3个原发位点检测,并收集患者病史及其临床资料,进行统计学分析. 结果 110例LHON先证者中,11778位点突变者100例,占90.9%;3460位点突变者2例,占1.8%;14484位点突变者8例,占7.3%.不同突变位点的LHON患者发病时视力分布:125人(250眼)11778位点突变患眼中发病时视力≤0.01(占17.6%),视力介于0.01至0.1之间(占52.1%),视力≥0.1(占30.3%);28人(56眼)14484位点突变患眼中无患眼视力低于0.01,视力介于0.01至0.1之间(占12.7%),视力≥0.1(占87.3%);3人(6眼) 3460位点突变患眼视力均介于0.03至0.08之间.视力恢复情况:250只11778位点突变的患眼中,6.97%的眼视力有所恢复, 平均最终视力0.03(指数~0.07);56只14484位点突变的患眼中,50%的眼视力有所恢复,占50%,平均最终视力0.8(0.3~1.2).结论中国人LHON患者mtDNA 3个原发致病突变中,以11778A位点突变为主、14484C位点突变较少、3460A罕见.LHON的临床表现与致病突变位点有关,14484C突变患者的发病视力及视力恢复情况明显好于11778A患者.

  13. La maison des mathématiques

    CERN Document Server

    Villani, Cédric; Moncorgé, Vincent

    2014-01-01

    Comment travaillent les mathématiciens ? C'est peut-être en se promenant dans les couloirs de la première des " maisons des mathématiques " de France, l'institut Henri Poincaré, que l'on trouvera quelques réponses. Le mathématicien Cédric Villani et le physicien Jean-Philippe Uzan nous invitent à découvrir cette discipline et ses acteurs. Au fil des pages on suit, à travers de superbes images signées du photographe Vincent Moncorgé, la façon dont se fabrique cette science qui reste souvent mystérieuse. Toutes les dimensions, scientifique, esthétique et poétique, des mathématiques sont convoquées grâce à des regards croisés : la diversité des inspirations des chercheurs, la source de leur créativité, l'imaginaire littéraire et artistique des mathématiques, la drôle de tribu des mathématiciens. Un voyage au cœur de cette " auberge espagnole " des mathématiques, campus " à la française " accueillant des centaines de chercheurs du monde entier, devenu un lieu d'émulation et d'éc...

  14. La compaction des sols forestiers en Wallonie

    OpenAIRE

    Destain, Marie-France

    2014-01-01

    Dans nos pays industrialisés, l’exploitation forestière fait appel à des machines de plus en plus lourdes pour assurer la vidange des coupes et le débardage des grumes. Lorsque des charges élevées sont appliquées sur des sols sensibles, une compaction du sol peut se produire entraînant une réduction de porosité, avec des conséquences néfastes sur la vitalité des peuplements. Au niveau environnemental, du fait de la compaction, l’infiltration de l’eau dans le sol est réduite, principalement...

  15. Etude des erreurs d'estimation des populations par la méthode des captures successives (DeLURY, 2 captures et des captures-recaptures (PETERSEN

    Directory of Open Access Journals (Sweden)

    LAURENT M.

    1978-01-01

    Full Text Available L'estimation des populations naturelles par capture-recapture et par captures successives est souvent entachée d'erreur car, dans de nombreux cas, l'hypothèse fondamentale d'égalité des probabilités de captures pour tous les individus dans le temps et dans l'espace n'est pas respectée. Dans le cas des populations de poissons envisagés ici, les captures ont lieu par la pêche électrique. On a pu chiffrer l'ordre de grandeur des erreurs systématiques faites sur l'estimation des peuplements, en fonction des conditions particulières, biotiques et abiotiques, des différents milieux inventoriés.

  16. Recherche des oscillations de Neutrinos $\

    CERN Document Server

    Gangler, E

    1997-01-01

    Le detecteur nomad, place sur le faisceau de neutrinos wide-band-beam du sps, de contamination en neutrino tau marginale, permet de rechercher des oscillations neutrino muon - tau dans la region de pertinence cosmologique et de distinguer statistiquement les courants charges des neutrinos tau essentiellement par leur mesure cinematique. Une large part du travail de these a donc ete consacree a la reconstruction des evenements dans les chambres a derive, cible instrumentee et cur de l'experience, dont la physique de detection est decrite. Une methode de recherche de traces fut developpee, utilisant certaines informations d'un autre sous-detecteur de nomad, le trd. Pour combler une perte d'efficacite de reconstruction, une methode de recherche de traces courtes s'appuyant sur des vertex deja constitues fut developpee en exploitant les potentialites du filtre de kalman, algorithme iteratif d'ajustement de traces. Ces methodes sont utilisees en production par la collaboration. Cette these porte sur la recherche d...

  17. Reduction des effectifs ou licenciements

    CERN Multimedia

    Maiani, Luciano

    2002-01-01

    "Vous faites un amalgame entre la reduction en cours des effectifs du CERN (organisation europeenne pour la recherche nucleaire) et les economies que le laboratoire doit realiser dans les cinq ans a venir pour financer le projet de grand collisionneur de hadrons (Le Monde du 4 septembre)" (1/2 page).

  18. Bangalore, ville des nouvelles technologies

    Directory of Open Access Journals (Sweden)

    Clarisse Didelon

    2003-06-01

    Full Text Available Bangalore est devenue la Silicon Valley de l’Inde. Une partie de ses habitants y vit à l’occidentale mais le reste de la population souffre de la croissance spectaculaire de la ville. Face à l’insuffisance des infrastructures, Bangalore devient de moins en moins attractive pour les entreprises internationales.

  19. Advances in research of the onset mechanism underlying leber's hereditary optic neuropathy%Leber遗传性视神经病变发病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    许倩倩

    2012-01-01

    Leber 遗传性视神经病变(Leber's hereditary optic neuropathy,LHON) 是一种以中心视力减退为主要症状的线粒体遗传病,是导致青壮年人群视力下降、视神经萎缩的疾病之一.已确认13 个原发基因突变与LHON 有关,异质性、种族、继发突变、核基因和营养状态等多种因素可影响其临床表型.本文结合国内外研究进展,对LHON 发病的分子生物学机制进行综述.

  20. Osteoporose und Genetik des Knochenstoffwechsels

    Directory of Open Access Journals (Sweden)

    Obermayer-Pietsch B

    2002-01-01

    Full Text Available Osteoporose ist in hohem Maß genetisch determiniert. Neue Wege der molekularbiologischen Forschung haben sich in den letzten Jahren auf diesem Gebiet etabliert. "Gene mapping" mit polymorphen genetischen Markern auf der Suche nach Phänotyp-assoziierten Genen ist ein aufwendiges, aber vielversprechendes Verfahren und wird durch die Erkenntnisse des Human Genome Projects beschleunigt. So wurde jüngst u. a. das Low-density Lipoprotein 5-Gen als wichtig für den Knochenstoffwechsel identifiziert. Kandidaten-gene wie Hormonrezeptor-, Cytokin- oder Kollagen-Gene werden hinsichtlich ihrer Gen-Gen- und Gen-Umwelt- Interaktionen untersucht und erlauben neue funktionelle Einsichten in Erkrankungen des Knochenstoffwechsels. Mutationen der Kollagen-Gene sind bei einigen seltenen Erkrankungen, wie dem Osteoporose-Pseudogliom-Syndrom oder der Osteogenesis imperfecta gefunden worden, könnten aber auch für häufige Varianten von Bindegewebsstörungen wie der congenitalen Hüftdysplasie verantwortlich sein, die etwa 10 % der weiblichen kaukasischen Bevölkerung in unterschiedlichem Ausmaß betrifft. Osteoporose am Schenkelhals und erhöhte Gelenkslaxizität sowie andere generalisierte Veränderungen des Knochen- und Kollagenstoffwechsels können hier möglicherweise ebenfalls durch Störungen des Kollagen I alpha 1-Gens erklärt werden. In Summe können wir zahlreiche neue Einsichten in die Pathophysiologie des Skelettsystems erwarten, die uns auch neue Zugangswege für Diagnostik und Therapie unserer Patienten ermöglichen werden.

  1. L'astronomie des Anciens

    Science.gov (United States)

    Nazé, Yaël

    2009-04-01

    Quelle que soit la civilisation à laquelle il appartient, l'être humain cherche dans le ciel des réponses aux questions qu'il se pose sur son origine, son avenir et sa finalité. Le premier mérite de ce livre est de nous rappeler que l'astronomie a commencé ainsi à travers les mythes célestes imaginés par les Anciens pour expliquer l'ordre du monde et la place qu'ils y occupaient. Mais les savoirs astronomiques passés étaient loin d'être négligeables et certainement pas limités aux seuls travaux des Grecs : c'est ce que l'auteur montre à travers une passionnante enquête, de Stonehenge à Gizeh en passant par Pékin et Mexico, fondée sur l'étude des monuments anciens et des sources écrites encore accessibles. Les tablettes mésopotamiennes, les annales chinoises, les chroniques médiévales, etc. sont en outre d'une singulière utilité pour les astronomes modernes : comment sinon remonter aux variations de la durée du jour au cours des siècles, ou percer la nature de l'explosion qui a frappé tant d'observateurs en 1054 ? Ce livre offre un voyage magnifiquement illustré à travers les âges, entre astronomie et archéologie.

  2. Tambov. Le camp des Malgré Nous alsaciens et mosellans prisonniers des Russes

    OpenAIRE

    Claerr-Stamm, Gabrielle

    2012-01-01

    « La faim, le froid, l’injustice. Et puis le silence… Tambov égale silence. Silence de la grande majorité de ceux qui en sont revenus, silence dans les familles, silence des historiens, silence des archives, silence des écrivains et des artistes, silence de l’opinion publique ». « Il a fallu l’opiniâtre courage de poignées d’individus – anciens prisonniers, responsables d’associations, quelques élus, des historiens et des journalistes – pour que la parole et la reconnaissance trouvent progres...

  3. Vers une typologie des formes spatiales des limites de l’Europe

    OpenAIRE

    de Ruffray, Sophie

    2013-01-01

    Penser l’Europe et ses limites consiste souvent à rechercher une identité européenne, un projet ou des comportements communs dans l’espace. L’approche par les représentations mentales permet de compléter par des perspectives plus subjectives, la perception des frontières. Cet article, réalisé à partir des résultats de l’enquête du projet de recherches Eurobroadmap sur la vision de l’Europe dans le monde permet de mettre en évidence une typologie des formes spatiales des limites de l’Europe. D...

  4. Modern CT and PET/CT imaging of the liver; Moderne CT- und PET/CT-Bildgebung der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Klasen, J.; Heusner, T.A.; Riegger, C.; Reichelt, D.; Kuhlemann, J.; Antoch, G.; Blondin, D. [Medizinische Fakultaet, Heinrich-Heine-Universitaet Duesseldorf, Institut fuer Diagnostische und Interventionelle Radiologie, Duesseldorf (Germany)

    2011-08-15

    Computed tomography (CT) is now widely available and represents an important and rapid method for the diagnostics of acute liver disease, characterization of focal liver lesions, planning of interventional therapy measures and postintervention control. In recent years CT has not become less important despite the increasing value of magnetic resonance imaging (MRI). By the use of different contrast medium phases good characterization of space-occupying lesions can be achieved. For the diagnostics of hepatocellular carcinoma (HCC) a triphasic examination protocol should always be implemented. The introduction of dual energy CT increased the sensitivity of imaging of hypervascularized and hypovascularized liver lesions and by the use of virtual native imaging it has become possible to avoid additional native imaging which reduces the x-ray exposition of patients. Positron emission tomography (PET) has an advantage for imaging in oncology because nearly the complete body of the patient can be screened and this is the main indication for PET/CT (whole-body staging). For purely hepatic problems 18F-fluorodeoxyglucose (FDG)-PET/CT using diagnostic CT data has a higher precision than CT alone but is inferior to MRI. (orig.) [German] Die Computertomographie (CT) ist heute breit verfuegbar und stellt eine wichtige und schnelle Methode zur Diagnostik akuter Lebererkrankungen, der Artdiagnostik fokaler Leberlaesionen und der Planung interventioneller Therapiemassnahmen sowie der postinterventionellen Kontrolle dar. In den letzten Jahren hat die CT trotz des zunehmenden Stellenwerts der Magnetresonanztomographie (MRT) nicht an Bedeutung verloren. Durch den Einsatz unterschiedlicher Kontrastmittelphasen kann meist eine gute Charakterisierung von Raumforderungen erfolgen. Bei der Diagnostik des hepatozellulaeren Karzinoms (HCC) sollte beispielsweise immer ein triphasisches Untersuchungsprotokoll angewendet werden. Mit Einfuehrung der Dual-energy-CT hat die Sensitivitaet in der

  5. Radiation dose for investigation of the chest and abdomen. Comparison of sequential, spiral and electron beam computed tomography; Strahlenexposition bei der CT-Untersuchung des Thorax und Abdomens. Vergleich von Einzelschicht-, Spiral- und Elektronenstrahlcomputertomographie

    Energy Technology Data Exchange (ETDEWEB)

    Becker, C.R.; Schaetzl, M.; Bruening, R.; Schoepf, U.J.; Reiser, M.F. [Klinikum Grosshadern, Muenchen (Germany). Inst. fuer Radiologische Diagnostik; Feist, H. [Muenchen Univ. (Germany). Radiologische Klinik und Poliklinik; Baeuml, A. [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). Inst. fuer Strahlenhygiene

    1998-09-01

    Comparison of radiation exposure applied by different types of CT scanners for the investigation of the chest and abdomen. Determination of radiation exposure applied by multi-phase spiral CT. Estimation of the dose in air in the system axis of the scanner, the CT dose index (CTDI) and the effective dose for electron beam tomography (EBT) and two conventional CT scanners (sequence, SEQ; spiral, SCT). For EBT, dose in system axis for investigation of the abdomen was above 50 mGy. Effective dose for investigation of the chest and abdomen was higher with EBT (11 and 26 mSv, respectively), than with conventional CT (SEQ, 4 and 20 mSv; SCT, 2 and 7 mSv). The effective dose for a biphasic investigation (liver 5 mSv, kidney 4 mSv) was below, for a triphasic investigation of the abdomen (6 mSv). Investigation of the abdomen with the EBT should only be performed for certain indications. With spiral CT, effective dose is much lower than with EBT. (orig.) [Deutsch] Die Strahlenexposition bei der Untersuchung von Thorax und Abdomen mit verschiedenen CT-Scannertypen sollte verglichen werden. Zusaetzlich sollte die Exposition beim Mehrphasen-Spiral-CT ermittelt werden. Die Dosis in der Systemachse, gemessen in freier Luft, (Achsendosis), der Computertomographie-Dosis-Index (CTDI) und die effektive Dosis nach ICRP 60 wurden bei einem Elektronenstrahl-CT (EBT) und zwei konventionellen CT-Scannern (sequentiell=SEQ, spiral=SCT) bestimmt. Beim EBT liegt die Achsendosis bei der Untersuchung des Abdomens ueber 50 mGy. Die effektive Dosis fuer die Untersuchung von Thorax und Abdomen war bei der EBT (11 bzw. 26 mSv) hoeher als beim konventionellen CT (SEQ 4 bzw. 20 mSv; SCT 2 bzw. 7 Sv). Die effektive Dosis einer 2-Phasen-Untersuchung (Leber 5 mSv, Niere 4 mSv) liegt unter, die einer 3-Phasen-Untersuchung (Leber 7 mSv) ueber der effektiven Dosis einer Untersuchung des gesamten Abdomens (6 mSv). Die Untersuchung des Abdomens sollte mit dem EBT nur nach strenger Indikationsstellung

  6. Administration et gestion des contrats XL

    CERN Document Server

    Senouf, J

    2000-01-01

    Les grands contrats de travaux génèrent un grand nombre de commandes (OSVC) passées par un grand nombre de responsables techniques. Ils sont généralement basés sur des bordereaux de prix associés à un éventail de conditions économiques adaptées aux besoins complexes et variés des multiples utilisateurs du CERN nécessitant des calculs sophistiqués. L'administration des commandes, le suivi des travaux et de la facturation doivent répondre aux besoins de tous les acteurs. Les responsables techniques doivent jouir de la plus large indépendance administrative dans le respect des règlements CERN et des conditions contractuelles. Le contrôle des métrés et décomptes doit être rigoureux et d'une traçabilité complète. L'utilisation des bases de données Oracle a déjà permis l'intégration des données administratives et techniques. Le Web nous invite à une communication totale et transparente entre les utilisateurs, les services techniques et les contractants. De nouveaux types de contrat so...

  7. Enquête de satisfaction des restaurants

    CERN Multimedia

    Staff Association

    2016-01-01

    Comité de surveillance des restaurants L’Association du personnel est représentée dans plusieurs comités dont le Comité de surveillance des restaurants (CSR) qui a pour mandat : de donner son avis sur toute question relative à la politique générale de l’Organisation en matière de restauration sur le site, y compris en ce qui concerne les termes et l’attribution des contrats d’exploitation des restaurants ; de définir dans le cadre des contrats d’exploitation des restaurants, les prestations correspondant aux besoins et, dans la mesure du possible, aux désirs du personnel ; de surveiller les prestations des restaurants, y compris en ce qui concerne la qualité et la préparation des produits ; de négocier avec les concessionnaires des restaurants au sujet des tarifs et de surveill...

  8. La territorialisation des politiques environnementales

    Directory of Open Access Journals (Sweden)

    Amédée Mollard

    2010-10-01

    Full Text Available Le point de départ de cet article est la grande variabilité de la pollution nitrique diffuse de l’eau due à l’agriculture. Celle-ci dépend en particulier du climat, des types de sol et des systèmes de production agricole. Nos recherches réalisées de façon interdisciplinaire à partir de deux sites différents en France, montrent que cette hétérogénéité spatio-temporelle conditionne les pratiques agricoles mises en œuvre pour réduire la pollution au niveau de la norme admise. De ce fait, les pratiques les plus « coût-efficaces » diffèrent d’un territoire à l’autre, en fonction des caractéristiques locales. Ces résultats mettent donc en évidence une efficacité potentielle d’une territorialisation des politiques publiques. En théorie, de telles politiques sont considérées comme optimales par les économistes, car elles incitent les agents à moduler leurs efforts en fonction de la sensibilité du milieu. Mais, selon les études empiriques, cet avantage serait annulé par un coût élevé de mise en œuvre, de contrôle et de surveillance. Pour maintenir leur avantage sur des politiques uniformes, les politiques territorialisées devraient être mises en œuvre à un niveau spatial optimal. Un tel niveau devrait au minimum atteindre un compromis entre l’économie réalisée grâce à une modulation adaptée aux conditions locales et les sur-coûts dus à la décentralisation des solutions mises en œuvre. Cet article analyse la pertinence d’une prise en compte de ces spécificités par des politiques territorialisées. L’efficacité d’une régulation différenciée de la pollution nitrique est étudiée ici en évaluant l’importance de la variabilité spatiale des paramètres physiques et des coûts de la territorialisation.The paper starts with the wide variability of nonpoint water nitrogenous pollution generated by agriculture. This variability depends especially on climate, soil types and farming

  9. Evaluation des systèmes existants pour le suivi à long terme des déformations des ponts

    OpenAIRE

    BURDET, Olivier; Muttoni, Aurelio

    2006-01-01

    Le projet de recherche Evaluation des systèmes existants pour le suivi à long terme des déformations des ponts a été initié dans le but de préparer sous forme condensée une présentation et une évaluation des systèmes de mesure existants pour le suivi à long terme des déformations de ponts ainsi que des recommandations en vue d’applications particulières. Ce sujet est d’actualité car d’une part il importe de gérer au mieux les ouvrages et les ressources et d’autre part parce que plusieurs cas ...

  10. Géographie des interfaces. Une nouvelle vision des territoires

    Directory of Open Access Journals (Sweden)

    Marie Redon

    2011-07-01

    Full Text Available Littéralement, une interface est une surface de séparation entre deux états distincts de la matière. Le terme, ayant cheminé de la physique à la biologie, et aussi désormais d’usage répandu en informatique. En géographie, l’usage du mot s’est développé dans les années 1980 et peut être défini comme un espace permettant la mise en relation de deux espaces/territoires différents, influencé par des échanges entre l’un et l’autre, et se distinguant par là-même des deux espaces contigus. Intégrant...

  11. Evaluation des performances des protocoles de routage Ad hoc

    OpenAIRE

    Boushaba, Abdelali; Oumsis, Mohammed; Benabbou, Rachid

    2010-01-01

    International audience; L'objectif de ce travail est d'une part, de confronter par la simulation, à l'aide de NS-2, les performances de quatre protocoles de routage Ad hoc: DSR, AODV, OLSR et DSDV et d'autre part, d'examiner l'impact de la charge du trafic, de la mobilité et de la densité des nœuds sur le comportement de ces protocoles. Les résultats montrent qu'il n'y a pas un protocole qui est favori pour tous les critères d'évaluation. En effet, chaque protocole a des comportements différe...

  12. Marie-Pierre Lassus, Gaston Bachelard musicien. Une philosophie des silences et des timbres

    OpenAIRE

    Marida Rizzuti

    2012-01-01

    Marie-Pierre Lassus, Gaston Bachelard musicien. Une philosophie des silences et des timbres (Villeneuve d’Ascq, Presses Universitaires du Septentrion, 2010, 268 pp. ISBN: 978-275-740-1613) di     Marida Rizzuti

  13. Leber Congenital Amaurosis

    Science.gov (United States)

    ... Resources Low Vision Specialists Retinal Physicians My Retina Tracker Registry Genetic Testing Clinical Trials Join the Fight ... which measure visual function, detect little if any activity in the retina. A low level of retinal ...

  14. Étude des impacts écologiques du dynamisme spatio-temporel des ...

    African Journals Online (AJOL)

    4 nov. 2013 ... du changement des habitats naturels sur les espèces menacées de sa faune. ... le contexte des changements climatiques. La situation de la .... naturels des espèces de la faune menacée dans la région évo- luent au cours du ... distribution des espèces cibles a ensuite été cartographiée sur la couche ...

  15. Beeinflussung des Essentiellen Tremors und des Tremors beim Morbus Parkinson durch transkranielle Gleichstromstimulation

    OpenAIRE

    Hellriegel, Helge

    2010-01-01

    Ziel dieser Arbeit war es die Rolle des primärmotorischen Kortex bei der Entstehung und Weiterleitung des Essentiellen Tremors und des Tremors beim Morbus Parkinson zu untersuchen. Hierzu wurde eine transkranielle Gleichstromstimulation über dem primärmotorischen Kortex bei Patienten mit oben genannten Tremorsyndromen durchgeführt und die klinischen sowie elektrophysiologisch messbaren Änderungen des Tremors beurteilt.

  16. Contribution à la Gestion des Cercosporioses du bananier dues à ...

    African Journals Online (AJOL)

    SARAH

    31 mai 2017 ... the state of disease progression after each treatment. Results and applications ..... 2007, des logiciels SPSS (Statistical Package for Social. Sciences) version ... un facteur suivies d'un test de comparaison des moyennes des ...

  17. La gestion des adoptions internationales

    OpenAIRE

    Boéchat, Hervé

    2011-01-01

    Après les rumeurs nées lors du tsunami et le désastre avéré de L’Arche de Zoé, l’adoption – et plus généralement le sort des enfants – est devenue une préoccupation majeure en cas de catastrophe naturelle ou de conflit. Haïti, pays depuis longtemps ouvert à l’adoption internationale, n’a pas échappé à la polémique. Hervé Boéchat nous livre l’appréciation de son institution sur cet épisode qui n’a sans doute pas contribué à apaiser le ressentiment des Haïtiens contre la « communauté internati...

  18. Catalogue ostéologique des oiseaux

    NARCIS (Netherlands)

    Oort, van E.D.

    1907-01-01

    Je le crois utile de faire précéder le présent Catalogue par quelques remarques. J’ai énuméré autant que possible les parties, qui font défaut aux squelettes. L’absence de plusieurs osselets, comme des doigts, des vertèbres caudales, des côtes etc. au même échantillon, est indiqué par „incomplet” ou

  19. Le piratage des biens d'information

    OpenAIRE

    Paul Belleflamme

    2003-01-01

    Où se situe le juste milieu entre les propos alarmistes des uns (“le piratage tue la production musicale!”) et les appels libertaires des autres (“l'accès à toute information doit être libre!”) ? Une analyse économique simple nous permet de mieux comprendre les enjeux et de dégager des pistes de réflexion pour l'avenir.

  20. 79 Influences des rejets des eaux usées domestiques dans les ...

    African Journals Online (AJOL)

    PR BOKO

    L'usage agricole d'effluents liquides peut être considéré comme une ... Rares sont celles qui sont alimentées par une eau de source [8]. ... nutriments, des Eléments Traces Métalliques (ETM) [9], des micro- ... essentiels pour la croissance des plantes ; ils provoquent cependant une prolifération excessive d' algues. La.

  1. Présentation des textes

    OpenAIRE

    Freitag, Michel

    2015-01-01

    Les textes choisis n’ont pas pour but la reconstitution ou le survol d’une carrière, mais la mise en valeur des étapes saillantes d’une double éclosion, celle d’Elizabeth Cady Stanton comme féministe et avec elle celle du mouvement de défense des droits des femmes aux États-Unis. Un tel objectif implique donc des limites temporelles en amont et en aval de l’événement fondateur que fut la Convention de Seneca Falls en 1848, origine du texte non moins fondateur de la Déclaration de sentiments r...

  2. Annuaire du Bureau des longitudes - 2006

    Science.gov (United States)

    Imcce; Bureau Des Longitudes

    2005-07-01

    This annual publication provides ephemerides and data to the use of professionnal and amateur astronomers. Divided in 11 chapters it covers concordance of various calendars, explanation of fondamental astronomy and various time scales, explanation for the use of ephemerides; tables provide ephemerides (positions, rise/set/passage) of the Sun and the Moon, planets, planetary satellites, asteroids, comets, bright stars; data and explanation for the physical observation of the surface of the Sun, the Moon, and planets; chart of the sky and a list of constellations and galaxies; prediction and ephemerides for astronomical phenomenon: occultation by the moon, stellar occultations by asteroids and appulses, solar eclipses and lunar eclipses; and an additional review about a hot scientific topic, this year: "Legendre et le méridien terrestre, 200 ans après". Cette publication annuelle fournit des éphémérides et des données à l'usage des astronomes professionnels et des astronomes amateurs. Composée de 11 chapitres elle comprend les rubriques sur les différents calendriers et leurs concordance, les fêtes légales en France, les dates et décrets sur les heures légales en France métropolitaine ; une introduction à l'astronomie fondamentale et aux différentes échelles de temps, des explications sur l'utilisation des éphémérides ; des tables fournissent les éphémérides (positions, heures de lever/coucher/passage) du Soleil et de la Lune, de planètes, de satellites naturels, d'astéroïdes, de comètes, d'étoiles brillantes ; des données pour l'observation de la surface du Soleil, de la Lune, et des planètes ; des cartes du ciel ainsi qu'une liste de constellations et de galaxies ; des prédictions des phénomènes astronomiques : occultation par la Lune, occultation stellaires par des astéroïdes et appulses, éclipses de Soleil et de la Lune; la liste et les coordonnées des observatoires astronomiques les plus connus ; et enfin un cahier th

  3. Vivre et survivre au bord des villes

    Directory of Open Access Journals (Sweden)

    Michel Péraldi

    1996-04-01

    Full Text Available De quels revenus vivent, ou plutôt survivent, les populations des quartiers dits défavorisés ? Telle est, malgré son apparente banalité, la question qui initie aujourd'hui une partie de nos recherches. Question banale en effet puisque les médias et le débat politique nous donnent une réponse sans appel, statistiquement fiable : dans ces univers sociaux où se croisent des communautés issues des plus récentes migrations et les fractions les plus fragiles économiquement des classes populaires fr...

  4. La compaction des sols agricoles en Wallonie

    OpenAIRE

    Destain, Marie-France

    2014-01-01

    Dans nos pays industrialisés, l’agriculture fait appel à des machines de plus en plus lourdes. Lorsque des charges élevées sont appliquées sur des sols sensibles, une compaction du sol peut se produire conduisant à des diminutions de rendements suite aux difficultés que rencontrent les racines pour prélever l’eau et les nutriments et à la perturbation de l’activité de la pédofaune. Au niveau environnemental, du fait de la compaction, l’infiltration de l’eau dans le sol est réduite, princip...

  5. EFFET DES TRAITEMENTS THERMIQUES SUR LA REACTION ENTRE DES COUCHES MINCES DE TITANE ET DES SUBSTRATS EN ACIER

    Directory of Open Access Journals (Sweden)

    D Slimani

    2015-06-01

    Full Text Available Des couches minces du titane pur ont été déposées avec la méthode de pulvérisation cathodique sur des substrats en acier, type FF80 K-1 contenants ~1% mass. en carbone. La réaction entre les deux parties du système substrat-couche mince est activée avec des traitements thermiques sous vide dans l’intervalle de températures de 400 à900°Cpendant 30 minutes. Les Spectres de diffraction de rayons x confirment l’inter- diffusion des éléments  chimiques du système résultants la formation et la croissance des nouvelles phases en particulier le carbure binaire TiC ayant des caractéristiques thermomécaniques importantes. L’analyse morphologique des échantillons traités  avec le microscope électronique à balayage (MEB montre l’augmentation du flux de diffusion atomique avec la température de recuit, notamment la diffusion du manganèse et du fer vers la surface libre des échantillons aux températures élevées provoquant la dégradation des propriétés mécaniques des revêtements contrairement au premiers stades d’interaction où on a obtenu des bonnes valeurs de la microdureté.

  6. Transport quantique dans des nanostructures

    Science.gov (United States)

    Naud, C.

    2002-09-01

    structure des oscillations de conductance en fonction du flux du champ magnétique de période h/e dont l'amplitude est beaucoup plus importante que celle mesurée sur un réseau carré de même dimension. Cette différence constitue une signature d'un effet de localisation induit par le champ magnétique sur la topologie mathcal{T}3. Pour des valeurs spécifiques du champ magnétique, du fait des interférences destructives Aharonov-Bohm, la propagation des fonctions d'ondes est limitée à un ensemble fini de cellule du réseau appelé cage. De la dépendance en température des oscillations de période h/e mesurées sur le réseau mathcal{T}3 nous avons tiré une longueur caractéristique qui peut être rattachée au périmètre des cages. Un phénomène inattendu fut l'observation, pour des champs magnétiques plus importants, d'un doublement de fréquence des oscillations. Ces oscillations de période h/2e pouvant avoir une amplitude supérieure aux oscillations de période h/e, une interprétation en terme d'harmonique n'est pas possible. Enfin, l'influence de la largeur électrique des fils constituant le réseau et donc celle du nombre de canaux par brin a été étudiée en réalisant des grilles électrostatique. Les variations de l'amplitude des signaux en h/e et h/2e en fonction de la tension de grille ont été mesurés.

  7. Impact de la preparation des anodes crues et des conditions de cuisson sur la fissuration dans des anodes denses

    Science.gov (United States)

    Amrani, Salah

    La fabrication de l'aluminium est realisee dans une cellule d'electrolyse, et cette operation utilise des anodes en carbone. L'evaluation de la qualite de ces anodes reste indispensable avant leur utilisation. La presence des fissures dans les anodes provoque une perturbation du procede l'electrolyse et une diminution de sa performance. Ce projet a ete entrepris pour determiner l'impact des differents parametres de procedes de fabrication des anodes sur la fissuration des anodes denses. Ces parametres incluent ceux de la fabrication des anodes crues, des proprietes des matieres premieres et de la cuisson. Une recherche bibliographique a ete effectuee sur tous les aspects de la fissuration des anodes en carbone pour compiler les travaux anterieurs. Une methodologie detaillee a ete mise au point pour faciliter le deroulement des travaux et atteindre les objectifs vises. La majorite de ce document est reservee pour la discussion des resultats obtenus au laboratoire de l'UQAC et au niveau industriel. Concernant les etudes realisees a l'UQAC, une partie des travaux experimentaux est reservee a la recherche des differents mecanismes de fissuration dans les anodes denses utilisees dans l'industrie d'aluminium. L'approche etait d'abord basee sur la caracterisation qualitative du mecanisme de la fissuration en surface et en profondeur. Puis, une caracterisation quantitative a ete realisee pour la determination de la distribution de la largeur de la fissure sur toute sa longueur, ainsi que le pourcentage de sa surface par rapport a la surface totale de l'echantillon. Cette etude a ete realisee par le biais de la technique d'analyse d'image utilisee pour caracteriser la fissuration d'un echantillon d'anode cuite. L'analyse surfacique et en profondeur de cet echantillon a permis de voir clairement la formation des fissures sur une grande partie de la surface analysee. L'autre partie des travaux est basee sur la caracterisation des defauts dans des echantillons d'anodes crues

  8. Using XML to encode TMA DES metadata

    Directory of Open Access Journals (Sweden)

    Oliver Lyttleton

    2011-01-01

    Full Text Available Background: The Tissue Microarray Data Exchange Specification (TMA DES is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  9. Using XML to encode TMA DES metadata.

    Science.gov (United States)

    Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

    2011-01-01

    The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  10. Zur nacheiszeitlichen Gletschergeschichte des Liefdefjords (Spitzbergen (Ergebnisse der Geowissenschaftlichen Spitzbergenexpedition 1990

    Directory of Open Access Journals (Sweden)

    G. Furrer

    interdisziplinären Spitzbergenexpedition SPE '90. Schwerpunkte der Forschungsarbeiten sind nacheiszeitliche und aktuelle geomorphologische und geoökologische Prozesse in diesem vom Menschen noch fast völlig unberührten Raum. Das Expeditionsgebiet besitzt zahlreiche Kar- und einzelne Talgletscher sowie ein stark differenziertes, «alpin» anmutendes Relief. Mit unserem Teilprojekt «Gletscherentwicklung und Moränendatierung» wird versucht, einen Beitrag zur noch wenig bekannten Gletschergeschichte Spitzbergenszuleisten: – Viele Gletscher – so der Monacobreen – münden heute direkt ins Meer oder enden nahe der Küste. Die Gletschervorfelder sind in der Regel durch einen markanten Wallmoränenkomplex (Moränenwall umschlossen. Das Moränenmaterial im gletschernahen Bereich wurde von Vorstößen der Neuzeit (ab 16. Jahrhundert abgelagert. – Im Liefdefjorden und Bockfjorden konnten aber durch Grabungen an der Außenseite der Moränenwälle mehrere, von Gletschern überfahrene, fossileorganische Bodenhorizonte (fAh gefunden werden. Deren Radiokarbondatierungen lassen auf Gletschervorstöße im frühen und späten Älteren Subatlantikum (2800 – 1000 yBP und im frühen und mittleren Jüngeren Subatlantikum (ab 1000 yBP schließen. – Mächtigkeit und Polleninhalt der datierten fossilen Boden- und Torfbildungen deuten daraufhin, daß die Vegetation zur Zeit der organischen Sedimentation ähnlich wie heute in Küstennähe entwickelt war. Die klimatischen Bedingungen dürften während der früheren Torf-/Bodenbildungsphasen zumindest nicht ungünstiger gewesen sein als heute. Diese Resultate führen zur Schlußfolgerung, daß die heutigen Gletschervorfelder von Moränenwällen umschlossen sind, die aus Material von verschiedenen Gletschervorstößen zusammengesetzt sind, und daß die maximale Ausdehnung der Gletscherhochstände in den letzten 2800 Jahren (vermutlich im ganzen Holozän stets etwa dieselbe war. Diese Charakteristika treffen auch für die

  11. APPRENTISSAGE DES LANGUES AUTOUR DES MéDIATIONS ARTISTIQUES (ART-THéRAPIE DE COLORIAGE)

    OpenAIRE

    KONEVA (HAAN) MARINA GENNADIEVNA

    2014-01-01

    L’article est consacré aux problématiques liées à l’acquisition des compétences lexicales à partir des textes littéraires et des œuvres de coloriage de l’art-thérapie. En s’appuyant sur l’analyse psycholinguistique du fonctionnement des émotions dans la production des images mentales des mots, on propose une méthode pédagogique, basée sur la synergie des émotions, sensations et cognition. La méthode peut être utilisée dans le cadre institutionnel (collège, lycée, université), ainsi que pour l...

  12. Vers une meilleure comprehension des savoirs disciplinaires et curriculaires des enseignants ou Ie paradigme retrouve

    Directory of Open Access Journals (Sweden)

    Stephane Martineau

    1999-01-01

    Full Text Available eet article se veut essentieUement un travail de synthese sous la forme d 'une breve revue de litterature au sujet des savoirs disciplinaires et curriculaires en enseignement. Plus specifiquement, il vise a determiner queUes sont les principales conclusions qui se degagent de la lecture des recherches empiriques sur les savoirs disciplinaires et curriculaires des enseignants des ordres d'enseignement primaire et secondaire. Il propose donc une classification des differentes dimensions constitutives du rapport entre les savoirs disciplinaires et curriculaires et la pratique enseignante. Les resultats mis au jour permettent d 'une part, d'identifier les facteurs qui entrainent des differences dans les connaissances disciplinaires et curriculaires des enseignants et d'autre part, de mieux saisir comment ces connaissances de l'enseignant peuvent influencer en retour sa pratique.

  13. GENOMIQUE ET LIPIDES Génomique et métabolisme des lipides des plantes

    Directory of Open Access Journals (Sweden)

    Delseny Michel

    2002-03-01

    Full Text Available Il existe dans les bases de données publiques une énorme quantité de séquences d’ADN dérivées de plantes, et notamment la séquence complète du génome d’Arabidopsis thaliana, une plante modèle pour les oléagineux, proche parente du colza. Ces données constituent une ressource importante non seulement pour la compréhension de métabolisme lipidique et de sa régulation, mais aussi pour la sélection et le développement de variétés nouvelles d’oléagineux produisant davantage d’huiles ou des huiles de composition nouvelle. Cette abondance de séquences peut être exploitée, en utilisant les recherches d’homologies, pour identifier les gènes, pour obtenir des informations sur leur fonction, comme pour repérer des gènes candidats codant des fonctions nouvelles. L’analyse de ces bases de données a révélé que la majeure partie des gènes codant des enzymes impliquées dans le métabolisme lipidique appartient à des petites familles multigéniques, reflétant la diversification des fonctions des isoformes. Une analyse du catalogue des ADNc séquencés en aveugle reflète les niveaux d’expression des différents gènes et fournit un aperçu des régulations des flux au travers des voies métaboliques conduisant à la biosynthèse des lipides de réserve. La disponibilité de mutants et de lignées transgéniques d’Arabidopsis et le développement de puces à ADN qui permettent l’analyse simultanée de plusieurs milliers de gènes conduiront à une meilleure compréhension des facteurs qui régulent le métabolisme des huiles dans les graines. Une telle connaissance facilitera la manipulation de la composition des huiles et des quantités produites dans les graines.

  14. Catégorisation aspectuelle des concepts

    Directory of Open Access Journals (Sweden)

    Karolak Stanisław

    2008-01-01

    Full Text Available (francuski Le contenu de l'article est le problème connu en aspectologie comme celui de la dépendance entre le sens lexical des verbes et l'aspect. Les contraintes qu'imposent les langues à la distribution des grammèmes d'aspect ont fait supposer qu'il existe des règles de leur co-occurrence avec les sémantèmes. Le problème est posé ici dans une perspective conceptuelle. Dans cette perspective, les verbes dont les sémantèmes ont tel ou tel aspect n'exigent pas la co-occurrence avec des grammèmes qui véhiculent le même aspect. En revanche, ils peuvent se combiner avec des grammèmes de sens aspectuel opposé pour dériver des catégories de verbes secondaires à partir des catégories primaires. On postule l'existence d'un mécanisme dérivationnel qui engendre des verbes polyaspectuels.

  15. Supply Chain et Gestion des ressources humaines

    OpenAIRE

    Nondonfaz, Robert

    2010-01-01

    Rappels de quelques exigences de la Supply Chain en matière de gestion des ressources humaines; spécificités de certains métiers : chauffeur, magasinier, acheteur, gestionnaire de stock, gestion des imprévus

  16. internationalisation et nouvelles implantations des firmes ...

    African Journals Online (AJOL)

    Administrateur

    de disparités culturelles ou dans les pratiques des affaires ou encore dans le .... plus pertinents afin d'expliquer l'évolution du modèle (cas de la distance psychique par ..... Elles constituent plutôt une lecture globale et intégrée des processus.

  17. La tuberculose des amygdales palatines

    Directory of Open Access Journals (Sweden)

    Oudidi Abdelatif

    2010-01-01

    Full Text Available INTRODUCTION:La localisation tuberculeuse des amygdales palatines est très rare même dans un pays d’endémie tuberculeuse. Le diagnostic peut être suspecté cliniquement dans un contexte évocateur, mais il ne peut être certifié qu’au stade histologique. PATIENTS ET METHODES:Cinq cas de tuberculose des amygdales palatine ont été diagnostiqués sur une période de 5 ans et inclus dans une étude rétrospective. Nous avons recensé trois hommes et deux femmes (âge moyen de 28 ans. La dysphagie haute était le maître symptôme. L’examen a objectivé une hypertrophie amygdalienne chez tous les patients avec des ulcérations chez trois d’entre eux. Une biopsie a été effectuée chez trois patients et une amygdalectomie a été réalisée chez les deux autres. L’étude anatomopathologique a posé le diagnostic chez tous les patients. Un traitement médical antituberculeux selon un régime court allant de 6 à 9 mois a été instauré. Dans tous les cas, l’évolution à long terme a été favorable avec un recul moyen de 13 mois. CONCLUSION: La tuberculose amygdalienne est rare. Son diagnostic repose essentiellement sur le résultat anatomopathologique de la biopsie où de l’amygdalectomie. L’évolution sous traitement anti-bacillaire est souvent favorable, la récidive est exceptionnelle.

  18. Schopenhauer und die Paradoxien des Erhabenen

    Directory of Open Access Journals (Sweden)

    François Arnaud

    2012-08-01

    Full Text Available http://dx.doi.org/10.5007/1677-2954.2012v11nesp1p145Die Hauptunterscheidung zwischen den Schopenhauerschen und Kantschen Auffassungen des Erhabenen liegt nach diesem Artikel darin, dass der Zuschauer im letzten Fall zu einer nur möglichen Gefahr muss unterworfen werden, während er im Ersten wirklich erschreckt sein muss. Die Haupttriebfeder des Gefühls des Erhabenen ist nämlich bei Schopenhauer der Einsatz des Willens, der also wirklich bedroht werden muss. Daraus folgen einige Paradoxien und Originalitäten der Schopenhauerschen Lehre des Erhabenen, hauptsächlich aus dem ethischen Aussichtspunkt, deren Spuren ich zu folgen versuche.

  19. Improved Mask Protected DES using RSA Algorithm

    Directory of Open Access Journals (Sweden)

    Asha Latha S.

    2016-01-01

    Full Text Available The data encryption standard is a pioneering and farsighted standard which helped to set a new paradigm for encryption standards. But now DES is considered to be insecure for some application. Asymmetric mask protected DES is an advanced encryption method for effectively protecting the advanced DES. There are still probabilities to improve its security. This paper propose a method, which introduce a RSA key generation scheme in mask protected DES instead of plain key, which result in enhancement in the security of present asymmetric mask protected DES. We further propose a Vedic mathematical method of RSA implementation which reduce the complexity of computation in RSA block thereby resulting in reduced delay (four timesthat improves the performance of overall system. The software implementation was performed using Xilinx 13.2 and Model-Sim was used for the simulation environment.

  20. Des fantômes

    Directory of Open Access Journals (Sweden)

    Sjef Houppermans

    2012-12-01

    Full Text Available La première pièce de théâtre de Laurent Mauvignier, Tout mon amour, est créée en 2012 par la compagnie Les Possédés. La thématique habituelle de Mauvignier (secrets des familles, solitude, violence sociale s’y retrouve, mais tout en utilisant pleinement les moyens de la scène (distanciation, présence physique, espace théâtral, discours rythmés.

  1. Fast capillary electrophoresis-laser induced fluorescence analysis of ligase chain reaction products: human mitochondrial DNA point mutations causing Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Muth, J; Williams, P M; Williams, S J; Brown, M D; Wallace, D C; Karger, B L

    1996-12-01

    High speed capillary electrophoresis-laser-induced fluorescence (CE-LIF) has been used to separate and detect point mutations using the ligase chain reaction (LCR). The method utilizes short capillary columns (7.5 cm effective length) and fields of 400 V/cm to analyze DNA-ethidium bromide complexes using an He/Ne laser. The method was first demonstrated with a commercially available kit for LCR based on a lacI gene fragment inserted in a Bluescript II phagemid. LCR-CE-LIF was then applied to detect point mutations in human mitochondrial DNA, resulting in Leber's hereditary optic neuropathy (LHON). Three severe mutations were analyzed in which the original base is substituted by a thymidine base at positions 3460, 11778 and 14459. Appropriate primers were designed with polyT tails for length discrimination of pooled samples. Successful detection of mutated samples was achieved, with appropriate correction for small amounts of nonspecific ligated product. The method is rapid, easy to implement, and automatable.

  2. Yeast NDI1 improves oxidative phosphorylation capacity and increases protection against oxidative stress and cell death in cells carrying a Leber's hereditary optic neuropathy mutation.

    Science.gov (United States)

    Park, Jeong Soon; Li, You-Fen; Bai, Yidong

    2007-05-01

    G11778A in the subunit ND4 gene of NADH dehydrogenase complex is the most common primary mutation found in Leber's hereditary optic neuropathy (LHON) patients. The NDI1 gene, which encodes the internal NADH-quinone oxidoreductase in Saccharomyces cerevisiae, was introduced into the nuclear genome of a mitochondrial defective human cell line, Le1.3.1, carrying the G11778A mutation. In transformant cell lines, LeNDI1-1 and -2, total and complex I-dependent respiration were fully restored and largely resistant to complex I inhibitor, rotenone, indicating a dominant role of NDI1 in the transfer of electrons in the host cells. Whereas the original mutant Le1.3.1 cell grows poorly in medium containing galactose, the transformants have a fully restored growth capacity in galactose medium, although the ATP production was not totally recovered. Furthermore, the increased oxidative stress in the cells carrying the G11778A mutation was alleviated in transformants, demonstrated by a decreased reactive oxygen species (ROS) level. Finally, transformants were also shown to be desensitized to induction to apoptosis and also exhibit greater resistance to paraquat-induced cell death. It is concluded that the yeast NDI1 enzyme can improve the oxidative phosphorylation capacity in cells carrying the G11778A mutation and protect the cells from oxidative stress and cell death.

  3. Leber遗传性视神经病变的遗传学进展%Genetic research progrees in Leber hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    贺江梅; 郑梅玲

    2006-01-01

    1871年德国眼科医生Theodor Leber首次描述了一种遗传性眼病,主要表现为双眼急性或亚急性中心视力下降。多累及青年男性,随后便将此病命名为Leber遗传性视神经病变(Leber hereditary optic neuropathy,LHON)。现已证实该病为母系遗传性疾病,其主要病因是线粒体DNA(mitochondrial DNA,mtDNA)某些位点发生突变,是一种最为常见的线粒体遗传病。尽管现在对此病已进行了深入研究。但有很多方面尚需进一步讨论,例如:有关LHON突变基因位点的研究、LHON的不完全外显性、LHON的遗传种族差异性以及突变位点与临床表现和预后的关系等,本文就这几方面进行综述。

  4. LHON患者携带新的线粒体多态位点%A new polymorphism locus of mitochondrial DNA in patients with Leber's hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    许倩倩; 刘铁城; 郭光; 袁慧军; 金鑫

    2009-01-01

    目的:寻找此Leber遗传性视神经病变(leber's hereditary optic neuropathy,LHON)家系的致病突变位点.方法:采集静脉血,提取全基因组DNA,聚合酶链反应(PCR)扩增目的片段,酶切和直接测序反应寻找碱基改变位点.结果:患者mtDNA序列存在G11778A突变,发现4个多态性位点,其中G14476A为未报道的多态位点,该位点未引起编码蛋白质的改变,属无义突变.该多态位点在100例正常人中所占比例为3%.结论:该家系以G11778A为致病突变,G14476A为新的线粒体多态位点.

  5. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: Evidence from segregation analysis for dependence on X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Xiangdong Bu; Rotter, J.I. (Cedars-Sinai Medical Center, Los Angeles, CA (United States) Univ. of California, Los Angeles (United States))

    1991-09-15

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

  6. Leber's hereditary optic neuropathy: biochemical mechanisms and gene therapy%Leber遗传性视神经病的生化机制和基因治疗

    Institute of Scientific and Technical Information of China (English)

    黄淑娟; 田国红; 张晓君

    2012-01-01

    Leber遗传性视神经病(LHON)是由于线粒体基因突变导致的母系遗传性致盲性疾病,青少年多见.LHON发病的生化机制有呼吸链复合酶I功能障碍、活性氧生成增多及细胞凋亡学说等.对LHON理想的治疗措施是基因治疗.目前基因治疗采用异位表达、转染缺陷基因及抗氧化基因等方法.但临床上基因治疗LHON的开展及远期疗效尚需更多的研究证据.%Leber's hereditary optic neuropathy ( LHON),a common blinding disease,is a maternally inherited degeneration of the optic nerve caused by point mutations of mitochondrial DNA.Complex I dysfunction,reactive oxygen species (ROS) overproduction,and cell apoptosis are the hypothesis of biochemical mechanism in LHON.Gene therapy is the ideal treatment for the disease.So far,the gene therapies used include allotropic expressing,transfecting with wild gene,and transfecting with antioxidant gene and so on.However,further investigation has to be done before clinical trials.

  7. Two families with Leber's hereditary optic neuropathy carrying G11778A and T14502C mutations with haplogroup H2a2a1 in mitochondrial DNA.

    Science.gov (United States)

    Qiao, Chen; Wei, Tanwei; Hu, Bo; Peng, Chunyan; Qiu, Xueping; Wei, Li; Yan, Ming

    2015-08-01

    The mitochondrial haplogroup has been reported to affect the clinical expression of Leber's hereditary optic neuropathy (LHON). The present study aimed to investigate the interaction between mutations and the haplogroup of mitochondrial DNA (mtDNA) in families. Two unrelated families with LHON were enrolled in the study, and clinical, genetic and molecular characterizations were determined in the affected and unaffected family members. Polymerase chain reaction direct sequencing was performed using 24 pairs of overlapping primers for whole mtDNA to screen for mutations and haplogroup. Bioinformatics analysis was performed to evaluate the pathogenic effect of these mtDNA mutations and the haplogroup. The G11778A mutation was identified in the two families. In addition, the members of family 2 exhibited the T14502C mutation and those in family 1 exhibited the T3394C and T14502C mutations, which were regarded as secondary mutations. The penetrance of visual loss in families 1 and 2 were 30.8 and 33.3%, respectively. In addition, the two families were found to be in the H2a2a1 haplogroup. In this limited sample size, it was demonstrated that the H2a2a1 haplogroup had a possible protective effect against LHON. Additional modifying factors, including environmental factors, lifestyle, estrogen levels and nuclear genes may also be important in LHON.

  8. Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis.

    Science.gov (United States)

    Cideciyan, Artur V; Aleman, Tomas S; Jacobson, Samuel G; Khanna, Hemant; Sumaroka, Alexander; Aguirre, Geoffrey K; Schwartz, Sharon B; Windsor, Elizabeth A M; He, Shirley; Chang, Bo; Stone, Edwin M; Swaroop, Anand

    2007-11-01

    Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with Joubert syndrome and are the most common cause of the childhood recessive blindness known as Leber congenital amaurosis (LCA). An in-frame deletion in Cep290 shows rapid degeneration in the rod-rich mouse retina. To explore the mechanisms of the human retinal disease, we studied CEP290-LCA in patients of different ages (7-48 years) and compared results to Cep290-mutant mice. Unexpectedly, blind CEP290-mutant human retinas retained photoreceptor and inner laminar architecture in the cone-rich central retina, independent of severity of visual loss. Surrounding the cone-rich island was photoreceptor loss and distorted retina, suggesting neural-glial remodeling. The mutant mouse retina at 4-6 weeks of age showed similar features of retinal remodeling, with altered neural and synaptic laminae and Muller glial activation. The visual brain pathways in CEP290-LCA were anatomically intact. Our findings of preserved foveal cones and visual brain anatomy in LCA with CEP290 mutations, despite severe blindness and rapid rod cell death, suggest an opportunity for visual restoration of central vision in this common form of inherited blindness.

  9. Leber遗传性视神经病变与细胞凋亡%Leber's hereditary optic neuropathy and cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    陈晨; 接传红; 童绎; 胡世兴

    2005-01-01

    Leber遗传性视神经病变(leber's hereditary optic neuropathy,LHON)是一种严重威胁青少年视功能的不可逆致盲性眼病,发病机制目前尚无统一的认识.以往对其病理机制的研究和假说都集中在酶生物活性的缺陷上,但缺乏足够的证据.Steven发现,LHON表现出来的视神经节细胞的死亡是凋亡,它由Fas启动,被半胱氨酸蛋白酶(caspase)抑制剂阻断,表现出caspase活性及caspase-3分解蛋白质的能力增强,并且细胞Annexin-V染色阳性.11778,3460位点病理性突变增强了细胞对Fas介导的凋亡的敏感性,可能是最直接的原因.这一发现可能揭示LHON的发病机制,也暗示了可以运用抗凋亡药物对其进行治疗.

  10. Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Mansergh, Fiona C; Chadderton, Naomi; Kenna, Paul F; Gobbo, Oliviero L; Farrar, G Jane

    2014-11-01

    Primary mitochondrial disorders occur at a prevalence of one in 10 000; ∼50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease.

  11. Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations in Leber hereditary optic neuropathy: Molecular, biochemical, and clinical findings

    Energy Technology Data Exchange (ETDEWEB)

    Oostra, R.J.; Bleeker-Wagemakers, E.M.; Zwart, R. [Ophthalmic Research Institute, Amsterdam (Netherlands)] [and others

    1995-10-01

    Three mtDNA point mutations at nucleotide position (np) 3460, at np 11778 and at np 14484, are thought to be of primary importance in the pathogenesis of Leber hereditary optic neuropathy (LHON), a maternally inherited disease characterized by subacute central vision loss. These mutations are present in genes coding for subunits of complex I (NADH dehydrogenase) of the respiratory chain, occur exclusively in LHON maternal pedigrees, and have never been reported to occur together. Johns and Neufeld postulated that an mtDNA mutation at np 9438, in the gene coding for one of the subunits (COX III) of complex IV (cytochrome c oxidase), was also of primary importance. Johns and Neufeld (1993) found this mutation, which changed a conserved glycine to a serine, in 5 unrelated LHON probands who did not carry one of the presently known primary mutations, but they did not find it in 400 controls. However, the role of this sequence variant has been questioned in the Journal when it has been found to occur in apparently healthy African and Cuban individuals. Subsequently, Johns et al. described this mutation in two Cuban individuals presenting with optic and peripheral neuropathy. 22 refs., 1 fig., 1 tab.

  12. Reevaluation of the linkage of an optic atrophy susceptibility gene to X-chromosomal markers in Finnish families with Leber hereditary optic neuroretinopathy (LHON)

    Energy Technology Data Exchange (ETDEWEB)

    Juvonen, V.; Aula, P.; Vilkki, J.; Nikoskelainen, E.; Savontaus, M.-L.

    1993-07-01

    One of the commonest reasons for sudden-onset optic nerve degeneration in young men can be attributed to maternally inherited Leber hereditary optic neuroretinopathy (LHON) (Nikoskelainen et al. 1987). Specific point mutations at either np 11778 (Wallace et al. 1988) or np 3460 (Howell et al. 1991; Huoponen et al. 1991) in mitochondrial DNA (mtDNA) encoding for respiratory enzyme complex I subunits (i.e., ND4 or ND1) can be found in 70% of families. These mutations exist as being either homoplasmic or heteroplasmic, but the correlation between the degree of heteroplasmy and the risk of developing optic atrophy is far from clear (Holt et al. 1989; Vilkki et al. 1990). Neither does heteroplasmy explain the strong male bias seen in LHON families, when the sex ratio of patients with visual impairment is observed. Earlier results indicated that susceptibility to optic atrophy in Finnish families with LHON was probably determined by an X-chromosomal gene closely linked to DXS7. Contradictory results prompted reevaluation of the existence of an X-chromosomal visual loss susceptibility gene in Finnish LHON families. The results of this present study clearly demonstrate that the earlier close linkage to DXS7 is implausible. The altered Z is due to revised pedigrees, the use of liability classes, and separation of the families according to the associated mtDNA mutation. 16 refs., 1 fig., 1 tab.

  13. Mitochondrial tRNAThr 15891C>G mutation was not associated with Leber's hereditary optic neuropathy in Han Chinese patients.

    Science.gov (United States)

    Jiang, Zhaochang; Yu, Jinfang; Xia, Bohou; Zhuo, Guangchao

    2016-01-01

    Mutations in mitochondrial DNA (mtDNA) were the most important causes of Leber's hereditary optic neuropathy (LHON). To date, approximately 25 LHON-associated mtDNA mutations have been identified in various ethnic populations. Three primary mutations, the 3460G > A, 11778G > A and 14484T > C, in genes encoding the subunits of respiratory chain complex I, were the most common LHON-associated mtDNA mutations. Moreover, secondary mutations in mt-tRNA genes have been reported increasingly to be associated with LHON, simply due to the high mutation rates of mt-tRNAs. There is a lack of functional analysis and a poor genetic evaluation of a certain mt-tRNA mutation, which failed to meet the classic pathogenicity scoring system. As a result, how to classify a pathogenic mutation in mt-tRNA gene became important for both geneticist and clinician to diagnosis the LHON or the suspicious of LHON. In this study, we reassessed the role of a point mutation in mt-tRNA(Thr) gene which had been reported to be a mutation associated with LHON, the pathogenicity of this mutation has been discussed in this context.

  14. Applications of the method of high resolution melting analysis for diagnosis of Leber's disease and the three primary mutation spectrum of LHON in the Han Chinese population.

    Science.gov (United States)

    Cui, Guanglin; Ding, Hu; Xu, Yujun; Li, Bin; Wang, Dao Wen

    2013-01-01

    Current screening methods, such as single strand conformational polymorphism (SSCP), denaturing high performance liquid chromatography (dHPLC) and direct DNA sequencing that are used for detecting mutation in Leber's hereditary optic neuropathy (LHON) subjects are time consuming and costly. Here we tested high-resolution melt (HRM) analysis for mtDNA primary mutations in LHON patients. In this study, we applied the high resolution melting (HRM) technology to screen mtDNA primary mutations in 50 LHON patients from their peripheral blood. In order to evaluate the reliability of this technique, we compared the results obtained by HRM and direct mtDNA sequencing. We also investigated the spectrum of three most common mtDNA mutations implicated in LHON in the Han Chinese population. The results showed HRM analysis differentiated all of the mtDNA primary mutations and identified 4 additional mtDNA mutations from 50 patients in the blind study. The prevalence of three primary mutations were 11778G>A (87.9%), 14484T>C (6.5%) and 3460G>A (1.7%) in the Han Chinese population. In conclusion, HRM analysis is a rapid, reliable, and low-cost tool for detecting mtDNA primary mutations and has practical applications in molecular genetics.

  15. [Optic nerve swelling and gadolinium contrast enhancement on magnetic resonance imaging in the subacute stage of Leber's hereditary optic neuropathy: a case report].

    Science.gov (United States)

    Furuki, Misako; Ohkubo, Takuya; Ota, Kiyobumi; Ishikawa, Kinya; Yokota, Takanori; Mizusawa, Hidehiro

    2012-01-01

    We report the case of a 50-year-old man with subacute onset of bilateral visual field loss and visual acuity loss. His visual acuity was 0.07 OD/0.09 OS and Goldmann perimetry showed central scotomas. The optic fundi were normal bilaterally. Magnetic resonance imaging (MRI) showed hyperintensity in the right optic nerve on T(2) weighted imaging and swelling of the optic chiasm with slight enhancement of the bilateral optic nerves and the optic chiasm on gadolinium-enhanced imaging. Since sensory disturbance in the left hand and leg was noted in addition to the visual problem, multiple sclerosis (MS) was suspected initially. The patient was treated with intravenous methylprednisolone (1,000 mg/day), plasma exchange therapy, and immunosuppressant therapy. However, his visual disturbance did not improve. He had a history of deafness and family history of visual disturbance, because of which we performed an analysis of mitochondrial DNA. G11778A point mutation was found, and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. Although gadolinium contrast enhancement and swelling of the optic nerve are rare, this case shows that these findings are not in conflict with LHON. The present case also suggests that mitochondrial dysfunction may trigger the onset of MS-like extraocular symptoms in patients with LHON.

  16. Very high penetrance and occurrence of Leber's hereditary optic neuropathy in a large Han Chinese pedigree carrying the ND4 G11778A mutation.

    Science.gov (United States)

    Zhou, Xiangtian; Zhang, Hongxing; Zhao, Fuxin; Ji, Yanchun; Tong, Yi; Zhang, Juanjuan; Zhang, Yu; Yang, Li; Qian, Yaping; Lu, Fan; Qu, Jia; Guan, Min-Xin

    2010-08-01

    We report here the clinical, genetics and molecular characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strikingly, this family exhibits very high penetrance and occurrence of optic neuropathy. In particular, 25 (10 males/15 females) of 30 matrilineal relatives exhibited the variable severity, ranging from profound to mild of visual impairment. This penetrance of optic neuropathy in this Chinese family is much higher than those in many families with LHON worldwide. The age-at-onset for visual impairment in matrilineal relatives in this Chinese family varied from 7 to 24years old, with the average of 15 years old. Furthermore, the ratio between affected male and female matrilineal relatives is 1:1.5 in the Chinese family. This observation is in contrast with the typical features in LHON pedigrees that there was predominance of affected males in LHON in many families from different ethnic origins. Molecular analysis of mitochondrial genome identified the known ND4 G11778A mutation and 51 variants, belonging to Asian haplogroup C4a1. The absence of other known secondary LHON-associated and functionally significant mtDNA mutations in this Chinese family suggested that mitochondrial variants may not play an important role in the phenotypic manifestation of the G11778A mutation in this Chinese family. Therefore, nuclear modifier gene(s) may be responsible for very high penetrance and occurrence of optic neuropathy in this Chinese pedigree.

  17. Severe manifestation of Leber's hereditary optic neuropathy due to 11778G>A mtDNA mutation in a female with hypoestrogenism due to Perrault syndrome.

    Science.gov (United States)

    Badura-Stronka, Magdalena; Wawrocka, Anna; Zawieja, Krzysztof; Silska, Sylwia; Krawczyński, Maciej Robert

    2013-11-01

    Perrault syndrome (PS) is a rare autosomal recessive condition with ovarian dysgenesis, hearing deficit and neurological abnormalities in female patients. The molecular basis of the syndrome is heterogeneous, mutations in the HSD17B4 gene have been identified in one family and mutations in the HARS2 gene have been found in another one. We have excluded pathogenic changes in the HSD17B4 gene and in the HARS2 gene by a direct sequencing of all coding exons in a female with clinical hallmarks of PS, ataxia and mild mental retardation. In addition, the patient suffers from severe Leber's hereditary optic neuropathy (LHON) due to 11778G>A mtDNA mutation. This case is the first reported patient with PS and LHON. Possible influence of hypoestrogenism on the manifestation of optic neuropathy in this patient is discussed in the context of recent findings concerning the crucial role of estrogens in supporting the vision capacity in LHON-related mtDNA mutation carriers.

  18. Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL gene.

    Science.gov (United States)

    Acar, Ceren; Mears, Alan J; Yashar, Beverly M; Maheshwary, Anjali S; Andreasson, Sten; Baldi, Alfonso; Sieving, Paul A; Iannaccone, Alessandro; Musarella, Maria A; Jacobson, Samuel G; Swaroop, Anand

    2003-01-24

    To determine if mutations in the retinal transcription factor gene NRL are associated with retinopathies other than autosomal dominant retinitis pigmentosa (adRP). Genomic DNA was isolated from blood samples obtained from 50 patients with Leber Congenital Amaurosis (LCA), 17 patients with the Enhanced S-Cone Syndrome (ESCS), and a patient with an atypical retinal degeneration that causes photoreceptor rosettes with blue cone opsin. The 5' upstream region (putative promoter), untranslated exon 1, coding exons 2 and 3, and exon-intron boundaries of the NRL gene were analyzed by direct sequencing of the PCR-amplified products. Complete sequencing of the NRL gene in DNA samples from this cohort of patients revealed only one nucleotide change. The C->G transversion at nucleotide 711 of NRL exon 3 was detected in one LCA patient; however, this change did not alter the amino acid (L237L). No potential disease causing mutation was identified in the NRL gene in patients with LCA, ESCS, or the atypical retinal degeneration. Together with previous studies, our results demonstrate that mutations in the NRL gene are not a major cause of retinopathy. To date, only missense changes have been reported in adRP patients, and sequence variations are rare. It is possible that the loss of NRL function in humans is associated with a more complex clinical phenotype due to its expression in pineal gland in addition to rod photoreceptors.

  19. Des pauvres de la politique à la politique des pauvres

    Directory of Open Access Journals (Sweden)

    Ratiba Hadj-Moussa

    2012-01-01

    Full Text Available S’attachant aux nouvelles modalités de production du politique issues des études subalternes, l’article situe dans un premier temps ces travaux et, dans un deuxième temps, en fait une présentation en s’appuyant sur les éléments qui y sont privilégiés et qui font le lien entre « les pauvres et la production du politique ». Cette présentation s’appuie essentiellement sur les travaux portant sur les pays du Sud, en particulier l’Inde et quelques pays du Moyen Orient (l’Égypte et l’Iran. Elle réfère aussi au Maghreb qui est le terrain principal de l’analyse. La présentation tient compte en particulier des travaux qui s’appuient sur des recherches empiriques substantielles mais dont la portée théorique est très peu discutée. Enfin, si le renvoi aux études subalternes ou postcoloniales est dans ce texte non négligeable, il est aussi fait recours à des travaux produits dans des contextes pluralistes, comme la France.Poor Policy to the Policy of the PoorThis article has its origins in the new methods of production of policy based on subaltern studies. Firstly, it will locate these studies and then it will present its main arguments as well as the relationship between “the poor and policy production”. This presentation is based essentially on the works on countries of the south, particularly India, and few other countries from the Middle East (Egypt and Iran. It also refers to North Africa, which is the major fieldwork of this analysis. This presentation takes into account the works that rely upon substantial empirical research but for which the theoretical range is very little. Finally, if the referral to subaltern or postcolonial studies is significant in this article, it also refers to works produced in pluralistic contexts such as France.De los pobres de la política a la política de los pobresBasándose en estudios subalternos, el artículo se sitúa dentro del marco de los nuevos modos de producci

  20. Évaluation des émissions de gaz à effet de serre des filières de traitement et de valorisation des boues issues du traitement des eaux usées

    OpenAIRE

    Reverdy, A.L.; Pradel, M.

    2011-01-01

    / Ce rapport présente l'inventaire des différentes consommations énergétiques, en consommables et des GES pour chaque poste de traitement et de valorisation des boues issues du traitement des eaux usées.

  1. Distribution spatiale intra-urbaine des particules fines : monitoring ...

    African Journals Online (AJOL)

    SARAH

    30 sept. 2014 ... Intra-urban spatial distribution of particulate matter: monitoring by leaf Saturation Isothermal Remanent ... les changements microclimatiques au sein des villes ... déterminer l'impact des saisons sur la teneur des ... Ce District jouit d'un climat de type ... Sélection et description des espèces : Un inventaire.

  2. Performances de production des cobayes (Cavia porcellus L.) en ...

    African Journals Online (AJOL)

    Au Cameroun, l'élevage des cobayes se pratique encore dans les cuisines et à même le sol et leur ..... Figure 1 : Evolution des poids des mères allaitantes de la naissance au sevrage des petits. .... lecture critique du manuscrit ; EM a participé.

  3. Isomers chart; Table des isomeres

    Energy Technology Data Exchange (ETDEWEB)

    Dupont-Gautier, P.; Chantelot, S.; Moisson, N. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The nuclear isomers are nuclides offering the same mass number and the same atomic number, but different energy levels. In the following chart the zero energy ground states are omitted and the metastable isomers, i.e. of non-zero energy, known and of measurable lifetime, are listed. The lower limit of this lifetime was set here to 0.1 x 10{sup -6} s. The various isomers were classified in increasing lifetimes. (authors) [French] Les isomeres nucleaires sont des nucleides presentant le meme nombre de masse et le meme numero atomique, mais des niveaux energetiques differents. Dans la table suivante, on a neglige les etats fondamentaux d'energie nulle et on a recense les isomeres metastables, c'est-a-dire d'energie non nulle, connus et de periode mesurable. La limite inferieure de cette periode a ete fixee ici a 0,1 x 10{sup -6} s. Les differents isomeres ont ete classes par periodes croissantes. (auteurs)

  4. Isomers chart; Table des isomeres

    Energy Technology Data Exchange (ETDEWEB)

    Dupont-Gautier, P.; Chantelot, S.; Moisson, N. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The nuclear isomers are nuclides offering the same mass number and the same atomic number, but different energy levels. In the following chart the zero energy ground states are omitted and the metastable isomers, i.e. of non-zero energy, known and of measurable lifetime, are listed. The lower limit of this lifetime was set here to 0.1 x 10{sup -6} s. The various isomers were classified in increasing lifetimes. (authors) [French] Les isomeres nucleaires sont des nucleides presentant le meme nombre de masse et le meme numero atomique, mais des niveaux energetiques differents. Dans la table suivante, on a neglige les etats fondamentaux d'energie nulle et on a recense les isomeres metastables, c'est-a-dire d'energie non nulle, connus et de periode mesurable. La limite inferieure de cette periode a ete fixee ici a 0,1 x 10{sup -6} s. Les differents isomeres ont ete classes par periodes croissantes. (auteurs)

  5. Etude des effets du martelage repetitif sur les contraintes residuelles

    Science.gov (United States)

    Hacini, Lyes

    L'assemblage par soudage peut engendrer des contraintes residuelles. Ces contraintes provoquent des fissurations prematurees et un raccourcissement de la duree de vie des composants. Dans ce contexte, le martelage robotise est utilise pour relaxer ces contraintes residuelles. Trois volets sont presentes: le premier est l'evaluation des effets des impacts unitaires repetes sur le champ de contraintes developpe dans des plaques d'acier inoxydable austenitique 304L vierges ou contenant des contraintes residuelles initiales. Dans la deuxieme partie de ce projet, le martelage est applique grace au robot SCOMPI. Les contraintes residuelles induites et relaxees par martelage sont ensuite mesurees par la methode des contours, qui a ete adaptee a cet effet. Dans la troisieme partie, le martelage est modelise par la methode des elements finis. Un modele axisymetrique developpe grace au logiciel ANSYS permet de simuler des impacts repetes d'un marteau elastique sur une plaque ayant un comportement elastoplastique.

  6. À l’aube des dieux

    Directory of Open Access Journals (Sweden)

    Pascal Semonsut

    2011-03-01

    Full Text Available De l’avis même des préhistoriens, la Préhistoire assiste à la naissance du sentiment religieux. Cette religion des origines, quelle image en ont les Français ? Telle est la question que cet article aborde à partir de l’étude des manuels scolaires et des œuvres de fiction (littérature, cinéma et bande dessinée de la seconde moitié du XXe siècle. Si l’enseignement et la fiction n’accordent pas la même place à ce thème, en revanche tous deux font des préhistoriques des polythéistes adorant le soleil, construisant des mégalithes et prenant le plus grand soin de leurs morts. Ce mélange d’obscurantisme et de vraie spiritualité n’a qu’un but : montrer que notre espèce ne pouvait être que victorieuse dans ce combat qu’est l’humanisation.

  7. 75 caracteristiques et evolution des operations de fusions ...

    African Journals Online (AJOL)

    Nous décrivons dans un premier temps l'évolution de l'économie tunisienne et ..... grossistes, a réalisé en 2004 près de 88 % du chiffre d'affaires des transactions .... d'actions reste une opération soumise au droit commun des contrats et au droit des ..... tairement des opérations horizontales mettant en relation des entrepri-.

  8. L'espace mondial des grandes manifestations sportives internationales

    Directory of Open Access Journals (Sweden)

    Daniel MATHIEU

    1989-06-01

    Full Text Available La carte des grandes manifestations sportives mondiales montre une forte concentration des épreuves dans un petit nombre de pays développés, en particulier l'Europe occidentale. L'examen des nations concernées par les tournois majeurs du tennis et par le cyclisme professionnel soulignent, avec les nuances propres à chacun des sports, l'étroitesse des espaces intéressés.

  9. Infektionen mit darmpathogenen Escherichia coli.

    NARCIS (Netherlands)

    Friedrich, Alexander; Stein, Jürgen; Dignass, Axel

    2001-01-01

    E. coli ist ein wesentlicher Bestandteil der physiologischen Darmflora des Menschen. Die üblicherweise im Darm vorkommenden Kolibakterien sind apathogen und für den Menschen eher nützlich (Sonnenborn u. Greinwald 1990). Allerdings kennen wir bei dieser Bakterienspezies auch ein breites Spektrum von

  10. Ueber Pietaet

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Redaktionelle Vorbemerkung:In der Entwicklung der menschlichen Geschichte hat sich ein Moralkodex etabliert, der das Verhalten des Menschen reglementiert und Menschen dadurch paedagogisiert. Er baut sich-in der oestlichen wie in der westlichen Kultur-auf einem hierarchischen Herrschaftssystem auf,

  11. De la manipulation des images 3D

    Directory of Open Access Journals (Sweden)

    Geneviève Pinçon

    2012-04-01

    Full Text Available Si les technologies 3D livrent un enregistrement précis et pertinent des graphismes pariétaux, elles offrent également des applications particulièrement intéressantes pour leur analyse. À travers des traitements sur nuage de points et des simulations, elles autorisent un large éventail de manipulations touchant autant à l’observation qu’à l’étude des œuvres pariétales. Elles permettent notamment une perception affinée de leur volumétrie, et deviennent des outils de comparaison de formes très utiles dans la reconstruction des chronologies pariétales et dans l’appréhension des analogies entre différents sites. Ces outils analytiques sont ici illustrés par les travaux originaux menés sur les sculptures pariétales des abris du Roc-aux-Sorciers (Angles-sur-l’Anglin, Vienne et de la Chaire-à-Calvin (Mouthiers-sur-Boëme, Charente.If 3D technologies allow an accurate and relevant recording of rock art, they also offer several interesting applications for its analysis. Through spots clouds treatments and simulations, they permit a wide range of manipulations concerning figurations observation and study. Especially, they allow a fine perception of their volumetry. They become efficient tools for forms comparisons, very useful in the reconstruction of graphic ensemble chronologies and for inter-sites analogies. These analytical tools are illustrated by the original works done on the sculptures of Roc-aux-Sorciers (Angles-sur-l’Anglin, Vienne and Chaire-à-Calvin (Mouthiers-sur-Boëme, Charente rock-shelters.

  12. Vorsicht Stufe!

    OpenAIRE

    2016-01-01

    In dieser Arbeit werden verschiedene Entwicklungsmodelle des Menschen vorgestellt und in ihrem Gebrauch in und für die Pädagogik kritisch reflektiert. Zunächst werden Vorüberlegungen zur Etymologie und Systematik der Begriffe Entwicklung (zwischen Natur und Kultur) und Modell (gegenüber Theorie, Simulation und Schema) angestellt. Anhand des Gangs von Beispiel zu Beispiel (Günther Buck) werden jeweils die Entwicklungsmodelle des Menschen von Rudolf Steiner, Maria Montessori, Jean Piaget, Lawre...

  13. Mécanique des fluides fondamentale

    CERN Document Server

    Zeytounian, Radyadour K

    1991-01-01

    Ce cours de mecanique des fluides est avant tout un cours theorique qui repond aux questions fondamentales de ce sujet de recherche. Les quatre premiers chapitres presentent les equations propres a determiner l'ecoulement de fluide considere et diverses solutions. Les chapitres 5 et 6sont consacres aux problemes lies la stabilite, aux bifurcations et aux comportements chaotiques. Le livre donne un vision globale des questions traitees en mecanique des fluides qui sont a la base de toute la recherche, de la modelisation et de toutes les applications dans ce domaine.

  14. Écriture scientifique et évolution des croyances, des connaissances ou des conceptions des enseignants en reprise d’étude

    Directory of Open Access Journals (Sweden)

    Delarue-Breton Catherine

    2016-01-01

    Full Text Available Si l’on s’accorde assez unanimement – c’est à dire aux plans simultanément scientifique et institutionnel – à reconnaitre que l’initiation à la recherche est devenue nécessaire dans la formation des enseignants, les modalités de cette initiation, ses visées et ses effets font cependant peu l’objet, encore, d’un consensus, et dans certains cas, divisent. Nous avons pu étudier à diverses reprises, à partir de différentes versions des mémoires, le rôle de l’écriture scientifique dans l’appropriation des concepts théoriques par les étudiants de master MEEF (Métiers de l’Enseignement, de l’Éducation, de la Formation en formation initiale, autrement dit par les étudiants issus de licence, se destinant au métier de professeur des écoles. Nous avons ainsi pu mettre au jour d’une part la diversité de ces modes d’appropriation conceptuelle, et, en corrélation avec celle-ci, la diversité des modes d’analyse des situations scolaires, et d’autre part des formes d’évolution ou de stagnation des croyances, connaissances, conceptions de ces futurs enseignants sur le métier, sur les élèves, sur les disciplines, sur l’apprentissage. Notre propos est ici de nous poser des questions comparables, concernant le rapport entre appropriation théorique et évolution des conceptions non pas d’enseignants en formation initiale, mais d’enseignants titulaires en reprise d’étude, parfois eux-mêmes formateurs, inscrits en master MEEF avec validation des acquis. Nous questionnons ainsi le rôle de la recherche et de l’écriture scientifique dans la formation continue des enseignants.

  15. MESURE DE LA PERFORMANCE GLOBALE DES ENTREPRISES

    OpenAIRE

    Renaud, Angèle; Berland, Nicolas

    2007-01-01

    International audience; L'engagement des entreprises dans le développement durable consiste à conjuguer performance et responsabilité. La performance financière ne suffit plus à apprécier la performance d'une entreprise. Dès lors, les entreprises doivent mesurer leurs progrès à partir d'une performance plus globale incluant, en dehors de la dimension économique, des dimensions sociale et environnementale. A présent, comment mesurer cette performance globale ? Existe-il des outils de mesure gl...

  16. A l'écoute des professionnels

    CERN Document Server

    Lebre-Peytard, Monique

    1994-01-01

    Cet ouvrage s'adresse aux étudiants de niveau moyen ou avancé en français. Il propose un travail d'écoute, de réflexion et d'expression autour d'interview authentiques. Des professionnels parlent de leur métier, des entreprises où ils travaillent, des fonctions qu'ils occupent... Ils appartiennent à divers secteurs de l'économie : banque, mode, tourisme, agriculture, télécommunications, etc.

  17. Physostigmin in der Aufwachphase des Hundes nach zwei l-Methadon-Narkoseprotokollen

    OpenAIRE

    2010-01-01

    Störungen der Aufwachphase sind sowohl in der Human-, als auch Veterinäranästhesiologie von Bedeutung. So kann eine verlängerte, aber auch eine unruhige exzitatorische Aufwachphase zusätzlichen intensivmedizinischen, zeitlichen und finanziellen Aufwand bedeuten. Eine Vielzahl von metabolischen und neuropathologischen, aber auch pharmakologischen Insulten werden insbesondere beim Menschen als Ursachen derartiger Aufwachstörungen beschrieben. Unter anderem scheint auch ein zentra...

  18. Was bleibt vom Industriellen Gartenreich? Die Entwicklungsgeschichte des Kraftwerks Vockerode - ein Nachtrag zum Abriss

    OpenAIRE

    Barz, Andreas

    2002-01-01

    Die kulturelle, aber auch gewerbliche Inwertsetzung ehemals industriell genutzter Baudenkmale ist eine anspruchsvolle, aber auch lohnende Aufgabe. Das hat die Internationale Bauausstellung Emscher Park in den neunziger Jahren bewiesen und findet in der Internationalen Bauausstellung „Fürst Pückler Land“ für periphere Regionen seine Fortsetzung. Das Kraftwerk Vockerode, dessen kulturelle Inbesitznahme 1998 so hoffnungsvoll begann und das von den Menschen in Vockerode fast liebevoll mit der unt...

  19. Des Widerspenstigen Zähmung: Subjektives Alter(n), qualitativ erforscht

    OpenAIRE

    Graefe, Stefanie

    2013-01-01

    Der Beitrag präsentiert Forschungsergebnisse einer qualitativen Interviewstudie zur subjektiven Alter(n)serfahrung von Menschen in der zweiten Lebenshälfte sowie aus dem Forschungsprozess resultierende Überlegungen zur Frage, wie sich die soziale Erfahrung Alter(n) methodologisch konzeptualisieren und empirisch erforschen lässt. Die Auswertung erfolgte angelehnt an die Grounded-Theory- Methodologie. Ausgehend von der "relativen (subjektiven) Alterslosigkeit" als fallübergreifender Schlüsselka...

  20. Contrôle des Circuits Auxiliaires des PFW (arrêt machines 2002/2003)

    CERN Document Server

    Ottaviani, J

    2003-01-01

    Les PFW sont des nappes polaires installées sur les pôles des aimants du PS. Elles sont au nombre de 4 par unité d aimant et constituées d un circuit principal (dans lequel circule le courant désiré selon le cycle magnétique utilisé) et de circuits auxiliaires. Les circuits auxiliaires sont des enroulements de correction (boucles de tour et pick-up brasés sur les enroulements). Pendant la variation du champ magnétique de l aimant PS, on utilise des tensions induites dans ces circuits auxiliaires pour corriger les erreurs de champ dues aux courants de Foucault dans la chambre à vide. Chaque année, pendant l arrêt machine, on vérifie si les caractéristiques des circuits auxiliaires correspondent aux normes (mesures des résistances des boucles de tours, résistances entre pick-up et isolation des circuits) afin de faire un suivi. Les 404 PFW sont ainsi vérifiées. Dans cette note, on ne relèvera que les PFW ayant des défauts (valeurs hors tolérances, boucles ouvertes ou en court-circuit, déf...

  1. Exploitation des connaissances issues des processus de retour d'expérience industriels

    OpenAIRE

    Jabrouni, Hicham

    2012-01-01

    Depuis plusieurs années, dans le secteur industriel, l’amélioration continue constitue un aspect important de la famille de normes ISO 9000 maintenue par l’organisation ISO (International Organization for Standardization). Elle se concentre sur l’amélioration de la satisfaction du client en passant par des améliorations continues et incrémentales des produits, des services et des processus. Afin de répondre à ces exigences, un point clé consiste à optimiser le processus de résolution de probl...

  2. Des changements concevables pour le secteur des transports dans l'objectif "Facteur 4"

    OpenAIRE

    Raux, Charles

    2007-01-01

    Au niveau mondial, les transports consomment 20% de l'énergie, dont 80% dans les transports routiers et 10% dans les transports aériens, et 95% de cette énergie est à base de pétrole. Le secteur des transports est l'un des principaux émetteurs de gaz à effet de serre dans la plupart des pays, et notamment du CO2 issu de la combustion des carburants fossiles. Pour que les transports contribuent significativement à l'objectif du « Facteur 4 » en 2050, trois pistes différentes mais complémentair...

  3. Typologie des investisseurs institutionnels et performance des firmes dans le contexte français

    OpenAIRE

    Jean-Michel SAHUT; Othmani Gharbi, Hidaya

    2011-01-01

    L’objet de cet article est d’analyser la relation entre les investisseurs institutionnels et la performance financière des firmes. Dans ce contexte, nous proposons une nouvelle typologie fondée sur la variété des comportements des institutionnels (passifs ou engagés (actifs)) vis-à-vis de la gestion et du gouvernement des firmes qu’ils détiennent en portefeuille, et identifions les principaux facteurs pouvant influencer ces comportements. Nos résultats corroborent, en général, un impact posit...

  4. Etude structurale des sites de nodulation et induction des nodules caulinaires chez Sesbania pubescens

    OpenAIRE

    TOMEKPE, Kodjo; Traore, A S; Ndiaye, S.; Spencer-Barreto, M.M.; Détrez, C.

    1992-01-01

    #Sesbania pubescens$ est une légumineuse annuelle voisine de #Sesbania rostrata$ qui se rencontre généralement sur les sols temporairement inondés de l'Afrique de l'Ouest. Des sites de nodulation préformes ont été mis en évidence sur sa tige et ses branches. Ces sites prennent naissance à l'aisselle des cotylédons et des feuilles. Comme chez la plupart des légumineuses à nodules de tige, les sites de nodulation caulinaire de #S. pubescens$ se développent en racines lorsque les tiges sont imme...

  5. Molekularbiologische Untersuchungen des Leitgewebes und der Stressphysiologie des Breitwegerichs (Plantago major L.)

    OpenAIRE

    Pommerrenig, Benjamin

    2008-01-01

    Die Leitbündel Höherer Pflanzen stellen die wesentlichen Gewebe zur Verteilung von Assimilaten, zum Transport von Wasser und zur Übermittlung von Informationen innerhalb und zwischen den einzelnen pflanzlichen Organen dar. Die Zellen des vaskulären Gewebes unterscheiden sich von denen des Mesophylls nicht nur in ihrer Gestalt und Funktion, sondern vor allem in ihrer Genexpression. In dieser Arbeit wurde zur Untersuchung des vaskulären Transkriptoms des Breitwege-richs (Plantago major) eine cD...

  6. Les lexiques des jeunes dans les discours écrits des blogs : pour une approche descriptive

    Directory of Open Access Journals (Sweden)

    Lorenz Paulina

    2014-07-01

    Full Text Available S’il ne faut pas confondre ce qui est appelé communément « langage SMS » et « langage des jeunes », nous avancerons toutefois que les pratiques langagières écrites des jeunes sur les supports modernes de communication, et notamment dans les blogs, présentent des particularités encore peu étudiées. Les traits observables les plus saillants sont ceux de la morphologie graphique, mais il n’en reste pas moins que certains jeunes utilisent des lexiques particuliers dans les blogs qui méritent une attention particulière. Nous nous proposons donc d’étudier les différents lexiques utilisés par des jeunes de 12 à 22 ans dans les blogs de la plateforme skyrock.com aux niveaux de sa diversité, de ses usages sémantiques variable d’un scripteur à l’autre pour un même mot, et de ses particularités morphosyntaxiques. En effet, nous observerons des lexiques divers allant des lexiques perçus comme relevant des cités à des lexiques perçus comme étant « branchés-jeunes », ou encore à des lexiques propres aux supports modernes de communication. Ainsi, nous analyserons des lexiques variés dans leurs usages écrits tels que bolos, bédave, gérer, ouf, tigen, ou encore des lexiques empruntés tels que mouv, full, etc., ainsi que des emplois particuliers de séquences autonomes comme lol. Quelques questions périphériques complèteront notre analyse telle que celles qui concerne l’influence des usages lexicaux entre pairs et le savoir partagé, la distinction de différentes communautés en fonction des lexiques utilisés, ou encore la variabilité des représentations graphiques d’un même mot.

  7. Peste des Petits Ruminants Virus.

    Science.gov (United States)

    Baron, M D; Diallo, A; Lancelot, R; Libeau, G

    2016-01-01

    Peste des petits ruminants virus (PPRV) causes a severe contagious disease of sheep and goats and has spread extensively through the developing world. Because of its disproportionately large impact on the livelihoods of low-income livestock keepers, and the availability of effective vaccines and good diagnostics, the virus is being targeted for global control and eventual eradication. In this review we examine the origin of the virus and its current distribution, and the factors that have led international organizations to conclude that it is eradicable. We also review recent progress in the molecular and cellular biology of the virus and consider areas where further research is required to support the efforts being made by national, regional, and international bodies to tackle this growing threat. © 2016 Elsevier Inc. All rights reserved.

  8. Utilisation des mousses et des pâtes syntactiques pour combler les lacunes des poteries archéologiques

    Directory of Open Access Journals (Sweden)

    Viviane Bechoux

    2008-10-01

    Full Text Available Filling potteries missing parts with plaster raises now complex problems during the de-restoration treatments. Ceramics restorers have recurrently questions on the use of plaster in the field of archaeological ceramics restoration. Some researches point to the choice of other filling materials. At the present time other methods can be devised by proposing plaster replacement by a lightened composite material: syntactic foams and pastes.Le comblement des lacunes des poteries à partir du plâtre pose actuellement des problèmes complexes lors des traitements de dérestauration. Les restaurateurs de céramiques s'interrogent de manière récurrente sur l'utilisation du plâtre dans le domaine de la restauration des céramiques archéologiques. Des recherches s'orientent vers le choix d'autres matériaux d'obturation. Actuellement, d'autres méthodes peuvent être mises en place en proposant le remplacement du plâtre par un matériau composite allégé, les mousses et les pâtes syntactiques.

  9. Des Balkans About the Balkans

    Directory of Open Access Journals (Sweden)

    Predrag Matvejević

    2012-05-01

    Full Text Available Les Balkans témoignent de contradictions géographiques et politiques, perceptibles dans le changement d’appellation des lieux au cours de l’Histoire : de la péninsule illyrienne, grecque, byzantine à la « Turquie d’Europe » plus récente. Il est resté une dénomination venue des Turcs, les « Balkans ». Cette presqu’île n’offre pas de frontières naturelles difficiles à franchir. Les délimitations des géographes et historiens sont relatives et souvent arbitraires, et donc contestées. Sa définition est difficile, car, étant associée à la progression des troupes ottomanes, cette « zone de turbulences » garde aux yeux de certains un caractère négatif. Marqués par les bouleversements telluriques et historiques, les Balkans témoignent d’une pluralité et d’une variété démographiques, ce qui pose un grand nombre de questions en termes de rapports ethniques, de constructions identitaires et territoriales. Les revendications s’appuient aussi bien sur le mythe que sur l’Histoire. L’apparition de l’État-nation a constitué dans ces régions de multiples fractures à l’image du schisme chrétien de 1054, divisant Églises et croyances, empires et pouvoirs, styles et écritures. L’islam a engendré de nouvelles oppositions ou intolérances. Les puissances étrangères sont intervenues dans ce jeu pour tenter de le stabiliser tout en déterminant leurs sphères d’influence, figeant par le jeu des traités une multitude de questions irrésolues ou conflictuelles, sans apporter de réponse durable. Cet inachevé, dans une histoire faite de partages, suscite des frustrations, et nécessite une réécriture qui tarde à se faire jour, faute d’apaisement entre les différentes sensibilités. La littérature se fait l’écho de ces situations par l’évocation de la cruauté, sous l’occupation ottomane (cf. Ivo Andrić notamment, mais aussi dans l’actualité récente. « Cet espace qui produit

  10. La reputation scientifique contestee des freres Bogdanov

    CERN Multimedia

    Morin, H

    2002-01-01

    "Les celebres jumeaux sont revenus a la television apres avoir obtenu des theses en mathematiques et physique theorique. Depuis, ils sont la cible de virulentes critiques portant sur la qualite reelle de leurs travaux" (1 page).

  11. The enhancement of existing DES Maplet interface

    Science.gov (United States)

    Abdullah, Nur Lina; Mutalip, Rasidah Abdull; Abdullah, Kamilah

    2014-07-01

    This study pertains to the process of Data Encryption Standard, DES. DES consists of encryption and decryption processes linked with mathematical elements such as algebra and number theory. Preliminary, studies revealed that most of mathematics students face a problem in understanding the complicated process of DES. In modern learning methods, learning environment becomes more interesting with the use of computer and a variety of mathematical software packages. Several mathematical softwares such as Maple, Mathematica, Mathlab and Sage were developed in order to fulfill the specific calculation requirements. Correspondingly, motivated from that, this study incorporated with Maple to enhance the existing DES Maplet interface to be more interactive and user-friendly compared to the original version.

  12. GROSSESSE GEMELLA IRE ET EVOLUTION DES JUMEAUX

    OpenAIRE

    SALAH, HANANE; ALLAOUI, AMINA

    2012-01-01

    Cette étude prospective succincte nous a permis de réunir les informations suivantes - La grande fréquence des grossesses gémellaires dans le mois de septembre. - L'âge jeune des mamans. - La plupart des jumeaux occupent la première ou la deuxième place dans la fratrie. - Le bon état de santé des mamans avant la grossesse par l'absence d'antécédents pathologiques chez elles. - Un très faible tôt d'antécédent personnel de grossesse gémellaire antérieure contre une...

  13. Pyrotechnie : une évaluation des risques

    OpenAIRE

    Aufauvre, Lionel; Marlair, Guy; Michot, Christian

    2006-01-01

    Depuis une dizaine d'années, la pyrotechnie tend à se démocratiser, comme en témoigne le développement du marché des artifices de divertissement pour le grand public en France. Elle touche de même l'ensemble de la population dans des applications comme les équipements de sécurité des véhicules automobiles de type airbags ou prétensionneurs de ceinture de sécurité. En effet, ces équipements mettent en oeuvre des matériaux énergétiques adaptés au temps de réaction, extrêmement court, nécessaire...

  14. Wood duck studies : Des Lacs NWR

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This memorandum summarizes wood duck studies on Des Lacs National Wildlife Refuge and provides a brief history on the status of wood ducks on the edge of their...

  15. Table des abréviations

    OpenAIRE

    2015-01-01

    A Textes juridiques al. : alinéa art. : article A.u.-Com. : Acte uniforme portant droit commercial général A.u.-Compt. : Acte uniforme portant harmonisation des comptabilités des entreprises A.u.-Proc.coll. : Acte uniforme portant organisation des procédures collectives d’apurement du passif A.u.-Soc. : Acte uniforme relatif aux sociétés commerciales et au groupement d’intérêt économique C.ass. : Code des assurances C.civ. : Code civil C.com. : Code de commerce C.E.S.D.H. : Convention europée...

  16. Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis.

    Science.gov (United States)

    Hanein, Sylvain; Perrault, Isabelle; Gerber, Sylvie; Tanguy, Gaëlle; Barbet, Fabienne; Ducroq, Dominique; Calvas, Patrick; Dollfus, Hélène; Hamel, Christian; Lopponen, Tuija; Munier, Francis; Santos, Louisa; Shalev, Stavit; Zafeiriou, Dimitrios; Dufier, Jean-Louis; Munnich, Arnold; Rozet, Jean-Michel; Kaplan, Josseline

    2004-04-01

    Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies, responsible for congenital blindness. Disease-associated mutations have been hitherto reported in seven genes. These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium but they are involved in strikingly different physiologic pathways resulting in an unforeseeable physiopathologic variety. This wide genetic and physiologic heterogeneity that could largely increase in the coming years, hinders the molecular diagnosis in LCA patients. The genotyping is, however, required to establish genetically defined subgroups of patients ready for therapy. Here, we report a comprehensive mutational analysis of the all known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases. Mutations were identified in 47.5% patients. GUCY2D appeared to account for most LCA cases of our series (21.2%), followed by CRB1 (10%), RPE65 (6.1%), RPGRIP1 (4.5%), AIPL1 (3.4%), TULP1 (1.7%), and CRX (0.6%). The clinical history of all patients with mutations was carefully revisited to search for phenotype variations. Sound genotype-phenotype correlations were found that allowed us to divide patients into two main groups. The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rod-cone dystrophy. Besides, objective ophthalmologic data allowed us to subdivide each group into two subtypes. Based on these findings, we have drawn decisional flowcharts directing the molecular analysis of LCA genes in a given case. These flowcharts will hopefully lighten the heavy task of genotyping new patients but only if one has access to the most precise clinical history since birth.

  17. Leber's hereditary optic neuropathy caused by the homoplasmic ND1 m.3635G>A mutation in nine Han Chinese families.

    Science.gov (United States)

    Zhang, Juanjuan; Jiang, Pingping; Jin, Xiaofen; Liu, Xiaoling; Zhang, Minglian; Xie, Shipeng; Gao, Min; Zhang, Sai; Sun, Yan-Hong; Zhu, Jinping; Ji, Yanchun; Wei, Qi-Ping; Tong, Yi; Guan, Min-Xin

    2014-09-01

    In this report, we investigated the molecular mechanism underlying Leber's hereditary optic neuropathy (LHON)-associated mitochondrial m.3635G>A (p.S110N, ND1) mutation. A mutational screening of ND1 gene in a cohort of 1070 Han Chinese subjects LHON identified the m.3635G>A mutation in nine Chinese families with suggestively maternally transmitted LHON. Thirty-eight (22 males/16 females) of 162 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. Molecular analysis of their mitochondrial genomes identified the homoplasmic m.3635G>A mutation and distinct sets of polymorphisms belonging to the Asian haplogroups G2a1, R11a, D4, R11a, M7b2, G1a, F1a1, B4, and N9a3, respectively. Using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from one Chinese family into mtDNA-less (ρ(0)) cells, we showed ~27% decrease in the activity of NADH:ubiquinone oxidoreductase (complex I) in mutant cybrids carrying the m.3635G>A mutation, compared with control cybrids. The respiratory deficiency caused by the m.3635G>A mutation results in decreased efficiency of mitochondrial ATP synthesis. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cybrids. The data provide the direct evidence for the m.3635G>A mutation leading to LHON. Our findings may provide new insights into the understanding of pathophysiology of LHON.

  18. Biochemical evidence for a mitochondrial genetic modifier in the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    Science.gov (United States)

    Jiang, Pingping; Liang, Min; Zhang, Chaofan; Zhao, Xiaoxu; He, Qiufen; Cui, Limei; Liu, Xiaoling; Sun, Yan-Hong; Fu, Qun; Ji, Yanchun; Bai, Yidong; Huang, Taosheng; Guan, Min-Xin

    2016-08-15

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disease. Mitochondrial modifiers are proposed to modify the phenotypic expression of primary LHON-associated mitochondrial DNA (mtDNA) mutations. In this study, we demonstrated that the LHON susceptibility allele (m.14502T > C, p. 58I > V) in the ND6 gene modulated the phenotypic expression of primary LHON-associated m.11778G > A mutation. Twenty-two Han Chinese pedigrees carrying m.14502T > C and m.11778G > A mutations exhibited significantly higher penetrance of optic neuropathy than those carrying only m.11778G > A mutation. We performed functional assays using the cybrid cell models, generated by fusing mtDNA-less ρ(o) cells with enucleated cells from LHON patients carrying both m.11778G > A and m.14502T > C mutations, only m.14502T > C or m.11778G > A mutation and a control belonging to the same mtDNA haplogroup. These cybrids cell lines bearing m.14502T > C mutation exhibited mild effects on mitochondrial functions compared with those carrying only m.11778G > A mutation. However, more severe mitochondrial dysfunctions were observed in cell lines bearing both m.14502T > C and m.11778G > A mutations than those carrying only m.11778G > A or m.14502T > C mutation. In particular, the m.14502T > C mutation altered assemble of complex I, thereby aggravating the respiratory phenotypes associated with m.11778G > A mutation, resulted in a more defective complex I. Furthermore, more reductions in the levels of mitochondrial ATP and increasing production of reactive oxygen species were also observed in mutant cells bearing both m.14502T > C and m.11778G > A mutation than those carrying only 11778G > A mutation. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between primary and secondary mtDNA mutations.

  19. [The analysis of Leber's hereditary optic neuropathy associated with mitochondrial tRNAAla C5601T mutation in seven Han Chinese families].

    Science.gov (United States)

    Zhou, Hui-Hui; Dai, Xian-Ning; Lin, Bei; Mi, Hui; Liu, Xiao-Ling; Zhao, Fu-Xin; Zhang, Juan-Juan; Zhou, Xiang-Tian; Sun, Yan-Hong; Wei, Qi-Ping; Qu, Jia; Guan, Min-Xin

    2012-08-01

    We reported here the clinical, genetic, and molecular characterization of Leber's hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families.

  20. Fifteen novel mutations in the mitochondrial NADH dehydrogenase subunit 1, 2, 3, 4, 4L, 5 and 6 genes from Iranian patients with Leber's hereditary optic neuropathy (LHON).

    Science.gov (United States)

    Rezvani, Zahra; Didari, Elmira; Arastehkani, Ahoura; Ghodsinejad, Vadieh; Aryani, Omid; Kamalidehghan, Behnam; Houshmand, Massoud

    2013-12-01

    Leber's hereditary optic neuropathy (LHON) is an optic nerve dysfunction resulting from mutations in mitochondrial DNA (mtDNA), which is transmitted in a maternal pattern of inheritance. It is caused by three primary point mutations: G11778A, G3460A and T14484C; in the mitochondrial genome. These mutations are sufficient to induce the disease, accounting for the majority of LHON cases, and affect genes that encode for the different subunits of mitochondrial complexes I and III of the mitochondrial respiratory chain. Other mutations are secondary mutations associated with the primary mutations. The purpose of this study was to determine MT-ND variations in Iranian patients with LHON. In order to determine the prevalence and distribution of mitochondrial mutations in the LHON patients, their DNA was studied using PCR and DNA sequencing analysis. Sequencing of MT-ND genes from 35 LHON patients revealed a total of 44 nucleotide variations, in which fifteen novel variations-A14020G, A13663G, C10399T, C4932A, C3893G, C10557A, C12012A, C13934T, G4596A, T12851A, T4539A, T4941A, T13255A, T14353C and del A 4513-were observed in 27 LHON patients. However, eight patients showed no variation in the ND genes. These mutations contribute to the current database of mtDNA polymorphisms in LHON patients and may facilitate the definition of disease-related mutations in human mtDNA. This research may help to understand the disease mechanism and open up new diagnostic opportunities for LHON.

  1. [The analysis of mitochondrial DNA haplogroups and variants for Leber's hereditary optic neuropathy in Chinese families carrying the m.14484T >C mutation].

    Science.gov (United States)

    Meng, Xiangjuan; Zhu, Jinping; Gao, Min; Zhang, Sai; Zhao, Fuxin; Zhang, Juanjuan; Liu, Xiaoling; Wei, Qiping; Tong, Yi; Zhang, Minglian; Qu, Jia; Guan, Minxin

    2014-04-01

    The m.14484T>C mutation in mitochondrial ND6 gene (MT-ND6) is a primary mutation underlying the development of Leber's hereditary optic neuropathy (LHON) , but by itself not enough to cause visual loss. To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T>C mutation, we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON. A total of 67 affected subjects carried the homoplasmic m.14484T>C mutation, accounting for 5.7% of this LHON population. The penetrances of optic neuropathy among 51 pedigrees carrying the m.14484T>C mutation ranged from 5.6% to 100.0%, with the average of 21.5%. The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups. The frequencies of haplogroup A and haplogroup F were sig-nificantly less in the LHON mtDNA samples than those in 106 Chinese controls. On the other hand, the haplogroup M10a accounted for 9.8% of the patient's mtDNA samples but was absent in 106 Chinese controls. Strikingly, the average pene-trance (46.13%) of optic neuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those car-rying other mtDNA haplogroups. These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss.

  2. Progress in gene therapy study of Leber congenital amaurosis%Leber先天性黑矇的基因治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    潘珊珊; 郑钦象; 李文生; 庞继景

    2011-01-01

    Leber congenital amaurosis (LCA)is an early onset retinal dystrophy that causes severe visual impairment. With the development of molecular genetics and the therapeutic gene replacement technology, the adeno-associated viral (AAV) vector-mediated gene therapy for LCA achieved encouraging progress in the past decade. The success of the Phase Ⅰ clinical trials of human RPE65 gene therapy for LCA Ⅱ patients makes it a pioneer in the field of retinal gene therapy and brings light to the cure of other hereditary retinopathy. This article briefly reviews the recent developments in the preclinical animal experiments and Phase Ⅰ clinical trials for LCA.%Leber先天性黑矇(LCA)是一种严重的先天性致肓遗传性视网膜疾病.近1O年来,随着分子遗传学的发展及基因治疗技术的进步,以腺相关病毒载体介导的LCA基因治疗研究取得了令人鼓舞的进展,尤其是对LCAⅡ患者进行的RPE65基因治疗的Ⅰ期临床试验的成功使其成为眼科遗传性疾病基因治疗领域中的先行者,为今后进行其他遗传性视网膜疾病的基因治疗开辟了光明的前景.本文就目前LCA基因治疗的临床前研究及Ⅰ期临床试验的进展等方面作一综述.

  3. Therapeutic approaches to clinical patients with Leber's hereditary optic neuropathy%Leber遗传性视神经病变治疗探讨

    Institute of Scientific and Technical Information of China (English)

    左炜; 胡世兴

    2004-01-01

    目的探讨Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)的临床治疗方法及效果.方法观察28例LHON患者,其中22例DNA检测阳性,6例DNA检测阴性者有明确的家族遗传史和典型的临床特点.所有患者接受了神经营养和保护剂的治疗,包括中药血管扩张剂或微循环改善剂、针灸以及复方樟柳碱颞侧皮下注射等综合治疗.治疗和观察时间平均为13.6天.结果28例LHON患者的56只眼经综合治疗后26只眼视力有所提高,治疗总有效率为46.5%.其中视力≥0.05者9只眼,占16%,6只眼的视力恢复至0.4,占11%.30只眼视力无改善,占53.6%.结论DNA的检测有助于LHON患者及家系的诊断、治疗及遗传咨询.综合疗法对部分患者显示一定的治疗效果,LHON的治疗概念将会被重新认识.

  4. A simple oligonucleotide biochip capable of rapidly detecting known mitochondrial DNA mutations in Chinese patients with Leber's hereditary optic neuropathy (LHON).

    Science.gov (United States)

    Du, Wei-Dong; Chen, Gang; Cao, Hui-Min; Jin, Qing-Hui; Liao, Rong-Feng; He, Xiang-Cheng; Chen, Da-Ben; Huang, Shu-Ren; Zhao, Hui; Lv, Yong-Mei; Tang, Hua-Yang; Tang, Xian-Fa; Wang, Yong-Qing; Sun, Song; Zhao, Jian-Long; Zhang, Xue-Jun

    2011-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis.

  5. Very low penetrance of Leber's hereditary optic neuropathy in five Han Chinese families carrying the ND1 G3460A mutation.

    Science.gov (United States)

    Tong, Yi; Sun, Yan-Hong; Zhou, Xiangtian; Zhao, Fuxin; Mao, Yijian; Wei, Qi-ping; Yang, Li; Qu, Jia; Guan, Min-Xin

    2010-04-01

    We report here the clinical, genetic, and molecular characterization of five Han Chinese families with Leber's hereditary optic neuropathy (LHON). Strikingly, there were very low penetrances of visual impairment in these Chinese families, ranging from 4.2% to 22.2%, with an average of 10.2%. In particular, only 7 (4 males/3 females) of 106 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The age-at-onset for visual impairment in matrilineal relatives in these families, varied from 20 to 25 years, with an average of 21.8 years old. Molecular analysis of mitochondrial genomes identified the homoplasmic ND1 G3460A mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, C4a1, D5, F1, and R9, respectively. This suggests that the G3640A mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of known secondary LHON-associated mtDNA mutations in these Chinese families. Very low penetrance of visual loss in these five Chinese pedigrees strongly indicated that the G3640A mutation was itself insufficient to develop the optic neuropathy. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G3640A mutation in those Chinese families with low penetrance of vision loss. However, nuclear modifier genes, epigenetic and environmental factors appear to be modifier factors for the phenotypic manifestation of the G3640A mutation in these Chinese families.

  6. Gene Therapy Fully Restores Vision to the All-Cone Nrl(-/-) Gucy2e(-/-) Mouse Model of Leber Congenital Amaurosis-1.

    Science.gov (United States)

    Boye, Sanford L; Peterson, James J; Choudhury, Shreyasi; Min, Seok Hong; Ruan, Qing; McCullough, K Tyler; Zhang, Zhonghong; Olshevskaya, Elena V; Peshenko, Igor V; Hauswirth, William W; Ding, Xi-Qin; Dizhoor, Alexander M; Boye, Shannon E

    2015-09-01

    Mutations in GUCY2D are the cause of Leber congenital amaurosis type 1 (LCA1). GUCY2D encodes retinal guanylate cyclase-1 (retGC1), a protein expressed exclusively in outer segments of photoreceptors and essential for timely recovery from photoexcitation. Recent clinical data show that, despite a high degree of visual disturbance stemming from a loss of cone function, LCA1 patients retain normal photoreceptor architecture, except for foveal cone outer segment abnormalities and, in some patients, foveal cone loss. These results point to the cone-rich central retina as a target for GUCY2D replacement. LCA1 gene replacement studies thus far have been conducted in rod-dominant models (mouse) or with vectors and organisms lacking clinical translatability. Here we investigate gene replacement in the Nrl(-/-) Gucy2e(-/-) mouse, an all-cone model deficient in retGC1. We show that AAV-retGC1 treatment fully restores cone function, cone-mediated visual behavior, and guanylate cyclase activity, and preserves cones in treated Nrl(-/-) Gucy2e(-/-) mice over the long-term. A novel finding was that retinal function could be restored to levels above that in Nrl(-/-) controls, contrasting results in other models of retGC1 deficiency. We attribute this to increased cyclase activity in treated Nrl(-/-) Gucy2e(-/-) mice relative to Nrl(-/-) controls. Thus, Nrl(-/-) Gucy2e(-/-) mice possess an expanded dynamic range in ERG response to gene replacement relative to other models. Lastly, we show that a candidate clinical vector, AAV5-GRK1-GUCY2D, when delivered to adult Nrl(-/-) Gucy2e(-/-) mice, restores retinal function that persists for at least 6 months. Our results provide strong support for clinical application of a gene therapy targeted to the cone-rich, central retina of LCA1 patients.

  7. Gene therapy rescues cone structure and function in the 3-month-old rd12 mouse: a model for midcourse RPE65 leber congenital amaurosis.

    Science.gov (United States)

    Li, Xia; Li, Wensheng; Dai, Xufeng; Kong, Fansheng; Zheng, Qinxiang; Zhou, Xiangtian; Lü, Fan; Chang, Bo; Rohrer, Bärbel; Hauswirth, William W; Qu, Jia; Pang, Ji-jing

    2011-01-01

    RPE65 function is necessary in the retinal pigment epithelium (RPE) to generate chromophore for all opsins. Its absence results in vision loss and rapid cone degeneration. Recent Leber congenital amaurosis type 2 (LCA with RPE65 mutations) phase I clinical trials demonstrated restoration of vision on RPE65 gene transfer into RPE cells overlying cones. In the rd12 mouse, a naturally occurring model of RPE65-LCA early cone degeneration was observed; however, some peripheral M-cones remained. A prior study showed that AAV-mediated RPE65 expression can prevent early cone degeneration. The present study was conducted to test whether the remaining cones in older rd12 mice can be rescued. Subretinal treatment with the scAAV5-smCBA-hRPE65 vector was initiated at postnatal day (P)14 and P90. After 2 months, electroretinograms were recorded, and cone morphology was analyzed by using cone-specific peanut agglutinin and cone opsin-specific antibodies. Cone degeneration started centrally and spread ventrally, with cells losing cone-opsin staining before that for the PNA-lectin-positive cone sheath. Gene therapy starting at P14 resulted in almost wild-type M- and S-cone function and morphology. Delaying gene-replacement rescued the remaining M-cones, and most important, more M-cone opsin-positive cells were identified than were present at the onset of gene therapy, suggesting that opsin expression could be reinitiated in cells with cone sheaths. The results support and extend those of the previous study that gene therapy can stop early cone degeneration, and, more important, they provide proof that delayed treatment can restore the function and morphology of the remaining cones. These results have important implications for the ongoing LCA2 clinical trials.

  8. Long-term preservation of cones and improvement in visual function following gene therapy in a mouse model of leber congenital amaurosis caused by guanylate cyclase-1 deficiency.

    Science.gov (United States)

    Mihelec, Marija; Pearson, Rachael A; Robbie, Scott J; Buch, Prateek K; Azam, Selina A; Bainbridge, James W B; Smith, Alexander J; Ali, Robin R

    2011-10-01

    Leber congenital amaurosis (LCA) is a severe retinal dystrophy manifesting from early infancy as poor vision or blindness. Loss-of-function mutations in GUCY2D cause LCA1 and are one of the most common causes of LCA, accounting for 20% of all cases. Human GUCY2D and mouse Gucy2e genes encode guanylate cyclase-1 (GC1), which is responsible for restoring the dark state in photoreceptors after light exposure. The Gucy2e(-/-) mouse shows partially diminished rod function, but an absence of cone function before degeneration. Although the cones appear morphologically normal, they exhibit mislocalization of proteins involved in phototransduction. In this study we tested the efficacy of an rAAV2/8 vector containing the human rhodopsin kinase promoter and the human GUCY2D gene. Following subretinal delivery of the vector in Gucy2e(-/-) mice, GC1 protein was detected in the rod and cone outer segments, and in transduced areas of retina cone transducin was appropriately localized to cone outer segments. Moreover, we observed a dose-dependent restoration of rod and cone function and an improvement in visual behavior of the treated mice. Most importantly, cone preservation was observed in transduced areas up to 6 months post injection. To date, this is the most effective rescue of the Gucy2e(-/-) mouse model of LCA and we propose that a vector, similar to the one used in this study, could be suitable for use in a clinical trial of gene therapy for LCA1.

  9. Gene therapy using self-complementary Y733F capsid mutant AAV2/8 restores vision in a model of early onset Leber congenital amaurosis.

    Science.gov (United States)

    Ku, Cristy A; Chiodo, Vince A; Boye, Sanford L; Goldberg, Andrew F X; Li, Tiansen; Hauswirth, William W; Ramamurthy, Visvanathan

    2011-12-01

    Defects in the photoreceptor-specific gene aryl hydrocarbon receptor interacting protein-like 1 (Aipl1) are associated with Leber congenital amaurosis (LCA), a childhood blinding disease with early-onset retinal degeneration and vision loss. Furthermore, Aipl1 defects are characterized at the most severe end of the LCA spectrum. The rapid photoreceptor degeneration and vision loss observed in the LCA patient population are mimicked in a mouse model lacking AIPL1. Using this model, we evaluated if gene replacement therapy using recent advancements in adeno-associated viral vectors (AAV) provides advantages in preventing rapid retinal degeneration. Specifically, we demonstrated that the novel self-complementary Y733F capsid mutant AAV2/8 (sc-Y733F-AAV) provided greater preservation of photoreceptors and functional vision in Aipl1 null mice compared with single-stranded AAV2/8. The benefits of sc-Y733F-AAV were evident following viral administration during the active phase of retinal degeneration, where only sc-Y733F-AAV treatment achieved functional vision rescue. This result was likely due to higher and earlier onset of Aipl1 expression. Based on our studies, we conclude that the sc-Y733F-AAV2/8 viral vector, to date, achieves the best rescue for rapid retinal degeneration in Aipl1 null mice. Our results provide important considerations for viral vectors to be used in future gene therapy clinical trials targeting a wider severity spectrum of inherited retinal dystrophies.

  10. Herkömmliche, modifizierte und neue Messmethoden zur kephalometrischen Untersuchung der pränatalen craniofacialen Morphogenese des Menschen anhand von bilateralen und frontalen Darstellungen von 3D-Rekonstruktionen und von Aufhellungspräparaten menschlicher Embryonen und Föten von 19 mm SSL bis 145 mm SSL

    OpenAIRE

    Gruda, Agron

    2010-01-01

    The aim of this thesis was to analyse growth, local differences in growth and dislocations of craniofacial bone. Modified and new measurement techniques were applied in addition to conventional cephalometric testing methods according to Broadbent (1937). Fourteen whole mount preparations ranging from 35 mm to 150 mm crown-rump-length (CRL) and 3D reconstructions of histological serial sections of embryos and fetuses sized 19 mm to 53 mm CRL were used for this study. Frontal and lateral ...

  11. L 'Analyse des Organisations en Afrique:

    African Journals Online (AJOL)

    croissance économique, développement des techniques industrielles, nécessité d'une plus ... légale se caractérise par la consécration des règles de droit et d'un certain nombre ..... mais un système ouvert qui entretient avec son environnement une relation .... C'est l'affaire de tous, que l'on soit supérieur ou subordonné.

  12. Tabanidae (Diptera) des pays-bas

    NARCIS (Netherlands)

    Leclercq, M.

    1967-01-01

    INTRODUCTION Cette mise au point des Tabanides des Pays-Bas a été rendue possible grâce à la collaboration de M. V. S. van der Goot, département d'Entomologie, Zoölogisch Museum, Amsterdam, que nous remercions pour son amabilité. Nous avons pu étudier aussi les collections du Rijksmuseum van Natuurl

  13. Probleme des elektiven Mutismus bei Jugendlichen

    OpenAIRE

    1983-01-01

    Nach einem Exkurs zur Terminologie des Begriffs elektiver Mutismus und zur Symptomatologie dieser Erkrankung wird anhand einer Krankengeschichte die Hauptproblematik der Psychotherapie mit einem jugendlichen Mutisten erörtert. Besondere Erwähnung finden dabei 1. der äußerst schwierige Abschnitt von der Kontaktaufnahme bis zur "regelrechten" Gesprächspsychotherapie und 2. der Konflikt, der in diesem speziellen Fall der Entstehung des Mutismus zugrunde liegt. Hinweise zur Arbeit mit de...

  14. Der Machtmensch: zur Dramatologie des Politikers

    OpenAIRE

    Hitzler, Ronald

    1991-01-01

    Der Beitrag erörtert das Anforderungsprofil des modernen Politikers, wobei unter anderem folgende Aspekte beleuchtet werden: (1) Die Darstellungskompetenz, (2) Machiavellismus, (3) die typische Persönlichkeit des Politikers (Harold D. Laswell), (4) Politik als Beruf (M. Weber), (5) die wichtigsten Bedingungen für eine erfolgreiche Politikerkarriere, (6) politisches Handeln verstanden als Inszenierungsarbeit, (7) Politik als Ritual (Murray Edelman), (8) die Dramatologie der Politik sowie (9) d...

  15. Analyse de la mobilité des paysages et des systèmes sociaux en Thessalie : l’apport des images Landsat TM

    Directory of Open Access Journals (Sweden)

    Bernard Helly

    2000-05-01

    Full Text Available Une équipe pluridisciplinaire tente d’identifier la répartition des sites observables ou enfouis dans la plaine de Larissa. L’analyse d’image Landsat TM a permis d’identifier l’extension réelle des épandages, des systèmes de failles mais aussi des trames anthropiques qu’aucun autre document n’illustre.

  16. Caracterisation des proprietes acoustiques des materiaux poreux a cellules ouvertes et a matrice rigide ou souple

    Science.gov (United States)

    Salissou, Yacoubou

    L'objectif global vise par les travaux de cette these est d'ameliorer la caracterisation des proprietes macroscopiques des materiaux poreux a structure rigide ou souple par des approches inverses et indirectes basees sur des mesures acoustiques faites en tube d'impedance. La precision des approches inverses et indirectes utilisees aujourd'hui est principalement limitee par la qualite des mesures acoustiques obtenues en tube d'impedance. En consequence, cette these se penche sur quatre problemes qui aideront a l'atteinte de l'objectif global precite. Le premier probleme porte sur une caracterisation precise de la porosite ouverte des materiaux poreux. Cette propriete en est une de passage permettant de lier la mesure des proprietes dynamiques acoustiques d'un materiau poreux aux proprietes effectives de sa phase fluide decrite par les modeles semi-phenomenologiques. Le deuxieme probleme traite de l'hypothese de symetrie des materiaux poreux selon leur epaisseur ou un index et un critere sont proposes pour quantifier l'asymetrie d'un materiau. Cette hypothese est souvent source d'imprecision des methodes de caracterisation inverses et indirectes en tube d'impedance. Le critere d'asymetrie propose permet ainsi de s'assurer de l'applicabilite et de la precision de ces methodes pour un materiau donne. Le troisieme probleme vise a mieux comprendre le probleme de transmission sonore en tube d'impedance en presentant pour la premiere fois un developpement exact du probleme par decomposition d'ondes. Ce developpement permet d'etablir clairement les limites des nombreuses methodes existantes basees sur des tubes de transmission a 2, 3 ou 4 microphones. La meilleure comprehension de ce probleme de transmission est importante puisque c'est par ce type de mesures que des methodes permettent d'extraire successivement la matrice de transfert d'un materiau poreux et ses proprietes dynamiques intrinseques comme son impedance caracteristique et son nombre d'onde complexe. Enfin, le

  17. Rapid genetic analysis in the diagnosis of primary Leber's hereditary optic neuropathy by using multiplex allele-specific polymerase chain reaction (MAS-PCR) with whole blood%MAS-PCR法快速诊断分析Leber's遗传性视神经病变原发性致病突变位点

    Institute of Scientific and Technical Information of China (English)

    阳菊华; 童绎; 朱益华; 林宇岚; 陈贻锴; 林建银

    2006-01-01

    目的 探索一种简易、快速、高效的临床基因诊断分析原发性Leber's遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)位点的新方法.方法 根据已知的LHON患者线粒体DNA上的3个原发性LHON致病突变位点(G11778A、T14484C和G3460A),设计3条突变位点特异性聚合酶链反应(polymerase chain reaction,PCR)引物,直接以全血样为模板的等位基因特异性多重PCR(multiplex allelespecific polymerase chain reaction,MAS-PCR)分析3个原发性LHON致病突变位点.以此方法检测24例确诊的LHON患者,其中18例为线粒体DNA G11778A突变,4例为T14484C突变,2例为G3460A突变;同时,以20份正常血样标本作阴性对照.结果 优化的MAS-PCR条件为94℃/3 min,94℃/30 s、59.8℃/30 s、72℃/30 s,30个循环,72℃/3 min;以此方法检测了44份血样标本,其结果与预期结果一致,表明利用该方法筛查3个原发性LHON致病突变位点是可行的.同时,混和血液样本模拟实验结果显示,该方法可检测含多个原发性LHON致病突变位点的血液样本,且整个分析过程只需约2 h.结论 该方法直接以全血样作为PCR的模板,不需从血样中纯化DNA;单管一次性行PCR,可同时筛查3个原发性LHON致病突变位点.因此,该方法具有快速、高效、费用低、特异性好以及只需微量血液样本等优点.

  18. TENDANCES ACTUELLES EN MARKETING DES SERVICES

    Directory of Open Access Journals (Sweden)

    George NICULESCU

    2010-09-01

    Full Text Available Les activités de services sont difficiles à gérer dans le cadre du marketing-mix traditionnel car, contrairement aux biens tangibles produits la qualité des services est très dépendante de facteurs personnels. De même, la nature intangible des services n’est pas prise en compte dans la plupart des analyses du marketing-mix. Par exemple, la distribution physique ne coïncide pas avec la distribution d’éléments invisibles et la politique de communication de l’approche traditionnelle du marketingmix (4P’s ne reconnaît pas la communication des services établie sur le lieu de rencontre entre le personnel de contact de la firme et les clients. Même si les opinions sont partagées et que le débat n’est pas clos, on peut considérer que des éléments supplémentaires s’imposent pour élaborer un marketing qui permette de satisfaire les attentes des parties contractantes de la façon la plus satisfaisante possible

  19. Wiktor Stoczkowski, Des hommes, des dieux et des extraterrestres. Ethnologie d’une croyance moderne

    OpenAIRE

    Lepoutre, David

    2006-01-01

    Voici un ouvrage qui nous fait entrer de plain-pied dans une subculture contemporaine généralement perçue comme marginale et qui s’avère pourtant être d’une importance sociale considérable. Il s’agit de l’univers, exotique s’il en est, des parasciences et de la pensée occultiste. Le lecteur curieux y trouvera un ensemble de développements remarquablement bien documentés et ordonnés sur un certain nombre de sujets et de thèmes liés à cette pensée contemporaine dont les ramifications tentaculai...

  20. The new radiation protection ordinance from the viewpoint of the nuclear medicine technologist; Die neue Strahlenschutzverordnung aus der Sicht der medizinisch-technischen Radiologieassistentin/des medizinisch-technischen Radiologieassistenten

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, S. [Klinik und Poliklinik fuer Nuklearmedizin, Ludwig-Maximilians-Univ. Muenchen (Germany)

    2002-05-01

    The new radiation protection ordinance for the first time acknowledges the role of the nuclear medicine technologists for the technical assistance in the use of radiopharmaceuticals and radiation with human beings in medicine. Therefore changes are required for the technologists in terms of their qualification and continuing education during their professional life and in the daily routine in a nuclear medicine department. The new ordinance clearly defines which group of people is allowed to work as nuclear medicine technologists and also which special knowledge in radiation protection is mandatory to make sure that nobody without this certified education is performing the work of a nuclear medicine technologist. The new effective dose limit for people working with radiation will not change the daily work, but new regulations for pregnant women or breastfeeding mothers working in nuclear medicine will bring dramatic changes. (orig.) [German] Die neue Strahlenschutzverordnung beruecksichtigt zum ersten Mal ausdruecklich die Rolle des medizinisch-technischen Personals bei der 'technischen Mitwirkung bei der Anwendung radioaktiver Stoffe oder ionisierender Strahlung am Menschen in der Heilkunde oder der Zahnheilkunde'. Dadurch ergeben sich fuer die MTRA neue Anforderungen in Bezug auf Ausbildungsvoraussetzungen, berufliche Fortbildung und auch auf die Ablaeufe in der taeglichen Routine. Der Personenkreis, der zur technischen Mitwirkung berechtigt ist, wurde genau definiert, ebenso wie dessen Fachkunde, mit der nun sichergestellt werden soll, dass keine Personen ohne Kenntnisse im Strahlenschutz die Taetigkeiten der MTRA ausfuehren. Die neu festgelegte Obergrenze der effektiven Dosis fuer beruflich strahlenexponiertes Personal wird fuer das technische Personal keine merkbaren Auswirkungen mit sich bringen, dafuer aber die Neuerungen bezueglich der Beschaeftigung von Schwangeren und stillenden Frauen. (orig.)